Annals of Coloproctology

Original Article

Colorectal cancer

Preventive efficacy of hydrocortisone enema for radiation proctitis in rectal cancer patients undergoing short-course radiotherapy: a phase II randomized placebo-controlled clinical trial: Mohammad Mohammadianpanah, Maryam Tazang, Nam Phong Nguyen, Niloofar Ahmadloo, Shapour Omidvari, Ahmad Mosalaei, Mansour Ansari, Hamid Nasrollahi, Behnam Kadkhodaei, Nezhat Khanjani, Seyed Vahid Hosseini; Ann Coloproctol. 2024;40(5):506-514. Published online October 22, 2024; DOI: https://doi.org/10.3393/ac.2024.00192.0027

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Abstract PDF: Purpose
This study aimed to investigate the efficacy of hydrocortisone enema in preventing radiation proctitis in patients with rectal cancer undergoing short-course radiotherapy (SCRT).
Methods
This phase II randomized controlled trial enrolled patients with newly diagnosed locally advanced rectal cancer (clinically staged T3–4 and/or N1–2M0). Participants received a median of 4 cycles of neoadjuvant chemotherapy (capecitabine plus oxaliplatin) followed by 3-dimensional conformal SCRT (25 Gy in 5 fractions). Patients were randomly assigned to receive either a hydrocortisone enema (n=50) or a placebo (n=51) once daily for 5 consecutive days during SCRT. The primary endpoint was the incidence and severity of acute proctitis.
Results
Of the 111 eligible patients, 101 were included in the study. Baseline characteristics, including sex, age, performance status, and tumor location, were comparable across the treatment arms. None of the patients experienced grade 4 acute gastrointestinal toxicity or had to discontinue treatment due to treatment-related adverse effects. Patients in the hydrocortisone arm experienced significantly less severe proctitis (P<0.001), diarrhea (P=0.023), and rectal pain (P<0.001) than those in the placebo arm. Additionally, the duration of acute gastrointestinal toxicity following SCRT was significantly shorter in patients receiving hydrocortisone (P<0.001).
Conclusion
Hydrocortisone enema was associated with a significant reduction in the severity of proctitis, diarrhea, and rectal pain compared to placebo. Additionally, patients treated with hydrocortisone experienced shorter durations of gastrointestinal toxicity following SCRT. This study highlights the potential benefits of hydrocortisone enema in managing radiation-induced toxicity in rectal cancer patients undergoing radiotherapy.

Reviews

Colorectal cancer

The role of lateral pelvic lymph node dissection in advanced rectal cancer: a review of current evidence and outcomes: Gyu-Seog Choi, Hye Jin Kim; Ann Coloproctol. 2024;40(4):363-374. Published online August 30, 2024; DOI: https://doi.org/10.3393/ac.2024.00521.0074

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Abstract PDF

Metastatic lateral pelvic lymph nodes (LPNs) in rectal cancer significantly impact the prognosis and treatment strategies. Western practices emphasize neoadjuvant chemoradiotherapy (CRT), whereas Eastern approaches often rely on LPN dissection (LPND). This review examines the evolving role of LPND in the context of modern treatments, including total neoadjuvant therapy (TNT), and the impact of CRT on the management of clinically suspicious LPNs. We comprehensively reviewed the key literature comparing the outcomes of LPND versus preoperative CRT for rectal cancer, focusing on recent advancements and ongoing debates. Key studies, including the JCOG0212 trial and recent multicenter trials, were analyzed to assess the efficacy of LPND, particularly in conjunction with preoperative CRT or TNT. Current evidence indicates that LPND can reduce local recurrence rates compared to total mesorectal excision alone in patients not receiving radiation therapy. However, the benefit of LPND in the context of neoadjuvant CRT is influenced by the size and pretreatment characteristics of LPNs. While CRT can effectively control smaller metastatic LPNs, larger or clinically suspicious LPNs may require LPND for optimal outcomes. Advances in surgical techniques, such as robotic-assisted LPND, offer potential benefits but also present challenges and complications. The role of TNT in controlling metastatic LPNs and improving patient outcomes is emerging but remains underexplored. The decision to perform LPND should be individualized based on patient-specific factors, including LPN size, response to neoadjuvant treatment, and surgeon expertise. Future research should focus on optimizing treatment protocols and further evaluating the role of TNT in managing metastatic LPNs.

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From the Editor: Uniting expertise, a new era of global collaboration in coloproctology
In Ja Park
Annals of Coloproctology.2024; 40(4): 285. CrossRef

Colorectal cancer

Survival outcomes of salvage surgery in the watch-and-wait approach for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis: Wenjie Lin, Ian Jun Yan Wee, Isaac Seow-En, Aik Yong Chok, Emile Kwong-Wei Tan; Ann Coloproctol. 2023;39(6):447-456. Published online December 28, 2023; DOI: https://doi.org/10.3393/ac.2022.01221.0174

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Abstract PDF Supplementary Material

