Publications by authors named "Byung Soh Min"

201 Publications

Role of Preoperative Chemoradiotherapy in Clinical Stage II/III Rectal Cancer Patients Undergoing Total Mesorectal Excision: A Retrospective Propensity Score Analysis.

Front Oncol 2020 18;10:609313. Epub 2021 Jan 18.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.

Background: Although the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve survival and increases the likelihood of preoperative overtreatment, especially in patients without circumferential resection margin (CRM) involvement.

Methods: Stage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received PCRT followed by total mesorectal excision (TME) (PCRT group) and upfront surgery (US) with TME (US group) between 2010 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching for stage, age, and distance from the anal verge. Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between the two groups.

Results: A total of 202 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up duration was 62 months (interquartile range, 46-87). There was no difference in the 3-year disease-free survival rate between the PCRT and US groups (83 vs. 88%, respectively; p=0.326). Likewise, there was no significant difference in the 3-year OS (89 vs. 91%, respectively; p=0.466). The 3-year locoregional recurrence rates (3 vs. 2% with US, p=0.667) and distant metastasis rates (16 vs. 11%, p=0.428) were not significantly different between the two groups. Time to completion of curative treatment was significantly shorter in the US group (132 days) than in the PCRT group (225 days) (p<0.001).

Conclusion: Using MRI-guided selection for better risk stratification, US without neoadjuvant therapy can be considered in early stage patients with good prognosis. PCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-proven intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted.
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http://dx.doi.org/10.3389/fonc.2020.609313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848147PMC
January 2021

Single-incision laparoscopic surgery compared to conventional laparoscopic surgery for appendiceal mucocele: a series of 116 patients.

Surg Endosc 2021 Jan 27. Epub 2021 Jan 27.

Division of Colorectal Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Korea.

Background: Although the safety and feasibility of conventional laparoscopic surgery (CLS) for appendiceal mucocele (AM) has been reported, studies on single-incision laparoscopic surgery (SILS) for AM have not been reported. Here, we aimed to compare the perioperative and short-term outcomes between SILS and CLS for AM and to evaluate the oncological safety of SILS.

Methods: We retrospectively analyzed the medical records of patients, diagnosed based on computed tomography findings, who underwent laparoscopic surgery for AM between 2010 and 2018 at one institution. We excluded patients strongly suspected of having malignant lesions and those with preoperative appendiceal perforation. Patients were divided into two groups-CLS and SILS. Pathological outcomes and long-term results were investigated. The median follow-up period was 43.7 (range: 12.3-118.5) months.

Results: Ultimately, 116 patients (CLS = 68, SILS = 48) were enrolled. Patient demographic characteristics did not differ between the groups. The preoperative mucocele diameter was greater in the CLS than in the SILS group (3.2 ± 2.9 cm vs. 2.3 ± 1.4 cm, P = 0.029). More extensive surgery (right hemicolectomies and ileocecectomies) was performed in the CLS than in the SILS group (P = 0.014). Intraoperative perforation developed in only one patient per group. For appendectomies and cecectomies, the CLS group exhibited a longer operation time than the SILS group (63.3 ± 24.5 min vs. 52.4 ± 17.3 min, P = 0.014); the same was noted for length of postoperative hospital stay (2.9 ± 1.8 days vs. 1.7 ± 0.6 days, P < 0.001). The most common AM etiology was low-grade appendiceal mucinous neoplasm (71/116 [61.2%] patients); none of the patients exhibited mucinous cystadenocarcinoma. Among these 71 patients, there were 8 patients with microscopic appendiceal perforation or positive resection margins. No recurrence was detected.

Conclusions: SILS for AM is feasible and safe perioperatively and in the short-term and yields favorable oncological outcomes. Despite the retrospective nature of the study, SILS may be suitable after careful selection of AM patients.
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http://dx.doi.org/10.1007/s00464-020-08263-3DOI Listing
January 2021

Impact of laparoscopic surgical experience on the learning curve of robotic rectal cancer surgery.

Surg Endosc 2020 Oct 8. Epub 2020 Oct 8.

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: Robotic surgery has advantages in terms of the ergonomic design and expectations of shortening the learning curve, which may reduce the number of patients with adverse outcomes during a surgeon's learning period. We investigated the differences in the learning curves of robotic surgery and clinical outcomes for rectal cancer among surgeons with differences in their experiences of laparoscopic rectal cancer surgery.

Methods: Patients who underwent robotic surgery for colorectal cancer were reviewed retrospectively. Patients were divided into five groups by surgeons, and their clinical outcomes were analyzed. The learning curve of each surgeon with different volumes of laparoscopic experience was analyzed using the cumulative sum technique (CUSUM) for operation times, surgical failure (open conversion or anastomosis-related complications), and local failure (positive resection margins or local recurrence within 1 year).

Results: A total of 662 patients who underwent robotic low anterior resection (LAR) for rectal cancer were included in the analysis. Number of laparoscopic LAR cases performed by surgeon A, B, C, D, and E prior to their first case of robotic surgery were 403, 40, 15, 5, and 0 cases, respectively. Based on CUSUM for operation time, surgeon A, B, C, D, and E's learning curve periods were 110, 39, 114, 55, and 23 cases, respectively. There were no significant differences in the surgical and oncological outcomes after robotic LAR among the surgeons.

Conclusions: This study demonstrated the limited impact of laparoscopic surgical experience on the learning curve of robotic rectal cancer surgery, which was greater than previously reported curves.
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http://dx.doi.org/10.1007/s00464-020-08059-5DOI Listing
October 2020

The Role of Primary Tumor Resection in Colorectal Cancer Patients with Asymptomatic, Synchronous, Unresectable Metastasis: A Multicenter Randomized Controlled Trial.

Cancers (Basel) 2020 Aug 16;12(8). Epub 2020 Aug 16.

Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea.

We aimed to assess the survival benefits of primary tumor resection (PTR) followed by chemotherapy in patients with asymptomatic stage IV colorectal cancer with asymptomatic, synchronous, unresectable metastases compared to those of upfront chemotherapy alone. This was an open-label, prospective, randomized controlled trial (ClnicalTrials.gov Identifier: NCT01978249). From May 2013 to April 2016, 48 patients (PTR, = 26; upfront chemotherapy, = 22) diagnosed with asymptomatic colorectal cancer with unresectable metastases in 12 tertiary hospitals were randomized (1:1). The primary endpoint was two-year overall survival. The secondary endpoints were primary tumor-related complications, PTR-related complications, and rate of conversion to resectable status. The two-year cancer-specific survival was significantly higher in the PTR group than in the upfront chemotherapy group (72.3% vs. 47.1%; = 0.049). However, the two-year overall survival rate was not significantly different between the PTR and upfront chemotherapy groups (69.5% vs. 44.8%, = 0.058). The primary tumor-related complication rate was 22.7%. The PTR-related complication rate was 19.2%, with a major complication rate of 3.8%. The rates of conversion to resectable status were 15.3% and 18.2% in the PTR and upfront chemotherapy groups. While PTR followed by chemotherapy resulted in better two-year cancer-specific survival than upfront chemotherapy, the improvement in the two-year overall survival was not significant.
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http://dx.doi.org/10.3390/cancers12082306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464811PMC
August 2020

Prognosis of Synchronous Colorectal Liver Metastases After Simultaneous Curative-Intent Surgery According to Primary Tumor Location and KRAS Mutational Status.

