Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients.

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

Risk factors for the failure of endoscopic balloon dilation to manage anastomotic stricture from colorectal surgery: retrospective cohort study.

BACKGROUND: An anastomotic stricture after colorectal surgery is principally managed by endoscopic balloon dilation (EBD). Although this intervention is effective, however, subsequent procedures or surgical interventions are often required. This study aimed to assess the long-term outcomes of EBD for anastomotic stricture arising from colorectal cancer surgery. MATERIALS AND METHODS: We analyzed 173 patients who received curative surgery for colorectal cancer at our hospital between January 2000 and December 2022 and had undergone EBD to manage anastomotic stricture. The medical records of these cases were retrospectively reviewed to assess the outcomes and risk factors for restenosis and permanent stoma. RESULTS: Of the 173 study patients, 41 (23.7%) presented with restenosis with a median time to recurrence of 49 [37-150] days. The restenosis group was significantly younger (55.6 years versus 60.8 years), with a more prominent rectal location (80.5% versus 57.6%), a higher incidence of hand-sewn anastomosis (24.4% versus 5.3%), and a higher percentage of neoadjuvant radiotherapy (34.1% versus 5.3%, P < 0.001). Multivariable analysis indicated neoadjuvant radiotherapy (adjusted HR 2.48; 95% CI 1.03-5.95) and cerebral vascular disease (adjusted HR 6.97; 95% CI 2.15-22.54) as independent prognostic factors for restenosis. Fourteen patients (8.1%) required a permanent stoma due to treatment failure. All cases needing a permanent stoma were male (14 patients, 100%, P = 0.007) and this group had a higher rate of neoadjuvant radiotherapy, adjuvant chemotherapy, and hand-sewn anastomosis. CONCLUSION: Patients receiving neoadjuvant radiotherapy are most prone to restenosis after an EBD intervention to manage an anastomotic stricture. Neoadjuvant radiotherapy is also a strong risk factor for requiring a permanent stomas due to treatment failure.

Influence of additional prophylactic oral antibiotics during mechanical bowel preparation on surgical site infection in patients receiving colorectal surgery.

BACKGROUND: Prophylactic antibiotics (PAs) are standard for preventing surgical site infections (SSIs) post-colorectal surgery. This study aims to compare the effect of additional empiric oral antibiotics (OAs) alongside routine PAs to identify SSI risk factors. METHODS: A retrospective observatory analysis was conducted from January 2019 to December 2022 at Asan Medical Center, Seoul, Korea. The cohort was divided into two groups: PA given 1 h before surgery and discontinued within 24 h, and OA administered empiric OAs during mechanical bowel preparation in addition to PA. RESULTS: From a total of 6736 patients, 3482 were in the PA group and 3254 in the OA group. SSI incidence showed no significant intergroup difference (p = 0.374) even after propensity score matching (p = 0.338). The multivariable analysis revealed male sex [odds ratio (OR): 2.153, 95% confidence interval (CI): 1.626-2.852, and p = 0.001], open surgery (OR: 3.335, 95% CI: 2.456-4.528, and p = 0.001), dirty wound (OR: 2.171, 95% CI: 1.256-3.754, and p = 0.006), and an operation time of more than 145 min (OR: 2.110, 95% CI: 1.324-3.365, and p = 0.002) as SSI risk factors. In rectal surgery subgroup, OA demonstrated a protective effect against SSI (OR: 0.613, 95% CI: 0.408-0.922, and p = 0.019) and in laparoscopic approach (OR: 0.626, 95% CI: 0.412-0.952, and p = 0.028). CONCLUSIONS: OA did not affect SSI incidence in colorectal surgeries. Male sex, open surgery, dirty wounds, and longer operation time were risk factors for SSI. However, for rectal and laparoscopic surgery, OA was a protective factor for SSI.

Optimal surgical management of duodenal fistula in Crohn's disease: a Korean multicenter cohort study.

PURPOSE: Duodenal fistula in Crohn's disease (CDF) is a rare condition with an unclear optimal surgical management approach. We reviewed a Korean multicenter cohort of CDF surgery cases and assessed their perioperative outcomes to evaluate the effectiveness of the surgical interventions. METHODS: The medical records of patients who underwent CD surgery between January 2006 and December 2021 from three tertiary medical centers were retrospectively reviewed. Only CDF cases were included in this study. The demographic and preoperative characteristics, perioperative details, and postoperative outcomes were analyzed. RESULTS: Among the initial population of 2149 patients who underwent surgery for CD, 23 cases (1.1%) had a CDF operation. Fourteen of these patients (60.9%) had a history of previous abdominal surgery, and 7 had duodenal fistula at the previous anastomosis site. All duodenal fistulas were excised and primarily repaired via a resection of the originating adjacent bowel. Additional procedures such as gastrojejunostomy, pyloric exclusion, or T-tube insertion were performed in 8 patients (34.8%). Eleven patients (47.8%) experienced postoperative complications including for anastomosis leakages. Fistula recurrence was noted in 3 patients (13%) of which one patient required a re-operation. Biologics administration was associated with fewer adverse events by multivariable analysis (P = 0.026, odds ratio = 0.081). CONCLUSION: Optimal perioperative conditioning of patients receiving a primary repair of a fistula and resection of the original diseased bowel can successfully cure CDF. Along with primary repair of the duodenum, other complementary additional procedures should be considered for better postoperative outcomes.