Purpose
This systematic review and meta-analysis compared the outcomes of the watch-and-wait (WW) approach versus radical surgery (RS) in rectal cancers with clinical complete response (cCR) after neoadjuvant chemoradiotherapy.
Methods
This study followed the PRISMA guidelines. Major databases were searched to identify relevant articles. WW and RS were compared through meta-analyses of pooled proportions. Primary outcomes included overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis rates. Pooled salvage surgery rates and outcomes were also collected. The Newcastle-Ottawa scale was employed to assess the risk of bias.
Results
Eleven studies including 1,112 rectal cancer patients showing cCR after neoadjuvant chemoradiation were included. Of these patients, 378 were treated nonoperatively with WW, 663 underwent RS, and 71 underwent local excision. The 2-year OS (risk ratio [RR], 0.95; P = 0.94), 5-year OS (RR, 2.59; P = 0.25), and distant metastasis rates (RR, 1.05; P = 0.80) showed no significant differences between WW and RS. Local recurrence was more frequent in the WW group (RR, 6.93; P < 0.001), and 78.4% of patients later underwent salvage surgery (R0 resection rate, 97.5%). The 2-year DFS (RR, 1.58; P = 0.05) and 5-year DFS (RR, 2.07; P = 0.02) were higher among RS cases. However, after adjustment for R0 salvage surgery, DFS showed no significant between-group difference (RR, 0.82; P = 0.41).
Conclusion
Local recurrence rates are higher for WW than RS, but complete salvage surgery is often possible with similar long-term outcomes. WW is a viable strategy for rectal cancer with cCR after neoadjuvant chemoradiation, but further research is required to improve patient selection.

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Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer
Francesco Giulio Sullo, Alessandro Passardi, Chiara Gallio, Chiara Molinari, Giorgia Marisi, Eleonora Pozzi, Leonardo Solaini, Alessandro Bittoni
Journal of Clinical Medicine.2024; 13(9): 2562. CrossRef
Tailoring rectal cancer surgery: Surgical approaches and anatomical insights during deep pelvic dissection for optimal outcomes in low‐lying rectal cancer
Youn Young Park, Nam Kyu Kim
Annals of Gastroenterological Surgery.2024; 8(5): 761. CrossRef
Combined Transanal and Laparoscopic Approach for Full-Thickness Local Excision of Locally Advanced Rectal Cancer Following Near-Complete Response after Chemotherapy
Joshua S. H. Lim, Si-Lin Koo, Iain Beehuat Tan, Isaac Seow-En
World Journal of Colorectal Surgery.2024; 13(3): 95. CrossRef
Watch‐and‐Wait Approach Following Neoadjuvant Chemo‐Radiotherapy for Locally Advanced Rectal Cancer: A Retrospective Single‐Center Cohort Study
Georgi Kalev, Sylvia Buettner, Tianzuo Zhan, Ralf‐Dieter Hofheinz, Judit Boda‐Heggemann, Christoph Reissfelder, Steffen Seyfried, Georgi Vassilev, Julia Hardt
Journal of Surgical Oncology.2024;[Epub] CrossRef

Original Article

Malignant disease, Rectal cancer,Prognosis and adjuvant therapy,Colorectal cancer,Epidemiology & etiology

Characteristics of Patients Presented With Metastases During or After Completion of Chemoradiation Therapy for Locally Advanced Rectal Cancer: A Case Series: Radwan Torky, Mohammed Alessa, Ho Seung Kim, Ahmed Sakr, Eman Zakarneh, Fozan Sauri, Heejin Bae, Nam Kyu Kim; Ann Coloproctol. 2021;37(3):186-191. Published online September 18, 2020; DOI: https://doi.org/10.3393/ac.2020.08.10.1

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Abstract PDF

Purpose
Locally advanced rectal cancer (LARC) is managed by chemoradiotherapy (CRT), followed by surgery. Herein we reported patients with metastases during or after CRT.
Methods
Data of patients with LARC who received CRT from 2008 to 2017 were reviewed. Patients with metastases after CRT were included. Those with metastatic tumors at the initial diagnosis were excluded.
Results
Fourteen patients (1.3%) of 1,092 who received CRT presented with metastases. Magnetic resonance circumferential resection margin (mrCRM) and mesorectal lymph nodes (LNs) were positive in 12 patients (85.7%). Meanwhile, magnetic resonance extramural vascular invasion (mrEMVI) was positive in 10 patients (71.4%). Magnetic resonance tumor regression grade (mrTRG) 4 and mrTRG5 was detected in 5 and 1 patient respectively. Ten patients (71.4%) underwent combined surgery and 3 (21.4%) received palliative chemotherapy.
Conclusion
Patients with metastases after CRT showed a higher rate of positive mrCRM, mrEMVI, mesorectal LNs, and poor tumor response. Further studies with a large number of patients are necessary for better survival outcomes in LARC.

Citations

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Unveiling the profound advantages of total neoadjuvant therapy in rectal cancer: a trailblazing exploration
Kyung Uk Jung, Hyung Ook Kim, Hungdai Kim, Donghyoun Lee, Chinock Cheong
Annals of Surgical Treatment and Research.2023; 105(6): 341. 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
Recent Advance in the Surgical Treatment of Metastatic Colorectal Cancer-An English Version
Eun Jung Park, Seung Hyuk Baik
Journal of the Anus, Rectum and Colon.2022; 6(4): 213. CrossRef
Update on Diagnosis and Treatment of Colorectal Cancer
Chan Wook Kim
The Ewha Medical Journal.2022;[Epub] CrossRef

Review

How to Achieve a Higher Pathologic Complete Response in Patients With Locally Advanced Rectal Cancer Who Receive Preoperative Chemoradiation Therapy: Suk-Hwan Lee; Ann Coloproctol. 2019;35(1):3-8. Published online February 28, 2019; DOI: https://doi.org/10.3393/ac.2019.02.17

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3 Citations

Abstract PDF

The current standard of care for treating patients with locally advanced rectal cancer includes preoperative chemoradiation therapy (PCRT) followed by a total mesorectal excision and postoperative adjuvant chemotherapy. A subset of these patients has achieved a pathologic complete response (pCR) and they have shown improved disease-free and overall survival compared to non-pCR patients. Thus, many efforts have been made to achieve a higher pCR through PCRT. In this review, results from various ongoing and recently completed clinical trials that are being or have been conducted with an aim to improve tumor response by modifying therapy will be discussed.