Ann Surg Oncol 2020 Dec 18;27(13):5150-5158. Epub 2020 Aug 18.

Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Background: Tumor location and KRAS mutational status have emerged as prognostic factors of colorectal cancer. We aimed to define the prognostic impact of primary tumor location and KRAS mutational status among synchronous colorectal liver metastases (CRLM) patients who underwent simultaneous curative-intent surgery (SCIS).

Methods: We compared the clinicopathologic characteristics and long-term outcomes of 227 patients who underwent SCIS for synchronous CRLM, according to tumor location and KRAS mutational status. We cross-classified tumor location and KRAS mutational status and compared survival outcomes between the four resulting patient groups.

Results: Forty-one patients (18.1%) had right-sided (RS) tumors and 186 (81.9%) had left-sided (LS) tumors. One-third of tumors (78/227) harbored KRAS mutations. The KRAS mutant-type (KRAS-mt) was more commonly observed among RS tumors than among LS tumors [21/41 (51.2%) vs. 57/186 (30.6%), p = 0.012]. Median follow-up time was 43.4 months. Patients with RS tumors had shorter survival times than those with LS tumors [median disease-free survival (DFS): RS, 9.9 months vs. LS, 12.1 months, p = 0.003; median overall survival (OS): RS, 49.7 months vs. LS, 88.8 months, p = 0.039]. RS tumors were a negative prognostic factor for DFS [hazard ratio (HR) 1.878, p = 0.001] and OS (HR 1.660, p = 0.060). RS KRAS-mt and LS KRAS wild-type (KRAS-wt) tumors had the worst and best oncological outcomes, respectively.

Conclusion: Tumor location has a prognostic impact in patients who underwent SCIS for CRLM, and RS KRAS-mt tumors yielded the worst oncological outcome. These results may allow for more tailored multimodality treatments.
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http://dx.doi.org/10.1245/s10434-020-09041-0DOI Listing
December 2020

Survival outcomes after isolated local recurrence of rectal cancer and risk analysis affecting its resectability.

J Surg Oncol 2020 Dec 13;122(7):1470-1480. Epub 2020 Aug 13.

Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.

Background And Objectives: This study aimed to investigate the clinical course and prognostic factors after isolated local recurrence (iLR) and to identify the predictive factors for R0 resection of locally recurrent rectal cancer (LRRC).

Methods: We retrospectively reviewed the medical records of 76 patients with iLR who had undergone radical surgery for a primary tumor from 2003 to 2015.

Results: The iLR rate was 2.5%. From 76 patients, 39 patients underwent R0 resection for iLR. Multivariate analysis revealed that initial open surgery, neoadjuvant chemoradiation, and p/ypT ≥ 3 were poor prognostic factors after iLR as regard to the variables related to the primary tumor; and symptom presence at the time of iLR diagnosis, higher fixity, and no chemotherapy after iLR were associated with shorter overall survival after iLR, and R0 resection of LRRC was the only favorable prognostic factor for progression-free survival after iLR as regard to the variables related to LRRC. Higher tumor level, negative pathologic circumferential margin of the primary tumor, and low fixity of LRRC were favorable factors in achieving R0 resection of LRRC.

Conclusions: Early detection of iLR before symptom development, use of chemotherapy after iLR and R0 resection of LRRC should be considered to improve survival outcomes after iLR.
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http://dx.doi.org/10.1002/jso.26161DOI Listing
December 2020

Early recurrence after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: Characteristics and risk factors.

Asian J Surg 2021 Jan 25;44(1):298-302. Epub 2020 Jul 25.

Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

Background/objective: Some locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (CRT) prior to total mesorectal excision (TME) show early recurrence with a short disease-free interval. This is unacceptable for patients and their families, necessitating re-evaluation of the treatment process. We aimed to evaluate the risk factors and prognostic impact of early recurrence in patients who received preoperative CRT (pCRT) followed by TME for LARC.

Methods: Of 714 patients who underwent curative resection after pCRT for LARC from January 2010 to December 2016, we included 139 who developed recurrence after resection. Patients were divided into an early recurrence group, diagnosed <12 months after primary surgery, and a late recurrence group, diagnosed ≥12 months after primary surgery.

Results: Forty-nine patients experienced early recurrence and 90 experienced late recurrence. Multivariate analysis revealed that tumor regression grade (hazard ratio [HR] 2.962, 95% confidence interval [CI] 1.434-6.119, P = 0.003) and positive ypN stage (HR 2.110, 95% CI 1.144-3.892, P = 0.017) correlated with early recurrence. The 5-year overall survival rates for early and late recurrences were not significantly different (P = 0.121).

Conclusion: In patients with early recurrence after pCRT followed by TME, tumor regression grade and ypN stage positivity were independent predictors of the early recurrence.
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http://dx.doi.org/10.1016/j.asjsur.2020.07.014DOI Listing
January 2021

Metachronous metastasis confined to isolated lymph node after curative treatment of colorectal cancer.

Int J Colorectal Dis 2020 Nov 21;35(11):2089-2097. Epub 2020 Jul 21.

Division of colorectal surgery, Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Ku, Seoul, 03722, South Korea.

Background: The incidence of lymph node metastasis (LNM) in colorectal cancer is known to be 2-6%, but little data are available regarding metachronous metastasis confined to isolated LN. The aim of this study is to determine the distribution of isolated LNM and the risk factors for survival of isolated LNM in colorectal cancer.

Methods: We retrospectively reviewed consecutive patients with colorectal adenocarcinoma between January 2008 and December 2015 at a tertiary referral center. A total of 5902 patients with biopsy-proven colorectal adenocarcinoma treated via surgery were included. Multivariate Cox proportional hazards analysis was used to identify prognostic factors for overall survival.

Results: Of the 5902 patients, recurrent cases were 1326. Among the relapsed patients, 301 patients had isolated LNM (22.69%). Para-aortic (48.8%), pelvic (29.9%), and Lung hilum (10.0%) were the most common sites of isolated LNM; there were statistically significant differences in the distribution of isolated LNM between the colon and rectal cancer (p = 0.02). Approximately 80% of isolated LNM were diagnosed within 3 years. Multidisciplinary therapy for LNM, diagnosis time to LNM, the T-stage, and histological type of primary cancer were identified as independent prognostic factors for overall survival.