Clinical Implication of Perineural and Lymphovascular Invasion in Rectal Cancer Patients Who Underwent Surgery After Preoperative Chemoradiotherapy.

BACKGROUND: Lymphovascular and perineural invasion are well-known negative prognostic indicators in rectal cancer, but previous studies on their significance are not consistent. OBJECTIVE: This study assessed the prognostic value of lymphovascular and perineural invasion in rectal cancer patients who received preoperative chemoradiotherapy followed by curative resection. DESIGN: This is a retrospective analysis. SETTING: This study was performed at a tertiary cancer center. PATIENTS: Rectal cancer patients who underwent curative resection after preoperative chemoradiotherapy between January 2000 and December 2010. MAIN OUTCOME MEASURES: The primary outcomes were disease-free survival and overall survival. The survival rates were estimated using Kaplan-Meier analysis, and group comparisons were conducted using a log-rank test. RESULTS: Of the 1156 included patients, 109 (9.4%) presented with lymphovascular invasion and 137 (11.9%) presented with perineural invasion. Lymphovascular and perineural invasion were associated with T and N downstaging after preoperative chemoradiotherapy ( p < 0.001). In the ypN0 patients, the 5-year disease-free survival rates were 70.8% and 78.5% ( p = 0.150) for the lymphovascular invasion and absent groups, respectively. In the perineural invasion group, the 5-year disease-free survival rate was 59.0% compared to 80.2% in the absent group ( p = 0.001). Among the ypN+ patients, the 5-year disease-free survival rates were 36.9% and 44.4% for the lymphovascular invasion and absent groups, respectively ( p = 0.211). The perineural invasion group had a poorer 5-year disease-free survival rate compared to the absent group (29.7% vs 46.7%; p = 0.011). By multivariable analyses, perineural invasion correlated with a poor disease-free survival (HR 1.412, 95% CI 1.082-1.843; p = 0.011) and also in ypN0 subgroup analysis (HR 1.717, 95% CI 1.093-2.697; p = 0.019). LIMITATIONS: This study was a retrospective study conducted at a single center. CONCLUSIONS: Perineural invasion is a reliable independent predictor of recurrence in rectal cancer patients treated with preoperative chemoradiotherapy. Patients with perineural invasion should be considered for closer surveillance even with ypN0 status. See Video Abstract at http://links.lww.com/DCR/B833 .IMPLICACIÓN CLÍNICA DE LA INVASIÓN PERINEURAL Y LINFOVASCULAR EN PACIENTES CON CÁNCER DE RECTO SOMETIDOS A CIRUGÍA DESPUÉS DE QUIMIORRADIOTERAPIA PREOPERATORIA. ANTECEDENTES: La invasión linfovascular y perineural en cancer de recto, son indicadores pronósticos negativos bien conocidos, pero estudios previos sobre su significancia, no son consistentes. OBJETIVO: El estudio evaluó el valor pronóstico de la invasión linfovascular y perineural en pacientes con cáncer de recto sometidos a quimiorradioterapia preoperatoria seguida de resección curativa. DISEO: Es un análisis retrospectivo. ENTORNO CLINICO: El estudio se realizó en un centro oncológico terciario. PACIENTES: Pacientes con cáncer de recto sometidos a resección curativa después de quimiorradioterapia preoperatoria entre enero de 2000 y diciembre de 2010. PRINCIPALES MEDIDAS DE VALORACION: Los resultados primarios fueron la supervivencia libre de enfermedad y la supervivencia general. Las tasas de supervivencia se estimaron mediante el análisis de Kaplan-Meier y las comparaciones de grupos se realizaron mediante una prueba de rango logarítmico. RESULTADOS: De los 1156 pacientes incluidos, 109 (9,4%) presentaron invasión linfovascular y 137 (11,9%) invasión perineural. La invasión linfovascular y perineural se asoció con reducción del estadio de T y N después de la quimiorradioterapia preoperatoria ( p < 0,001). En los pacientes ypN0, las tasas de supervivencia libre de enfermedad a 5 años fueron del 70,8% y el 78,5% ( p = 0,150) para los grupos con y sin invasión linfovascular, respectivamente. En el grupo de invasión perineural, la tasa de supervivencia libre de enfermedad a 5 años fue del 59,0%, en comparación con el 80,2% en el grupo ausente ( p = 0,001). Entre los pacientes ypN +, las tasas de supervivencia sin enfermedad a 5 años fueron del 36,9% y 44,4% para los grupos con y sin invasión linfovascular, respectivamente ( p = 0,211). El grupo de invasión perineural mostró una tasa de supervivencia libre de enfermedad a 5 años menor, en comparación con el grupo ausente (29,7% versus 46,7%, p = 0,011). Mediante análisis multivariable, la invasión perineural se correlacionó con una pobre tasa de supervivencia de enfermedad (índice de riesgo 1,412; intervalo de confianza del 95%: 1,082-1,843; p = 0,011) y también en el análisis de subgrupos ypN0 (índice de riesgo 1,717; intervalo de confianza del 95%: 1,093-2,697; p = 0,019). LIMITACIONES: Estudio retrospectivo realizado en un solo centro. CONCLUSIONES: La invasión perineural es un predictor independiente y confiable de recurrencia en pacientes con cáncer de recto tratados con quimiorradioterapia preoperatoria. Los pacientes con invasión perineural deben considerarse para una vigilancia más estrecha incluso con estadio ypN0. Consulte Video Resumen en http://links.lww.com/DCR/B833 . (Traducción-Dr. Fidel Ruiz Healy ).