Citations

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Predictors of Pathologic Response After Total Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: A National Cancer Database Analysis
David M McDermott, Sarah A Singh, Paul B Renz, Shaakir Hasan, Josh Weir
Cureus.2021;[Epub] CrossRef
Can Pretreatment Blood Biomarkers Predict Pathological Response to Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer?
Marina Morais, Telma Fonseca, Raquel Machado-Neves, Mrinalini Honavar, Ana Rita Coelho, Joanne Lopes, Elisabete Barbosa, Emanuel Guerreiro, Silvestre Carneiro
Future Oncology.2021; 17(35): 4947. CrossRef
Pretreatment Blood Biomarkers Predict Pathologic Responses to Neo-Crt in Patients with Locally Advanced Rectal Cancer
Aijie Li, Kewen He, Dong Guo, Chao Liu, Duoying Wang, Xiangkui Mu, Jinming Yu
Future Oncology.2019; 15(28): 3233. CrossRef

Original Article

Prognostic Impact of Immunonutritional Status Changes During Preoperative Chemoradiation in Patients With Rectal Cancer: Yong Joon Lee, Woo Ram Kim, Jeonghee Han, Yoon Dae Han, Min Soo Cho, Hyuk Hur, Kang Young Lee, Nam Kyu Kim, Byung Soh Min; Ann Coloproctol. 2016;32(6):208-214. Published online December 31, 2016; DOI: https://doi.org/10.3393/ac.2016.32.6.208

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Abstract PDF

Purpose

Previous studies have demonstrated the prognostic impact of the prognostic nutritional index (PNI), a proposed indicator of immunonutritional statuses of surgical patients, on patients with various gastrointestinal cancers. Although the prognostic impact of the PNI on patients with colorectal cancer has been well established, its value has not been studied in patients treated with preoperative chemoradiation (pCRT). This study aimed to evaluate the prognostic impact of PNI on patients receiving pCRT for locally advanced rectal cancer (LARC).

Methods

Patients with LARC who underwent curative pCRT followed by surgical resection were enrolled. The PNI was measured in all patients before and after pCRT, and the difference in values was calculated as the PNI difference (dPNI). Patients were classified according to dPNI (<5, 5–10, and >10). Clinicopathologic parameters and long-term oncologic outcomes were assessed according to dPNI classification.

Results

No significant intergroup differences were observed in clinicopathologic parameters such as age, histologic grade, tumor location, tumor-node-metastasis stage, and postoperative complications. Approximately 53% of the patients had a mild dPNI (<5); only 15% had a high dPNI (>10). Univariate and multivariate analyses identified the dPNI as an independent prognostic factor for disease-free status (P < 0.01; hazard ratio [HR], 2.792; 95% confidence interval [CI], 1.577–4.942) and for cancer-specific survival (P = 0.012; HR, 2.469; 95%CI, 1.225–4.978).

Conclusion

The dPNI is predictive of long-term outcomes in pCRT-treated patients with LARC. Further prospective studies should investigate whether immune-nutritional status correction during pCRT would improve oncologic outcomes.

Citations

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Preoperative albumin-to-globulin ratio and prognostic nutritional index predict the prognosis of colorectal cancer: a retrospective study
JunHu Li, Na Zhu, Cheng Wang, LiuPing You, WenLong Guo, ZhiHan Yuan, Shuai Qi, HanZheng Zhao, JiaYong Yu, YueNan Huang
Scientific Reports.2023;[Epub] CrossRef
The modified Glasgow prognostic score is a reliable predictor of oncological outcomes in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy
Atsushi Shimada, Takeru Matsuda, Ryuichiro Sawada, Hiroshi Hasegawa, Kimihiro Yamashita, Hitoshi Harada, Naoki Urakawa, Hironobu Goto, Shingo Kanaji, Taro Oshikiri, Yoshihiro Kakeji
Scientific Reports.2023;[Epub] CrossRef
Prognostic Value of Postoperative Neutrophil and Albumin: Reassessment One Month After Gastric Cancer Surgery
Ali Guner, Minah Cho, Yoo-Min Kim, Jae-Ho Cheong, Woo Jin Hyung, Hyoung-Il Kim
Frontiers in Oncology.2021;[Epub] CrossRef
Pelvimetric and Nutritional Factors Predicting Surgical Difficulty in Laparoscopic Resection for Rectal Cancer Following Preoperative Chemoradiotherapy
Yanwu Sun, Jianhua Chen, Chengwei Ye, Huiming Lin, Xingrong Lu, Ying Huang, Pan Chi
World Journal of Surgery.2021; 45(7): 2261. CrossRef
Inflammation‐nutritional markers of peripheral blood could predict survival in advanced non‐small‐cell lung cancer patients treated with PD‐1 inhibitors
Dan Pu, Qian Xu, Lai‐Yan Zhou, Yu‐Wen Zhou, Ji‐Yan Liu, Xue‐Lei Ma
Thoracic Cancer.2021; 12(21): 2914. CrossRef
Preoperative change of modified Glasgow prognostic score after stenting predicts the long-term outcomes of obstructive colorectal cancer
Ryuichiro Sato, Masaya Oikawa, Tetsuya Kakita, Takaho Okada, Tomoya Abe, Takashi Yazawa, Haruyuki Tsuchiya, Naoya Akazawa, Masaki Sato, Tetsuya Ohira, Yoshihiro Harada, Haruka Okano, Kei Ito, Noriaki Ohuchi, Takashi Tsuchiya
Surgery Today.2020; 50(3): 232. CrossRef
Prognostic impact of preoperative immunonutritional status in rectal mucinous adenocarcinoma
Yanwu Sun, Zhekun Huang, Huiming Lin, Pan Chi
Future Oncology.2020; 16(8): 339. CrossRef
Low Prognostic Nutritional Index Predicts Poor Clinical Outcomes in Patients with Stage IIIB Non-small-cell Lung Carcinoma Undergoing Chemoradiotherapy

