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.

Novel temperature-responsive hydrogel injected to the incision site for postoperative pain relief in laparoscopic abdominal surgery: a single-blind, randomized, pivotal clinical trial.

BACKGROUND: A temperature-responsive hydrogel (PF-72; TGel Bio, Inc., Ltd, Seoul, Korea), developed as a sustained drug delivery device, can be mixed with ropivacaine to reduce pain in the incision area. The hydrogel is soluble at low temperatures (2-8 °C) and is converted into a gel at high temperatures (> 30 °C). We aimed to evaluate whether the administration of ropivacaine using PF-72 at incision sites reduces pain until 72 h postoperatively in patients undergoing laparoscopic stomach or colorectal surgery. METHODS: Patients were randomly assigned to the control group (0.75% ropivacaine) or PF-72 group (PF-72 mixed with 0.75% ropivacaine). Before surgical incision closure, 0.75% ropivacaine or PF-72 mixed with 0.75% ropivacaine was injected into the subcutaneous fat and muscle of all incisions. Postoperative pain was evaluated by the Numerical Rating Scale (NRS, 0 = no pain, 10 = most severe pain) for wound pain at 3, 6, 24, 48, and 72 h after the end of surgery. RESULTS: Ninety-nine patients (control, n = 51; PF-72, n = 48) were included in the analysis. The areas under the curve of NRS for wound pain until 72 h in the control group and the PF-72 group were 188.7 ± 46.1 and 135.3 ± 49.9 h, respectively (P < 0.001). The frequency of the administration of rescue analgesics in the general ward was similar between the two groups. CONCLUSION: PF-72 mixed with 0.75% ropivacaine reduced postoperative pain until 72 h in patients undergoing laparoscopic surgery. Although the study population was not large enough for safety evaluation, no adverse events associated with PF-72 were observed.

Re-evaluation of controversial issues in the treatment of cT3N0-2 rectal cancer: a 10-year cohort analysis using propensity-score matching.

BACKGROUND: Although neoadjuvant treatment is thought to provide optimal local control for stage II and III rectal cancers, many patients have been reported cured by total mesorectal excision (TME), alone or with additional chemotherapy (CTX). METHODS: This study retrospectively evaluated outcomes in 2643 patients with cT3N0-2 rectal cancers undergoing curative TME during 2005-2015. Recurrence and survival outcomes were measured in three propensity-score matched groups, consisting of patients who underwent preoperative chemoradiotherapy (CRT) with postoperative CTX (NAPOC), postoperative CRT (POCRT), and exclusively postoperative CTX (EPOCT). RESULTS: Near-complete or complete TME was conducted in more than 95.9% of patients and 80% of scheduled dose of postoperative CTX was completed in 99%. Except for higher SR rate in the POCRT group than the NAPOC group (p = 0.008), 5-year cumulative local and systemic recurrence (LR and SR) rates were 4.9% and 15.2% for cT3N0, and 4.2% and 21% for cT3N1-2 patients (LR, p = 0.703; SR, 0.065), respectively, with no significant differences associated with treatment exposure (p = 0.11-1). The 5-year cumulative disease-free (75.6% vs 65.7%, p = 0.018) and overall survival (87.1% vs 79.4%, p = 0.018 each) rates were higher in the NAPOC group than the POCRT group with cT3N1-2. However, any significant survival differences were not identified between the NAPOC and EPOCT groups according to tumor sub-stages or locations (p = 0.395-0.971). CONCLUSIONS: We found any treatment modalities including competent TME and postoperative adjuvant CTX efficiently reducing LR generating robust survival outcome in the propensity-matched cohorts, demanding further randomized controlled trials by clinical sub-stages II-III.

When should we add a diverting loop ileostomy to laparoscopic ileocolic resection for primary Crohn's disease?