Involvement of tissue changes induced by neoadjuvant treatment in total mesorectal excision (TME): novel suggestions for determining TME quality.

BACKGROUND: Few studies to date have investigated morphological changes after neoadjuvant treatment (NAT) and their implications in total mesorectal excision (TME). This study was primarily designed to evaluate whether tissue changes associated with NAT affected the quality of TME and additionally to suggest a more objective method evaluating TME quality. METHODS: This study enrolled 1322 consecutive patients who underwent curative robot-assisted surgery for rectal cancer. Patients who did and did not receive NAT were subjected to propensity-score matching, yielding 402 patients in each group. RESULTS: NAT independently reduced complete achievement of TME [odds ratio (OR) = 2.056, p = 0.017]. Intraoperative evaluation identified seven tissue changes significantly associated with NAT, including tumor perforation, mucin pool, necrosis, fibrosis, fat degeneration, and rectal or perirectal edema NAT (p < 0.001-0.05). Tumor perforation (OR = 5.299, p = 0.001) and mucin pool (OR = 14.053, p = 0.002) were independently associated with inappropriate (near-complete + incomplete) TME. Complete TME resulted in significantly reduced local recurrence (4.3% vs 15.3%, p = 0.003) and increased 5-year DFS rate (80.6% vs 67.6%, p = 0.047) compared with inappropriate one. By contrast, two tiers of complete and near-complete TMEs vs incomplete TME did not. Notably, among patients with complete TME, those who received NAT had a lower 5-year DFS than those who did not (77.8% vs 83.3%, p = 0.048). CONCLUSIONS: NAT-associated tissue changes, somewhat interrupting complete TME, may provide unsolved clue to the relative inability of NAT to improve overall survival. The conventional three-tier grading of TME seems to be simplified into two tiers as complete and inappropriate.

Comparative survival risks in patients undergoing abdominoperineal resection and sphincter-saving operation for rectal cancer: a 10-year cohort analysis using propensity score matching.

PURPOSE: Abdominoperineal resection (APR) has been considered to have a higher risk of local recurrence and poorer survival outcome than sphincter-saving operation (SSO) in patients with rectal cancer. This study compared long-term oncologic outcomes and prognostic parameters in propensity score-matched patients who underwent APR and SSO. METHODS: This study analyzed 958 consecutive patients with lower rectal cancer who underwent preoperative chemoradiotherapy followed by APR or SSO between 2005 and 2015. Propensity score matching analysis was performed to adjust baseline characteristics, including clinical stage, tumor distance from the anal verge, and tumor size. RESULTS: In the entire cohort, the APR group had larger and lower tumors and showed significantly shorter 5-year disease-free survival (DFS) than the SSO group (64.5% vs. 75.8%, p = 0.01). After propensity score matching, there were no significant between-group differences in local (9.5% vs. 8.0%, p = 0.59) and systemic (27.9% vs. 23.4%, p = 0.3) recurrence rates, and 5-year DFS (67.5% vs. 69.9%, p = 0.49) and overall survival (80.8% vs. 82.9%, p = 0.65) rates. A lower number of lymph nodes retrieved was independently associated with recurrence and survival outcomes in the APR group, whereas poorly differentiated histology was an independent associated parameter in the SSO group. Advanced stage and perineural invasion were identified as independent prognostic parameters in both groups. CONCLUSIONS: This study indicated that the long-term oncologic outcomes of APR were comparable to those of SSO. Because prognostic parameters associated with oncologic outcomes differed between the respective procedures, correctable parameters could be ameliorated through complete total mesorectal excision and personalized systemic treatment.

