Clinical Significance of Prognostic Nutrition Index in Patients with Crohn's Disease after Primary Bowel Resection.

PURPOSE: Although advancements in medical treatments have been made, approximately half of patients with intestinal Crohn's disease (CD) require intestinal resections during their lifetime. It is well-known that the nutritional status of CD patients can impact postoperative morbidity. The objective of this study was to evaluate the clinical significance of prognostic nutritional index (PNI) in patients with intestinal CD who underwent primary bowel resection. MATERIALS AND METHODS: We retrospectively investigated patients who were diagnosed with CD and underwent intestinal surgery at Severance Hospital between January 2005 and October 2018. The patients were divided into two groups: PNI ≤40 (n=150) and PNI >40 (n=77). We assessed the clinical significance of PNI in terms of the incidence of postoperative infectious complications (PICs) and the postoperative recurrence of CD. RESULTS: The low PNI group had significantly higher rates of infectious complications (32.0% vs. 10.4%, p=0.001) compared to the high PNI group. Multivariable analysis identified low PNI (≤40) and longer operation time (>180 min) as independent risk factors associated with PICs [odds ratio (OR)=2.754, 95% confidence interval (CI)=1.140-6.649, p=0.024; OR=2.986, 95% CI=1.451-6.143, p=0.003]. PICs were significantly associated with surgical recurrence (hazard ratio=2.217, 95% CI=1.064-4.617, p=0.034). CONCLUSION: Preoperative PNI could serve as a predictive factor for PICs in CD patients who undergo intestinal resection. Additionally, PICs are significantly associated with a higher risk of surgical recurrence in CD.

Long-term bowel functional outcomes following anal sphincter-preserving surgery for upper and middle rectal cancer: a single-center longitudinal study.

PURPOSE: Despite advances in neoadjuvant chemoradiotherapy and anal sphincter-preserving surgery for rectal cancer, bowel dysfunction is still unavoidable and negatively affects patients' quality of life. In this longitudinal study, we aimed to investigate the changes in bowel function with follow-up time and the effect of neoadjuvant chemoradiotherapy on bowel function following low anterior resection for rectal cancer. METHODS: In this study, 171 patients with upper or middle rectal cancer who underwent low anterior resection between 2012 and 2018 were included. Bowel function was assessed longitudinally with Memorial Sloan Kettering Cancer Center Bowel Function Instrument and Wexner scores every 6 months after restoration of bowel continuity. Patients with at least 2 follow-up visits were included. RESULTS: Overall, 100 patients received neoadjuvant chemoradiotherapy. Urgency, soilage, and fecal incontinence were noted within 24 months in the patients treated with neoadjuvant chemoradiotherapy. After 2 years of follow-up, significant bowel dysfunction and fecal incontinence were observed in the neoadjuvant chemoradiotherapy group. Low tumor level and neoadjuvant chemoradiotherapy were associated with delayed bowel dysfunction. CONCLUSION: Neoadjuvant chemoradiotherapy in combination with low tumor level was significantly associated with delayed bowel dysfunction even after 2 years of follow-up. Therefore, careful selection and discussion with patients are paramount.

Pretreatment MRI-detected extramural venous invasion as a prognostic and predictive biomarker for neoadjuvant chemoradiotherapy in non-metastatic rectal cancer: a propensity score matched analysis.

