Advances in study of colorectal mucinous adenocarcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

QIN Xiusen , GUO Wentai , CAO Wuteng ,  WANG Hui

The Sixth Affiliated Hospital, Sun Yat-sen University & Guangdong Provincial Institute of Gastroenterology & Guangdong Provincial KeyLaboratory of Colorectal and Pelvic Floor Disease, Guangzhou 510655, P. R. China;

Corresponding author：

WANG Hui, Email: wanghuislh@hotmail.com

Keywords：

colorectal cancer; mucinous adenocarcinoma; pathogenesis; clicopathologic characteristics

DOI：

10.7507/1007-9424.201911001

Video：

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Objective To summarize the research progress of colorectal mucinous adenocarcinoma.Method The articles about colorectal mucinous adenocarcinoma in recent years were reviewed.Results The colorectal mucinous adenocarcinoma was a pathological subtype of colorectal cancer, which had unique clinicopathologic characteristics, relatively low incidence, and poor prognosis. The current studies suggested that the BRAF mutation, microsatellite instability, CpG island methylation, and mucin expression were related to the occurrence and development of colorectal mucinous adenocarcinoma, but its molecular mechanism was still unclear. The colorectal mucinous adenocarcinoma was more common in the proximal colon and female patients. The multiple metastases, extrahepatic and peritoneal metastases were also common. The preoperative MRI examination was very valuable. The main treatment was surgery, and the multidisciplinary discussions were still needed to determine the best treatment for patients in the advanced stage. Compared with other types of colorectal adenocarcinoma, patients with colorectal mucinous adenocarcinoma had a poor prognosis.Conclusions Although we have a certain understanding of colorectal mucinous adenocarcinoma, the study results are limited due to the small sample size of many related articles and the lack of prospective randomized controlled studies. Therefore, more studies are needed in the future to improve the cognition of colorectal mucinous adenocarcinoma. Future research should focus on the molecular mechanism and treatment of colorectal mucinous adenocarcinoma.