Conclusion: This study suggests that multidisciplinary management is a potentially effective treatment strategy for isolated LNM. Since time to LNM, the T-stage, and histological type are prognostic factors, an active follow-up program for colorectal cancer is required.
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http://dx.doi.org/10.1007/s00384-020-03695-8DOI Listing
November 2020

Prospective study of oncologic outcomes after laparoscopic modified complete mesocolic excision for non-metastatic right colon cancer (PIONEER study): study protocol of a multicentre single-arm trial.

BMC Cancer 2020 Jul 14;20(1):657. Epub 2020 Jul 14.

Department of Surgery, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-ku, Seoul, 120-752, South Korea.

Background: The introduction of complete mesocolic excision (CME) with central vascular ligation (CVL) for right-sided colon cancer has improved the oncologic outcomes. Recently, we have introduced a modified CME (mCME) procedure that keeps the same principles as the originally described CME but with a more tailored approach. Some retrospective studies have reported the favourable oncologic outcomes of laparoscopic mCME for right-sided colon cancer; however, no prospective multicentre study has yet been conducted.

Methods: This study is a multi-institutional, prospective, single-arm study evaluating the oncologic outcomes of laparoscopic mCME for adenocarcinoma arising from the right side of the colon. A total of 250 patients will be recruited from five tertiary referral centres in South Korea. The primary outcome of this study is 3-year disease-free survival. Secondary outcome measures include 3-year overall survival, incidence of surgical complications, completeness of mCME, and distribution of metastatic lymph nodes. The quality of laparoscopic mCME will be assessed on the basis of photographs of the surgical specimen and the operation field after the completion of lymph node dissection.

Discussion: This is a prospective multicentre study to evaluate the oncologic outcomes of laparoscopic mCME for right-sided colon cancer. To the best of our knowledge, this will be the first study to prospectively and objectively assess the quality of laparoscopic mCME. The results will provide more evidence about oncologic outcomes with respect to the quality of laparoscopic mCME in right-sided colon cancer.

Trial Registration: ClinicalTrials.gov ID: NCT03992599 (June 20, 2019). The posted information will be updated as needed to reflect protocol amendments and study progress.
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http://dx.doi.org/10.1186/s12885-020-07151-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362526PMC
July 2020

Clinical outcome for management of colonic diverticulitis: characteristics and surgical factor based on two institution data at South Korea.

Int J Colorectal Dis 2020 Sep 27;35(9):1711-1718. Epub 2020 May 27.

Division of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.

Purpose: The aim of this study was to analyze clinical outcomes after surgical and/or conservative management of patients with colonic diverticulitis.

Material And Methods: Between January 2001 and November 2018, data for 1175 patients (right (Rt.) side: n = 1037, left (Lt.) side: n = 138) who underwent conservative management (n = 987) and surgical management (n = 188) for colonic diverticulitis were retrieved from a retrospective database. The Rt. sided was defined up to the proximal two-thirds of the transverse colon and Lt. sided was defined from the distal one-third of the transverse colon.

Results: The overall incidence of colonic diverticulitis is gradually increasing. The mean age of all patients was 43.2 ± 17 and was significantly higher in patients with Lt.-sided (57.0 ± 15.7) than with Rt.-sided (41.4 ± 13.4) diverticulitis (p = 0.001). The most common lesion site was cecum (71.7%, n = 843). First-time attacks were the most common (91.0%, n = 1069). The surgical rate was 12.2% on the right. sided and 44.9% on the left sided (p < 0.005). The mean age, age distribution, BMI, open surgery rate, stoma formation rate, and Hinchey types III and IV rate were significantly higher in Lt. sided than in Rt. sided (p < 0.005). Older age, higher BMI (≥ 25), and Hinchey types III and IV were significantly associated with surgical risk factors of diverticulitis (p < 0.005).

Conclusion: Base on present study, Lt.-sided colonic diverticulitis tends to be more severe than Rt. sided, and surgery is more often required. In addition, colonic diverticulitis that requires surgery seems to be older and more obese on Lt. sided.
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http://dx.doi.org/10.1007/s00384-020-03639-2DOI Listing
September 2020

Late anastomotic leakage after anal sphincter saving surgery for rectal cancer: is it different from early anastomotic leakage?

Int J Colorectal Dis 2020 Jul 5;35(7):1321-1330. Epub 2020 May 5.

Division of Colon and Rectal Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, South Korea.

Purpose: Although multiple studies have examined anastomotic leakage (AL) after low anterior resection (LAR), their definitions of AL varied, and few have studied late diagnosed AL after surgery. This study aimed to characterize late AL after anal sphincter saving surgery (SSS) for rectal cancer by examining clinical characteristics, risk factors, and management of patients with late AL compared with early AL.

Methods: Data from January 2005 to December 2014 were collected from a total of 1903 consecutive patients who underwent anal sphincter saving surgery for rectal cancer and were retrospectively reviewed. Late AL was defined as AL diagnosed more than 30 days after surgery. Variables and risk factors associated with early and late diagnosed AL were analyzed by multivariate logistic regression.

Results: Overall, early, and late rates of AL were 13.7%, 6.7%, and 7%, respectively. Receiving neoadjuvant chemoradiotherapy (nCRT) was a risk factor for developing late AL, but not early AL (OR, 3.032; 95% CI, 1.947-4.722; p < 0.001). Protective ileostomy did not protect against late AL. Among the 134 patients with late AL, 26 (19.4%) were classified as asymptomatic and 108 patients (80.6%) as symptomatic. The most frequent symptomatic complications related to late AL were fistula (42 cases, 39.7%), chronic sinus (33 cases, 31.1%), and stenosis (31 cases, 29.2%).

Conclusion: Clinical characteristics, risk factors, and management of patients with late AL after SSS were different from early AL. Close attention should be given to consider late AL as the continuation of early AL.
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http://dx.doi.org/10.1007/s00384-020-03608-9DOI Listing
July 2020

Upfront radical surgery with total mesorectal excision followed by adjuvant FOLFOX chemotherapy for locally advanced rectal cancer (TME-FOLFOX): an open-label, multicenter, phase II randomized controlled trial.

Trials 2020 Apr 7;21(1):320. Epub 2020 Apr 7.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Background: Preoperative chemoradiotherapy (PCRT) followed by surgery and adjuvant chemotherapy is the current standard treatment for stage II/III rectal cancer. However, radiotherapy in the pelvic area is commonly associated with complications such as anastomotic leakage, sexual dysfunction, and fecal incontinence. Recently, the MERCURY study showed that preoperative high-resolution magnetic resonance imaging (MRI) helped to selectively avoid PCRT. It remains unclear whether PCRT is necessary in patients who can achieve a negative circumferential resection margin (CRM) with surgery alone and in patients with cTN or cTN without CRM involvement and lateral lymph node metastasis. This study aims to evaluate the efficacy of upfront radical surgery with total mesorectal excision (TME) followed by adjuvant chemotherapy with folinic acid (or leucovorin), fluorouracil, and oxaliplatin (FOLFOX) versus the current standard treatment in patients with surgically resectable, locally advanced rectal cancer.