Re-evaluation of possible vulnerable sites in the lateral pelvic cavity to local recurrence during robot-assisted total mesorectal excision.

BACKGROUND: Despite mechanical and technical improvements in laparoscopic and robot-assisted (LAR) rectal cancer procedures, the absence of prognostic disparities among various approaches cannot improve the quality of TME. The present study re-evaluated robot-assisted total mesorectal excision (TME) procedures to determine whether these procedures may reveal technical faults that may increase the rate of local recurrence (LR). METHODS: This study enrolled 886 consecutive patients with rectal cancer, who underwent curative robot-assisted LAR at Asan Medical Center (Seoul, Korea) between July 2010 and August 2017 (the first vs second period; n = 399 vs 487). The quality of TME and lateral pelvic mesorectal excision (LPME) were analyzed, as were LR rates and survival outcomes. RESULTS: Complete TME and LPME were achieved in 89.2% and 80.1% of these patients, respectively, with ≤ 1% having incomplete TME excluding intramesorectal excision. LR rates were 13.5 and 14.5 times higher in patients with incomplete TME and LPME, respectively, than in patients with complete TME and LPME (14.8% vs 1.1% and 8.7% vs 0.6%; p < 0.001 each by univariate analyses). Multivariate analyses showed that defective LPME was independently associated with incomplete TME and vice versa (p < 0.001). Cox regression analysis showed that defective LPME was independently correlated with reduced 5-year disease-free survival rate (hazard ratio, 1.563; 95% confidence interval, 1.052-2.323; p = 0.027). CONCLUSIONS: LR in rectal cancer patients was largely due to incomplete LPME, which was significantly associated with incomplete TME. Complete LPME may enhance the likelihood of complete TME, reducing LR rates.

The Clinical Significance of Anastomotic Ulcers After Ileocolic Resection to Predict Postoperative Recurrence of Crohn's Disease.

BACKGROUND: The Rutgeerts score is used to predict postoperative recurrence in CD patients after ileocolic resection and is primarily based on endoscopic findings at the neoterminal ileum. However, the optimal assessment of anastomotic ulcers (AUs) remains subject to debate. AIMS: We aimed to investigate the association between anastomotic ulcers (AUs) and endoscopic recurrence in postoperative Crohn's disease (CD) patients. METHODS: This single-center retrospective study, conducted between 2000 and 2016, evaluated postoperative CD patients with endoscopic remission at the first ileocolonoscopy within 1 year after ileocolic resection and those who underwent subsequent ileocolonoscopic follow-up. The study outcome was the clinical significance of AUs in predicting endoscopic recurrence. RESULTS: Among 116 patients who were in endoscopic remission defined as the RS of i0 to i1 at the index postoperative ileocolonoscopy, 84.5% (98/116) underwent subsequent ileocolonoscopies. During the median 30.0 months (interquartile range, 21.3-53.3) of follow-up after the first ileocolonoscopy, 56.1% (55/98) of patients showed endoscopic recurrence. Furthermore, 65.8% (48/73) with AUs and 75.5% (40/53) with major AUs, defined as either an ulcer occupying ≥ 1/4 of the circumference, ≥ 3 ulcers confined to anastomotic ring, or any ulcers extending to the ileocolonic mucosa, showed endoscopic recurrence. On multivariable analysis, AUs (adjusted hazard ratio [aHR], 4.33; 95% confidence interval [CI], 1.87-10.0; P < 0.001) and major AUs (aHR, 3.64; 95% CI, 1.95-79; P < 0.001) were associated with endoscopic recurrence. CONCLUSIONS: AUs are associated with a significantly high risk of endoscopic recurrence in postoperative CD patients who are in endoscopic remission.

Characteristics and Prognosis of Colorectal Cancer after Liver or Kidney Transplantation.