Yurday Ozdemir, Erkan Topkan, Huseyin Mertsoylu, Ugur Selek
Cancer Management and Research.2020; Volume 12: 1959. CrossRef
Peripheral blood markers predictive of outcome and immune-related adverse events in advanced non-small cell lung cancer treated with PD-1 inhibitors
Lihong Peng, Yong Wang, Fen Liu, Xiaotong Qiu, Xinwei Zhang, Chen Fang, Xiaoyin Qian, Yong Li
Cancer Immunology, Immunotherapy.2020; 69(9): 1813. CrossRef
The prognostic value of the prognostic nutritional index and inflammation-based markers in obstructive colorectal cancer
Ryuichiro Sato, Masaya Oikawa, Tetsuya Kakita, Takaho Okada, Tomoya Abe, Takashi Yazawa, Haruyuki Tsuchiya, Naoya Akazawa, Masaki Sato, Tetsuya Ohira, Yoshihiro Harada, Haruka Okano, Kei Ito, Takashi Tsuchiya
Surgery Today.2020; 50(10): 1272. CrossRef
Preoperative Fibrinogen-Albumin Ratio Index (FARI) is a Reliable Prognosis and Chemoradiotherapy Sensitivity Predictor in Locally Advanced Rectal Cancer Patients Undergoing Radical Surgery Following Neoadjuvant Chemoradiotherapy

Siyi Lu, Zhenzhen Liu, Xin Zhou, Bingyan Wang, Fei Li, Yanpeng Ma, Wendong Wang, Junren Ma, Yuxia Wang, Hao Wang, Wei Fu
Cancer Management and Research.2020; Volume 12: 8555. CrossRef
Immunonutritional status and pulmonary cavitation in patients with tuberculosis: A revisit with an assessment of neutrophil/lymphocyte ratio
Makoto Nakao, Hideki Muramatsu, Sosuke Arakawa, Yusuke Sakai, Yuto Suzuki, Kohei Fujita, Hidefumi Sato
Respiratory Investigation.2019; 57(1): 60. CrossRef
Temporal changes in immune cell composition and cytokines in response to chemoradiation in rectal cancer
Yong Joon Lee, Sat Byol Lee, Suk Kyung Beak, Yoon Dae Han, Min Soo Cho, Hyuk Hur, Kang Young Lee, Nam Kyu Kim, Byung Soh Min
Scientific Reports.2018;[Epub] CrossRef
Impairment of Immunonutritional Status During Treatment is a Factor Associated With Oncologic Outcomes in Patients With Rectal Cancer Treated With Preoperative Chemoradiotherapy
In Ja Park
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Review

Update and Debate Issues in Surgical Treatment of Middle and Low Rectal Cancer: Nam Kyu Kim, Min Sung Kim, Sami F. AL-Asari; J Korean Soc Coloproctol. 2012;28(5):230-240. Published online October 31, 2012; DOI: https://doi.org/10.3393/jksc.2012.28.5.230

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Abstract PDF

Based on a review of the literature, this paper provides an update on surgical treatment of middle and low rectal cancer and discusses issues of debate surrounding that treatment. The main goal of the surgical treatment of rectal cancer is radical resection of the tumor and surrounding lymphatic tissue. Local excision of early rectal cancer can be another treatment option, in which the patient can avoid possible complications related to radical surgery. Neoadjuvant chemoradiation therapy (CRT) has been recommended for patients with cT3-4N0 or any T N+ rectal cancer because CRT shows better local control and less toxicity than adjuvant CRT. However, recent clinical trials showed promising results for local excision after neoadjuvant CRT in selected patients with low rectal cancer. In addition, the "wait and see" concept is another modality that has been reported for the management of tumors that show complete clinical remission after neoadjuvant CRT. Although radical surgery for middle and low rectal cancer is the cornerstone therapy, an ultralow anterior resection with or without intersphincteric resection (ISR) has become an alternative standard surgical method for selected patients. Many studies have reported on the oncological safety of the ISR, but few of them have addressed the issue the functional outcome. Furthermore, an abdominoperineal resection (APR) has problems with high rates of tumor perforations and positive circumferential resection margins, and those factors have contributed to its having a high rate of local recurrence and a poor survival rate for rectal cancer compared with sphincter-saving procedures. Recently, great efforts have been made to reduce these problems, and the total levator excision or the extended APR concept has emerged. Surgical management for low rectal cancer should aim to radically excise the tumor and to preserve as much of the sphincter function as possible by using multidisciplinary approaches. However, further prospective clinical trials are needed for tailored treatment of rectal cancer patients.