Methods: This study, named TME-FOLFOX, is a prospective, open-label, multicenter, phase II randomized trial. Patients with locally advanced rectal cancer will be randomized to receive PCRT followed by TME and adjuvant chemotherapy (arm A) or upfront radical surgery with TME followed by adjuvant FOLFOX chemotherapy (arm B). Clinical stage II/III rectal cancer without CRM involvement and lateral lymph node metastasis will be defined using preoperative MRI. The primary endpoint is 3-year disease-free survival (DFS). Secondary endpoints include 5-year DFS, local recurrence rate, systemic recurrence rate, cost-effectiveness, and overall survival. We hypothesized that our experimental group (arm B) will have a 3-year DFS of 75% and a non-inferiority margin of 15%.

Discussion: Identifying whether patients require PCRT is one of the critical issues in locally advanced rectal cancer. This study aims to elucidate whether PCRT may not be required for all patients with stage II/III rectal cancer, especially for the MRI-based intermediate-risk group (with cTN or cTN) without CRM involvement and lateral lymph node metastasis. If the findings indicate that our proposed treatment, which omits PCRT, is non-inferior to the standard treatment, then patients may avoid unnecessary radiation-related toxicity, have a shorter treatment duration, and save on medical costs.

Trial Registration: ClinicalTrials.gov, NCT02167321. Registered on 19 June 2014.
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http://dx.doi.org/10.1186/s13063-020-04266-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140505PMC
April 2020

Clinical Significance of Preoperative Serum Carcinoembryonic Antigen Within the Normal Range in Colorectal Cancer Patients Undergoing Curative Resection.

Ann Surg Oncol 2020 Aug 16;27(8):2774-2783. Epub 2020 Mar 16.

Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Serum carcinoembryonic antigen (CEA) is a widely used tumor marker in colorectal cancer (CRC), but within normal range of preoperative CEA levels the clinical significance of CEA is unknown.

Objective: The aim of this study was to evaluate the usefulness of CEA within the normal range as a prognosticator of non-metastatic CRC.

Methods: This retrospective cohort study included 2021 CRC patients with normal preoperative CEA who underwent elective curative surgery (discovery group). We determined the optimal cut-off value for disease-free survival (DFS) discrimination using the Contal and O'Quigley method. We also assessed the prognostic significance of the cut-off value in a prospective cohort of 171 stage III colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (validation group).

Results: The optimal cut-off CEA value was 2.1 ng/mL in the discovery group. The DFS rates were significantly poorer in patients with high-normal preoperative CEA levels (2.1-5.0 ng/mL) than in those with low-normal CEA levels (< 2.1 ng/mL) in both groups. A high-normal CEA level was an independent risk factor for DFS in both groups, and was associated with inferior DFS in patients with stage II and III disease and in never or former smokers. The correlation between DFS and CEA levels was more distinct in left-sided colon and rectal cancer.

Conclusions: A high-normal preoperative CEA level (≥ 2.1 ng/mL), even within the normal range, was an independent prognosticator for poor DFS in CRC. The usefulness of CEA was influenced by smoking status and tumor location in addition to tumor stage.
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http://dx.doi.org/10.1245/s10434-020-08256-5DOI Listing
August 2020

Plasma Lysyl-tRNA Synthetase 1 (KARS1) as a Novel Diagnostic and Monitoring Biomarker for Colorectal Cancer.

J Clin Med 2020 Feb 15;9(2). Epub 2020 Feb 15.

Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul 08826, Korea.

Colorectal cancer (CRC) is one of the leading causes of world cancer deaths. To improve the survival rate of CRC, diagnosis and post-operative monitoring is necessary. Currently, biomarkers are used for CRC diagnosis and prognosis. However, these biomarkers have limitations of specificity and sensitivity. Levels of plasma lysyl-tRNA synthetase (KARS1), which was reported to be secreted from colon cancer cells by stimuli, along with other secreted aminoacyl-tRNA synthetases (ARSs), were analyzed in CRC and compared with the currently used biomarkers. The KARS1 levels of CRC patients (n = 164) plasma were shown to be higher than those of healthy volunteers (n = 32). The diagnostic values of plasma KARS1 were also evaluated by receiving operating characteristic (ROC) curve. Compared with other biomarkers and ARSs, KARS1 showed the best diagnostic value for CRC. The cancer specificity and burden correlation of plasma KARS1 level were validated using azoxymethane (AOM)/dextran sodium sulfate (DSS) model, and paired pre- and post-surgery CRC patient plasma. In the AOM/DSS model, the plasma level of KARS1 showed high correlation with number of polyps, but not for inflammation. Using paired pre- and post-surgery CRC plasma samples (n = 60), the plasma level of KARS1 was significantly decreased in post-surgery samples. Based on these evidence, KARS1, a surrogate biomarker reflecting CRC burden, can be used as a novel diagnostic and post-operative monitoring biomarker for CRC.
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http://dx.doi.org/10.3390/jcm9020533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073917PMC
February 2020

Can better surgical outcomes be obtained in the learning process of robotic rectal cancer surgery? A propensity score-matched comparison between learning phases.

Surg Endosc 2021 Feb 13;35(2):770-778. Epub 2020 Feb 13.

Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Korea.

Background: Although studies of robotic rectal cancer surgery have demonstrated the effects of learning on operation time, comparisons have failed to demonstrate differences in clinicopathological outcomes between unadjusted learning phases. This study aimed to investigate the learning curve of robotic rectal cancer surgery for clinicopathological outcomes and compare surgical outcomes between adjusted learning phases. Study design We enrolled 506 consecutive patients with rectal adenocarcinoma who underwent robotic resection by a single surgeon between 2007 and 2018. Risk-adjusted cumulative sum (RA-CUSUM) for surgical failure was used to analyze the learning curve. Surgical failure was defined as the occurrence of any of the following: conversion to open surgery, severe complications (Clavien-Dindo grade ≥ 3a), insufficient number of harvested lymph nodes (LNs), or R1 resection. Comparisons between learning phases analyzed by RA-CUSUM were performed before and after propensity score matching.

Results: In RA-CUSUM analysis, the learning curve was divided into two learning phases: phase 1 (1st-177th cases, n = 177) and phase 2 (178th-506th cases, n = 329). Before matching, patients in phase 2 had deeper tumor invasion and higher rates of positive LNs on pretreatment images and preoperative chemoradiotherapy. After matching, phase 1 (n = 150) and phase 2 (n = 150) patients exhibited similar clinical characteristics. Phase 2 patients had lower rates of surgical failure overall and these components: conversion to open surgery, severe complications, and insufficient harvested LNs.