BACKGROUND: The purpose of this study was to evaluate the characteristics and prognosis of de novo CRC patients who underwent liver or kidney transplantation. METHODS: We retrospectively reviewed the medical records of 66 de novo CRC patients selected from 8,734 liver transplant (LT) or kidney transplant (KT) recipients. We analyzed characteristics and survival outcomes of de novo CRC patients and sporadic CRC patients who underwent radical surgery with stage I-III in Asan Medical Center between 2005 and 2016. Survival outcomes were analyzed via the 1:4 matching method. RESULTS: The standard incidence ratio (SIR) of de novo CRC in KT recipients is 1.67 in men and 2.54 in women. That in LT recipients is 3.10 in men and 2.25 in women. Compared with sporadic CRC patients, de novo CRC patients had more colon cancer than rectal cancer (p=0.041). In 9 patients (13.6%), CRC was diagnosed within one year after transplantation, 21 patients (31.8%) were diagnosed between 1-5 years, and the remaining 36 patients (54.6%) were diagnosed thereafter. There were no significant differences in recurrence-free survival and overall survival between the two groups (p=0.211 and p=0.324, respectively). CONCLUSIONS: The risk of developing de novo CRC in transplant recipients was higher than in the general population. The survival outcome of de novo CRC was no different compared with the sporadic CRC. Therefore, regular surveillance is essential for timely diagnosis and treatment for transplantation patients. A large prospective study for an intense CRC surveillance program in transplantation patients is needed.

Oncological and anorectal functional outcomes of robot-assisted intersphincteric resection in lower rectal cancer, particularly the extent of sphincter resection and sphincter saving.

BACKGROUND: Few investigations to date assessing the effectiveness of robot-assisted intersphincteric resection (ISR) have included sufficient patients and follow-up period. This study assessed the utility and safety of robot-assisted ISR by comparing groups of patients who underwent low anterior resection (LAR) with or without ISR and ISR extent. METHODS: This study enrolled 897 patients who underwent curative LAR between 2010 and 2017. Patients were divided into those who did (ISR+) and did not (ISR-) undergo ISR, with the former group subdivided by ISR extent (partial, subtotal, and total). Tumor recurrence and survival were compared in the two groups by one-to-one nearest neighbor matching (218 patients each). RESULTS: Robot-assisted ISR was performed via an entirely transabdominal approach in 93% of patients who underwent LAR. The rate of circumferential margin positivity was ≤ 2% in all patients and did not differ in the ISR- and ISR+ groups or in the three ISR+ subgroups. Mean fecal incontinence score and manometric values deteriorated significantly during postoperative until 12-24 months (p < 0.05 to < 0.001), but recovered subsequently. The 5-year cumulative rates of local recurrence in the ISR+ and ISR- groups were 2.5% and 2.9%, respectively (p = 0.731). The 5-year cumulative rates of overall (86.7% vs. 84.2%, p = 0.899) and disease-free (80.7% vs. 78.5%, p = 0.934) survival did not differ significantly in the ISR+ and ISR- groups. CONCLUSIONS: Because ISR involves resection of low-lying tumors and complex pelvic dissection, robot-assisted ISR via a mostly transabdominal procedure may be technically more efficient, providing lasting anorectal function and good oncologic outcomes.

Incidence and Outcomes of Perianal Disease in an Asian Population with Crohn's Disease: A Nationwide Population-Based Study.

BACKGROUND: Little is known about the natural history of perianal fistulas in Asian populations with Crohn's disease (CD). AIMS: We investigated the incidence and outcomes of perianal CD (pCD) in Korean CD patients. METHODS: A nationwide population-based cohort of 6265 CD patients diagnosed in 2010-2014 was analyzed to investigate the incidence and outcomes of pCD. The results were validated in a hospital-based cohort of 2923 CD patients diagnosed in 1981-2015. Factors associated with pCD development were analyzed. The incidence and outcomes of pCD were compared between the prebiologic and biologic eras. RESULTS: pCD occurred in 39.2% of the population-based cohort and 56.1% of the hospital-based cohort during the median follow-up of 4.2 and 8.5 years, respectively. The cumulative incidence of pCD was 40.0% at 5 years after CD diagnosis in the population-based cohort and 62.5% at 20 years in the hospital-based cohort. In multivariate analysis, pCD development was positively associated with male sex, younger age and colonic involvement at diagnosis, early diagnosis, and CD diagnosis in the prebiologic era. The cumulative probability of proctectomy at 10, 20, and 30 years after pCD diagnosis was 2.9%, 12.2%, and 16.2%, respectively. The cumulative incidence of pCD occurring after CD diagnosis and the cumulative probability of proctectomy were significantly lower in the biologic era than in the prebiologic era (p < 0.001 and p = 0.03, respectively). CONCLUSIONS: Compared with Western patients with CD, Korean patients show a high incidence of pCD but have a low probability of proctectomy, suggesting the favorable course of pCD.

