Annals of Coloproctology

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Original Article

Metastasis or chemotherapy

Effectiveness of oxaliplatin-based second-line therapy following cetuximab+FOLFIRI or bevacizumab+FOLFIRI in KRAS wild-type metastatic colorectal cancer without primary tumor resection: Yi-Chia Su, Chien-Chou Su, Pei-Ting Lee, Chih-Chien Wu; Ann Coloproctol. 2025;41(4):319-329. Published online August 21, 2025; DOI: https://doi.org/10.3393/ac.2025.00087.0012

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Abstract PDF: Purpose
Wild-type unresectable metastatic colorectal cancer (mCRC) poses challenges for treatment optimization. Effective first-line targeted therapies are crucial for improving outcomes, particularly when combined with second-line oxaliplatin-based chemotherapies. This study examined the effects of first-line cetuximab+FOLFIRI versus bevacizumab+FOLFIRI, followed by second-line oxaliplatin-based chemotherapy, on survival among patients with KRAS wild-type mCRC without primary tumor resection (PTR).
Methods
A retrospective analysis of Taiwanese data (2013–2019) included patients with KRAS wild-type unresectable mCRC who received first-line cetuximab+FOLFIRI or bevacizumab+FOLFIRI, followed by second-line oxaliplatin-based chemotherapy. Survival outcomes—overall survival (OS) and time to treatment discontinuation (TTD)—were compared between these regimens using stabilized inverse probability of treatment weighting to adjust for potential confounders, followed by multivariate Cox proportional hazards regression analysis to account for clinical and biological variables.
Results
In patients without PTR, first-line cetuximab+FOLFIRI with second-line oxaliplatin-based chemotherapy significantly improved OS from the start dates of first- and second-line treatment compared to first-line bevacizumab+FOLFIRI with second-line oxaliplatin-based therapy, yielding adjusted hazard ratios (HRs) of 0.60 (95% confidence interval [CI], 0.46–0.78) and 0.56 (95% CI, 0.42–0.73), respectively. No significant difference in TTD was observed (HR, 0.82; 95% CI, 0.65–1.04).
Conclusion
First-line cetuximab+FOLFIRI followed by second-line oxaliplatin-based chemotherapy offers superior OS compared to bevacizumab+FOLFIRI followed by second-line oxaliplatin‑based chemotherapy in KRAS wild-type mCRC without PTR. These findings underscore the importance of personalized treatment sequencing, highlighting the need for further research to optimize mCRC management.

Review

Translational/basic research

Tissue engineering and regenerative medicine approaches in colorectal surgery: Bigyan B. Mainali, James J. Yoo, Mitchell R. Ladd; Ann Coloproctol. 2024;40(4):336-349. Published online August 30, 2024; DOI: https://doi.org/10.3393/ac.2024.00437.0062

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Abstract PDF

Tissue engineering and regenerative medicine (TERM) is an emerging field that has provided new therapeutic opportunities by delivering innovative solutions. The development of nontraditional therapies for previously unsolvable diseases and conditions has brought hope and excitement to countless individuals globally. Many regenerative medicine therapies have been developed and delivered to patients clinically. The technology platforms developed in regenerative medicine have been expanded to various medical areas; however, their applications in colorectal surgery remain limited. Applying TERM technologies to engineer biological tissue and organ substitutes may address the current therapeutic challenges and overcome some complications in colorectal surgery, such as inflammatory bowel diseases, short bowel syndrome, and diseases of motility and neuromuscular function. This review provides a comprehensive overview of TERM applications in colorectal surgery, highlighting the current state of the art, including preclinical and clinical studies, current challenges, and future perspectives. This article synthesizes the latest findings, providing a valuable resource for clinicians and researchers aiming to integrate TERM into colorectal surgical practice.

Citations

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Organ-on-chip platforms for nanoparticle toxicity and efficacy assessment: Advancing beyond traditional in vitro and in vivo models
Ana Regina Sampaio, Renata Faria Maia, Maria Camilla Ciardulli, Hélder A. Santos, Bruno Sarmento
Materials Today Bio.2025; 33: 102053. CrossRef
From the Editor: Uniting expertise, a new era of global collaboration in coloproctology
In Ja Park
Annals of Coloproctology.2024; 40(4): 285. CrossRef

Guideline

Colorectal cancer

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment: Hyo Seon Ryu, Hyun Jung Kim, Woong Bae Ji, Byung Chang Kim, Ji Hun Kim, Sung Kyung Moon, Sung Il Kang, Han Deok Kwak, Eun Sun Kim, Chang Hyun Kim, Tae Hyung Kim, Gyoung Tae Noh, Byung-Soo Park, Hyeung-Min Park, Jeong Mo Bae, Jung Hoon Bae, Ni Eun Seo, Chang Hoon Song, Mi Sun Ahn, Jae Seon Eo, Young Chul Yoon, Joon-Kee Yoon, Kyung Ha Lee, Kyung Hee Lee, Kil-Yong Lee, Myung Su Lee, Sung Hak Lee, Jong Min Lee, Ji Eun Lee, Han Hee Lee, Myong Hoon Ihn, Je-Ho Jang, Sun Kyung Jeon, Kum Ju Chae, Jin-Ho Choi, Dae Hee Pyo, Gi Won Ha, Kyung Su Han, Young Ki Hong, Chang Won Hong, Jung-Myun Kwak, Korean Colon Cancer Multidisciplinary Committee; Ann Coloproctol. 2024;40(2):89-113. Published online April 30, 2024; DOI: https://doi.org/10.3393/ac.2024.00059.0008

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10 Web of Science
11 Citations

Abstract PDF Supplementary Material

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Citations

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Optimal extent of lymph node dissection in clinical early-stage right colon cancer: a retrospective analysis
Hyeung-min Park, Jaram Lee, Soo Young Lee, Suk Hee Heo, Yong Yeon Jeong, Hyeong Rok Kim, Chang Hyun Kim
Annals of Surgical Treatment and Research.2025; 108(1): 49. CrossRef
Effects of Microsatellite Instability on the Clinical and Pathological Characteristics of Colon Cancer and the Diagnostic Accuracy of Preoperative Abdominal CT Scans
Rıdvan Yavuz, Orhan Aras, Hüseyin Çiyiltepe, Onur İlkay Dinçer, Ahmet Şükrü Alparslan, Tebessüm Çakır
Diagnostics.2025; 15(2): 190. CrossRef
Epigenetic Regulation of Nuclear Factor Erythroid-2-Related Factor 2 in Colorectal Cancer Cells Resistant to Ionizing Radiation
Kyoung Ah Kang, Jinny Park, Mei Jing Piao, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna, Jung-Hwan Kim, Suk Ju Cho, Jin Won Hyun
Biomolecules & Therapeutics.2025; 33(1): 182. CrossRef
Meeting report on the 8th Asian Science Editors’ Conference and Workshop 2024
Eun Jung Park
Science Editing.2025; 12(1): 66. CrossRef
The Diagnostic Value of Virtual Colonoscopy in Colonic Diseases
İhsaniye Süer Doğan, Esin Çakmakçı Midia, Yıldıran Songür, Baki Hekimoğlu
Turkish Journal of Clinics and Laboratory.2025; 16(1): 27. CrossRef
National Guidelines for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Peritoneal Malignancies: A Worldwide Systematic Review and Recommendations of Strength Analysis
Marco Tonello, Carola Cenzi, Elisa Pizzolato, Manuela Martini, Pierluigi Pilati, Antonio Sommariva
Annals of Surgical Oncology.2025; 32(8): 5795. CrossRef
Advancements in Image‐Based Analyses for Morphology and Staging of Colon Cancer: A Comprehensive Review
Samuel Arthur Ameyaw, Derrick Adu Afari, John Boateng, Marcello Maida
BioMed Research International.2025;[Epub] CrossRef
2023 Korean Multidisciplinary Guidelines for Colon Cancer Management: Summary of Radiological Points
Nieun Seo, Hyo Seon Ryu, Myungsu Lee, Sun Kyung Jeon, Kum Ju Chae, Joon-Kee Yoon, Kyung Su Han, Ji Eun Lee, Jae Seon Eo, Young Chul Yoon, Sung Kyung Moon, Hyun Jung Kim, Jung-Myun Kwak
Korean Journal of Radiology.2024; 25(9): 769. CrossRef
Effect of Fluorescence Lymph Node Mapping on Improving Diagnostic Values of CT D3 Lymph Node Staging for Right-Sided Colon Cancer
Gyung Mo Son, Tae Un Kim, Mi Sook Yun, ChangYeop Kim, In Young Lee, Su Bum Park, Dong-Hoon Shin, Gi Won Ha
Cancers.2024; 16(20): 3496. CrossRef
Nuclear medicine based multimodal molecular imaging facilitates precision medicine for gastrointestinal tumors
Jing Zhao, Fei Wang, Rong-Fu Wang
World Chinese Journal of Digestology.2024; 32(10): 727. CrossRef
Impact of Early Oral Feeding on Postoperative Outcomes after Elective Colorectal Surgery: A Systematic Review and Meta-Analysis
Soo Young Lee, Eon Chul Han
Digestive Surgery.2024; : 1. CrossRef

Reviews

Inflammatory bowel diseases

Colorectal surgical management of colitis induced by vasculitis in the absence of inflammatory bowel disease: a case report and literature review: Jessica A. Paynter, Kirby R. Qin, Georgia Seamer, Ruchira Fernando, Janelle Brennan, Chun Hin Angus Lee; Ann Coloproctol. 2023;39(3):193-203. Published online November 16, 2022; DOI: https://doi.org/10.3393/ac.2022.00584.0083

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Abstract PDF

Colitis caused by vasculitis is a rare and poorly understood pathology. Little evidence exists on its clinical presentation, path to diagnosis, and surgical management. In this report, we present a case report and literature review. A healthy 20-year-old male patient presented with hemorrhagic colitis requiring total colectomy with end ileostomy. Pathological examination showed pancolitis with multiple ulcers, transmural inflammation, hemorrhage, and microvascular thrombosis. Extensive serological testing revealed elevated cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) and eosinophilia, leading to a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) and vasculitis-induced colitis. A literature review was subsequently conducted. Nineteen studies were found documenting vasculitis-induced colitis in the absence of inflammatory bowel disease (IBD). Systemic signs of vasculitis, hemorrhagic colitis, and progression to fulminant colitis were present. Of all patients, 40.0% required colorectal surgery and 62.5% of those patients received a stoma; 25% underwent emergency surgery following failed immunosuppression. All cases relied on clinical correlation with serology and/or histopathology to reach a final diagnosis. We report a case of vasculitis-induced colitis caused by c-ANCA−positive EGPA. The review shows that vasculitis-induced colitis without IBD is an important differential that clinicians should be aware of in patients presenting with colitis.