OBJECTIVES: This study evaluated pretreatment magnetic resonance imaging (MRI)-detected extramural venous invasion (pmrEMVI) as a predictor of survival after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Medical records of 1184 patients with rectal adenocarcinoma who underwent TME between January 2011 and December 2016 were reviewed. MRI data were collected from a computerized radiologic database. Cox proportional hazards analysis was used to assess local, systemic recurrence, and disease-free survival risk based on pretreatment MRI-assessed tumor characteristics. After propensity score matching (PSM) for pretreatment MRI features, nCRT therapeutic outcomes according to pmrEMVI status were evaluated. Cox proportional hazards analysis was used to identify risk factors for early recurrence in patients receiving nCRT. RESULTS: Median follow-up was 62.8 months. Among all patients, the presence of pmrEMVI was significantly associated with worse disease-free survival (DFS; HR 1.827, 95% CI 1.285-2.597, p = 0.001) and systemic recurrence (HR 2.080, 95% CI 1.400-3.090, p < 0.001) but not local recurrence. Among patients with pmrEMVI, nCRT provided no benefit for oncological outcomes before or after PSM. Furthermore, pmrEMVI( +) was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT. CONCLUSIONS: pmrEMVI is a poor prognostic factor for DFS and SR in patients with non-metastatic rectal cancer and also serves as a predictive biomarker of poor DFS and SR following nCRT in LARC. Therefore, for patients who are positive for pmrEMVI, consideration of alternative treatment strategies may be warranted. CLINICAL RELEVANCE STATEMENT: This study demonstrated the usefulness of pmrEMVI as a predictive biomarker for nCRT, which may assist in initial treatment decision-making in patients with non-metastatic rectal cancer. KEY POINTS: • Pretreatment MRI-detected extramural venous invasion (pmrEMVI) was significantly associated with worse disease-free survival and systemic recurrence in patients with non-metastatic rectal cancer. • pmrEMVI is a predictive biomarker of poor DFS following nCRT in patients with LARC. • The presence of pmrEMVI was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT.

Postchemoradiation magnetic resonance imaging circumferential resection margin predicts treatment failure after multidisciplinary directed sphincter preservation in low rectal cancer.

BACKGROUND: This study aimed to review the magnetic resonance imaging (MRI) features of patients with low rectal cancer (LRC) undergoing preoperative chemoradiotherapy (CRT) and investigate the risk factors for treatment failure after sphincter preserving surgery following preoperative CRT based on multidisciplinary approach. OBJECTIVES: Patients who underwent standard CRT and sphincter preserving radical surgery for LRC between January 2000 and December 2011 were retrospectively reviewed. Sphincter preservation failure (SPF) was defined as any one of the following: positive pathologic circumferential resection margin, local recurrence, failure to repair ileostomy, or permanent stoma formation due to anastomotic complications. RESULTS: Among the 191 patients, there were no overall significant differences between sphincter preservation success (n = 161) and SPF (n = 30) groups. SPF group showed a higher MRI circumferential resection margins (mrCRM) positive rate before and after CRT (before CRT: 33.3% vs. 16.1%, p = 0.027; after CRT: 23.3% vs. 6.2%, p = 0.002). Multivariate analysis showed that only mrCRM after CRT was associated with SPF (hazard ratio = 4.596, p = 0.005). SPF group showed worse 5-year cancer-specific survival (51% vs. 92.7%, p < 0.001). CONCLUSIONS: MRI-based assessment of the tumor after CRT plays a crucial role in predicting the success and feasibility of sphincter preservation as well as oncological outcomes in patients with LRC.

Neoadjuvant chemotherapy versus upfront surgery as the initial treatment for patients with resectable, synchronous colorectal cancer liver metastases.

BACKGROUND: Although perioperative chemotherapy has been the standard treatment for colorectal cancer with resectable liver metastases (CRLM), studies that have compared neoadjuvant chemotherapy (NAC) and upfront surgery, especially in the setting of synchronous metastases are rare. METHODS: We compared perioperative outcomes, overall survival (OS) and overall survival after recurrence (rOS) in a retrospective study of 281 total and 104 propensity score-matched (PSM) patients who underwent curative resection, with or without NAC, for synchronous CRLM, from 2006 to 2017. A Cox regression model was developed for OS. RESULTS: After PSM, 52 NAC and 52 upfront surgery patients with similar baseline characteristics were compared. Postoperative morbidity, mortality, and 5-year OS rate (NAC: 78.9%, surgery: 64.0%; p = 0.102) were similar between groups; however, the NAC group had better rOS (NAC: 67.3%, surgery: 31.5%; p = 0.049). Initial cancer stage (T4, N1-2), poorly differentiated histology, and >1 hepatic metastases were independent predictors of worse OS. Based on these factors, patients were divided into low-risk (≤1 risk factor, n = 115) and high-risk (≥2 risk factors, n = 166) groups. For high-risk patients, NAC yielded better OS than upfront surgery (NAC: 74.5%, surgery: 53.2%; p = 0.024). CONCLUSIONS: Although NAC and upfront surgery-treated patients had similar perioperative outcomes and OS, better postrecurrence survival was shown in patients with NAC. In addition, NAC may benefit patients with worse prognoses; therefore, physicians should consider patient disease risk before initiating treatment to identify patients who are most likely to benefit from chemotherapy.