Conclusions: For robotic rectal cancer surgery, surgical outcomes improved after the 177th case. Further studies by other robotic surgeons are required to validate our results.
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http://dx.doi.org/10.1007/s00464-020-07445-3DOI Listing
February 2021

The impact of early adjuvant chemotherapy in rectal cancer.

PLoS One 2020 31;15(1):e0228060. Epub 2020 Jan 31.

Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.

Purposes: Although adjuvant chemotherapy (AC) has been established as a standard of treatment for advanced rectal cancer, there is no guideline regarding the timing of AC initiation. In this study, we aimed to evaluate the oncologic outcome of early AC initiation and clarify the ideal time to AC among rectal cancer patients receiving preoperative chemo-radiotherapy (preCRT).

Methods: The medical records of 719 patients who underwent curative resection followed by AC for rectal cancer were analyzed retrospectively. Data distributions were compared according to the calculated cut-off for AC initiation, survival results, and chemotherapy-induced toxicity. Additionally, patients were divided into two groups according to preCRT status and compared with respect to differences in the optimal time to AC.

Results: Overall, a cut-off time point of 20 days after surgery for AC initiation was identified as the optimal interval; this yielded a significant difference in disease-free survival but no significant difference in AC toxicity. In the cut-off analysis of patients treated without preCRT, 19 days was identified as the optimal time to AC. However, for patients treated with preCRT, no significant value affected the survival outcome.

Conclusions: Earlier initiation of AC (within approximately 3 weeks) was associated with better oncological outcomes among patients with rectal cancer. Additionally, the optimal timing of AC was unclear among patients who received preCRT; this might be attributable to an undetermined role of AC after preCRT or the effects of complications such as anastomotic leakage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228060PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993968PMC
May 2020

Functions of human liver CD69CD103CD8 T cells depend on HIF-2α activity in healthy and pathologic livers.

J Hepatol 2020 06 24;72(6):1170-1181. Epub 2020 Jan 24.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea. Electronic address:

Background & Aims: Human liver CD69CD8 T cells are ~95% CD103 and ~5% CD103. Although CD69CD103CD8 T cells show tissue residency and robustly respond to antigens, CD69CD103CD8 T cells are not yet well understood.

Methods: Liver perfusate and paired peripheral blood were collected from healthy living donors and recipients with cirrhosis during liver transplantation. Liver tissues were obtained from patients with acute hepatitis A. Phenotypic and functional analyses were performed by flow cytometry. Gene expression profiles were determined by microarray and quantitative reverse transcription PCR. PT-2385 was used to inhibit hypoxia-inducible factor (HIF)-2α.

Results: Human liver CD69CD103CD8 T cells exhibited HIF-2α upregulation with a phenotype of tissue residency and terminal differentiation. CD103 cells comprised non-hepatotropic virus-specific T cells as well as hepatotropic virus-specific T cells, but CD103 cells exhibited only hepatotropic virus specificity. Although CD103 cells were weaker effectors on a per cell basis than CD103 cells, following T cell receptor or interleukin-15 stimulation, they remained the major CD69CD8 effector population in the liver, surviving with less cell death. An HIF-2α inhibitor suppressed the effector functions and survival of CD69CD103CD8 T cells. In addition, HIF-2α expression in liver CD69CD103CD8 T cells was significantly increased in patients with acute hepatitis A or cirrhosis.

Conclusions: Liver CD69CD103CD8 T cells are tissue resident and terminally differentiated, and their effector functions depend on HIF-2α. Furthermore, activation of liver CD69CD103CD8 T cells with HIF-2α upregulation is observed during liver pathology.

Lay Summary: The immunologic characteristics and the role of CD69CD103CD8 T cells, which are a major population of human liver CD8 T cells, remain unknown. Our study shows that these T cells have a terminally differentiated tissue-resident phenotype, and their effector functions depend on a transcription factor, HIF-2α. Furthermore, these T cells were activated and expressed higher levels of HIF-2α in liver pathologies, suggesting that they play an important role in immune responses in liver tissues and the pathogenesis of human liver disease.
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http://dx.doi.org/10.1016/j.jhep.2020.01.010DOI Listing
June 2020

Significance of Radial Margin in Patients Undergoing Complete Mesocolic Excision for Colon Cancer.

Dis Colon Rectum 2020 04;63(4):488-496

Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Background: Comparable to circumferential resection margin in rectal cancer, radial margin is a potential prognostic factor in colon cancer that has just begun to be studied. No previous studies have investigated the influence of radial margin in the context of complete mesocolic excision.

Objective: This study aimed to examine the impact of radial margin on oncologic outcomes after complete mesocolic excision for colon cancer.

Design: We retrospectively reviewed patients with stage I to III colon cancer who underwent curative resection from October 2010 to March 2013.

Settings: This study was conducted using the prospective colorectal cancer registry of Severance hospital.

Patients: A total of 834 consecutive patients who underwent complete mesocolic excision for colon adenocarcinoma were included.

Interventions: We assigned patients into 3 groups according to radial margin distance: group A, radial margin ≥2.0 mm; group B, 1.0 ≤ radial margin < 2.0 mm; group C, radial margin <1 mm.

Main Outcomes And Measures: Overall survival and disease-free survival were estimated.

Results: On adjusted Cox regression analysis, only group C was predictive of reduced overall survival (HR, 1.90; 95% CI, 1.11-3.25; p = 0.018) and disease-free survival (HR, 1.93; 95% CI, 1.28-2.89; p = 0.001). We thereby defined radial margin threatening as radial margin <1 mm. Postoperative 5-fluorouracil (HR, 0.86; 95% CI, 0.35-2.10; p = 0.743) and FOLFOX (HR, 1.23; 95% CI, 0.57-2.64; p = 0.581) chemotherapy did not affect disease-free survival in patients with radial margin threatening.

Limitations: This study has the limitations inherent in all retrospective, single-institution studies.