Local excision in mid-to-low rectal cancer patients who revealed clinically total or near-total regression after preoperative chemoradiotherapy; a proposed trial.

BACKGROUND: Preoperative chemoradiotherapy (pre-CRT) followed by total mesorectal excision (TME) is currently a standard therapy for locally advanced mid-to-low rectal cancer. Less aggressive, organ-preserving option such as local excision (LE) or watchful wait can alternatively be used for patients who respond well to pre-CRT. High-resolution rectal magnetic resonance imaging (MRI) is one of the most useful methods to assess pre-CRT response, and the MERCURY group has shown that the MR tumor regression grade (mrTRG) correlated with the pathologic TRG. The aim of this study is to compare postoperative complication and oncologic outcomes between LE and TME in mid-to-low rectal cancer patients whose tumors are mrTRG grade 1 (radiological complete remission) or 2 (predominant fibrosis; near-complete remission) after pre-CRT. METHODS: A prospective, double-arm, randomized, open-labeled, single center, clinical trial will be conducted in patients with mid-to-low rectal cancer whose tumors are mrTRG 1/2 after pre-CRT at the Asan Medical Center, Seoul, Korea, after approval from the Institution Review Board. Patient medical records will be de-identified using a serial number to protect personal information. Inclusion criteria will include rectal adenocarcinoma with an inferior border < 8 cm from the anal verge, mrTRG 1/2, age > 20, and provision of informed consent. Postoperative complications will be assessed by Clavien-Dindo Classification Grade. Oncologic and functional outcomes will be collected and risk factors related to these outcomes will be investigated. DISCUSSION: We believed that the rate of postoperative complication of LE will be comparable to that of TME in mid-to-low advanced rectal cancer patients with a favorable response after pre-CRT. TRIAL REGISTRATION: KCT0002579 ( https://cris.nih.go.kr ) Dec-2017.

Local excision for ypT2 rectal cancer following preoperative chemoradiation therapy: it should not be justified.

PURPOSE: Among individuals who respond well to preoperative chemoradiation therapy (CRT) for ypT0-1, local excision (LE) could provide acceptable oncological outcomes. However, in ypT2 cases, the oncological safety of LE has not been determined. This study aimed to compare oncological outcomes between LE and total mesorectal excision of ypT2-stage rectal cancer after chemoradiation therapy and investigate the oncological safety of LE in these patients. METHODS: We included 351 patients who exhibited ypT2-stage rectal cancer after CRT followed by LE (n = 16 [5%]) or total mesorectal excision (TME) (n = 335 [95%]) after preoperative CRT between January 2007 and December 2013. After propensity matching, oncological outcomes between LE group and TME group were compared. RESULTS: The median follow-up period was 57 months (range, 12-113 months). In the LE group, local recurrence occurred more frequently (18 vs. 4%; p = 0.034) but not distant metastases (12 vs. 11%; p = 0.690). The 5-year local recurrence-free (76 vs. 96%; p = 0.006), disease-free (64 vs. 84%; p = 0.075), and overall survival (79 vs. 93%; p = 0.045) rates of the LE group were significantly lower than those of the TME group. After propensity matching, 5-year local recurrence-free survival of the LE group was significantly lower than that of the TME group (76 vs. 97%, p = 0.029). CONCLUSION: The high local failure rate and poor oncological outcomes for ypT2-stage rectal cancer patients who undergo CRT followed by LE cannot be justified as an indication for LE. Salvage surgery should be recommended in these patients.

Prognostic and Oncologic Significance of Perineural Invasion in Sporadic Colorectal Cancer.

BACKGROUND: The presence of perineural invasion (PNI) in colorectal cancer (CRC) indicates a more aggressive phenotype, resulting in a poor prognosis. The aims of this study were to evaluate the oncologic outcome of PNI+ tumors and to investigate whether PNI status affects patient survival. METHODS: The study retrospectively enrolled 3807 patients from a single institution who underwent surgery for colorectal adenocarcinoma between January 2006 and December 2010. The patients were classified into two groups based on PNI status: PNI+ and PNI-. RESULTS: The PNI+ group included 565 patients (14.8 %) and had significantly more involved circumferential resection margins (p = 0.001) and a more advanced TNM stage (p = 0.001) than the PNI- group. Compared with the PNI- group, the PNI+ group had worse 5-year overall survival (65 vs. 88 %; p = 0.001) and 5-year disease-free survival (63 vs. 85 %; p = 0.001). Among PNI+ patients with stage IIA disease, those who received adjuvant therapy had significantly greater 5-year overall survival than those who did not (89.3 vs. 50.8 %; p = 0.001). In multivariate analyses, PNI+ was an independent negative prognostic factor for 5-year overall survival (hazard ratio [HR] 1.518, 95 % confidence interval [CI] 1.175-1.961; p = 0.001) and 5-year disease-free survival (HR 1.495, 95 % CI 1.237-1.806; p = 0.001). CONCLUSIONS: PNI positivity is an independent predictor of aggressive behavior and unfavorable prognosis in CRC. Further evaluation is needed to confirm the impact of PNI status on survival in stage IIA CRC.