Development of a home health care service platform for ostomy patient management.

Purpose: The use of an ostomy for urination and defecation leads to reduced quality of life. Although many ostomy management strategies are needed, such strategies are often implemented by patients. Thus, there is a need for a home health care service platform that can be used in ostomy patient management. Methods: We developed an ostomy patient management platform by identifying the needs of patients and medical staff through the Chronic Care Ostomy Self-Management Training Program in the United States and from studies conducted in Korea. Results: The platform encompassed physical management, psychological management, maintenance of social function, spiritual stability, and home medical care. These components were implemented through monitoring, self-care guidance, and a community platform. For the monitoring function, a patient entered their health status in a mobile application (app); the medical staff at the affiliated hospital then monitored the stoma status through a web interface. Conclusion: Our platform allows medical staff to monitor ostomy patients through a web interface and help such patients to fully manage their ostomy at home using an app. We expect that the continued development of patient-oriented functions in our app will allow ostomy patients to experience quality of life improvements.

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

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.

Long-term oncologic outcomes of single-incision laparoscopic surgery for colon cancer.

BACKGROUND: Studies find similar perioperative outcomes between single-incision laparoscopic surgery (SILS) and conventional laparoscopic surgery (CLS) for colon cancer. However, few have reported long-term outcomes of SILS versus CLS. We aimed to compare long-term postoperative and oncologic outcomes as well as perioperative outcomes between SILS and CLS for colon cancer. METHODS: A total of 641 consecutive patients who underwent laparoscopic surgery for colon cancer from July 2009 to September 2014 were eligible for the study. Data from 300 of these patients were used for analysis after propensity score-matching (n = 150 per group). Variables associated with short- and long-term outcomes were analyzed. RESULTS: The SILS group had a shorter mean total incision length, less postoperative pain, and a similar mean rate of incisional hernia (2.7% versus 3.3%) compared with the CLS group. The 7-year overall and disease-free survival rates were 92.7% versus 94% (p = 0.673) and 85.3% versus 84.7% (p = 0.688) in the SILS and CLS groups, respectively. CONCLUSIONS: Compared with CLS, SILS for colon cancer appeared to be safe in terms of perioperative and long-term postoperative and oncologic outcomes. The results suggested that SILS is a reasonable treatment option for colon cancer for a selected group of patients.

Association of perioperative serum carcinoembryonic antigen level and recurrence in low-risk stage IIA colon cancer.

BACKGROUND: The purpose is to investigate prognosis according to serum CEA levels before and after surgery in patients with stage IIA colon cancer who do not show high-risk features. METHODS: Among the patients diagnosed with colon adenocarcinoma between April 2011 and December 2017, 462 patients were confirmed as low-risk stage IIA after surgery and enrolled. The ROC curve was used to determine cut-off values of pre- and postoperative CEA. Patients were classified into three groups using these new cut-off values. RESULTS: All recurrence occurred in 52 of 463 patients (11.2%). However, recurrence in group H was 15.9%, which was slightly higher than the other two groups (P = 0.04). Group L and M showed 10.5% and 12.8% overall survival, group H was higher at 21.0% (P = 0.005). Recurrence was the only risk factor in group H was significantly higher in group L (HR 2.008, 95% CI, 1.123-3.589, P = 0.019). Mortality was similar to recurrence (HR 1.975, 95% CI 1.091-3.523, P = 0.044). CONCLUSION: Among patients with low-risk stage IIA colon cancer, recurrence and mortality rates were higher when perioperative serum CEA levels were above a certain level. Therefore, high CEA level should be considered a high-risk feature and adjuvant chemotherapy should be performed.

Plasma Membrane Localized GCaMP-MS4A12 by Orai1 Co-Expression Shows Thapsigargin- and Ca2+-Dependent Fluorescence Increases.