Citations

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Systemic Lupus Erythematosus Vasculitis Causing Perforation Peritonitis in Miliary Tuberculosis: A Disease in Disguise
Soumyajit Jana, Monika Gureh, Ankur Cheleng, Ayush Vardhan
Cureus.2025;[Epub] CrossRef

Gene and protein expression of epithelial to mesenchymal transition for intestinal and anal fistula: a systematic review: Nadila Haryani Osman, Ruhi Fadzlyana Jailani, Hayati Abd Rahman, Nazefah Abdul Hamid; Ann Coloproctol. 2023;39(2):106-114. Published online December 3, 2021; DOI: https://doi.org/10.3393/ac.2021.00584.0083

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Abstract PDF

Purpose
Intestinal fibrosis is a common complication of inflammatory bowel diseases. However, the possible involvement of epithelial-mesenchymal transition (EMT) has been scarcely investigated. This systematic review aims to search through research papers that are focusing on messenger RNA (mRNA) and protein expression profile in EMT in fistula or in intestinal fibrosis.
Methods
Electronic exploration was performed until April 24, 2019 through PubMed, Ovid, Science Direct, and Scopus databases with the terms of “fistula” OR “intestinal fibrosis” AND “epithelial-mesenchymal transition”. Two independent reviewers scrutinized the suitability of the title and abstract before examining the full text that met the inclusion criteria. For each study, the sample types that were used, methods for analysis, and genes expressed were identified. The list of genes was further analyzed using DAVID (Database for Annotation, Visualization, and Integrated Discovery) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway.
Results
There were 896 citations found; however, only 3 studies fulfilled the requirements. Among the EMT-related genes, 5 were upregulated genes at mRNA level while 6 were at protein level. However, only 2 downregulated genes were found at each mRNA and protein level. Of the 4 inflammation-related genes found, 3 genes were upregulated at mRNA level and 1 at protein level. These genes were confirmed to be involved in the development of inflammatory induced fibrosis and fistula through EMT. Results from quantitative real-time polymerase chain reaction analysis were consistent with the process of EMT, confirmed by the western blot protein analysis.
Conclusion
Many significant genes which are involved in the process of EMT in fistula and intestinal fibrosis have been identified. With high-end technology many more genes could be identified. These genes will be good molecular targets in the development of biomarkers for precision drug targeting in the future treatment of intestinal fibrosis and fistula.

Citations

Citations to this article as recorded by

Curing cryptoglandular anal fistulas—Is it possible without surgery?
Chuang Wu, Zubing Mei, Zhenyi Wang
Heliyon.2025; 11(1): e41297. CrossRef
Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula
Marcin Włodarczyk, Jakub Włodarczyk, Kasper Maryńczak, Anna Waśniewska-Włodarczyk, Urszula Doboszewska, Piotr Wlaź, Łukasz Dziki, Jakub Fichna
International Journal of Molecular Sciences.2024; 25(3): 1501. CrossRef
Exosomes Derived from Colon Cancer Cells Promote Tumor Progression and Affect the Tumor Microenvironment
Minsung Kim, Il Tae Son, Gyoung Tae Noh, So-Youn Woo, Ryung-Ah Lee, Bo Young Oh
Journal of Clinical Medicine.2023; 12(12): 3905. CrossRef

Case Report

Benign bowel disease

Recurrent perianal abscess in a patient with Hermansky-Pudlak syndrome–associated granulomatous colitis: a case report: Ahmet Omak, Tevfik Kıvılcım Uprak, Wafi Attaallah; Ann Coloproctol. 2024;40(Suppl 1):S11-S14. Published online November 19, 2021; DOI: https://doi.org/10.3393/ac.2021.00437.0062

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Abstract PDF: Hermansky-Pudlak syndrome (HPS) is a rare genetic disease consisting of the triad of oculocutaneous albinism, bleeding diathesis, and pigmented reticuloendothelial cells. In HPS patients’ granulomatous colitis could be an additional feature and perianal abscess could be seen in such patients. We report a patient with HPS-associated granulomatous colitis, refractory to medical treatment, and perianal involvement. Patients with HPS-associated granulomatous colitis and perianal involvement may require multiple surgical interventions and there is no consensus yet for treatment in such patients.

Original Articles

Malignant disease,Colorectal cancer,Benign diesease & IBD,Biomarker & risk factor

Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples: Sungwon Jung, Jong Lyul Lee, Tae Won Kim, Jongmin Lee, Yong Sik Yoon, Kil Yeon Lee, Ki-hwan Song, Chang Sik Yu, Yong Beom Cho; Ann Coloproctol. 2022;38(1):72-81. Published online November 17, 2021; DOI: https://doi.org/10.3393/ac.2021.00290.0041

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2 Citations

Abstract PDF

Purpose
Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC.
Methods
From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated.
Results
Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors.
Conclusion
UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status.

Citations

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Impact of Postoperative Naples Prognostic Score to Predict Survival in Patients with Stage II–III Colorectal Cancer
Su Hyeong Park, Hye Seung Woo, In Kyung Hong, Eun Jung Park
Cancers.2023; 15(20): 5098. CrossRef
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus R0 resection for resectable colorectal cancer with peritoneal metastases and low peritoneal cancer index scores: A collaborative observational study from Korea and Japan
Daichi Kitaguchi, Eun Jung Park, Seung Hyuk Baik, Shoma Sasaki, Yuichiro Tsukada, Masaaki Ito
International Journal of Surgery.2023;[Epub] CrossRef

Incidence of anal fistula after pyogenic perianal abscess drainage in Kingdom of Bahrain: Zahra Abdulla Isa Yusuf Hasan, Bayan Mohamed, Rawaa AlSayegh, Raed AlMarzooq; Ann Coloproctol. 2023;39(1):27-31. Published online August 9, 2021; DOI: https://doi.org/10.3393/ac.2020.00962.0137

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5 Web of Science
5 Citations

Abstract PDF

Purpose
Perianal fistula is one of the most common anorectal diseases in adult patients, especially men. A relationship between pyogenic perianal abscess and fistula formation is established in multiple domains. This is the first exploration of such association among patients in the country as no related study has been published in Bahrain. We expect this study to be a foundation for future protocols and evidence-based practice.
Methods
A retrospective study was conducted in Salmaniya Medical Complex of Bahrain. A total of 109 patients with a diagnosis of anal abscess were included between 2015 and 2018. Data were collected from the electronic files database used in Salmaniya Medical Complex (iSeha) as well as phone calls to the patients. Collected data were analyzed using statistical software.
Results
The most predominant presentation of perianal abscess was pain. Over 50% of abscesses were classified as perianal (56.9%) and among those, left-sided abscesses were more common, followed by right-, posterior-, and anterior-sited, respectively. No recurrence of abscess was recorded among 80% of patients. A fistula developed following abscess drainage in 33.9% of patients. Most fistulas (37.8%) were diagnosed within 6 months or less from abscess drainage. Posterior fistulas were the most common, followed by anterior and left-sided fistulas.
Conclusion
The incidence of anal fistula in Bahrain after perianal abscess was 33.9%. Most of the patients who developed a fistula following pyogenic abscess drainage were males and above the age of 40 years. The most common site for fistula was posterior.

Citations

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Risk factors for perianal abscess recurrence after incision and drainage: a review of the literature
Kheira Gabsi
International Surgery Journal.2025; 12(2): 255. CrossRef
A Review of the Anatomy of Anal Glands Relevant to Cryptoglandular Fistulas; Are We on the Right Track?
James Church
ANZ Journal of Surgery.2025; 95(11): 2355. CrossRef
Anal Cryptoglandular Suppuration
Oladapo Akinmoladun, Quinton M. Hatch
Surgical Clinics of North America.2024; 104(3): 491. CrossRef
Proposal for a new classification of anorectal abscesses based on clinical characteristics and postoperative recurrence
Shan-Zhong Chen, Kui-Jun Sun, Yi-Fan Gu, Hong-Yuan Zhao, Dong Wang, Yun-Fang Shi, Ren-Jie Shi
World Journal of Gastrointestinal Surgery.2024; 16(11): 3425. CrossRef
Research Progress on Diagnosis and Surgical Treatment of Perianal Deep Space Abscess
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Advances in Clinical Medicine.2023; 13(01): 180. CrossRef

Case Report

Malignant disease,Rare disease & stoma

Extensive Resection for Treatment of Locally Advanced Primary Mucinous Adenocarcinoma Arising From Fistula-in-Ano: Jordan Au, Francis M. Hulme-Moir, Andrew Herd, Mathew A. Kozman; Ann Coloproctol. 2021;37(Suppl 1):S7-S10. Published online November 26, 2019; DOI: https://doi.org/10.3393/ac.2019.11.19

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3 Web of Science
4 Citations

Abstract PDF

We report a case of a 66-year-old male who presented with a locally advanced primary mucinous adenocarcinoma arising from a fistula-in-ano. The presentation was typical for perianal sepsis and fistula-in-ano with anal pain and chronic discharge. Initial treatments with fistula debridement and seton were performed. Subsequent review of histology revealed underlying adenocarcinoma, while magnetic resonance imaging (MRI) showed local invasion into the prostate. The patient received neoadjuvant chemoradiotherapy followed by pelvic exenteration to maximize the chance of achieving cure. Features of this case are discussed together with its implications, including treatment guidelines and typical MRI findings.

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Perianal Mucinous Adenocarcinoma: A Case Report and a Systematic Review of the Literature
Ioannis D. Gkegkes, Vassilis Milionis, Nikolaos Goutas, Ioannis Mantzoros, Antonia A. Bourtzinakou, Apostolos P. Stamatiadis
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
A Rare Presentation of Fournier’s Gangrene: Necrotizing Infection Traveling Through a Fistula From the Rectum to the Corpus Cavernosum
Donald Dennis, Michael Gentry
Cureus.2025;[Epub] CrossRef
Perianal Mucinous Adenocarcinoma Found Incidentally From Perianal Mass
Seyed Khalafi, Malini Riddle, Brittany Harper, Vid Fikfak
Cureus.2023;[Epub] CrossRef
Advances in the Treatment of Colorectal Cancer with Peritoneal Metastases: A Focus on Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
Youngbae Jeon, Eun Jung Park
The Ewha Medical Journal.2023;[Epub] CrossRef

Original Article

Association Between c-Met and Lymphangiogenic Factors in Patients With Colorectal Cancer: Han Jo Kim, Moo-Jun Baek, Dong Hyun Kang, Sang-Cheol Lee, Sang Byung Bae, Kyu Taek Lee, Namsu Lee, Hyungjoo Kim, Dongjun Jeong, Tae Sung Ahn, Moon Soo Lee, Dae Sik Hong, Jong-Ho Won; Ann Coloproctol. 2018;34(2):88-93. Published online April 30, 2018; DOI: https://doi.org/10.3393/ac.2017.10.10

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118 Download
5 Web of Science
4 Citations

Abstract PDF

Purpose
Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC.
Methods
A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed.
Results
Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found.
Conclusion
Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

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Expression Profile of Microenvironmental Factors in the Interface Zone of Colorectal Cancer: Histological-Stromal Biomarkers and Cancer Cell-Cancer-Associated Fibroblast-Related Proteins Combined for the Assessment of Tumor Progression
Ricella Souza da Silva, Eduardo M. Queiroga, Cynthia de Toledo Osório, Karin S. Cunha, Fabiana P. Neves, Julieth P. Andrade, Eliane P. Dias
Pathobiology.2024; 91(2): 99. CrossRef
Recent progress in the imaging of c‐Met aberrant cancers with positron emission tomography
Giuseppe Floresta, Vincenzo Abbate
Medicinal Research Reviews.2022; 42(4): 1588. CrossRef
Involvement of Met receptor pathway in aggressive behavior of colorectal cancer cells induced by parathyroid hormone-related peptide
María Belén Novoa Díaz, Pedro Carriere, Graciela Gigola, Ariel Osvaldo Zwenger, Natalia Calvo, Claudia Gentili
World Journal of Gastroenterology.2022; 28(26): 3177. CrossRef
The potential therapeutic and prognostic impacts of the c‐MET/HGF signaling pathway in colorectal cancer
Seyed Mostafa Parizadeh, Reza Jafarzadeh‐Esfehani, Danial Fazilat‐Panah, Seyed Mahdi Hassanian, Soodabeh Shahidsales, Majid Khazaei, Seyed Mohammad Reza Parizadeh, Majid Ghayour‐Mobarhan, Gordon A. Ferns, Amir Avan
IUBMB Life.2019; 71(7): 802. CrossRef

Review

The Future Medical Science and Colorectal Surgeons: Young Jin Kim; Ann Coloproctol. 2017;33(6):207-209. Published online December 31, 2017; DOI: https://doi.org/10.3393/ac.2017.33.6.207

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Abstract PDF

Future medical technology breakthroughs will build from the incredible progress made in computers, biotechnology, and nanotechnology and from the information learned from the human genome. With such technology and information, computer-aided diagnoses, organ replacement, gene therapy, personalized drugs, and even age reversal will become possible. True 3-dimensional system technology will enable surgeons to envision key clinical features and will help them in planning complex surgery. Surgeons will enter surgical instructions in a virtual space from a remote medical center, order a medical robot to perform the operation, and review the operation in real time on a monitor. Surgeons will be better than artificial intelligence or automated robots when surgeons (or we) love patients and ask questions for a better future. The purpose of this paper is looking at the future medical science and the changes of colorectal surgeons.