Citation： QIN Xiusen, GUO Wentai, CAO Wuteng, WANG Hui. Advances in study of colorectal mucinous adenocarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(7): 906-911. doi: 10.7507/1007-9424.201911001 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Chand M, Yu S, Swift RI, et al. Mucinous carcinoma of the rectum: a distinct clinicopathological entity. Tech Coloproctol, 2014, 18(4): 335-344.
3.	Fleming M, Ravula S, Tatishchev SF, et al. Colorectal carcinoma: Pathologic aspects. J Gastrointest Oncol, 2012, 3(3): 153-173.
4.	Parham D. Colloid carcinoma. Ann Surg, 1923, 77(1): 90-105.
5.	Hugen N, van Beek JJ, de Wilt JH, et al. Insight into mucinous colorectal carcinoma: clues from etiology. Ann Surg Oncol, 2014, 21(9): 2963-2970.
6.	Ott C, Gerken M, Hirsch D, et al. Advanced mucinous colorectal cancer: epidemiology, prognosis and efficacy of chemotherapeutic treatment. Digestion, 2018, 98(3): 143-152.
7.	Hugen N, Simons M, Halilović A, et al. The molecular background of mucinous carcinoma beyond MUC2. J Pathol Clin Res, 2014, 1(1): 3-17.
8.	Morikawa T, Kuchiba A, Qian ZR, et al. Prognostic significance and molecular associations of tumor growth pattern in colorectal cancer. Ann Surg Oncol, 2012, 19(6): 1944-1953.
9.	Reynolds IS, Furney SJ, Kay EW, et al. Meta-analysis of the molecular associations of mucinous colorectal cancer. Br J Surg, 2019, 106(6): 682-691.
10.	中国临床肿瘤学会结直肠癌专家委员会, 中国抗癌协会大肠癌专业委员会遗传学组, 中国医师协会结直肠肿瘤专业委员会遗传专委会. 结直肠癌及其他相关实体瘤微卫星不稳定性检测中国专家共识. 实用肿瘤杂志, 2019, 34(5): 381-389.
11.	Leopoldo S, Lorena B, Cinzia A, et al. Two subtypes of mucinous adenocarcinoma of the colorectum: clinicopathological and genetic features. Ann Surg Oncol, 2008, 15(5): 1429-1439.
12.	Verhulst J, Ferdinande L, Demetter P, et al. Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and meta-analysis. J Clin Pathol, 2012, 65(5): 381-388.
13.	Bergman Y, Cedar H. DNA methylation dynamics in health and disease. Nat Struct Mol Biol, 2013, 20(3): 274-281.
14.	Khan M, Loree JM, Advani SM, et al. Prognostic implications of mucinous differentiation in metastatic colorectal carcinoma can be explained by distinct molecular and clinicopathologic characteristics. Clin Colorectal Cancer, 2018, 17(4): e699-e709.
15.	Ogino S, Odze R D, Kawasaki T, et al. Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma. Am J Surg Pathol, 2006, 30(9): 1175-1183.
16.	Dunkin D, Iuga AC, Mimouna S, et al. Intestinal epithelial Notch-1 protects from colorectal mucinous adenocarcinoma. Oncotarget, 2018, 9(71): 33536-33548.
17.	Bu XD, Li N, Tian XQ, et al. Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma. World J Gastroenterol, 2010, 16(32): 4089-4094.
18.	Byrd JC, Bresalier RS. Mucins and mucin binding proteins in colorectal cancer. Cancer Metastasis Rev, 2004, 23(1-2): 77-99.
19.	Imai Y, Yamagishi H, Fukuda K, et al. Differential mucin phenotypes and their significance in a variation of colorectal carcinoma. World J Gastroenterol, 2013, 19(25): 3957-3968.
20.	Li L, Huang PL, Yu XJ, et al. Clinicopathological significance of Mucin 2 immuno-histochemical expression in colorectal cancer: a meta-analysis. Chin J Cancer Res, 2012, 24(3): 190-195.
21.	Weiss AA, Babyatsky MW, Ogata S, et al. Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues. J Histochem Cytochem, 1996, 44(10): 1161-1166.
22.	Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer, 2009, 9(12): 874-885.
23.	Shen P, Yang S, Sun H, et al. SCF/c-KIT signaling increased Mucin2 production by maintaining Atoh1 expression in mucinous colorectal adenocarcinoma. Int J Mol Sci, 2018, 19(5): E1541.
24.	Li G, Yang S, Shen P, et al. SCF/c-KIT signaling promotes mucus secretion of colonic goblet cells and development of mucinous colorectal adenocarcinoma. Am J Cancer Res, 2018, 8(6): 1064-1073.
25.	曹务腾, 王馨华, 李芳倩, 等. 直肠癌黏液湖比例对新辅助化疗疗效的影响探讨. 影像诊断与介入放射学, 2017, 26(1): 3-7.
26.	Shia J, Guillem JG, Moore HG, et al. Patterns of morphologic alteration in residual rectal carcinoma following preoperative chemoradiation and their association with long-term outcome. Am J Surg Pathol, 2004, 28(2): 215-223.
27.	Nagtegaal ID, Marijnen CA, Kranenbarg EK, et al. Short-term preoperative radiotherapy interferes with the determination of pathological parameters in rectal cancer. J Pathol, 2002, 197(1): 20-27.