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Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer
Incheol Seo, Hye Won Lee, Sang Jun Byun, Jee Young Park, Hyeonji Min, Sung Hwan Lee, Ju-Seog Lee, Shin Kim, Sung Uk Bae
Journal for ImmunoTherapy of Cancer.2021; 9(3): e001610. CrossRef
Anus-Preserving Surgery in Advanced Low-Lying Rectal Cancer: A Perspective on Oncological Safety of Intersphincteric Resection
Guglielmo Niccolò Piozzi, Se-Jin Baek, Jung-Myun Kwak, Jin Kim, Seon Hahn Kim
Cancers.2021; 13(19): 4793. CrossRef
Surgical Treatment of Low-Lying Rectal Cancer: Updates
Cristopher Varela, Nam Kyu Kim
Annals of Coloproctology.2021; 37(6): 395. CrossRef
Factors influencing changing bowel habits in patients undergoing sphincter‐saving surgery for rectal cancer
Hyeonju Jeong, JeongYun Park
International Wound Journal.2019; 16(S1): 71. CrossRef
Critical and Challenging Issues in the Surgical Management of Low-Lying Rectal Cancer
Aeris Jane D. Nacion, Youn Young Park, Seung Yoon Yang, Nam Kyu Kim
Yonsei Medical Journal.2018; 59(6): 703. CrossRef
Prognostic significance of tumor regression in locally advanced rectal cancer after preoperative radiochemotherapy
Mirko Omejc, Maja Potisek
Radiology and Oncology.2017; 52(1): 30. CrossRef
The influence of the distal resection margin length on local recurrence and long- term survival in patients with rectal cancer after chemoradiotherapy and sphincter- preserving rectal resection
Jan Grosek, Vaneja Velenik, Ibrahim Edhemovic, Mirko Omejc
Radiology and Oncology.2017; 51(2): 169. CrossRef
Robotic Total Mesorectal Excision using a Wristed Suction-irrigation Device for Efficient Traction and Visualization
Sung Uk Bae, Woon Kyung Jeong, Seong Kyu Baek
The Journal of Minimally Invasive Surgery.2017; 20(3): 120. CrossRef
The Role of Robotic Surgery for Rectal Cancer: Overcoming Technical Challenges in Laparoscopic Surgery by Advanced Techniques
Seungwan Park, Nam Kyu Kim
Journal of Korean Medical Science.2015; 30(7): 837. CrossRef
Oncological superiority of extralevator abdominoperineal resection over conventional abdominoperineal resection: a meta-analysis
Ao Huang, Hongchao Zhao, Tianlong Ling, Yingjun Quan, Minhua Zheng, Bo Feng
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Original Articles

Clinical Impact of Tumor Regression Grade after Preoperative Chemoradiation for Locally Advanced Rectal Cancer: Subset Analyses in Lymph Node Negative Patients: Byung Soh Min, Nam Kyu Kim, Ju Yeon Pyo, Hoguen Kim, Jinsil Seong, Ki Chang Keum, Seung Kook Sohn, Chang Hwan Cho; J Korean Soc Coloproctol. 2011;27(1):31-40. Published online February 28, 2011; DOI: https://doi.org/10.3393/jksc.2011.27.1.31

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Abstract PDF

Background

We investigated the prognostic significance of tumor regression grade (TRG) after preoperative chemoradiation therapy (preop-CRT) for locally advanced rectal cancer especially in the patients without lymph node metastasis.

Methods

One-hundred seventy-eight patients who had cT3/4 tumors were given 5,040 cGy preoperative radiation with 5-fluorouracil/leucovorin chemotherapy. A total mesorectal excision was performed 4-6 weeks after preop-CRT. TRG was defined as follows: grade 1 as no cancer cells remaining; grade 2 as cancer cells outgrown by fibrosis; grade 3 as a minimal presence or absence of regression. The prognostic significance of TRG in comparison with histopathologic staging was analyzed.

Results

Seventeen patients (9.6%) showed TRG1. TRG was found to be significantly associated with cancer-specific survival (CSS; P = 0.001) and local recurrence (P = 0.039) in the univariate study, but not in the multivariate analysis. The ypN stage was the strongest prognostic factor in the multivariate analysis. Subgroup analysis revealed TRG to be an independent prognostic factor for the CSS of ypN0 patients (P = 0.031). TRG had a stronger impact on the CSS of ypN (-) patients (P = 0.002) than on that of ypN (+) patients (P = 0.521). In ypT2N0 and ypT3N0, CSS was better for TRG2 than for TRG3 (P = 0.041, P = 0.048), and in ypN (-) and TRG2 tumors, CSS was better for ypT1-2 than for ypT3-4 (P = 0.034).

Conclusion

TRG was found to be the strongest prognostic factor in patients without lymph node metastasis (ypN0), and different survival was observed according to TRG among patients with a specific histopathologic stage. Thus, TRG may provide an accurate prediction of prognosis and may be used for f tailoring treatment for patients without lymph node metastasis.