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Development of artificial intelligence technology in diagnosis, treatment, and prognosis of colorectal cancer
Feng Liang, Shu Wang, Kai Zhang, Tong-Jun Liu, Jian-Nan Li
World Journal of Gastrointestinal Oncology.2022; 14(1): 124. CrossRef
Modern Machine Learning Practices in Colorectal Surgery: A Scoping Review
Stephanie Taha-Mehlitz, Silvio Däster, Laura Bach, Vincent Ochs, Markus von Flüe, Daniel Steinemann, Anas Taha
Journal of Clinical Medicine.2022; 11(9): 2431. CrossRef
Surgical safety in the COVID-19 era: present and future considerations
Young Il Kim, In Ja Park
Annals of Surgical Treatment and Research.2022; 102(6): 295. CrossRef
Introducing Mobile Collaborative Robots into Bioprocessing Environments: Personalised Drug Manufacturing and Environmental Monitoring
Robins Mathew, Robert McGee, Kevin Roche, Shada Warreth, Nikolaos Papakostas
Applied Sciences.2022; 12(21): 10895. CrossRef
7P pediatrics — Medicine of Development and Health Programming
Leyla S. Namazova-Baranova, Alexandr A. Baranov, Elena A. Vishneva, Anna A. Alekseeva, Valerii Y. Albitskiy, Irina A. Belyaeva, Viliya A. Bulgakova, Nato D. Vashakmadze, Olga B. Gordeeva, Irina V. Zelenkova, Elena V. Kaitukova, Georgii A. Karkashadze, Ele
Annals of the Russian academy of medical sciences.2021; 76(6): 622. CrossRef
Application and Prospect of a Mobile Hospital in Disaster Response
Xinlin Chen, Lu Lu, Jie Shi, Xin Zhang, Haojun Fan, Bin Fan, Bo Qu, Qi Lv, Shike Hou
Disaster Medicine and Public Health Preparedness.2020; 14(3): 377. CrossRef
The effect of diets delivered into the gastrointestinal tract on gut motility after colorectal surgery—a systematic review and meta-analysis of randomised controlled trials
Sophie Hogan, Daniel Steffens, Anna Rangan, Michael Solomon, Sharon Carey
European Journal of Clinical Nutrition.2019; 73(10): 1331. CrossRef

Original Articles

Association of LCT-13910 C/T Polymorphism and Colorectal Cancer: Genco Gençdal, Esin Salman, Ömer Özütemiz, Ulus S. Akarca; Ann Coloproctol. 2017;33(5):169-172. Published online October 31, 2017; DOI: https://doi.org/10.3393/ac.2017.33.5.169

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Abstract PDF

Purpose

The activity of epithelial lactase (LCT) is associated with a polymorphism 13910 bp upstream in the lactase encoding gene. Because the association between the LCT-13910 polymorphism and the risk for colorectal cancer is not clear, we investigated the role of the LCT-13910 polymorphism as a potential risk factor for colorectal cancer and colorectal polyps in the Turkish population.

Methods

One hundred sixty-six subjects (74 with polyps, 44 with colorectal cancer, 48 controls), who had undergone a total colonoscopy between January 2012 and November 2012 in our endoscopy unit were genotyped for the LCT-13910 polymorphism by using the polymerase chain reaction and minisequencing.

Results

The CC genotype in the lactose gene 13910 locus, which is accepted as the genetic indicator of lactase deficiency, was determined as 83.7%. The CC genotype rate was determined as 89.1% in patients who had a history of lactose intolerance and 81.5% in those without a history of lactose intolerance (P = 0.236). No difference was detected between the patients who had colorectal polyp(s) and/or cancer and the controls with regard to the LCT-13910 polymorphism. No differences were determined between groups when they were compared with regard to the C or the T allele.

Conclusion

No differences were detected between the patients who had colorectal polyp(s) and/or cancer and those with normal colonoscopy findings with regard to lactase gene polymorphisms. No differences were determined between the groups when they were compared with regard to the C or the T allele.

Citations

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Genetically Determined Circulating Lactase/Phlorizin Hydrolase Concentrations and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study
Sihao Han, Jiemin Yao, Hajime Yamazaki, Samantha A. Streicher, Jianyu Rao, Roch A. Nianogo, Zuofeng Zhang, Brian Z. Huang
Nutrients.2024; 16(6): 808. CrossRef
The Association of Lactose Intolerance With Colon and Gastric Cancers: Friend or Foe?
Mohammad Maysara Asfari, Osama Hamid, Muhammad Talal Sarmini, Katherine Kendrick, Lakshmi Priyanka Pappoppula, Humberto Sifuentes, Subbaramiah Sridhar
Cureus.2022;[Epub] CrossRef
Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer: a two-sample Mendelian randomization study
Susanna C. Larsson, Amy M. Mason, Siddhartha Kar, Mathew Vithayathil, Paul Carter, John A. Baron, Karl Michaëlsson, Stephen Burgess
BMC Medicine.2020;[Epub] CrossRef
Routine disaccharidase testing: are we there yet?
Antone R. Opekun, Bruno P. Chumpitazi, Mustafa M. Abdulsada, Buford L. Nichols
Current Opinion in Gastroenterology.2020; 36(2): 101. CrossRef
Lactose Intolerance and Colorectal Cancer
Jong-Woo Kim
Annals of Coloproctology.2017; 33(5): 157. CrossRef

Adipose-tissue-derived Stem Cells Enhance the Healing of Ischemic Colonic Anastomoses: An Experimental Study in Rats: Jong Han Yoo, Jae Ho Shin, Min Sung An, Tae Kwun Ha, Kwang Hee Kim, Ki Beom Bae, Tae Hyeon Kim, Chang Soo Choi, Kwan Hee Hong, Jeong Kim, Soo Jin Jung, Sun Hee Kim, Kuk Hwan Rho, Jong Tae Kim, Young Il Yang; J Korean Soc Coloproctol. 2012;28(3):132-139. Published online June 30, 2012; DOI: https://doi.org/10.3393/jksc.2012.28.3.132

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Abstract PDF

Purpose

This experimental study verified the effect of adipose-tissue-derived stem cells (ASCs) on the healing of ischemic colonic anastomoses in rats.

Methods

ASCs were isolated from the subcutaneous fat tissue of rats and identified as mesenchymal stem cells by identification of different potentials. An animal model of colonic ischemic anastomosis was induced by modifying Nagahata's method. Sixty male Sprague-Dawley rats (10-week-old, 370 ± 50 g) were divided into two groups (n = 30 each): a control group in which the anastomosis was sutured in a single layer with 6-0 polypropylene without any treatment and an ASCtreated group (ASC group) in which the anastomosis was sutured as in the control group, but then ASCs were locally transplanted into the bowel wall around the anastomosis. The rats were sacrificed on postoperative day 7. Healing of the anastomoses was assessed by measuring loss of body weight, wound infection, anastomotic leakage, mortality, adhesion formation, ileus, anastomotic stricture, anastomotic bursting pressure, histopathological features, and microvascular density.

Results

No differences in wound infection, anastomotic leakage, or mortality between the two groups were observed. The ASC group had significantly more favorable anastomotic healing, including less body weight lost, less ileus, and fewer ulcers and strictures, than the control group. ASCs augmented bursting pressure and collagen deposition. The histopathological features were significantly more favorable in the ASC group, and microvascular density was significantly higher than it was in the control group.

Conclusion

Locally-transplanted ASCs enhanced healing of ischemic colonic anastomoses by increasing angiogenesis. ASCs could be a novel strategy for accelerating healing of colonic ischemic risk anastomoses.

Citations

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Experimental models of high-risk bowel anastomosis in rats: A systematic review
Georgios Ntampakis, Manousos-Georgios Pramateftakis, Elissavet Anestiadou, Stefanos Bitsianis, Orestis Ioannidis, Chryssa Bekiari, George Koliakos, Maria Karakota, Anastasia Tsakona, Angeliki Cheva, Stamatios Angelopoulos
World Journal of Experimental Medicine.2024;[Epub] CrossRef
The Role of Adipose Tissue Mesenchymal Stem Cells in Colonic Anastomosis Healing in Inflammatory Bowel Disease: Experimental Study in Rats
Georgios Ntampakis, Manousos-Georgios Pramateftakis, Orestis Ioannidis, Stefanos Bitsianis, Panagiotis Christidis, Savvas Symeonidis, Georgios Koliakos, Maria Karakota, Chrysanthi Bekiari, Anastasia Tsakona, Angeliki Cheva, Stamatios Aggelopoulos
Journal of Clinical Medicine.2023; 12(19): 6336. CrossRef
The application of regenerative medicine in colorectal surgery
Ilan Kent, Michael R. Freund, Samir Agarwal, Steven D. Wexner
Surgery.2022; 171(4): 867. CrossRef
Stem cell therapy applied for digestive anastomosis: Current state and future perspectives
Jacobo Trébol, Tihomir Georgiev-Hristov, Isabel Pascual-Miguelañez, Hector Guadalajara, Mariano García-Arranz, Damian García-Olmo
World Journal of Stem Cells.2022; 14(1): 117. CrossRef
Stem Cell Therapies for Gastrointestinal Anastomotic Healing: A Systematic Review and Meta-Analysis on Results from Animal Studies
Apostolos Gaitanidis, Leonidas Kandilogiannakis, Eirini Filidou, Alexandra Tsaroucha, George Kolios, Michail Pitiakoudis
European Surgical Research.2022; 63(4): 173. CrossRef
Effect of Adipose-Derived Stem Cells on Colonic Anastomosis in Rats Immunosuppressed With Everolimus: An Experimental Study
Emre Karakaya, Aydincan Akdur, Alev Ok Atilgan, Ahmet Cagri Uysal, Huriye Eda Ozturan Ozer, Sedat Yildirim, Mehmet Haberal
Experimental and Clinical Transplantation.2021; 19(9): 970. CrossRef
The use of mesenchymal stem cells in animal models for gastrointestinal anastomotic leak: A systematic review
Joshua Richard Burke, Jack Helliwell, Jason Wong, Aaron Quyn, Sarah Herrick, David Jayne
Colorectal Disease.2021; 23(12): 3123. CrossRef
Human Oral Mucosal Stem Cells Reduce Anastomotic Leak in an Animal Model of Colonic Surgery
Ilan Kent, Cyrus Jahansouz, Amandeep Ghuman, Baruch Shpitz, Debora Kidron, Victoria Yaffe, Imad Abu El-Naaj, Shareef Araidy, Luciana Reina, Sandu Pitaru, Steven David Wexner, Shmuel Avital
European Surgical Research.2021; 62(1): 32. CrossRef
Anastomotic leak in colorectal cancer patients: New insights and perspectives
Caterina Foppa, Siew Chien Ng, Marco Montorsi, Antonino Spinelli
European Journal of Surgical Oncology.2020; 46(6): 943. CrossRef
Locally Transplanted Adipose Stem Cells Reduce Anastomotic Leaks in Ischemic Colorectal Anastomoses: A Rat Model
Andrew Morgan, Andrew Zheng, Kimberly M. Linden, Ping Zhang, Spencer A. Brown, Jeffrey P. Carpenter, Francis R. Spitz, Michael E. Kwiatt
Diseases of the Colon & Rectum.2020; 63(7): 955. CrossRef
The Proliferation and Differentiation of Adipose-Derived Stem Cells in Neovascularization and Angiogenesis
Greg Hutchings, Krzysztof Janowicz, Lisa Moncrieff, Claudia Dompe, Ewa Strauss, Ievgeniia Kocherova, Mariusz J. Nawrocki, Łukasz Kruszyna, Grzegorz Wąsiatycz, Paweł Antosik, Jamil A. Shibli, Paul Mozdziak, Bartłomiej Perek, Zbigniew Krasiński, Bartosz Kem
International Journal of Molecular Sciences.2020; 21(11): 3790. CrossRef
Wound healing and fibrosis: current stem cell therapies
Ruth Ellen Jones, Deshka S. Foster, Michael S. Hu, Michael T. Longaker
Transfusion.2019; 59(S1): 884. CrossRef
Protective effect of adipose tissue–derived mesenchymal stromal cells in an experimental model of high-risk colonic anastomosis
Valter Alvarenga, Pedro Teixeira da Silva, Natália Deoclécio Bonfá, Beatriz Pêgo, Hayandra Nanini, Cláudio Bernardazzi, Kalil Madi, Wagner Baetas da Cruz, Morgana Teixeira Castelo-Branco, Heitor Siffert Pereira de Souza, Alberto Schanaider
Surgery.2019; 166(5): 914. CrossRef
Adipose Tissue-Derived Stem Cell Sheet Application for Tissue Healing In Vivo: A Systematic Review
Panithi Sukho, Abigael Cohen, Jan Willem Hesselink, Jolle Kirpensteijn, Femke Verseijden, Yvonne M. Bastiaansen-Jenniskens
Tissue Engineering Part B: Reviews.2018; 24(1): 37. CrossRef
Adipose-Derived Mesenchymal Stromal Cells Improve the Healing of Colonic Anastomoses Following High Dose of Irradiation Through Anti-Inflammatory and Angiogenic Processes
Dirk Van de putte, Christelle Demarquay, Elke Van Daele, Lara Moussa, Christian Vanhove, Marc Benderitter, Wim Ceelen, Piet Pattyn, Noëlle Mathieu
Cell Transplantation.2017; 26(12): 1919. CrossRef
Autologous adipose-derived stem cell sheets enhance the strength of intestinal anastomosis
Yasuhiro Maruya, Nobuo Kanai, Shinichiro Kobayashi, Kurodo Koshino, Teruo Okano, Susumu Eguchi, Masayuki Yamato
Regenerative Therapy.2017; 7: 24. CrossRef
Effects of adipose stem cell sheets on colon anastomotic leakage in an experimental model: Proof of principle
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Novel therapy for pancreatic fistula using adipose-derived stem cell sheets treated with mannose
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Invasiveness of and Drug Sensitivity to Various Anti-cancer Regimens in Five Colorectal Cancer Cell Lines.: Lee, Yoo Mi , Yoon, Yong Sik , Roh, Seon Ae , Cho, Dong Hyung , Kim, Jin Cheon; J Korean Soc Coloproctol. 2010;26(2):98-104.; DOI: https://doi.org/10.3393/jksc.2010.26.2.98