Interpretative Guidelines and Possible Indications for Indocyanine Green Fluorescence Imaging in Robot-Assisted Sphincter-Saving Operations.

BACKGROUND: Since the introduction of indocyanine green angiography more than 25 years ago, few studies have presented interpretative guidelines for indocyanine green fluorescent imaging. OBJECTIVE: We aimed to provide interpretative guidelines for indocyanine green fluorescent imaging through quantitative analysis and to suggest possible indications for indocyanine green fluorescent imaging during robot-assisted sphincter-saving operations. DESIGN: This is a retrospective observational study. SETTINGS: This study was conducted at a single center. PATIENTS: A cohort of 657 patients with rectal cancer who consecutively underwent curative robot-assisted sphincter-saving operations was enrolled between 2010 and 2016, including 310 patients with indocyanine green imaging (indocyanine green fluorescent imaging+ group) and 347 patients without indocyanine green imaging (indocyanine green fluorescent imaging- group). MAIN OUTCOME MEASURES: We tried to quantitatively define the indocyanine green fluorescent imaging findings based on perfusion (mesocolic and colic) time and perfusion intensity (5 grades) to provide probable indications. RESULTS: The anastomotic leakage rate was significantly lower in the indocyanine green fluorescent imaging+ group than in the indocyanine green fluorescent imaging- group (0.6% vs 5.2%) (OR, 0.123; 95% CI, 0.028-0.544; p = 0.006). Anastomotic stricture was closely correlated with anastomotic leakage (p = 0.002) and a short descending mesocolon (p = 0.003). Delayed perfusion (>60 s) and low perfusion intensity (1-2) were more frequently detected in patients with anastomotic stricture and marginal artery defects than in those without these factors (p ≤ 0.001). In addition, perfusion times greater than the mean were more frequently observed in patients aged >58 years, whereas low perfusion intensity was seen more in patients with short descending mesocolon and high ASA classes (≥3). LIMITATIONS: The 300 patients in the indocyanine green fluorescent imaging- group underwent operations 3 years before indocyanine green fluorescent imaging. CONCLUSIONS: Quantitative analysis of indocyanine green fluorescent imaging may help prevent anastomotic complications during robot-assisted sphincter-saving operations, and may be of particular value in high-class ASA patients, older patients, and patients with a short descending mesocolon.

Robot-assisted intersphincteric resection facilitates an efficient sphincter-saving in patients with low rectal cancer.

PURPOSE: Few investigations of robot-assisted intersphincteric resection (ISR) are presently available to support this procedure as a safe and efficient procedure. We aimed to evaluate the utility of robot-assisted ISR by comparison between ISR and abdominoperineal resection (APR) using both robot-assisted and open approaches. METHODS: The 558 patients with lower rectal cancer (LRC) who underwent curative operation was enrolled between July 2010 and June 2015 to perform either by robot-assisted (ISR vs. APR = 310 vs. 34) or open approaches (144 vs. 70). Perioperative and functional outcomes including urogenital and anorectal dysfunctions were measured. Recurrence and survival were examined in 216 patients in which >3 years had elapsed after the operation. RESULTS: The robot-assisted approach was the most significant parameter to determine ISR achievement among potent parameters (OR = 3.467, 95% CI = 2.095-5.738, p < 0.001). Early surgical complications occurred more frequently in the open ISR group (16 vs. 7.7%, p = 0.01). The voiding and male sexual dysfunctions were significantly more frequent in the open ISR (p < 0.05). The fecal incontinence and lifestyle alteration score was greater in the open ISR than in the robot-assisted ISR at 12 and 24 months, respectively (p < 0.05). However, the 3-year cumulative rates of local recurrence and survival did not differ between the two groups. CONCLUSIONS: The current procedure of robot-assisted ISR replaced a significant portion of APR to achieve successful SSO via mostly transabdominal approach and double-stapled anastomosis. The robot-assisted ISR with minimal invasiveness might be a help to reduce anorectal and urogenital dysfunctions.

Factors affecting the postoperative morbidity and survival of patients with liver cirrhosis following colorectal cancer surgery.