28.	Rullier A, Laurent C, Vendrely V, et al. Impact of colloid response on survival after preoperative radiotherapy in locally advanced rectal carcinoma. Am J Surg Pathol, 2005, 29(5): 602-606.
29.	Nagtegaal I, Gaspar C, Marijnen C, et al. Morphological changes in tumour type after radiotherapy are accompanied by changes in gene expression profile but not in clinical behaviour. J Pathol, 2004, 204(2): 183-192.
30.	Yu SK, Chand M, Tait DM, et al. Magnetic resonance imaging defined mucinous rectal carcinoma is an independent imaging biomarker for poor prognosis and poor response to preoperative chemoradiotherapy. Eur J Cancer, 2014, 50(5): 920-927.
31.	Hussain SM, Outwater EK, Siegelman ES. Mucinous versus nonmucinous rectal carcinomas: differentiation with MR imaging. Radiology, 1999, 213(1): 79-85.
32.	Oberholzer K, Menig M, Kreft A, et al. Rectal cancer: mucinous carcinoma on magnetic resonance imaging indicates poor response to neoadjuvant chemoradiation. Int J Radiat Oncol Biol Phys, 2012, 82(2): 842-848.
33.	陈子敏, 李振辉, 董兴祥, 等. 结直肠黏液腺癌的 CT 表现. 中国临床医学影像杂志, 2016, 27(10): 729-731.
34.	Miyakita H, Sadahiro S, Ogimi T, et al. Mucinous components assessed by magnetic resonance imaging in primary rectal cancer tissue before and after chemoradiotherapy and tumor response. Int J Colorectal Dis, 2018, 33(8): 1135-1138.
35.	Kim HJ. Mucinous subtype in patients with colorectal cancer. Ann Coloproctol, 2017, 33(2): 44-45.
36.	Riihimäki M, Hemminki A, Sundquist J, et al. Patterns of metastasis in colon and rectal cancer. Sci Rep, 2016, 6: 29765.
37.	Hugen N, van de Velde CJ, de Wilt JH, et al. Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Ann Oncol, 2014, 25(3): 651-657.
38.	Hugen N, Verhoeven RH, Radema SA, et al. Prognosis and value of adjuvant chemotherapy in stage Ⅲ mucinous colorectal carcinoma. Ann Oncol, 2013, 24(11): 2819-2824.
39.	Numata M, Shiozawa M, Watanabe T, et al. The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease. World J Surg Oncol, 2012, 10: 109.
40.	国家卫生计生委医政医管局, 中华医学会肿瘤学分会. 中国结直肠癌诊疗规范 (2017 年版). 中华临床医师杂志 (电子版), 2018, 12(3): 145-159.
41.	Simha V, Kapoor R, Gupta R, et al. Mucinous adenocarcinoma of the rectum: a poor candidate for neo-adjuvant chemoradiation? J Gastrointest Oncol, 20124, 5(4): 276-279.
42.	Sun YW, Chi P, Lin HM, et al. Effect of neoadjuvant chemoradiotherapy on locally advanced rectal mucinous adenocarcinoma: a propensity score-matched study. Gastroenterol Res Pract, 2017, 2017: 5715219.
43.	Deng Y, Chi P, Lan P, et al. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: Initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase Ⅲ trial. J Clin Oncol, 2016, 34(27): 3300-3307.
44.	Sánchez-Hidalgo JM, Rodríguez-Ortiz L, Arjona-Sánchez Á, et al. Colorectal peritoneal metastases: Optimal management review. World J Gastroenterol, 2019, 25(27): 3484-3502.
45.	Hyngstrom JR, Hu CY, Xing Y, et al. Clinicopathology and outcomes for mucinous and signet ring colorectal adenocarcinoma: analysis from the National Cancer Data Base. Ann Surg Oncol, 2012, 19(9): 2814-2821.
46.	Nagtegaal ID, Quirke P. What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol, 2008, 26(2): 303-312.
47.	Hugen N, van de Velde CJ, Bosch SL, et al. Modern treatment of rectal cancer closes the gap between common adenocarcinoma and mucinous carcinoma. Ann Surg Oncol, 2015, 22(8): 2669-2676.
48.	Mekenkamp LJ, Heesterbeek KJ, Koopman M, et al. Mucinous adenocarcinomas: poor prognosis in metastatic colorectal cancer. Eur J Cancer, 2012, 48(4): 501-509.
49.	Catalano V, Loupakis F, Graziano F, et al. Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy. Br J Cancer, 2009, 100(6): 881-887.
50.	Negri FV, Wotherspoon A, Cunningham D, et al. Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer. Ann Oncol, 2005, 16(8): 1305-1310.
51.	Molavi D, Argani P. Distinguishing benign dissecting mucin (stromal mucin pools) from invasive mucinous carcinoma. Adv Anat Pathol, 2008, 15(1): 1-17.