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Abstract PDF

PURPOSE
Colorectal cancer (CRC) is one of the leading causes of cancer death in South Korea. Angiogenesis has been associated with invasion and metastasis of tumors and with the secretion of various growth factors. Bevacizumab is a humanized monoclonal antibody that recognizes and blocks vascular endothelial growth factor (VEGF) and that targets integrin alphaVbeta3 and matrix metalloproteinases (MMPs) as angiogensis inhibitors. The aims of this study were identification of the mechanism of target molecules related to angiogenesis and demonstration of identifiable invasion by using chemotherapeutic regimens in vitro.
METHODS
The five colorectal cancer cell lines were treated with bevacizumab using standard or combined regimens. The expression of integrin alphaVbeta3 was detected and the investigation of apoptosis was done by using flow cytometry. The activations of MMP-2 and MMP-9 were measured by using gelatin zymography.
RESULTS
The apoptotic cell death was significantly increased for the combined regimens, especially for FOLFOX (5-FU, leucovorin, and oxaliplatin) with bevacizumab. Bevacizumab inhibited the expression of integrin alphaVbeta3 in the HT29 (59%), LoVo (67%), and SW480 (17%) cell lines, but did not in the AMC5 and the RKO cell lines. The activations of MMP-2 and MMP-9 were significantly reduced by treatment with bevacizumab in the HT29 and the LoVo cell lines. In the HT29 and the LoVo cell lines, thus, bevacizumab inhibited invasion and metastasis activity through down-regulation of integrin alphaVbeta3 and MMPs.
CONCLUSION
Our results provide biological evidence of potent angiogenic activity and indicate that angiogenesis is a complex process that involves multiple factors, including VEGF, integrin alphaVbeta3, and MMPs.

Citations

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RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin–RGD interactions
Hossein Javid, Mahsa Akbari Oryani, Nastaran Rezagholinejad, Ali Esparham, Mahboubeh Tajaldini, Mehdi Karimi‐Shahri
Cancer Medicine.2024;[Epub] CrossRef

A Study of Epigenetic Alteration of the Bone Morphogenetic Protein-2 Gene in Human Colorectal Cancer.: Jang, Yong Sun , Kim, Kwang , Yun, Min Young , Choi, Sun Keun , Kim, Kyung Rae , Jang, Jun Hyeog , Koo, Ji Hoe; J Korean Soc Coloproctol. 2010;26(1):53-61.; DOI: https://doi.org/10.3393/jksc.2010.26.1.53

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Abstract PDF: PURPOSE
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta family and play an important role in cellular growth. Recent reports suggest that exogenous bone morphogenetic protein-2 (BMP-2) acts as an antiproliferative agent in a variety of cell lines. We will study whether BMP-2 is altered in human colorectal cancer.
METHODS
We analyzed 40 colorectal cancer cases and 6 colorectal cancer cell lines by using reverse transcription-polymerase chain reaction (RT-PCR) to determine the expression of BMP-2.
RESULTS
Thirteen of 40 colorectal cancers (33%) and 3 of 6 colorectal cancer cell lines (50%) revealed decreased expression of BMP-2. The rates of decreased expression were 0% (0/7), 42.1% (8/19), 28.6% (2/7), 33.3% (2/6), and 100% (1/1) in stages I, II, III, and IV, respectively. Histologically, the rates were 33.3% (2/6), 32.2% (10/21), 50% (1/2), and 0% (0/1) in well-differentiated, moderately-differentiated, poorly-differentiated and mucinous cancers, respectively. As for location, the rates for colon and rectal cancers were 27.8% (5/18) and 36.4% (8/22), respectively. We identified methylation in the CpG island of the BMP-2 gene in 60% of colorectal cancer cells and in 50% of colorectal cancer cell lines. The 13 cases without BMP-2 gene expression showed no significant correlation with clinicopathological factors. Epigenetic silencing through DNA methylation is one of the key steps during carcinogenesis.
CONCLUSION
We found, through an analysis using the methylation-specific polymerase chain reaction technique, CpG island methylation of the BMP-2 promoter region in colorectal cancer. Thus, aberrant BMP-2 methylation and the resultant loss of BMP-2 expression may be related to colorectal carcinogenesis.

Reviews

Muscle Regeneration: Research for the Treatment of Fecal Incontinence.: Kang, Sung Bum , Lee, Taek Gu; J Korean Soc Coloproctol. 2010;26(1):1-7.; DOI: https://doi.org/10.3393/jksc.2010.26.1.1

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Abstract PDF

Fecal incontinence remains a socially isolating condition, which can have a profound impact on all aspects of quality of life. It affects 2% to 17% of people living in the community and is an iatrogenic disease that develops after a restorative proctectomy for rectal cancer. Conservative management, such as biofeedback and medication, or surgical therapy may be ineffective, the symptomatic benefit being disappointing. In a few recent reports, autologous myoblasts injected into the urinary or anal sphincter were used successfully for the treatment of incontinence, and these cells improved the muscle function. These autologous cell therapies can avoid adverse events, such as tumor formation, compared to the use of embryonic stem cells. However, the limited regenerative capacity of cell therapy has prompted the development of replacing dysfunctional muscle tissue. Regenerative medicine for functioning muscles may be a therapeutic tool for fecal incontinence in the future. Now, many challenges remain to be overcome prior to reaching the ultimate goal of a fully functional 3-D vascularized engineered muscle: These include development of highly organized 3-D scaffolds, development of scaffolds that specifically direct cellular differentiation, development of co-culture systems of multiple cell types on smart surfaces, development of vascularized constructs, reduction of serum dependence, and innervation into constructed muscle. The successful generation of functional muscle tissues requires an in-depth knowledge of both muscle tissue physiology and advanced engineering practices. The recent advances in tissue engineering technique and cell biology suggest that artificially-derived muscle constructs may be used in clinical settings in the near future.

Citations

Citations to this article as recorded by

Feasibility of Neurovascular Antropylorus Perineal Transposition With Pudendal Nerve Anastomosis Following Anorectal Excision: A Cadaveric Study for Neoanal Reconstruction
Abhijit Chandra, Ashok Kumar, M Noushif, Nitish Gupta, Vijay Kumar, Navneet Kumar Chauhan, Vishal Gupta
Annals of Coloproctology.2013; 29(1): 7. CrossRef
Functional New Sphincter Ani Reconstruction by Using Neurovascualr Antropylorus Transposition After an Anorectal Excision
Bong Hwa Lee, Min Jung Kim, Hyoung Chul Park
Annals of Coloproctology.2013; 29(1): 5. CrossRef
Injection of porous polycaprolactone beads containing autologous myoblasts in a dog model of fecal incontinence
Sung-Bum Kang, Hye Seung Lee, Jae-Young Lim, Se Heang Oh, Sang Joon Kim, Sa-Min Hong, Je-Ho Jang, Jeong-Eun Cho, Sung-Min Lee, Jin Ho Lee
Journal of the Korean Surgical Society.2013; 84(4): 216. CrossRef

Classification of Colorectal Cancer Based on Clinical, Morphological and Molecular Features.: Park, Sunhoo; J Korean Soc Coloproctol. 2008;24(6):497-504.; DOI: https://doi.org/10.3393/jksc.2008.24.6.497

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Abstract PDF: Colorectal cancer (CRC) has been assumed for many years to be a homogenous condition with the vast majority developing within preexisting-adenomas. However, over the last two-decades, it has become clear that CRC evolves through multiple pathways at the genetic and the epigenetic level. Each of these processes is associated with a unique genetic or epigenetic signature identifiable in the tumor cells. The pathway may be defined on the basis of three molecular features: 1) chromosomal instability (CIN), 2) microsatellite instability (MSI), and 3) CpG island methylator phenotype (CIMP). Those molecular pathways are determined at an early evolutionary stage and are fully established within early cancer. Recently, five subgroups were outlined by using morphological findings and associated molecular changes: type 1 (CIN-stable/ MSI-H/CIMP-H), type 2 (CIN-stable/MSI-L or MSS/ CIMP-H), type 3 (CIN-unstable/MSI-L or MSS/CIMP-L), type 4 (CIN-instable/MSS/CIMP-neg), and type 5 (CIN- stable/MSI-H/CIMP-neg). This approach to the classification of CRC should accelerate understanding of causation and will have an impact on clinical management in the areas of both prevention and treatment.