Conclusions: Even with complete mesocolic excision, radial margin <1 mm was an independent predictor of survival and recurrence. This finding suggests that special efforts for obtaining a clear radial margin may be necessary in locally advanced colon cancer. See Video Abstract at http://links.lww.com/DCR/B125. IMPORTANCIA DEL MARGEN RADIAL EN PACIENTES SOMETIDOS A ESCISIÓN MESOCÓLICA COMPLETA PARA CÁNCER DEL COLON: Comparable al margen de resección circunferencial en cáncer rectal, el margen radial en cáncer de colon, es un factor pronóstico potencial, que recientemente comienza a estudiarse. Ningún estudio previo ha investigado la influencia del margen radial, en el contexto de la escisión mesocólica completa.Examinar en cáncer de colon, el impacto del margen radial en los resultados oncológicos, después de la escisión mesocólica completa.Revisión retrospectiva de pacientes con cáncer de colon en estadio I-III, sometidos a resección curativa de octubre 2010 a marzo 2013.Este estudio se realizó utilizando un registro prospectivo de cáncer colorrectal del hospital Severance.Se incluyeron un total de 834 pacientes consecutivos con adenocarcinoma de colon, sometidos a escisión mesocólica completa. Dividimos a los pacientes en 3 grupos según la distancia del margen radial: grupo A, margen radial ≥ 2.0 mm; grupo B, 1.0 ≤ margen radial <2.0 mm; grupo C, margen radial <1 mm.Se estimó la supervivencia general y la supervivencia libre de enfermedad.En el análisis de regresión de Cox ajustado, solo el grupo C fue predictivo de supervivencia global reducida (HR, 1.90; IC 95%, 1.11-3.25; p = 0.018) y supervivencia libre de enfermedad (HR, 1.93; IC 95%, 1.28-2.89; p = 0.001). Definimos como margen radial amenazante, un margen radial <1 mm. La quimioterapia posoperatoria con 5-FU (HR, 0,86; IC 95%, 0,35-2,10; p = 0.743) y FOLFOX (HR, 1,23; IC 95%, 0,57-2,64; p = 0,581), no afectó la supervivencia libre de enfermedad en pacientes con riesgo de margen radial.Este estudio tiene limitaciones inherentes a todos los estudios retrospectivos de una sola institución.Aun con la escisión mesocólica completa, el margen radial <1 mm fue un predictor independiente de supervivencia y recurrencia. Este hallazgo sugiere que pueden ser necesarios esfuerzos especiales para obtener un claro margen radial, en cáncer de colon localmente avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B125.
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http://dx.doi.org/10.1097/DCR.0000000000001569DOI Listing
April 2020

Status of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis from colorectal cancer.

J Gastrointest Oncol 2019 Dec;10(6):1251-1265

Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.

Peritoneal carcinomatosis (PC) was previously considered an incurable disease with a poor survival outcome. As our understanding of its biology evolved, the paradigm of the management of PC from colorectal cancer (CRC) has changed, including the combination of macroscopic disease control, cytoreductive surgery (CRS), maximal regional chemotherapy to treat residual microscopic disease, and hyperthermic intraperitoneal chemotherapy (HIPEC). As with many surgical innovations, CRS with HIPEC has evolved faster than data to support it, leaving many skeptics and critics. This review highlights the recent evidence of current practice and outcome of CRS with HIPEC. Furthermore, it also summarizes the ongoing clinical trials and potential future progress of this treatment modality.
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http://dx.doi.org/10.21037/jgo.2019.01.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955007PMC
December 2019

Impact of Adjuvant Chemotherapy Completion on Oncologic Outcomes in ypTNMstage 2 Rectal Cancer Patients.

Ann Coloproctol 2019 Dec 31;35(6):335-341. Epub 2019 Dec 31.

Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Purpose: Adjuvant chemotherapy (aCT) in rectal cancer patients who have undergone curative resection after neoadjuvant chemoradiation (nCRT) is controversial. We aimed to investigate the benefits of using aCT and the clinical impact of completing aCT in ypstage 2 rectal cancer patients.

Methods: We retrospectively reviewed clinicopathological data from patients who had undergone radical resection after nCRT between January 2006 and December 2012. In total, 152 patients with ypT3/4N0M0 rectal cancer were included. Of these patients, 139 initiated aCT, while 13 did not receive aCT (no-aCT). Among those who received aCT, 132 patients completed their planned cycles (aCT-completion) whereas 7 did not (aCT-incompletion). All patients received longcourse chemoradiation; a 5-fluorouracil-based regimen was used for nCRT in most patients. The prognostic factors affecting disease-free survival (DFS) and overall survival (OS) were analyzed.

Results: The median follow-up duration was 41 months. Demographic data did not differ significantly among the 3 groups. In multivariate analysis, open surgery, a tumor size >2 cm, retrieval of <12 lymph nodes, circumferential resection margin (CRM) positivity and aCT incompletion were independent prognostic factors for poor DFS. Old age (≥60 years), open surgery, CRM positivity, aCT incompletion, and lack of aCT initiation compared to aCT completion were independent prognostic factors for poor OS.

Conclusion: In ypstage 2 rectal cancer patients, aCT after nCRT and total mesorectal excision affected both DFS and OS; however, only patients who completed planned aCT exhibited survival benefits. Therefore, improving patients' compliance with the completion of aCT is desirable.
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http://dx.doi.org/10.3393/ac.2019.03.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968722PMC
December 2019

Short-term Outcomes After Upfront Chemotherapy Followed by Curative Surgery in Metastatic Colon Cancer: A Comparison With Upfront Surgery Patients.

Ann Coloproctol 2019 Dec 31;35(6):327-334. Epub 2019 Dec 31.

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Upfront systemic chemotherapy with target agents has been recommended for patients with stage IV colon cancer. Some with partial response are considered for curative resection. There is high risk of developing postoperative complications following upfront systemic chemotherapy. We aimed to evaluate short-term perioperative outcomes of curative surgery after upfront chemotherapy in comparison with upfront surgery in patients with metastatic colon cancer.

Methods: Between January 2010 and October 2015, 146 patients (80 in the surgery first group, 66 in the upfront chemotherapy group) who underwent surgical resection before or after systemic chemotherapy for metastatic colon cancer were included in the present study. All decisions for treatment were made through a multidisciplinary team. Postoperative clinical outcomes and complications were analyzed to compare the groups.

Results: There was no difference between the 2 groups in terms of postoperative clinical outcomes. Overall complication rates were not different between the groups (surgery first group: 46.3% vs. upfront chemotherapy group: 60.6%; P = 0.084). When classified according to the Clavien-Dindo method, there was no difference between the 2 groups in terms of major complications (grade 3 or more) (surgery first group: 18.9% vs. upfront chemotherapy group: 27.5%; P = 0.374).

Conclusion: There was no significant increase in major postoperative complications in metastatic colon cancer patients who received upfront chemotherapy followed by curative surgery. Careful patient selection and treatment planning are important.
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http://dx.doi.org/10.3393/ac.2019.03.04.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968719PMC
December 2019

A novel long noncoding RNA Linc-ASEN represses cellular senescence through multileveled reduction of p21 expression.

Cell Death Differ 2020 06 9;27(6):1844-1861. Epub 2019 Dec 9.

Department of Molecular Medicine, and Medical Research Center, Inha University College of Medicine, Incheon, Korea.