52.	Liu Z, Zhang XY, Shi YJ, et al. Radiomics analysis for evaluation of pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Clin Cancer Res, 2017, 23(23): 7253-7262.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Chand M, Yu S, Swift RI, et al. Mucinous carcinoma of the rectum: a distinct clinicopathological entity. Tech Coloproctol, 2014, 18(4): 335-344.
3. Fleming M, Ravula S, Tatishchev SF, et al. Colorectal carcinoma: Pathologic aspects. J Gastrointest Oncol, 2012, 3(3): 153-173.
4. Parham D. Colloid carcinoma. Ann Surg, 1923, 77(1): 90-105.
5. Hugen N, van Beek JJ, de Wilt JH, et al. Insight into mucinous colorectal carcinoma: clues from etiology. Ann Surg Oncol, 2014, 21(9): 2963-2970.
6. Ott C, Gerken M, Hirsch D, et al. Advanced mucinous colorectal cancer: epidemiology, prognosis and efficacy of chemotherapeutic treatment. Digestion, 2018, 98(3): 143-152.
7. Hugen N, Simons M, Halilović A, et al. The molecular background of mucinous carcinoma beyond MUC2. J Pathol Clin Res, 2014, 1(1): 3-17.
8. Morikawa T, Kuchiba A, Qian ZR, et al. Prognostic significance and molecular associations of tumor growth pattern in colorectal cancer. Ann Surg Oncol, 2012, 19(6): 1944-1953.
9. Reynolds IS, Furney SJ, Kay EW, et al. Meta-analysis of the molecular associations of mucinous colorectal cancer. Br J Surg, 2019, 106(6): 682-691.
10. 中国临床肿瘤学会结直肠癌专家委员会, 中国抗癌协会大肠癌专业委员会遗传学组, 中国医师协会结直肠肿瘤专业委员会遗传专委会. 结直肠癌及其他相关实体瘤微卫星不稳定性检测中国专家共识. 实用肿瘤杂志, 2019, 34(5): 381-389.
11. Leopoldo S, Lorena B, Cinzia A, et al. Two subtypes of mucinous adenocarcinoma of the colorectum: clinicopathological and genetic features. Ann Surg Oncol, 2008, 15(5): 1429-1439.
12. Verhulst J, Ferdinande L, Demetter P, et al. Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and meta-analysis. J Clin Pathol, 2012, 65(5): 381-388.
13. Bergman Y, Cedar H. DNA methylation dynamics in health and disease. Nat Struct Mol Biol, 2013, 20(3): 274-281.
14. Khan M, Loree JM, Advani SM, et al. Prognostic implications of mucinous differentiation in metastatic colorectal carcinoma can be explained by distinct molecular and clinicopathologic characteristics. Clin Colorectal Cancer, 2018, 17(4): e699-e709.
15. Ogino S, Odze R D, Kawasaki T, et al. Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma. Am J Surg Pathol, 2006, 30(9): 1175-1183.
16. Dunkin D, Iuga AC, Mimouna S, et al. Intestinal epithelial Notch-1 protects from colorectal mucinous adenocarcinoma. Oncotarget, 2018, 9(71): 33536-33548.
17. Bu XD, Li N, Tian XQ, et al. Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma. World J Gastroenterol, 2010, 16(32): 4089-4094.
18. Byrd JC, Bresalier RS. Mucins and mucin binding proteins in colorectal cancer. Cancer Metastasis Rev, 2004, 23(1-2): 77-99.
19. Imai Y, Yamagishi H, Fukuda K, et al. Differential mucin phenotypes and their significance in a variation of colorectal carcinoma. World J Gastroenterol, 2013, 19(25): 3957-3968.
20. Li L, Huang PL, Yu XJ, et al. Clinicopathological significance of Mucin 2 immuno-histochemical expression in colorectal cancer: a meta-analysis. Chin J Cancer Res, 2012, 24(3): 190-195.
21. Weiss AA, Babyatsky MW, Ogata S, et al. Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues. J Histochem Cytochem, 1996, 44(10): 1161-1166.
22. Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer, 2009, 9(12): 874-885.
23. Shen P, Yang S, Sun H, et al. SCF/c-KIT signaling increased Mucin2 production by maintaining Atoh1 expression in mucinous colorectal adenocarcinoma. Int J Mol Sci, 2018, 19(5): E1541.
24. Li G, Yang S, Shen P, et al. SCF/c-KIT signaling promotes mucus secretion of colonic goblet cells and development of mucinous colorectal adenocarcinoma. Am J Cancer Res, 2018, 8(6): 1064-1073.
25. 曹务腾, 王馨华, 李芳倩, 等. 直肠癌黏液湖比例对新辅助化疗疗效的影响探讨. 影像诊断与介入放射学, 2017, 26(1): 3-7.
26. Shia J, Guillem JG, Moore HG, et al. Patterns of morphologic alteration in residual rectal carcinoma following preoperative chemoradiation and their association with long-term outcome. Am J Surg Pathol, 2004, 28(2): 215-223.
27. Nagtegaal ID, Marijnen CA, Kranenbarg EK, et al. Short-term preoperative radiotherapy interferes with the determination of pathological parameters in rectal cancer. J Pathol, 2002, 197(1): 20-27.