Original Article

Expression of Hypoxia-inducible Factor-1alpha and Vascular Endothelial Growth Factor in Colon Cancer: Relationship to the Prognosis and Tumor Markers.: Choi, Yoon Young , Cho, Hyun Deuk , Park, Dong Guk , Kim, Sung Young , Lee, Moon Soo , Kim, Chang Ho , Cho, Moo Sik , Baek, Moo Jun; J Korean Soc Coloproctol. 2008;24(5):337-344.; DOI: https://doi.org/10.3393/jksc.2008.24.5.337

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Abstract PDF

PURPOSE
Angiogenesis is one of the key steps in solid tumor growth and metastasis. We investigated the prognostic significance of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) expressions as markers of angiogenesis in colon cancer.
METHODS
We retrospectively reviewed the medical records of 78 patients with colon or rectal cancer who underwent a surgical resection at Soonchunhyang University Hospital from January 2000 to December 2001, and we evaluated the expression of VEGF and HIF-1alpha in archival tumor tissues by using immunohistochemistry. We recorded the clinical and the pathological characteristics of the patients and analyzed their survival outcomes.
RESULTS
Thirty-four (34) patients were male, and the mean age of all the patients was 66.7 years. HIF-1alpha and VEGF were positive in 56% (44 patients) and 53% (42 patients) of the tumors, respectively. HIF-1alpha expression was significantly associated with several pathological parameters, such as TNM stage (P=0.001), lymph node metastasis (P=0.001). HIF-1alpha expression was also associated with VEGF expression (P=0.032). The survival of patients with HIF-1alpha expression was worse than that of patients with no HIF-1alpha expression (P=0.036). However, VEGF expression was not associated with other pathological characteristics.
CONCLUSIONS
We suggest that, in cases of colorectal cancer, HIF-1alpha expression may be associated with expression of VEGF, progression of tumors, and poor prognosis.

Citations

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Expression of LDH-5 in Colorectal Carcinomas: Correlation with Prognosis and Tumor Angiogenesis
Tae Sung Ahn, Chang Jin Kim, Dong Jun Jung, Dong Guk Park, Sung Woo Cho, Sung Young Kim, Moon Soo Lee, Chang Ho Kim, Moo Sik Cho, Moo Jun Baek
Journal of the Korean Society of Coloproctology.2010; 26(1): 62. CrossRef

Review

Update in the Pathogenesis of Inflammatory Bowel Disease.: Jang, Byung Ik , Lee, Si Hyung; J Korean Soc Coloproctol. 2008;24(4):302-309.; DOI: https://doi.org/10.3393/jksc.2008.24.4.302

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Abstract PDF

Inflammatory bowel disease (IBD) is a multifactorial disease characterized by abnormal immunologic responses to intestinal antigen, and its causes have not yet been clarified. IBD is known to be due to a complexity of environmental, genetic, and abnormal immunological responses. The hygiene hypothesis remains the key hypothesis for explaining the increase in the incidence of IBD, and smoking is the strongest of the known external environmental factors. Since the detection of the NOD2/CARD15 gene in 2001, rapid progress has occurred, and recently, an important relation between the IL23R gene and IBD has been established. Although studies of normal flora in IBD have some difficulties in methodology, the theory that the loss of immune tolerance to normal flora in the bowel results in IBD is still believed. Incomplete adaptation of innate and adaptive immunity is also one of the important pathogenesis. The toll-like receptor family and the NOD-like receptor family have a important role in the pathologic condition. As to adaptive immunity, in Crohn's disease, the Th1 phenotype is known to be involved, and in ulcerative colitis, the Th2 phenotype cytokines are known to be involved. However, recently, the roles of new cytokines and variable phenotypic lymphocytes have attracted interest. We can clarify the relations of inflammatory pathway-specific and molecular classification of the phenotypes of patients in 10~20 years if progress continues at the same rate as during the last 10 years. We also expected to develop a new therapeutic approach based on these efforts.

Citations

Citations to this article as recorded by

A MATHEMATICAL MODEL OF IMMUNE-MEDIATED DISORDER IN INFLAMMATORY BOWEL DISEASE
Anna Park, Il Hyo Jung
East Asian mathematical journal.2016; 32(1): 139. CrossRef
Two Cases of Crohn's Disease Presented with Hematochezia in Patients with Hemophilia
Jae Hyun Park, Hyo Jong Kim, Seong Dong Sohn, Young Hwangbo, Jaejun Shim, Jae Young Jang, Seok Ho Dong, Byung Ho Kim, Young Woon Chang, Rin Chang
Intestinal Research.2011; 9(1): 35. CrossRef

Original Articles

Differential Expressions of Genes in Colorectal Cancer with Liver Metastasis by using a cDNA Microarray Chip: A Pilot Study.: Kim, Jae O , Choi, Gyu Seog , Kim, Sang Geol , Chang, Eun Jung , Kim, Woo Ri , Lee, In Taek , Jun, Soo Han , Kim, Mun Kyu , Kim, Jeong Chul; J Korean Soc Coloproctol. 2007;23(2):116-128.; DOI: https://doi.org/10.3393/jksc.2007.23.2.116

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Abstract PDF: PURPOSE
Liver metastasis is the most common type of failure in the treatment of colorectal cancer. The identification of differential expressions of genes in colorectal cancer and liver metastasis is important to differentiate the genetic mechanism of carcinogenesis and liver metastasis from that of a normal mucosa. The aim of this study is to find candidate genes playing roles in liver metastasis of colorectal cancer by using cDNA microarray.
METHODS
We screened a group of genes differentially expressed in a normal mucosa and in cancer and liver metastasis by using a 4.7 K cDNA microarray chip in 8 patients with far advanced colorectal cancer from Jan 2003 to May 2004 at Kyungpook National University Hospital.
RESULTS
A comparison of mRNA expressions of genes in normal mucosa vs. cancer, normal mucosa vs. liver metastasis, and cancer vs. liver metastasis, 76 and 27 known and unknown genes were significantly over-expressed in cancer and liver metastasis, respectively. Also 62 and 26 genes were down- regulated in cancer and liver metastasis. Among those genes, TIMP-1, SRY-box9, Rattus norvegicus fibronectin 1, mitotic check point regulator, etc. were constantly up- regulated in cancer or metastasis, and hsgk, etc. were down-regulated in cancer or liver metastasis. CONSLUSIONS: The cDNA microarray chip technique could be a useful for robust screening of candidate genes involved in carcinogenesis or metastasis of colorectal cancer.

A Pilot Study as the Biochip Based Gene Expression Profiling in Patients with Hyperplastic Colonic Polyp.: Park, Ung Chae , Kim, Kyong Rae , Seong, Moo Kyung , Wang, Joon Ho , Lee, Jae Dong , Kim, Sang Yoon , Park, Seung Hwa , Choi, Dong Kug , Kim, Chan Gil; J Korean Soc Coloproctol. 2006;22(4):241-249.

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Abstract PDF: PURPOSE
A microarray-based gene expression analysis may offer a rapid and efficient means for assessing. However, the molecular genetic change in nonneoplastic colonic polyp is still poorly understood. To elucidate the molecular genetic basis, We now report the results of our initial microarray data to analyze the genom pattern in patients with hyperplastic polyps of colon.
METHODS
36 samples (18 pairs of colonic polyps and normal colonic mucosa were) harvested from colonoscopic biopsy. 3 of 18 colonic polyps were pathologically identified as the serrated type of hyperplastic polyp. We used the oligonucleotide microarray technique for analysis of the expression profiles of serrated polyps and normal mucosa. For the identification of differentially expressed genes, SAM (Significance Analysis of Microarray) package method was used. The result was analysed by using global normalization, intensity dependent normalization and block-wise normalization.
RESULTS
Polypectomy specimens microscopically showed the pathologically characteristic serration with a saw-teeth like luminal border (branching of the crypts). 8 genes including RHEB (Ras homolog enriched in brain), WASF2 (WAS protein family, member 2), TYRP1 (Tyrosinase-related protein 1), VSX1 (Visual system homeobox 1 homolog), ROS1 (V-ros UR2 sarcoma virus oncogene homolog 1), WEE1 (WEE1 homolog), TEC (Tec protein tyrosine kinase), TNFRSF10A (Tumor necrosis factor receptor superfamily, member 10a) in serrated polyp were up-regulated by more than 10 times as compared with normal colonic mucosa. On the other hand, 6 genes including SIAT7D (Sialyltransferase 7D), DRD1 (Dopamine receptor D1), SIAT1 (Sialyltransferase 1), ITSN1 (Intersectin 1), TNFSF12 (Tumor necrosis factor superfamily, member 12), CHES1 (Checkpoint suppressor 1) were down-regulated by less than a tenth of the expression as compared with normal colonic mucosa.
CONCLUSIONS
Serrated polyps as a subset of hyperplastic colonic polyps were analyzed with the oligonucleotide microarray technique. We authors could identify 14 genes (8 up-regulated and 6 down-regulated genes) that showed the significant change of expression as compared with normal colonic mucosa. Specifically, we believe that current study will serve as a fundamental base to offer a bioinformative characteristics of the serrated colonic polyp in future clinical applications.

Distributions of MTHFR Gene Polymorphism according to the Location of Colon Cancer.: Kim, Jong Woo , Oh, Doyeun , Chong, So Young , Yim, Dong Jin , Kim, Jin Kyeoung , Kim, Nam Keun; J Korean Soc Coloproctol. 2006;22(2):69-74.

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Abstract PDF: PURPOSE
Colon carcinogenesis seems to vary according to the original location of tumor, especially theright and the left sides. Two common methylenetetrahydrofolate reductase (MTHFR) polymorphisms, 677C->T and 1298A->C, are now known. Especially, the TT type of the 677C->T mutation shows reduced catalytic activity at a rate 30% that of wild type. The aim of this study is to investigate the distributions of MTHFR polymorphisms of 677C->T and 1298A->C according to the location of the colon cancer.
METHODS
Blood samples were collected from 112 patients diagnosed in our hospital, as having colon cancer: 34 proximal and 78 distal cases to the splenic flexure and 448 healthy control subjects. In order to characterize MTHFR polymorphisms, we applied the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
RESULTS
The distributions of MTHFR 677C->T polymorphisms as genotypes CC, CT, and TT were 32.4%, 53.1%, and 14.5% in the control group, and 34.8%, 58.0%, and 7.1% in the cancer group (P=0.056). In the 34 proximal cancers, the CC, CT, and TT distributions were 44.1%, 55.9%, and 0% (P<0.05), respectively. In the distal group, they were 30.8%, 59.0%, and 10.3%. The distributions of the MTHFR 1298 A->C polymorphism by genotypes, AA, AC, CC were 69.6%, 28.6%, and 1.8% in the control group, and 58.9%, 38.4%, and 2.7% in the cancer group. The proximal and the distal groups show genotype distributions of 44.1%, 53.0%, and 2.9% and 65.4%, 32.0%, and 2.6%, respectively, but the differences were not statistically significant.
CONCLUSIONS
There are no definite differences between control subjects and colon-cancer patients in the two polymorphisms 677C->T and 1298A->C. However, the TT genotype shows a lower frequency in the cancer group than in the control group with a marginal statistical value (P=0.056), which suggest a reduced risk of cancer incidence for this type, compared with a CC or a CT type.

Review

Epigenetic Alterations and Loss of Imprinting in Colorectal Cancer.: Kim, Jong Woo; J Korean Soc Coloproctol. 2005;21(3):181-190.