Citations

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Tumor Regression Grade as a Prognostic Factor in Metastatic Colon Cancer Following Preoperative Chemotherapy
Yufei Yang, Dakui Luo, Ruoxin Zhang, Sanjun Cai, Qingguo Li, Xinxiang Li
Clinical Colorectal Cancer.2022; 21(2): 96. CrossRef
Prediction of tumor response of rectal cancer cells via 3D cell culture and in�vitro cytotoxicity assay before initiating preoperative chemoradiotherapy
Jeonghyun Kang, Min Park, Jina Kim, Hyuk Hur, Byung Min, Seung Baik, Kang Lee, Nam Kim
Oncology Letters.2019;[Epub] CrossRef
Prognostic significance of tumour regression grade after neoadjuvant chemoradiotherapy for a cohort of patients with locally advanced rectal cancer: an 8‐year retrospective single‐institutional study
L. Xu, S. Cai, T. Xiao, Y. Chen, H. Qiu, B. Wu, G. Lin, X. Sun, J. Lu, W. Zhou, Y. Xiao
Colorectal Disease.2017;[Epub] CrossRef
Neoadjuvant chemoradiotherapy for rectal cancer: how important is tumour regression?
Melanie J. McCoy, Chris Hemmings, Simon Hillery, Cheryl Penter, Max K. Bulsara, Nik Zeps, Cameron F. Platell
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Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales
Muhammed R S Siddiqui, Jemma Bhoday, Nicholas J Battersby, Manish Chand, Nicholas P West, Al-Mutaz Abulafi, Paris P Tekkis, Gina Brown
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Interobserver agreement of radiologists assessing the response of rectal cancers to preoperative chemoradiation using the MRI tumour regression grading (mrTRG)
M.R.S. Siddiqui, K.L. Gormly, J. Bhoday, S. Balyansikova, N.J. Battersby, M. Chand, S. Rao, P. Tekkis, A.M. Abulafi, G. Brown
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The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer
K. I. Abdul‐Jalil, K. M. Sheehan, J. Kehoe, R. Cummins, A. O'Grady, D. A. McNamara, J. Deasy, O. Breathnach, L. Grogan, B. D. P. O'Neill, C. Faul, I. Parker, E. W. Kay, B. T. Hennessy, P. Gillen
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Pathological grading of regression: an International Study Group perspective
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Capecitabine-based Neoadjuvant Chemoradiation Therapy in Locally-advanced Rectal Cancer.: Choi, Hong Jo , Park, Ki Jae , Lee, Tae Moo , Ha, Sang Sik , Lee, Ho Young , Lee, Hyung Sik; J Korean Soc Coloproctol. 2010;26(2):137-144.; DOI: https://doi.org/10.3393/jksc.2010.26.2.137

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Abstract PDF: PURPOSE
The aim of the study was to evaluate the efficacy and the toxicity of preoperative treatment with capecitabine in combination with radiation therapy (RT) in patients with locally-advanced, resectable rectal cancer.
METHODS
Thirty-five patients with locally-advanced rectal cancer (cT3/4, N-/+) were treated with capecitabine (825 mg/m2, twice daily for 7 days/wk) and concomitant RT (50.4 Gy/28 fractions). Surgery was performed 6-8 wk after completion of the chemoradiation followed by 4-6 cycles of adjuvant capecitabine monotherapy (1,250 mg/m2, twice daily for 14 days every 3 wk).
RESULTS
The chemoradiation program was completed in all but 2 patients, for whom both capecitabine and RT were interrupted for 2 wk because of grade-3 diarrhea. A R0 resection under the principle of total mesorectal excision (low anterior resection, 26; intersphincteric resection, 6; abdominoperineal resection, 2) was performed in all but one patient with a low anterior resection with positive circumferential margin (R1). Primary tumor and node downstaging occurred in 57% and 60% of patients, respectively. The overall rate of downstaging, including both the primary tumor and node, was 77% (27 patients). A pathological complete response of the primary tumor was achieved in 4 patients (11%). No patient had grade-4 toxicity, and the only grade-3 toxicity developed was diarrhea in 2 patients (6%) during chemoradiation. During a median follow-up of 38 mo, distant metastases developed in 4 patients (multiple lung metastases, 2; aortocaval nodal metastases, 2), and another 2 patients showed local recurrence. The three-year disease-free survival was 83%.
CONCLUSION
This study suggests that preoperative capecitabine-based chemoradiation therapy is an effective and safe treatment modality for the tratment of locally-advanced, resectable rectal cancer.

Abdominoperineal Resection in the Treatment of Locally-advanced Low Rectal Cancer: Is Preoperative Chemoradiation Advantageous?.: Kim, Jeong Yeon , Kim, Jin Soo , Kim, Young Wan , Hur, Hyuk , Min, Byung Soh , Kim, Nam Kyu; J Korean Soc Coloproctol. 2010;26(2):129-136.; DOI: https://doi.org/10.3393/jksc.2010.26.2.129

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Abstract PDF: PURPOSE
An abdominoperineal resection (APR) has a poor prognosis. However, limited studies about the prognostic factors in APR and the role of preoperative chemoradiotherapy (CRT) have been performed even though in rectal cancer, the application of preoperative CRT provides better local control compared to postoperative CRT. The aim of this study was to identify the prognostic factors and the impact of preoperative CRT in patients who undergo an APR.
METHODS
A retrospective analysis was conducted with a total of 133 patients who underwent an APR, cT3, cT4, or cN(+) patients, for rectal cancer between January 1995 and October 2004. Fifty-one patients treated with preoperative CRT (Group 1) were compared with 82 APR patients treated with postoperative CRT (Group 2). Oncologic outcomes were compared between the two groups, and the clinicopathologic factors affecting the treatment outcomes were evaluated.
RESULTS
The median follow-up period was 61.2 mo (range 6 to 194 mo). Circumferential margin (CRM) involvement was significantly associated with local recurrence (LR) and with disease-free survival in APR patients (P<0.001, P=0.011). The 5-yr LR rate was significantly lower in Group 1 than in Group 2 (P=0.013) in the univariate analysis, but no difference was noted in multivariate analysis (P=0.315). In Group 1, CRM involvement, tumor size, and lymph node metastasis were significantly lower than they were in Group 2 (P=0.043, P=0.003, P<0.001).
CONCLUSION
For achieving adequate oncologic outcomes in APR patients, an adequate CRM should be acquired with an optimal operation. In addition, preoperative CRT would be helpful for high-risk APR patients with a threatening CRM margin, providing the benefit of tumor downstaging.