Long noncoding RNAs (lncRNAs) regulating diverse cellular processes implicate in many diseases. However, the function of lncRNAs in cellular senescence remains largely unknown. Here we identify a novel long intergenic noncoding RNA Linc-ASEN expresses in prematurely senescent cells. We find that Linc-ASEN associates with UPF1 by RNA pulldown mass spectrometry analysis, and represses cellular senescence by reducing p21 production transcriptionally and posttranscriptionally. Mechanistically, the Linc-ASEN-UPF1 complex suppressed p21 transcription by recruiting Polycomb Repressive Complex 1 (PRC1) and PRC2 to the p21 locus, and thereby preventing binding of the transcriptional activator p53 on the p21 promoter through histone modification. In addition, the Linc-ASEN-UPF1 complex repressed p21 expression posttranscriptionally by enhancing p21 mRNA decay in association with DCP1A. Accordingly, Linc-ASEN levels were found to correlate inversely with p21 mRNA levels in tumors from patient-derived mouse xenograft, in various human cancer tissues, and in aged mice tissues. Our results reveal that Linc-ASEN prevents cellular senescence by reducing the transcription and stability of p21 mRNA in concert with UPF1, and suggest that Linc-ASEN might be a potential therapeutic target in processes influenced by senescence, including cancer.
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http://dx.doi.org/10.1038/s41418-019-0467-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244501PMC
June 2020

β-catenin activation down-regulates cell-cell junction-related genes and induces epithelial-to-mesenchymal transition in colorectal cancers.

Sci Rep 2019 12 5;9(1):18440. Epub 2019 Dec 5.

Brain Korea 21 PLUS Project for Medical Science, Seoul, Korea.

WNT signaling activation in colorectal cancers (CRCs) occurs through APC inactivation or β-catenin mutations. Both processes promote β-catenin nuclear accumulation, which up-regulates epithelial-to-mesenchymal transition (EMT). We investigated β-catenin localization, transcriptome, and phenotypic differences of HCT116 cells containing a wild-type (HCT116-WT) or mutant β-catenin allele (HCT116-MT), or parental cells with both WT and mutant alleles (HCT116-P). We then analyzed β-catenin expression and associated phenotypes in CRC tissues. Wild-type β-catenin showed membranous localization, whereas mutant showed nuclear localization; both nuclear and non-nuclear localization were observed in HCT116-P. Microarray analysis revealed down-regulation of Claudin-7 and E-cadherin in HCT116-MT vs. HCT116-WT. Claudin-7 was also down-regulated in HCT116-P vs. HCT116-WT without E-cadherin dysregulation. We found that ZEB1 is a critical EMT factor for mutant β-catenin-mediated loss of E-cadherin and Claudin-7 in HCT116-P and HCT116-MT cells. We also demonstrated that E-cadherin binds to both WT and mutant β-catenin, and loss of E-cadherin releases β-catenin from the cell membrane and leads to its degradation. Alteration of Claudin-7, as well as both Claudin-7 and E-cadherin respectively caused tight junction (TJ) impairment in HCT116-P, and dual loss of TJs and adherens junctions (AJs) in HCT116-MT. TJ loss increased cell motility, and subsequent AJ loss further up-regulated that. Immunohistochemistry analysis of 101 CRCs revealed high (14.9%), low (52.5%), and undetectable (32.6%) β-catenin nuclear expression, and high β-catenin nuclear expression was significantly correlated with overall survival of CRC patients (P = 0.009). Our findings suggest that β-catenin activation induces EMT progression by modifying cell-cell junctions, and thereby contributes to CRC aggressiveness.
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http://dx.doi.org/10.1038/s41598-019-54890-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895046PMC
December 2019

Oncologic safety and bowel function after ultralow anterior resection with or without intersphincteric resection for low lying rectal cancer: Comparative cross sectional study.

J Surg Oncol 2019 Dec 3. Epub 2019 Dec 3.

Division of Colorectal Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Background: Despite acceptable oncologic outcomes of sphincter preserving surgeries for low rectal cancer, bowel dysfunction occurs. This study aimed to compare the oncologic and functional bowel outcomes between ultralow anterior resection (ULAR) and intersphincteric resection (ISR) for low rectal cancer.

Methods: One hundred sixty-four patients who underwent ULAR with or without ISR for low rectal cancer between December 2010 and May 2018 were included. The Wexner and Memorial Sloan Kettering Cancer Center (MSKCC) scores were used to evaluate the bowel function of patients. Overall survival (OS) and disease-free survival (DFS) were compared between patients.

Results: The ISR group had higher incidence of major fecal incontinence than the ULAR group (75.9% vs 49.3%; P = .016). The median Wexner score decreased from 12 to 9 (P = .062) at 1-year follow-up. However, the frequency and urgency/soilage subscales of MSKCC score improved significantly in the ULAR group. ISR and follow-up interval less than 1-year significantly increased the major incontinence risk. The OS in the ULAR and ISR groups was 91.4% and 91.7%. Whereas the DFS in both groups was 79% and 79.2%, respectively.

Conclusion: ULAR and ISR are comparable in oncologic outcomes. Severe bowel dysfunctions and major incontinence were noted in ISR group. Careful selection of patients is mandatory.
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http://dx.doi.org/10.1002/jso.25791DOI Listing
December 2019

Robotic simultaneous resection for colorectal liver metastasis: feasibility for all types of liver resection.

Langenbecks Arch Surg 2019 Nov 3;404(7):895-908. Epub 2019 Dec 3.

Department of Surgery, Yonsei University College of Medicine, #50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.

Background: A laparoscopic approach is increasingly being utilized in simultaneous colorectal and liver resection (SCLR) for colorectal cancer with liver metastasis. However, this approach is technically challenging and hence has not been widely adopted. Robotic surgical systems could potentially overcome this problem. We aim to describe the feasibility and outcomes of robotic SCLR for colorectal carcinoma with liver metastasis.

Methods: The medical records of 12 patients who underwent robotic SCLR for colorectal cancer with liver metastasis between January 2008 and September 2018 were reviewed retrospectively.

Results: The mean age was 59 years (range, 37-77 years). The liver resections were comprised of two right hepatectomies, one left hepatectomy, one left lateral sectionectomy, one segmentectomy of S3 and wedge resection (segment 7), one caudate lobectomy, one associated liver partition and portal vein ligation for staged hepatectomy, and five wedge resections involving segments 4, 5, 6, 7, or 8. The colorectal procedures involved seven low-anterior resections, two anterior resections, two right hemicolectomies, and one left hemicolectomy. The mean operative time was 449 min (range, 135-682 min) with a mean estimated blood loss of 274.3 mL (range, 40-780 mL). The mean length of hospital stay was 12 days (range, 5-28 days). No patients required conversion to laparotomy. Liver resection-related complications were two liver abscesses (Clavien-Dindo classification, one grade II and one grade III) and one case of ascites (grade I), whereas colorectal resection-related complications included one anastomosis leak (grade III) and one superficial wound infection (grade II). There were no deaths reported within 30 days of the procedure. With a mean follow-up duration of 31.5 ± 26.1 months, the overall survival and disease-free survival values were 75.2 and 47.1 months, respectively.