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Abstract PDF: Two forms of genomic instability have been described in colorectal cancer: chromosomal (CIN) and microsatellite instability (MIN). Colorectal cancer has been considered to progress through one of these two major pathways. However, recently a CpG island methylator pathway (CIMP) has been established among sporadic MIN cancers. Aberrant methylation of a promoter CpG island is associated with inactivation of tumor suppressor genes and is one of the epigenetic alterations identified to be involved in tumorigenesis. Now, several types of epigenetic alterations appear to play roles complementary to genetic mutations in colorectal carcinogenesis and seem to contribute to the progression of cancer. Epigenetic alterations also increase the probability that genetic changes will lead to cancer initiation. So far, major epigenetic alterations have been categorized into four groups of dysregulations: 1) hypomethylation with oncogene activation and chromosomal instability, 2) hypermethylation with tumor suppressor gene silencing, 3) chromatin modifications, and 4) loss of imprinting (LOI). Especially, LOI is a common epigenetic variant and should have a field effect on the colon, making it more vulnerable to genetic insults. Genomic imprinting is parental-origin-specific allele silencing, a form of gene silencing that is epigenetic in origin and does not involving alterations in the DNA sequence but does involve methylation and other modifications that are heritable during cell division. LOI is the loss of parental-origin-specific marks, leading either to aberrant activation of a normally silent allele of a growth promoter gene or to silencing of the growth inhibitor allele. Most of the attention has been focused on LOI of the IGF2 (insulin-like growth factor II) gene in a Wilms' tumor and colorectal cancer. LOI of IGF2 involves abnormal activation of a normally silent maternally inherited allele and has been associated with personal and family history of colorectal cancer, supporting a role for LOI in carcinogenesis. LOI may be a valuable predictive marker of an individual's risk for colorectal cancer. Now, epigenetics and imprinting are emerging areas in the study of human-cancer genetics.

Original Articles

c-Met Expression in Colorectal Carcinoma and Adenomas: Correlation with Clinicopathologic Parameters.: Kim, Jin , Kim, Jung Yun , Lee, Won Jin , Cho, Seong Jin , Min, Byoung Wook , Um, Jun Won , Cho, Min Young , Suh, Sung Ock , Moon, Hong Young , Hwang, Cheung Wung; J Korean Soc Coloproctol. 2004;20(4):205-210.

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Abstract PDF: PURPOSE
Hepatocyte growth factor (HGF) stimulates proliferation, migration, and morphogenesis of epithelial cells by specifically binding to its receptor c-met. Abnomalities of the c-met oncogene have been studied in cancers of many organs including thyroid, lung, pancreas, and stomach. However, little is known about the clinical significance of c-met oncogene abnormalities in colorectal carcinomas. In this study, we investigated over- expression of the c-met protein in colorectal adenomas and adenocarcinomas, and analyzed the clinicopathologic significance of this over-expression.
METHODS
Expression of the c-met protein localized in colorectal adenoma and adenocarcinoma tissues was analyzed by using immunohistochemistry. The results were compared with clinicopathologic parameters to find clinical correlation.
RESULTS
c-met protein was detected in 42.5% (17/40) of colorectal cancers and in 10.0% (4/40) of colorectal adenomas (P= 0.001). In colorectal cancer, the proportion of expression of c-met protein was 0% (0/40) in stage I, 47.6% (10/40) in stage II, 53.8% (7/40) in stage III and, 0% (0/40) in stage IV. c-met protein expression was 18.8% (3/40) in tumors with invasion into the muscularis propria (MP), and 58.3% (14/40) in tumors with invasion beyond the MP. The depth of tumor invasion was a statistically significant factor (P=0.022) for c-met expression.
CONCLUSIONS
The c-met protein expression was related to the depth of invasion of colorectal cancer and showed a significant difference in its rate of expression between adenoma and adenocarcinomas.

Thymidylate Synthase Gene Polymorphism as a Prognostic Factor for the Colorectal Cancer.: Kim, Joo Hyung , Kim, Young Bae , Choi, Jin Hyuk , Kim, Jeong Mi , Jeong, Soo Hyun , Suh, Kwang Wook; J Korean Soc Coloproctol. 2004;20(3):151-156.

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Abstract PDF: PURPOSE
Thymidylate synthase (TS) expression in colorectal cancer is regarded as both a prognostic marker and a predictor of response to fluoropyrimidine-based therapies targeting TS. However, results from immunohistochemical staining of TS show wide discrepancies. The human TS gene promoter is polymorphic, having either double or triple tandem repeats of a 28-bp sequence. Here, we determined the significance of this polymorphism in predicting the clinical outcomes for patients with operable colorectal cancer treated by a curative resection.
METHODS
The cases of 121 patients with stage II or III colorectal cancer, who underwent a curative resection, were reviewed. After DNA extraction from paraffin- embedded tissues, the promoter region of the TS gene was amplified by polymerase chain reaction.
RESULTS
Sixty-eight subjects were homozygotes for the triple repeat variant (group A, L/L, 250-bp), and 53 subjects (group B) were either homozygotes for the double repeat variant (S/S, 220-bp) or heterozygotes (S/L, 220 and 250- bp). The difference between stage II and stage III patients was significant with regard to the 5-year actuarial survival (87% vs 63%, P=0.0320). Examining the survival according to the TS polymorphism, we found a significant difference between group A and B (80% vs 53%, P=0.0481). In patients with stage II disease, the difference in survival rates between group A and B did not reach statistical significance (43% vs 86%, P=0.1678). However, the difference was significant between group A and B for stage III disease (77% vs 41%, P=0.0414).
CONCLUSIONS
We found the TS polymorphism to be a significant and independent prognostic factor for operable colorectal cancer. We think assay of the TS polymorphism can overcome the technical pitfalls of immunohistochemical staining and give more solid prognostic information in the treatment of colorectal cancer.

Expression of Vascular Endothelial Growth Factor and Tumor Necrosis Factor-alpha in Angiogenesis Induced by Lipopolysaccharide and Thalidomide in CT26 Murine Colon Cancer of BALB/c Mouse.: Choi, Dong Lak , Cho, Chang Ho , Jeong, Jin Sook , Hong, Sook Hee , Yoon, Ghil Suk; J Korean Soc Coloproctol. 2004;20(3):125-132.

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Abstract PDF: PURPOSE
The growth, progression, and metastasis of malignant neoplasms are influenced by the environment of the tumor and by proliferation of the tumor itself. Angiogenesis of a malignant neoplasm is a very important environmental factor of tumor growth and metastasis. Also, it is a prognostic factor for malignant neoplasms. The mechanism of angiogenesis, such as the effects of cytokines and angiogenesis-promoting factors, is incompletely understood.
METHODS
This study was designed to define the role of tumor necrosis factor-alpha (TNF-alpha) and the vascular endothelial growth factor (VEGF) in angiogenesis induced by lipopolysaccharide (LPS) and thalidomide (anticytokine drug) in CT26 murine colon cancer transplanted to BALB/c mice.
RESULTS
The tumor size in the LPS-treated group (n=3, 2.1+/-0.26 cm) was larger than it was in the LPS thalidomide-treated group (n=4, 1.95+/-0.19 cm) and in the control group (n=3, 1.6+/-0.20 cm) (P<0.05). The microvessel density determined by CD31 immunostaining was lowest for the control group and highest for the LPS- treated group, but the differences were not statistically significant. An immunohistochemical study showed that the expressions of TNF-alpha (P<0.01) and VEGF (P<0.05) were higher in the experimental groups than they were in the control group. Also, the LPS thalidomide-treated group had lower expressions of TNF-alpha (P<0.01) and VEGF (P<0.05) than the LPS-treated group. Western blots revealed that the TNF-alpha and the VEGF levels semiquantitatively increased from the control group to the LPS thalidomide-treated group to the LPS-treated group.
CONCLUSIONS
Our study revealed that low doses of LPS stimulated angiogenesis through increased expression of TNF-alpha and VEGF. Thalidomide decreased angiogenesis, probably through suppression of TNF-alpha with a decreased expression of VEGF. We conclude that TNF-alpha, suppressed by thalidomide, in the model of transplanted colon cancer may inhibit angiogenesis through coincident decrease in the expression of VEGF.

Clinical Analysis for 30 Cases of Total or Subtotal Abdominal Colectomy and Total Proctocolectomy.: Lee, Jun Hyun , Lee, In Kyu , Oh, Seong Taek , Jin, Hyung Min , Chang, Suk Kyun; J Korean Soc Coloproctol. 2004;20(2):93-98.

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Abstract PDF: PURPOSE
A total or a subtotal abdominal colectomy and a total proctocolectomy are performed occasionally for the surgical treatment of familial adenomatous polyposis, multiple colorectal cancers, ulcerative colitis, acute lower GI bleeding, and malignancy other than colorectal cancer. We studied 30 cases of patients who received either a total or a subtotal abdominal colectomy and a total proctocolectomy in one of the three hospitals affiliated with the Catholic University between January 1990 and December 2001. Our goal was to determine whether the total or subtotal abdominal colectomy and the total proctocolectomy are difficult and complicated procedures by comparing the mortality, the morbidity, the survival rate, and the complications to previously considered and reported results.
METHODS
Thirty patients treated with either total or subtotal abdominal colectomy and with a total proctocolectomy from January 1990 to December 2001 were chosen for this study. Their gender, age, underlying diseases, family history, hospital days, symptoms, changes in defecation habits following the procedure, complications, mortality, survival rate, and relationship to malignancy were evaluated.
RESULTS
Of the patients who received either total or subtotal abdominal colectomy and a total proctocolectomy, the average age was 44.6 years, the gender ratio was 1:1, and the underlying diseases were familial adenomatous polyposis (FAP) (43%), ulcerative colitis (UC) (20%), multiple colorectal cancers (17%), stomach cancer (7%), and Crohn's disease (3%). Diarrhea and rectal bleeding were the most common clinical symptoms, and abdominal pain and intestinal obstruction were frequently observed. A total proctocolectomy (TPC) with permanent ileostomy was the most frequently performed procedure (47%), and a TPC with ileoanal anastomosis was done in 10% of the cases. A total abdominal colectomy (TAC) with ileorectal anastomosis was applied in 23% of the cases, and subtotal abdominal colectomy (sTAC) with ileosigmoidal anastomosis was done in 20% of the cases. The operative mortality rate was 3% as one patient among thirty died. Postoperative complications developed in 33% of the patients. FAP and UC patients without cancer (45%) survived for over 4 or 5 years, but FAP and UC patients with cancer, especially an adenocarcinoma, survived for only 2.5 years.
CONCLUSIONS
A total or subtotal abdominal colectomy (TAC or sTAC) and a total proctocolectomy (TPC) are appropriate procedures with low mortality, low morbidity, and a low complication rate for several kinds of diseases. A TPC with ileorectal anastomosis is the procedure of choice for sparing the rectum in FAP and UC patients without coexisting cancer and without mutation of the APC gene after codon 1250, but a TPC with ileoanal anastomosis is recommended if there is a mutation of the APC gene after codon 1250. A TPC with ileostomy is the preferred method for FAP and UC patients with coexisting cancer.

Review

Mechanism of Genomic Instability and Its Clinical Applications.: Lee, Suk Hwan; J Korean Soc Coloproctol. 2004;20(1):64-73.

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Abstract PDF: Multiple genetic alterations are common prerequisite for carcinogenesis including colorectal cancers (CRCs). Recently, mutations within microsatellites have been described as a result of defective DNA mismatch repair (MMR) mechanisms, resulting in the phenomenon of microsatellite instability (MSI). This has been implicated in the etiology of hereditary non-polyposis colorectal cancer (HNPCC) and significant portions of sporadic colorectal cancers. However, the mechanisms underlying the MSI are different from hereditary CRCs and sporadic CRCs. While the germline mutation of MMR genes is responsible for HNPCC, the hypermethylation of MLH1 gene promoter regions, an epigenetic, not inherited alteration is responsible for most sporadic CRCs showing MSI. MSI tumors exhibit characteristic clinco- pathologic features, i.e, tumors are preferentially located to proximal to splenic flexure, poorly differentiated, mucinous cell type, frequently showing peritumoral lymphocytic infiltration, and, of importance, showing better survival in stage- matched cases. In this article, the results of recent investigations about MSI and its clinical applications are comprehensively reviewed. Knowledge of these biochemical mechanisms are likely to lead to more effective diagnosis and therapy of CRCs in the future

Original Articles

DCC Gene and Protein Expression in Colorectal Cancer.: Kim, Jong Ik , Jeong, Hae Jin , Yang, Young Il , Paik, Kye Hyung , Yoon, Hye Kyoung , Hong, Kwan Hee , Choi, Kyung Hyun; J Korean Soc Coloproctol. 2003;19(1):26-37.