Oncologic Result as According to Tumor Regression Grade after Neoadjuvant Chemoradiation Therapy in Locally Advanced Rectal Cancer.: Park, Jong Hyun , Song, Min Sang , Min, Hyo Suk , Kim, Ji Yeon; J Korean Soc Coloproctol. 2008;24(6):422-432.; DOI: https://doi.org/10.3393/jksc.2008.24.6.422

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PURPOSE
The effects of neoadjuvant chemoradiation therapy (NCRT) in cases of locally advanced rectal cancer include tumor downstaging with respect to a curative resection and a decreasing incidence of local recurrence. The aim of this study is to evaluate the oncologic results according to the tumor regression grade (TRG) after NCRT and radical surgical resection in cases of locally advanced rectal cancer.
METHODS
From 1999 to 2003, 140 consecutive patients, who suffered from locally advanced rectal cancer (T3 or T4, or lymph node positive) were enrolled in this study. They all received neoadjuvant chemoradiation therapy and a radical resection. Chemotherapy was based on 5-fluorouracil (5-FU), and the total radiation dose was 5,040 cGy over 6 weeks. A radical surgical resection, including a total mesorectal excision, was done 6 to 8 weeks after the completion of NCRT. We classified patients into subgroups by using the TRG; then, we investigated the overall and the disease-free survival rates and the local recurrence and the distant metastasis rates.
RESULTS
One hundred twenty-six (126, 90%) patients responded to radiation therapy. According to the TRG, the numbers of non- responders (Grade I, NR), partial responders (Grade II, PR), and patients who went into complete remission (Grade III, CR) were 14 (10%), 98 (70%), and 28 (20%), respectively. The overall survival (OS) and the disease-free survival (DFS) rates for 3 years (n=140) were 91.43% and 74.29%, and the rates for 5 years (n=117) were 81.20% and 67.52%, respectively. While there was no significant difference in the 3-year OS or DFS between the three groups stratified by TRG (P=0.1136, P=0.1215), the 5-year OS and DFS showed a statistical difference (P=0.0485, P=0.0458). Furthermore, the 3-year OS and DFS rates (P=0.0451, P=0.0458), as well as the 5-year OS and DFS rates (P=0.0139, P=0.0131) were significantly better for patients in the CR group than for the other patients. Still, no statistical significance differences existed between the CR group and the non-CR groups or between the TRG groups in terms of the local recurrence and the distant metastasis rates (P=0.447, P=0.271).
CONCLUSIONS
Any tumor response group that shows complete Rremission after NCRT and radical surgical resection has an oncologic benefit in overall survival and disease- free survival in our study.

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A Phase II Study of Additional Four-Week Chemotherapy With Capecitabine During the Resting Periods After Six-Week Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer
Kyung Ha Lee, Min Sang Song, Jun Boem Park, Jin Soo Kim, Dae Young Kang, Ji Yeon Kim
Annals of Coloproctology.2013; 29(5): 192. CrossRef

Disadvantages of Preoperative Chemoradiation in Rectal Cancer.: Lee, Seung Hyun , Ahn, Byung Kwon , Baek, Sung Uhn; J Korean Soc Coloproctol. 2007;23(4):250-256.; DOI: https://doi.org/10.3393/jksc.2007.23.4.250

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Abstract PDF: PURPOSE
Preoperative chemoradiation therapy for rectal cancer seems to improve local control, anal sphincter preservation, resectability, and possibly survival in patients. However, there are several adverse effects, too. The aim of this study is to analyze the disadvantages of preoperative chemoradiation for rectal cancer.
METHODS
We retrospectively reviewed 139 patients who were treated by using preoperative chemoradiation for an adenocarcinoma of the rectum between January 1995 and December 2004. All patients had fixed or locally advanced lesions, as determined by digital rectal examination. No distant metastasis was proven before preoperative chemoradiation. All of the patiedts received the full scheduled dose of radiation (range, 5,000~5,400 rad). Concurrent intravenous chemotherapy with 5-fluorouracil (425 mg/m2/day) and leucovorin (45 mg/day) was administered continuously on days 1~5 and 29~33. The mean interval between chemoradiation and surgery was 4~6 weeks. After preoperative chemoradiation, 117 patients underwent an operation. We reviewed the side effects of preoperative chemoradiation, postoperative complications, and distant metastases detected during the preoperative period after preoperative chemoradiation and during the operation.
RESULTS
The side effects of preoperative chemoradiation were diarrhea (23%), radiation dermatitis (2.2%), fistula (0.7%), sepsis (0.7%), and rectal bleeding (0.7%). Two patients died from sepsis and rectal bleeding. The postoperative complications were bowel obstruction in 9 cases (7.7%), wound seroma in 8 cases (6.8%), wound infection in 5 cases (4.3%), anastomotic leakage in 5 cases (7.1%), rectovaginal fistula in 2 cases (2.8%), an enterocutaneous fistula in 2 cases (1.7%), and a vesicocutaneous fistula in 1 case (0.8%). Distant metastases were detected in 14 patients (10.1%) after preoperative chemoradiation.
CONCLUSIONS
Although preoperative chemoradiation can be performed safely, careful management for the side effects of preoperative chemoradiation and for postoperative complications is necessary. We need a more sensitive study method for detecting distant metastasis of rectal cancer, especially during scheduled preoperative chemoradiation.

Transanal Endoscopic Microsurgery after Preoperative Concurrent Chemoradiation Therapy in Selected Distal Rectal Cancer Patients.: Park, Chi Min , Jung, Keuk Won , Han, Sang Ah , Yun, Seong Hyeon , Lee, Woo Yong , Chun, HoKyung; J Korean Soc Coloproctol. 2005;21(5):293-299.