28. Rullier A, Laurent C, Vendrely V, et al. Impact of colloid response on survival after preoperative radiotherapy in locally advanced rectal carcinoma. Am J Surg Pathol, 2005, 29(5): 602-606.
29. Nagtegaal I, Gaspar C, Marijnen C, et al. Morphological changes in tumour type after radiotherapy are accompanied by changes in gene expression profile but not in clinical behaviour. J Pathol, 2004, 204(2): 183-192.
30. Yu SK, Chand M, Tait DM, et al. Magnetic resonance imaging defined mucinous rectal carcinoma is an independent imaging biomarker for poor prognosis and poor response to preoperative chemoradiotherapy. Eur J Cancer, 2014, 50(5): 920-927.
31. Hussain SM, Outwater EK, Siegelman ES. Mucinous versus nonmucinous rectal carcinomas: differentiation with MR imaging. Radiology, 1999, 213(1): 79-85.
32. Oberholzer K, Menig M, Kreft A, et al. Rectal cancer: mucinous carcinoma on magnetic resonance imaging indicates poor response to neoadjuvant chemoradiation. Int J Radiat Oncol Biol Phys, 2012, 82(2): 842-848.
33. 陈子敏, 李振辉, 董兴祥, 等. 结直肠黏液腺癌的 CT 表现. 中国临床医学影像杂志, 2016, 27(10): 729-731.
34. Miyakita H, Sadahiro S, Ogimi T, et al. Mucinous components assessed by magnetic resonance imaging in primary rectal cancer tissue before and after chemoradiotherapy and tumor response. Int J Colorectal Dis, 2018, 33(8): 1135-1138.
35. Kim HJ. Mucinous subtype in patients with colorectal cancer. Ann Coloproctol, 2017, 33(2): 44-45.
36. Riihimäki M, Hemminki A, Sundquist J, et al. Patterns of metastasis in colon and rectal cancer. Sci Rep, 2016, 6: 29765.
37. Hugen N, van de Velde CJ, de Wilt JH, et al. Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Ann Oncol, 2014, 25(3): 651-657.
38. Hugen N, Verhoeven RH, Radema SA, et al. Prognosis and value of adjuvant chemotherapy in stage Ⅲ mucinous colorectal carcinoma. Ann Oncol, 2013, 24(11): 2819-2824.
39. Numata M, Shiozawa M, Watanabe T, et al. The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease. World J Surg Oncol, 2012, 10: 109.
40. 国家卫生计生委医政医管局, 中华医学会肿瘤学分会. 中国结直肠癌诊疗规范 (2017 年版). 中华临床医师杂志 (电子版), 2018, 12(3): 145-159.
41. Simha V, Kapoor R, Gupta R, et al. Mucinous adenocarcinoma of the rectum: a poor candidate for neo-adjuvant chemoradiation? J Gastrointest Oncol, 20124, 5(4): 276-279.
42. Sun YW, Chi P, Lin HM, et al. Effect of neoadjuvant chemoradiotherapy on locally advanced rectal mucinous adenocarcinoma: a propensity score-matched study. Gastroenterol Res Pract, 2017, 2017: 5715219.
43. Deng Y, Chi P, Lan P, et al. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: Initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase Ⅲ trial. J Clin Oncol, 2016, 34(27): 3300-3307.
44. Sánchez-Hidalgo JM, Rodríguez-Ortiz L, Arjona-Sánchez Á, et al. Colorectal peritoneal metastases: Optimal management review. World J Gastroenterol, 2019, 25(27): 3484-3502.
45. Hyngstrom JR, Hu CY, Xing Y, et al. Clinicopathology and outcomes for mucinous and signet ring colorectal adenocarcinoma: analysis from the National Cancer Data Base. Ann Surg Oncol, 2012, 19(9): 2814-2821.
46. Nagtegaal ID, Quirke P. What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol, 2008, 26(2): 303-312.
47. Hugen N, van de Velde CJ, Bosch SL, et al. Modern treatment of rectal cancer closes the gap between common adenocarcinoma and mucinous carcinoma. Ann Surg Oncol, 2015, 22(8): 2669-2676.
48. Mekenkamp LJ, Heesterbeek KJ, Koopman M, et al. Mucinous adenocarcinomas: poor prognosis in metastatic colorectal cancer. Eur J Cancer, 2012, 48(4): 501-509.
49. Catalano V, Loupakis F, Graziano F, et al. Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy. Br J Cancer, 2009, 100(6): 881-887.
50. Negri FV, Wotherspoon A, Cunningham D, et al. Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer. Ann Oncol, 2005, 16(8): 1305-1310.
51. Molavi D, Argani P. Distinguishing benign dissecting mucin (stromal mucin pools) from invasive mucinous carcinoma. Adv Anat Pathol, 2008, 15(1): 1-17.
52. Liu Z, Zhang XY, Shi YJ, et al. Radiomics analysis for evaluation of pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Clin Cancer Res, 2017, 23(23): 7253-7262.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Advances in study of colorectal mucinous adenocarcinoma

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