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Abstract PDF: PURPOSE
The germline, or somatic, inactivation of tumor suppressor genes, through point mutation, or deletion, plays an important role in carcinogenesis. Several gene alterations, such as adenomatous polyposis coli (APC), deleted in colorectal cancer (DCC) and p53, have been detected in the development of colorectal cancer. Within these genes, a loss of heterozygosity (LOH) at the DCC gene locus was frequently associated with colorectal tumors, and the LOH of the DCC gene, and the expression of the DCC protein, might be related to malignant formation and metastasis. The aim of this study was to determine the DCC LOH and the expression of DCC protein in colorectal cancers, and evaluate their prognostic value and relationship with the clinicopathological data. MTHODE: Fifty colorectal cancer tissues were obtained from resected specimens. Using formalin-fixed paraffin- embedded sections as a source of DNA, we examined the DCC protein in the tissue through immunohistochemical stainings and immunoblotting analysis, the DCC LOH through a polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP).
RESULTS
DCC LOH was observed in 24 of the 50 patients (48.0%). The expression of the DCC protein was decreased in the cancer tissue (62.3 23.6%) compared with the adjacent normal mucosa inform the immunoblotting analysis. A decreased DCC protein expression was also observed from the immunohistochemistry, which coincided with the immunoblotting analysis. However, both the DCC LOH and the decreased DCC protein were not related to the clinical and pathological parameters, such as location of tumor, tumor size, histological type and the venous, and lymphatic invasions. There were significant correlations between the DCC protein expression and tumor progression, and hematogenous metastasis (P<.05).
CONCLUSIONS
A decreased expression of the DCC protein was noted in human colorectal cancers, and there was a significant relationship between the expression of the DCC protein and distant metastasis, but there was no correlation between the DCC LOH and distant metastasis. These results suggest that the expression of the DCC protein might be related to tumor progression and metastatic potential, and the DCC protein immunoreactivity may be a useful prognostic factor in patients with colorectal cancers.

Genetic Instability and Mutations of Mismatch Repair (MMR) and p53 Gene in Colorectal Cancers with Multiple Polyps and Sporadic Colorectal Cancers.: Chun, Sung Won , Chang, Suk Kyun; J Korean Soc Coloproctol. 2002;18(6):353-362.

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Abstract PDF: PURPOSE
General conceptions of carcinogenic mechanisms by recent reports are ras-p53 gene pathway in sporadic colorectal cancers (SCC), MMR gene pathway in hereditary nonpolyposis colorectal cancer (HNPCC) and APC gene in familial adenomatous polyposis (FAP). But in the colorectal cancer with multiple polyps (CCMP), the carcinogenic pathway is not still defined exactly. In order to find out the which carcinogenic pathway control the CCMP and SCC, genetic instability were studied in CCMP and SCC.
METHODS
In this study, genetic instability on D2S123, D3S1029, D5S107, D6S87 and AP delta3 foci and gene mutations of hMLH1 (exon 2, 16, 19), hMSH2 (exon 11, 12, 13, 14) gene of MMR gene, p53 gene (exon 5, 6, 7, 8, 9) were studied on the 60 DNA samples of CCMP (30 cases) and SCC (30 cases).
RESULTS
1. Observed positive genetic instability was higher in CCMP (30%) than SCC (20%), and was higher in right colon cancers (33%) than left colon cancers (23%) or rectal cancers (17%), but not significant statisitically. And observed positive genetic instability was lower in moderate differentiated cancers (16%) than well (67%) or poorly (60%) differentiated cancers (P=0.005). 2. Any mutations of hMLH1 and hMSH2 gene of MMR gene were not observed in both of CCMP and SCC, but 3 cases (2 CCMPs and 1 SCC) point mutations of intron of hMSH2 gene, which were higher in positive genetic instability than negative (P=0.002). 3. This 3 cases point mutations were C for T which were on 6th bases upstream from codon 669. 4. From the results of SSCP for nucleotide sequencing of p53 gene, the abnormal bands were observed in 30% (9 of 30) of CCMP and SCC. Also the abnormal bands were observed in both of positive or negative genetic instability without differences.
CONCLUSIONS
With above results the authors suggested that the mechanism of genetic instability and mutations of p53 gene strongly affect the mechanism of carcinogenesis in SCC and CCMP. And there are relationship between genetic instability and point mutation at intron region of hMSH2 gene. However further evaluation and research is needed to establish relation between APC gene and other different kind of MMR gene.

Genetic Polymorphism of Xenobiotics Metabolizing Enzymes and Individual Susceptible Genes to Colorectal Cancer Patients in Korea.: Lee, Heung Woo , Kim, Min Soo , Jung, Pa Jong , Kim, Hyun Jun , Kong, Gu , Chun, HoKyung; J Korean Soc Coloproctol. 2002;18(4):205-215.

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Abstract PDF: Individual susceptibility to cancers may result from several factors including differences in xenobiotics metabolism, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. To determine the frequencies of the genotypes of phase I (CYP1A1 and CYP2E1) and phase II (GSTM1 and NAT2) metabolizing enzymes and to identify the high-risk genotypes of these metabolic enzymes to colon cancer in Korean, we have analyzed 113 colorectal cancer patients and corresponding age and sex matched healthy controls using polymerase chain reaction-restriction fragment length polymorphi(PCR-RFLP). In analysis of phase I enzymes, m1/m2, m2/m2 and Val/Val genotypes in CYP1A1 enzyme polymorphisms and C1/C2 genotype in CYP2E1 polymorphism were associated with high relative risks to colorectal cancers (Odds ratio; 1.51, 1.59, 1.76 and 1.38, respectively). Among the phase II enzymes polymorphisms, GSTM (-) genotype of GSTM1 enzyme and slow acetylator (S/S) of NAT2 enzyme had 1.48 and 1.34 times of relative risks to colorectal cancers, respectively. In combined genotyping of phase I enzymes and GSTM1 polymorphisms, the patients with m1/m2 and GSTM (-), Val/Val and GSTM (-), and C1/C2 and GSTM (-) combined genotypes had higher relative risk than the patients with each baseline of combined genotypes (Odds ratio; 2.15, 5.81 and 2.20, respectively). In combined genotyping of phase I enzyme and NAT2 polymorphisms, the combined genotypes of m1/m2 with slow acetylator and C1/C2 with slow acetylator were more susceptible to colorectal cancer (Odds ratio; 3.5 and 4.5, respectively). These results suggest that the combined genotypes of Val/Val and GSTM (-), m1/m2 and slow acetylator, and C1/C2 and slow acetylator were more susceptible to colorectal cancer in Korean. And genotyping of xenobiotics metabolizing enzymes could be useful for predicting an individual susceptibility to colorectal cancer.

Polymorphisms of the 5'-Flanking Region of the Human Tumor Necrosis Factor-alpha Gene in Korean Patients with Crohn's Disease.: Lee, Kil Yeon , Kim, Hyo Jong , Chi, Sung Gil , Oh, Soo Myung , Yoon, Choong , Lee, Kee Hyung; J Korean Soc Coloproctol. 2002;18(3):163-172.

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Abstract PDF: PURPOSE
Recently, a key role of tumor necrosis factor (TNF) in the development of inflammatory bowel disease (IBD), especially Crohn's disease (CD), has emerged. In Japan, 3 single base pair polymorphisms in the 5'-flanking region of the TNF-alpha gene at position 1031, 863, and 857, which are related to high transcriptional promoter activity, have been identified in the Japanese CD patients. And the polymorphisms of the TNF-alpha gene at position 308, 238 have been reported in western CD patients. So, in order to find the same polymorphisms in Korean population and CD patients, the author evaluate the patients diagnosed with CD, ulcerative colitis (UC) and healthy controls (HCs).
METHODS
Blood samples were obtained from 70 patients with CD, 72 patients with UC and 52 healthy controls. Polymorphisms in the TNF-alpha gene at their respective positions were analyzed by single strand conformational polymorphism (SSCP), and allele frequencies in CD and UC patients were compared with those in healthy controls.
RESULTS
Allele frequencies of 1031C, 863A, and 857T in health controls were 18.3%, 8.7%, and 19.2%, respectively. Polymorphic allele frequencies of 1031C, 863A, 857T were 22.9%, 27.1%, and 24.3% in CD patients respectively. The frequencies at all 3 positions were higher in CD patients than in HCs. However, the frequency at 863A was statistically significant (P=0.000). The allele frequencies of 308A and 238A alleles were 0.7% and 3.6% in CD, 0.7% and 2.1% in UC, and 1.9% and 4.8% in HCs, respectively. The allele frequency of 1031C was significantly higher in B3 than in B2 (P=0.033).
CONCLUSION
Polymorphisms of 5'-flanking region of the TNF-alpha at positions 1031 (T/C), 863 (C/A) and 857 (C/T) may be associated with susceptibility of CD.

Immunohistochemical Study of KAI1, a Tumor Metastasis Suppressor Gene, Expression in Rectal Cancer.: Kim, Ik Yong , Kim, Sang Hee , Kim, Jong Seok , Cho, Mee Won , Kim, Dae Sung , Rhoe, Byoung Seon; J Korean Soc Coloproctol. 2002;18(1):22-29.

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Abstract PDF: PURPOSE
KAI1/CD82 gene is a recently identified metastasis suppressor gene on human chromosome 11p11.2. Alteration to or reduction of this molecule may allow tumor cells to invade the surrounding tissue and blood vessels. Decreased KAI1 expression seems to be involved in the progression of human prostate, lung and possibly breast cancer, and recently has been demonstrated in several colorectal cell lines. The aim of this study is to determine whether the gene is altered to investigate it in the progression and metastatic process of rectal carcinoma. In addition, its prognostic significance is also evaluated.
METHODS
Total 108 tumor samples from primary, metastatic rectal carcinoma were prepared for immunohistochemical study with an anti-KAI1 polyclonal antibody. To analysis the correlation between KAI1 expression and clinicopathological parameter and to evaluate for relation expression and survival.
RESULTS
Decrease of KAI1 protein expression was associated with the depth of invasion of tumor (P < 0.0001) and node metastasis (P < 0.05). Liver metastasis showed reduced KAI1 expression when compared with their corresponding primary tumor. Although there was a trend for deteriorating survival from patients with KAI1-positive tumors to those with KAI1-decreased and -negative tumors, it was not significant statistically (P CONCLUSIONS
KAI1 may play a role in the malignant progression of rectal carcinoma through the down-regulation of expression. KAI1 might influence the metastatic ability of human rectal cancer. And its prognostic significance needs further investigation with a larger number of cases.

Expression of Glucose Transporter Gene in Colorectal Cancer.: Lee, Suk Hwan , Park, Jae Hoon , Kim, Yoon Wha , Oh, Soo Myung , Yoon, Choong , Joo, Hoong Zae , Lee, Kee Hyung; J Korean Soc Coloproctol. 2000;16(2):57-66.