PURPOSE: Data are lacking on the appropriate risk stratification of patients undergoing surgery for colorectal cancer (CRC). This study aimed to evaluate the predictive factors for perioperative morbidity and oncological outcomes in CRC patients with liver cirrhosis (LC). METHODS: A retrospective analysis of prospectively collected data was conducted. A total of 161 LC patients who underwent surgery for CRC were identified between January 2001 and December 2010. RESULTS: The mean patient age was 60 ± 10 years, and the median follow-up period was 54.0 months (range 0.5-170.0). The proportions of patients with Child-Pugh classifications for LC were as follows: A (n = 118; 73.3%), B (n = 39; 24.2%), and C (n = 4; 2.5%). The median model for end-stage liver disease (MELD) score was 8 (range 6-21). The postoperative morbidity rate was 37.3% (60/161). Hyperbilirubinemia (p = 0.002), prothrombin time (PT) prolongation (p = 0.020), and intraoperative transfusion (p = 0.003) were the significant factors for postoperative morbidity in multivariate analysis. The postoperative mortality rate was 3.1% (5/161), and the 5-year cancer-specific and 5-year overall survival rates were 86.1 and 59.9%, respectively. The significant clinical risk factors by multivariate analysis that influenced overall survival were the TNM stage of CRC (p = 0.035), MELD score (>8 points) (p < 0.001), and the coexistence of hepatocellular carcinoma (HCC) (p = 0.012). CONCLUSIONS: Hyperbilirubinemia, PT prolongation, and intraoperative transfusion are significant risk factors for postoperative morbidity in LC patients who undergo surgery for CRC. Additionally, not only advanced TNM stage but also a high MELD score and the coexistence of HCC are associated with poor overall survival in CRC patients with LC.

Identification of Recurrence-Predictive Indicators in Stage I Colorectal Cancer.

BACKGROUND: Patients with stage I colorectal cancer (CRC) rarely experience recurrences; therefore, few risk factors for recurrence are known. This study was designed to evaluate oncologic outcomes of patients with stage I CRC and to identify risk factors for recurrence after curative surgery. METHODS: A retrospective cohort of 860 patients from a single institution who underwent curative surgery for stage I CRC between July 1995 and June 2010 was enrolled. Patients who were diagnosed with hereditary, synchronous, or metachronous cancer and those who received preoperative chemoradiotherapy were excluded. Patients from whom fewer than 12 lymph nodes were retrieved were also excluded. RESULTS: The 860 patients included 402 (46.7%) with colon tumors and 458 (53.3%) with rectal tumors. Thirty-five patients (4.1%) experienced recurrences; local and systemic recurrence rates were 1.1 and 3.0%, respectively. The 5-year overall survival and recurrence-free survival (RFS) rates were 93.5 ± 0.8% and 95.7 ± 0.8%, respectively. Multivariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) concentration ≥6 ng/mL (hazard ratio [HR] 3.354, 95% confidence interval [CI] 1.373-8.195, p = 0.008) and lymphovascular invasion (LVI) (HR 2.676, 95% CI 1.097-6.531, p = 0.031) were independent risk factors for RFS. CONCLUSIONS: The overall recurrence rate among patients with stage I CRC after curative surgery was 4.1%. Elevated serum CEA and LVI were significantly associated with recurrence. Large-scale, multicenter studies are needed to confirm the prognostic value of these risk factors.

Palliative surgery for colorectal cancer with peritoneal metastasis: a propensity-score matching analysis.

PURPOSE: Peritoneal metastasis (PM) in patients with colorectal cancer (CRC) is associated with poor prognosis. We conducted this study to assess whether palliative resection (PR) of the primary tumor improved the overall survival (OS) of patients with PM-CRC. METHODS: We analyzed retrospectively, data collected prospectively from patients with CRC. PM was categorized into three subgroups according to the Japanese classification of PM. A propensity-score model was used to compare the outcomes of patients who underwent PR (PR group) and those who did not [non-resection (NR) group]. RESULTS: Among 1909 patients with metastatic CRC, 309 (16 %) had only peritoneal metastases and 255 of these patients who underwent palliative surgery (R2) were the subjects of our analysis: 161 in the PR group and 94 in the NR group. Median OS was significantly longer in the PR group than in the NR group (23 vs. 11 months, P < 0.001). Patients in the PR group had less extensive PM and a higher rate of receiving palliative chemotherapy than those in the NR group (P < 0.001). In a Cox multivariate analysis of 69 propensity-score matched pairs, PR resulted in significantly longer OS than NR (hazard ratio 0.496, 95 % confidence interval 0.268-0.919, P = 0.025). CONCLUSIONS: Our results show that PR resulted in better OS than NR for patients with PM-CRC, when their overall condition permitted a more aggressive approach.