Conclusion: Robotic SCLR for colorectal neoplasm with liver metastasis can be performed safely even in cases requiring major liver resections, especially in a specialized center with a well-trained team.
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http://dx.doi.org/10.1007/s00423-019-01833-7DOI Listing
November 2019

Single-center Experience of 24 Cases of Tailgut Cyst.

Ann Coloproctol 2019 Oct 31;35(5):268-274. Epub 2019 Oct 31.

Division of Colorectal Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Tailgut cysts are rare congenital or developmental lesions that arise from vestiges of the embryological hindgut. They are usually present in the presacral space. We report our single-center experience with managing tailgut cysts.

Methods: We conducted a retrospective analysis of 24 patients with tailgut cyst treated surgically at the Colorectal Surgery Department of Severance Hospital, Yonsei University, Seoul, South Korea, between 2007-2018.

Results: This study included 24 patients (18 females) with a median age of 51.5 years (range, 21-68 years). Ten cases were symptomatic and 14 were asymptomatic. Cysts were retrorectal in 21 patients. Cysts were below the coccyx level in 16 patients, opposite the coccyx in 6, and above the coccyx in 2. Cysts were supralevator in 5 patients, had a supra- and infralevator extension in 18 patients, and were infralevator in 1. Ten patients were managed using an anterior laparoscopic approach, 11 using a posterior approach, and 3 using a combined approach. Mean cyst size was 5.5 ± 2.7 cm. Postoperative complications were Clavien-Dindo (CD) classification grade II in 9 patients (37.5%) and CD grade III in 1 (4.2%). The posterior approach group showed the highest rate of complications (P = 0.021). Patients managed using a combined approach showed a larger cyst size (P < 0.001), longer operation times (P < 0.001), and a greater likelihood of tumor level above the coccyx (P = 0.002) compared to other approaches. The tumors of 2 male patients were malignant: 1 was a neuroendocrine tumor treated with radiotherapy, while the other was a closely followed adenocarcinoma. Median follow-up was 12 months (range, 1-66 months) with no recurrence.

Conclusion: Tailgut cysts are uncommon but can cause perineal or pelvic pain. Complete surgical excision via an appropriate approach according to tumor size, location, and correlation with adjacent pelvic floor muscles is the key treatment.
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http://dx.doi.org/10.3393/ac.2018.12.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863012PMC
October 2019

VEGF-A drives TOX-dependent T cell exhaustion in anti-PD-1-resistant microsatellite stable colorectal cancers.

Sci Immunol 2019 11;4(41)

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.

Although immune checkpoint blockade therapies have demonstrated clinical efficacy in cancer treatment, harnessing this strategy is largely encumbered by resistance in multiple cancer settings. Here, we show that tumor-infiltrating T cells are severely exhausted in the microsatellite stable (MSS) colorectal cancer (CRC), a representative example of PD-1 blockade-resistant tumors. In MSS CRC, we found wound healing signature to be up-regulated and that T cell exhaustion is driven by vascular endothelial growth factor-A (VEGF-A). We report that VEGF-A induces the expression of transcription factor TOX in T cells to drive exhaustion-specific transcription program in T cells. Using a combination of in vitro, ex vivo, and in vivo mouse studies, we demonstrate that combined blockade of PD-1 and VEGF-A restores the antitumor functions of T cells, resulting in better control of MSS CRC tumors.
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http://dx.doi.org/10.1126/sciimmunol.aay0555DOI Listing
November 2019

Prediction of tumor response of rectal cancer cells via 3D cell culture and cytotoxicity assay before initiating preoperative chemoradiotherapy.

Oncol Lett 2019 Oct 2;18(4):3863-3872. Epub 2019 Aug 2.

Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

The aim of the present study was to investigate the utility of 3D cell culture and cytotoxicity assays, performed using cells derived from biopsies obtained prior to the initiation of preoperative chemoradiotherapy (preop-CRT), in predicting tumor response to chemoradiotherapy following preop-CRT in rectal cancer. Biopsies were obtained from 49 patients with locally advanced rectal cancer that underwent preop-CRT between August 2015 and March 2017. Tumor tissue was obtained before initiating preop-CRT. The response to chemoradiation was assessed by cytotoxicity assay following 3D cell culture and radiation treatment. The associations between the results from the cytotoxicity assay, and tumor regression grade (TRG) and yp node (ypN) positivity were investigated. Among 49 patients, 26 patients were available for analysis. Cytotoxicity ranged from 25.5-72.6% (median, 47.6%). There was no difference in cytotoxicity according to the TRGs 1-5 (P=0.940), or good tumor response (TRGs 1-2 vs. TRGs 3-5; P=0.729). However, there was a significant difference in cytotoxicity between the ypN-negative and -positive groups (53.2±14.1 and 38.7±10.1, respectively; P=0.021). Following dichotomization of patients with 45% cut-off value, the cytotoxicity assay was the only factor that predicted ypN positivity in multivariate analysis (odds ratio, 13; 95% confidence interval, 1.2-133.2; P=0.031). In conclusion, the cytotoxicity assay using the 3D cell culture method can be used to predict tumor response, particularly ypN positivity, in patients with rectal cancer who are scheduled for preop-CRT.
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http://dx.doi.org/10.3892/ol.2019.10702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733010PMC
October 2019

Prediction of transabdominal total mesorectal excision difficulty according to the angle of pelvic floor muscle.

Surg Endosc 2020 07 3;34(7):3043-3050. Epub 2019 Sep 3.

Division of Colorectal Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, South Korea.

Background: Total mesorectal excision (TME) is challenging to perform in a deep, narrow pelvis. While previous studies used pelvimetry to assess bony pelvic structures, there is no consensus on exact definition of deep, narrow pelvis. We hypothesized that the shape of pelvic floor muscle may impact the performance of transabdominal pelvic dissection. We aimed to evaluate which parameters of the shape of pelvic floor muscle impact the difficulty of TME and present a predictive reference value for TME difficulty.

Methods: From January 2015 to December 2015, 85 consecutive patients who had undergone curative resection for middle to lower rectal cancer were retrospectively studied. Pelvimetry was performed using preoperative T2-weighted magnetic resonance imaging. Predictive factor analysis for surgical duration was studied using linear regression. Mann-Whitney U test, comparing surgical duration between two groups classified by predictive factor, was used for the analysis of reference value.

Results: Multivariate analysis revealed that body mass index, protective stoma, number of surgeon, and incline angle of pelvic floor muscle (β) were independent predictors of surgical duration. Test statistics of Mann-Whitney U for the difference in surgical duration between groups above and below a β of 54° were maximized.

Conclusions: The incline angle of pelvic floor muscle is an independent predictor of surgical duration. In patients with steeper incline of PFM, transabdominal TME is expected to be difficult. This index is novel, but needs to be further validated.
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http://dx.doi.org/10.1007/s00464-019-07102-4DOI Listing
July 2020