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Abstract PDF: PURPOSE
The primary metabolic characteristic of malignant cells is an increased uptake of glucose and its anaerobic glycolysis. Recent studies have demonstrated that facilitative glucose transport across the plasma membrane is mediated by a family of proteins, i.e., glucose transporters. PURPOSE: In order to evaluate the clinicopathologic correlations of glucose transporter genes expressed in colorectal cancer, the author studied the expression of glucose transporter genes in human colorectal cancer and analyzed their expression in normal and malignant colorectal tissues.
METHODS
A reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to quantitatively determine the levels of the glucose transporter genes, GLUT1 and GLUT3, from Crohnes diseases (N=2), adenomatous polyps (N=4), and colorectal cancers (N=40) and their normal counterparts.
RESULTS
The expresssion of the GLUT1 gene was detected in 50% of the inflammatory colonic mucosae and adenomatous polyp tissues, but the levels of expression were not significantly different from their normal counterparts. Among the 40 colorectal cancer patients, 23 patients (57.5%) showed GLUT1 gene expression and the levels of expression were increaed by 1.8 as compared to their normal counterparts (p<0.05). The expression of the GLUT3 gene was detected in almost all tissues examined, and the levels of expression were not significantly different from their normal counterparts. In colorectal cancers, there was correlation between GLUT1 expression, the extent of lymph node involvement and the stage of colorectal cancers (p<0.05). But, the correlation between the expressions of the GLUT3 gene and the clinicopathologic prognostic factors of colorectal cancers could not be determined because almost all tissues showed a GLUT3 gene expression.
CONCLUSIONS
In conclusion, the GLUT1 glucose transporter expression in colorectal cancer was associated with high possibilities of lymph node metastases and poorer prognosis, and the assessment of GLUT1 expression in colorectal cancer would be useful in identifying high risk patients.

Expression of hMSH2, hMLH1 Protein in Sporadic Colorectal Cancer and Corresponding Normal Tissue.: Jung, Jae Young , Park, Dong Kook , Shin, Ji Hyun; J Korean Soc Coloproctol. 1998;14(4):709-718.

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Abstract PDF: PURPOSE
DNA mismatch repair gene is responsible for hereditary nonpolyposis colorectal cancer. But it is not well known its role in sporadic colorectal cancer patients. We analysed normal hMSH2, hMLH1 protein expression in colorectal adenocarcinoma tissues and corresponding normal tissues to find out the role of mismatch repair gene in sporadic colorectal cancer by Western blotting.
METHODS
Normal hMSH2 and hMLH1 protein expression was studied on 25 colorectal cancer and corresponding normal tissue by Western blot with hMSH2 and hMLH1 monoclonal antibody. Normal protein band was expressed on 100 kD in hMSH2 and 87 kD in hMLH1. SW480 and LoVo cell line was used as positive and negative control for hMSH2 and LoVo and SW480 as positive and negative for hMLH1. And we analysed the relation between the hMSH2, hMLH1 protein expression and clinicopathological parameters.
RESULTS
It was 2 cases (8%) that both hMSH2 and hMLH1 protein expression was not observed. Three cases (12%) were negative for hMSH2 and 2 cases (8%) for hMLH1. One or both hMSH2, hMLH1 protein expression was not observed in 7 cases (28%) in total. There was no correlation for proximal occurrence (25% vs 35%), young age (37.5% vs 23.5%) and lymph node metastasis (50% vs 47%). But poorly and mucinous differentiation was regarded as having relation with negative expression of hMSH2 and hMLH1 (50% vs 17.6%) but not significant statistically.
CONCLUSION
Sporadic colorectal cancer with negative expression of normal hMSH2 and hMLH1 protein showed no relation to younger age, proximal site preference and lymph node metastasis. But it was suggested that mismatch repair gene protein was involved in cancer cell differentiation in sporadic colorectal cancer.

Pathogenesis and Surgical Treatment of Rectal Prolapse Syndrome.: Kim, Jin Cheon , Kim, Chang Nam , Park, Sang Kyu , Kim, Sook Young , Yu, Chang Sik; J Korean Soc Coloproctol. 1998;14(2):225-234.

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Abstract PDF: The rectal prolapse syndome is a disease entity includes rectocele and rectal prolapse, presenting prolapse(procidentia) of rectum. In rectocele, rectum is prolapsed anteriorly into the vagina, whereas in procidentia, inferiorly out of the anus. This study was aimed at analyzing pathogenesis and adequacy of surgical treatment in rectocele and rectal prolapse. Twenty-one patients with rectocele and 18 patients with rectal prolapse were assessed pre- and post-operatively in respect to symptoms and signs, pathogenesis, defecography, and manometry. In analysis of symptoms and sings, constipation was the commonest in both diseases(86% of rectocele and 67% of rectal prolapse) and incontinence was not infrequently found in both diseases as well(14% of rectocele and 33% of rectal prolapse). In analysis of the underlying causes, two patients with rectal prolapse had prolapse from childhood. Defecography showed anorectal angle of rectal prolapse in rest and push period. They were significantly wider than those of rectocele(p<0.05). The perineal descent of rectal prolapse was longer than that of rectocele. In analysis of the associated factors, average number of delivery was more than three times in both diseases(3.5 of rectocele and 5.1 of rectal prolapse). We could easily find previous operation history in both diseases. Among them, hysterectomy was the most frequent, especially in patients with rectocele. The hemorrhoids was associated more common in rectocele than in rectal prolapse(p<0.05). Preoperative maximal resting pressure of rectal prolapse was more significantly decreased than that of rectocele(p<0.05). The sensation of fullness was significantly decreased in patients with rectal prolapse postoperatively(p<0.05). Patients with rectocele underwent levator plication by transrectal or vaginal approach. Patients with rectal prolapse underwent posterior rectopexy in 11 patients, resection and rectopexy in 3 patients, Delorme's operation and Thiersch operation in 2 patients each. Constipation was significantly improved in patients with rectocele postoperatively(p<0.05). Incontinence was markedly improved in patients with rectal prolapse postoperatively(p<0.05). At the interview about subjective improvement of symptom, 95% of patients with rectocele and 89% of patients with rectal prolapse were satisfied with surgery. In conclusion, rectocele and rectal prolapse can be categorized as rectal prolapse syndrome because both diseases have anatomical derangements caused by similar pathogenesis such as altered bowel habits, anatomical factor, delivery, past history of hysterectomy, and hemorrhoids. Levator plication and posterior rectopexy seem to be useful surgical methods of anatomical repair for the respective disease.

NAT2 Polymorphism and Individual Genetic Susceptibility to Colorectal Cancer Patients in Korea.: Park, Young Seok , Lee, Kwang Soo , Jun, Kyu Young , Lee, Heung Woo , Chun, Ho Kyung , Kim, Hyun Jun , Kong, Gu; J Korean Soc Coloproctol. 1998;14(2):155-164.

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Abstract PDF: To determine the frequencies of the genotypes of NAT2 gene in healthy Korean populations and to identify the high-risk genotypes of NAT2 gene in colorectal cancer patients, 115 healthy controls and 109 cancer patients were analyzed using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The distribution of NAT2 polymorphism in healthy Korean was found to be 7.8% of S/S genotype, 48.7% of S/F genotype, and 43.5% of F/F genotype. And the frequency of phenotypes was 8% of slow acetylator and 92% of rapid acetylator. S/S genotype of colorectal cancer patients was slightly more frequent than that of healthy controls(11.9% vs 7.8%). The relative risk of S/S genotype to colorectal cancer was estimated to be 1.41, taking the risk of F/F genotype as a baseline(1.00). These results suggest that the distribution of frequencies of NAT2 genotypes is very unique in Korean characterized by extremely low frequency of slow acetylator geno type(S/S) in comparison to the other ethnic groups. And the slow acetylator genotype(S/S) in Korean was found to be more susceptible to colon cancer. Therefore, S/S genotype may have a certain role an colonic carcinogenesis in Korean.

Microsatellite Instability and hMSH2 Gene Mutations in Sporadic Colorectal Cancers.: Jeon, Hae Myung , Oh, Seung Tack , Kim, Jeong Soo , Chang, Suk Kyun , Kim, Jae Sung; J Korean Soc Coloproctol. 1998;14(1):41-49.

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Abstract PDF: Microsatellites are short nucleotide repeat sequences present throughout the human genome. Alterations of microsatellites, comprising extra or missing copies of these se quences, have been termed microsatellite instability(MSI, genetic instability, replication errors, RER(+) phenotype). To date, at least four genes involved in DNA mismatch repair, hMSH2, hMLH1, hPMS1 and hPMS2, are thought to account for the observation of microsatellite instability in tumor from Hereditary nonpolyposis colorectal cancer (HNPCC) patients. The genetic defect responsible for the MIN+ phenotype in sporadic colorectal cancer, however, has yet to be clearly delineated. The purpose of this study was to determine the presence of MSI in sporadic cancer and to correlate its occurrence with clinicopathological parameters, we have studied six microsatellite loci by use of polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis. We found that 20%(9 of 46 cases) sporadic colorectal cancers showed RER at two or several loci(RER+). Microsatellite instability was associated with location of the tumor in the proximal colon 66%(6 of 9 cases) and with poorly differentiated tumor phenotype 56%(5 of 9 cases). In order to better understand the role of somatic alterations within hMSH2 in the process of colorectal tumorigenesis, we examined the most conserved regions(codon 598~789) of this gene in nine patients with MIN spotadic colorectal cancer. 6 patient of RER(+) colorectal ca. patients had a polymorphism which was a T to C base change in the intron sequence at -6 position of the splice acceptor site at the 5'end of exon 13. This particular sequence variation is a polymorphism rather than a mutation which increase cancer susceptability. These data suggest that the genetic instability is detect ed in some colorectal cancers and play an important role in the pathogenesis of sporadic colorectal cancer.

Tumor Angiogenesis as a Prognostic Assay for Patients with Colorectal.: Hyun, Moon Soo , Choi, Hong Jo , Jung, Ghap Joong , Kim, Sang Soon; J Korean Soc Coloproctol. 1997;13(2):161-174.

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Abstract PDF: The growth and maintenance of solid tumors are dependent on new capillary ingrowth:a process called "angiogenesis." Thus, after a new tumor has attained a smallsize of a few millimeters in diameter(about 106 cells), further expansion of the tumor-cell population requires the induction of new capillary blood vessels. These new vessels also increase the opportunity for hematogenous or lymph node metastasis. Thus this study was designed to examine the microvessel count at the invasive margin in colorectal carcinoma to determine how angiogenesis correlates with clinicopathologic factors and prognosis. Paraffinembedded tissues from 127 patients with primary colorectal carcinomas that had been completely removed were retrieved and analyzed for angiogenesis. Vessels were immunostained with anti-factor VIII polyclonal antibody, and areas with the most discrete microvessels were counted in a 200 x field, which were defined as angiogenesis score(AS). The mean AS for anti-factor VIII antibody in this study was 55+/-08; therefore, cases were classified into two subgroups : AS high group(n=67), for which AS was greater than 55 and AS low group(n=60), for which AS was equal to 55 or less. There were no significant intergroup difference regarding sex ratio, histologic grade, depth of invasion, or lymphatic invasion. AS was, however, significantly related to tumor size, venous invasion, lymph node metastasis, and liver metastasis(P=0.000, P=0.001, P=0.021, and P=0.004, respectively). The incidence of high AS group in Antler-Coller D was significantly greater than that in Antler-Coller A and B, and Antler-Coller C(P<0.05, respectively). The recurrence rate in high AS group was 32.0%, which was, though statistically insignificant, higher than that in low AS group(17.2%). The 3 year survival rates of high AS group were significantly (P=0.004 both for overall cases and curatively-resected ones) worse than those of low AS group. This study suggests that the growth of colorectal carcinoma is dependent on ingrowth of new blood vessels, and that angiogenesis assessed by the microvessel count using immunohistochemical stains is an important predictor of tumor behavior and may identify patients at higher risk for recurrence and early death.

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