Uniquely expressed in the colon, MS4A12 exhibits store-operated Ca2+ entry (SOCE) activity. However, compared to MS4A1 (CD20), a Ca2+ channel and ideal target for successful leukaemia immunotherapy, MS4A12 has rarely been studied. In this study, we investigated the involvement of MS4A12 in Ca2+ influx and expression changes in MS4A12 in human colonic malignancy. Fluorescence of GCaMP-fused MS4A12 (GCaMP-M12) was evaluated to analyse MS4A12 activity in Ca2+ influx. Plasma membrane expression of GCaMP-M12 was achieved by homo- or hetero-complex formation with no-tagged MS4A12 (nt-M12) or Orai1, respectively. GCaMP-M12 fluorescence in plasma membrane increased only after thapsigargin-induced depletion of endoplasmic reticulum Ca2+ stores, and this fluorescence was inhibited by typical SOCE inhibitors and siRNA for Orai1. Furthermore, GCaMP-MS4A12 and Orai1 co-transfection elicited greater plasma membrane fluorescence than GCaMP-M12 co-transfected with nt-M12. Interestingly, the fluorescence of GCaMP-M12 was decreased by STIM1 over-expression, while increased by siRNA for STIM1 in the presence of thapsigargin and extracellular Ca2+. Moreover, immunoprecipitation assay revealed that Orai1 co-expression decreased protein interactions between MS4A12 and STIM1. In human colon tissue, MS4A12 was expressed in the apical region of the colonic epithelium, although its expression was dramatically decreased in colon cancer tissues. In conclusion, we propose that MS4A12 contributes to SOCE through complex formation with Orai1, but does not cooperate with STIM1. Additionally, we discovered that MS4A12 is expressed in the apical membrane of the colonic epithelium and that its expression is decreased with cancer progression.

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

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.

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

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.

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

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.

Comprehensive Immuno-Molecular Profiles for Liposarcoma: Roles of Programmed Death Ligand 1, Microsatellite Instability, and PIK3CA.

BACKGROUND: Developing personalized strategies for cancer has shown good efficacies. METHODS: We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and PIK3CA. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and PIK3CA mutation/amplification using pyrosequencing and fluorescence in situ hybridization. RESULTS: Seventeen (23%) cases were TIL+ (≥1 + expression) and associated with longer 5-year overall survival than those with TIL- tumors (84.4 vs. 60.8%, p = 0.007). Six (35.3%) PD-L1+ tumors were detected only in TIL+ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. PIK3CA mutation was detected in 7 (9.5%) [exon 9 (n = 4) and exon 20 (n = 3)] and only 1 Q546K mutation was a PD-L1+ tumor. PIK3CA copy number gain was detected in 18 (24.4%) and was associated with TIL+ tumors (p = 0.045). CONCLUSIONS: Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine.

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

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.

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

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.

Nomogram for prediction of pathologic complete remission using biomarker expression and endoscopic finding after preoperative chemoradiotherapy in rectal cancer.

OBJECTIVE: The aim of this study is to develop a nomogram for prediction of pathologic complete remission (pCR) after preoperative chemoradiotherapy (CRT) for rectal cancer. METHODS: mRNA expression levels of seven molecular markers [p53, p21, Ki-67, vascular endothelial growth factor (VEGF), CD133, CD24, CD44] were measured by reverse transcriptase polymerase chain reaction (RT-PCR) in 120 rectal cancers. Endoscopic findings of clinical complete remission (cCR) and biologic variables were used to construct nomogram in the training group (n=80), which was validated in the validation group (n=40). RESULTS: mRNA expression levels of four markers (p53, p21, Ki67, CD133) correlated with pCR (24/80, 30.0%) in the training group. Low expression of p53 and/or high expression of p21, Ki67 and CD133 showed greater pCR rate. pCR was shown in 18 (69.2%) of 26 cases showing endoscopic cCR in the training group. Higher pCR rate was demonstrated in lower tumor location than middle tumor (19/49, 38.8% vs. 5/31, 16.1%). A nomogram for prediction of pCR was developed from the multivariate prediction model using these six variables, which showed good discrimination ability in the training group [area under the curve (AUC)=0.945] and validation group (AUC=0.922). The calibration plot showed good agreement between actual and predicted pCR in both patient groups. CONCLUSIONS: Nomogram for assessment of pCR can be useful for making treatment decisions after CRT according to predicted responses.

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

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.

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

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.

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 cT1-2N1 or cT3N0 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 cT1-2N1 or cT3N0) 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.