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Preoperative concurrent chemoradiation (CCRT) therapy may allow higher rates of tumor resectability and sphincter-saving procedures. Transanal endoscopic microsurgery (TEM) has become increasingly common in the management of selected patients with early rectal cancer. The aim of this study is to evaluate the clinical outcomes of selected patients with distal rectal cancer treated with TEM after CCRT.
METHODS
Between June 2000 and August 2004, 7 patients with clinically T2 or T3 rectal cancer underwent TEM after CCRT. Pretreatment and preoperative clinical stages were estimated by using endorectal ultrasound or computed tomography and digital rectal exam. CCRT was performed with radiation therapy of 4,500 cGy/25 fractions over 5 weeks with 5-FU based chemosensitization. TEM was performed 4~7 weeks following the completion of therapy.
RESULTS
The mean age was 54.9 (35~70) years and the median follow-up period was 23.0 (5~57) months. The lesions were located between 2 to 6 cm above the anal verge (median 3.0 cm). Pre- treatment T staging was estimated as T3 in 1 case and T2 in 6 cases, and post-treatment T staging was estimated as complete remission (CR) in 2 cases, T1 in 3 cases, and T2 in 2 patients. Pathologic evaluation revealed tumor downstaging in 6 patients, including 3 patients (42.9%) with CR. In all cases, there was no tumor on the resection margin. There have been no recurrences during the follow-up period.
CONCLUSIONS
TEM after CCRT therapy appears to be an effective alternative treatment to radical resection for highly selected patients with T2 and T3 distal rectal cancer.

The Effect of Preoperative Concurrent Chemoradiation in Locally Advanced Rectal Cancer.: Cho, Hyeon Min , Kim, Jun Gi , Jung, Hun , Heo, Youn Jung , Won, Yong Sung , Chun, Kyung Hwa , Chin, Hyung Min , Park, Woo Bae , Chun, Chung Soo; J Korean Soc Coloproctol. 2005;21(2):89-99.

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Abstract PDF: PURPOSE
Tumor downstaging from preoperative chemoradiation has been associated with an increased probability of a sphincter-saving procedure and with improved local control and survival rate. We observed the effect and the prognostic value of pathologic tumor downstaging, including complete pathologic response to preoperative concurrent chemoradiation, resectability, sphincter-saving rate, disease- free survival, and overall survival in locally advanced rectal cancer patients.
METHODS
From January 2000 to December 2003, we recruited a total 78 patients with computed tomography stages II and III rectal cancer which was treated by using preoperative concurrent chemoradiation; all patients had a radical resection with total mesorectal excision. Surgical resection was performed 6 to 8 weeks after completing the radiation therapy. The average follow up was 25.40+/-13.64 months.
RESULTS
The number of patients according to CT stage before preoperative chemoradiation was 39 (II) and 39 (III). Tumor downstaging occurred in 51 (65.4%) patients, including 11 (14.1%) patients who had a complete pathologic response. Tumor size, radiation dose, and clinical stage were associated with tumor downstaging in the univariate analysis. None of the clinical or pathologic variables was associated with a complete pathologic response. The overall resectibality was 100%. The number of sphincter-saving procedures were 61 (78.2%). Recurrence occurred in 17 (21.8%) patients: local recurrence in 4 (5.1%) and distant metastasis in 13 (16.7%). None of the patients with a complete pathologic response recurred. Recurrences were 3 (17.6%)/7 (22.6%)/7 (36.8%) for pathologic stages I/II/III. Recurrence was more common among younger patients (P <0.05). Patients in the complete pathologic response group had more favorable disease-free survival compared with other group (yp stage I, II, III) (P=0.026).
CONCLUSION
Preoperative concurrent chemoradiation for locally advanced rectal cancer seems to afford some potential advantages: high tumor response, resectability, and feasible sphincter preservation, and even a complete pathologic response. A complete pathologic response to preoperative chemoradiation is associated with an improved disease-free survival.

Intersphincteric Resection for Very Low Rectal Cancer.: Kim, Jae hun , Oh, Nahm gun; J Korean Soc Coloproctol. 2004;20(6):364-370.

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Abstract PDF: PURPOSE
In the treatment of rectal cancer, sphincter saving resection is increased but low anterior resection is limited in treatment for low rectal cancer below 4 cm from the anal verge. In other reports intersphincteric resection can allow an oncologically safe resection margin and has good functional results in very low rectal cancer. The aim of this study is to evaluate the morbidity, mortality and the oncological and functional results of intersphincteric resection.
METHODS
Between 2000 and 2002, 18 patients (mean age 54 years, range 35~70) with adenocarcinoma of the rectum underwent intersphincteric resection by an transanal approach with a colonic J-pouch anal anastomosis and ileostomy. The mean distance between the tumor and anal verge was 3.75 (range 2.5~5) cm. Patients with T3 lesion were 8 and they were received preoperative radiochemotherapy. Others with T2 lesion were not received preoperative radiochemotherapy.
RESULTS
There was no postoperative mortality and local recurrance after median follow up of 32 (18~54) months. Morbidity occurred in 9 patient but were not serious. Two anastomotic leakages occurred. One was recovered after only conservative therapy, but the other one was received colostomy because of functional problem. Downstaging was observed in 62.5% (5/8) of the patients. Continence was good (Kirwan classification I, II) in 72% (13/18) of patients.
CONCLUSIONS
These results suggest that intersphincteric resection can be an alternative procedure to abdominoperineal resection for very low rectal cancer without losing chance of cure.

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