BACKGROUND: The aims of this study were to determine risk factors for morbidity associated with laparoscopic ileocolic resection (LICR) for Crohn's disease (CD) and whether the addition of a diverting ileostomy is associated with reduced morbidity. METHODS: Patients undergoing LICR for primary CD at our institution from 2005 to 2015 included in a prospectively maintained database were assessed. The decision to perform a diverting ileostomy was left at the discretion of the operating surgeon. Demographics, disease-related, and treatment-related variables were evaluated using univariate and multivariate analyses as possible factors associated with diverting ileostomy creation and 30-day perioperative septic complications (anastomotic leaks and/or abscess). Use of any immunosuppressive medication was defined as use of steroids, biologics, and immunomodulators either alone or in combination. RESULTS: For 409 patients, mortality was nil, overall morbidity rate was 40.6%, conversion rate 9.3%, and septic morbidity rate 7.6%. A diverting stoma was created in 22% of cases and was independently associated with BMI < 18.5 kg/m2 (P = 0.001), low serum albumin levels (P = 0.006), and longer operative time (P = 0.003). Use of any immunosuppressive medication was the only variable independently associated with septic complications, both in the overall population (OR 2.7, P = 0.036) and in the subgroup of undiverted patients (OR 3.1, P = 0.031). There was no association between septic morbidity and ileostomy creation, anastomotic configuration, penetrating disease, combined procedures (other resection or strictureplasty), BMI, albumin levels, and operative times. CONCLUSIONS: LICR is safe in selected cases of complex penetrating disease, including when combined procedures are necessary. Our data are unable to prove that a diverting stoma is associated with reduced morbidity.

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.

Supplementary Anal Imaging by Magnetic Resonance Enterography in Patients with Crohn's Disease Not Suspected of Having Perianal Fistulas.

BACKGROUND & AIMS: Few data are available to guide the use of anal imaging for patients with Crohn's disease (CD) who are not suspected of having perianal fistulas. We aimed to evaluate the role of anal imaging supplementary to magnetic resonance enterography (MRE) in these patients. METHODS: In a prospective study, we added a round of anal MR imaging (MRI), collecting axial images alone, to MRE evaluation of 451 consecutive adults who were diagnosed with or suspected of having CD but not believed to have perianal fistulas. Images were examined for perianal tracts; if present, colorectal surgeons reexamined patients to identify external openings or perianal inflammation or abscess. Patients were followed and data were collected on dedicated treatment for perianal fistulas or abscess. We calculated the diagnostic yield for anal MRI, associated factors, and outcomes of MRI-detected asymptomatic perianal tracts. RESULTS: A total of 440 patients (mean age, 29.6±8.9 years) met the inclusion criteria. Anal MRI revealed perianal tracts in 53 patients (12%; 95% CI, 9.3%-15.4%). Surgeons however did not identify any lesions that required treatment. The asymptomatic tracts were mostly single unbranched (83%), inter-sphincteric (72%), or had a linear dark signal at the tract margin (79%). Younger age at MRE, female sex, and CD activity index scores of 220-450 were independently associated with detection of perianal tracts. MRI detection of asymptomatic tracts was independently associated with later development of perianal fistulas or abscess that required treatment: 17.8% cumulative incidence at 37 months and an adjusted hazard ratio of 3.06 (95% CI, 1.01-9.27; P = .048). CONCLUSIONS: In a prospective study of patients with CD, we found that adding anal MRI evaluation to MRE resulted in early identification of patients at risk for perianal complications.

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.

Detailed pathological analysis of the advancing edge of the tumour can effectively stratify clinical T4b colorectal cancer patients.

AIMS: Pathological staging of colorectal cancers (CRCs) that involve adhesion to adjacent organs (clinical stages T4b, cT4b) is sometimes difficult because the morphology of the invasive front varies. To resolve this issue, we reviewed 492 surgically resected CRC samples, comprising 96 cT4b tumours and, for comparison, 335 typical pathological stages (p) T3 and 61 pT4a tumours. METHODS AND RESULTS: Cases were subdivided into four groups according to the presence or absence of microscopic tumour invasion into the muscular wall of the adjacent organs and peritumoral abscess along invasive front. Those that directly invaded the wall of the adjacent organs without peritumoral abscess were associated with a significantly worse overall (OS) and recurrence-free survival (RFS) than the other three types of cT4b tumours. Those with peritumoral abscess showed similar prognosis to typical pT3 tumours, even when the advancing edge of the tumour invaded the wall of adjacent organs (staged as pT4b). Tumours showing fibrous adhesions without tumour cell invasion into the muscular wall of the adjacent organs showed a similar prognosis to typical pT3 tumours and showed a better prognosis than pT4a tumours. CONCLUSION: Only CRCs with tumour cell invasion into the muscular wall of the adjacent organs should be classified as pT4b, and it might be better to avoid 'the presence of tumour cells in fibrous adhesion' to define pathological T4b CRCs. In addition, the presence of a peritumoral abscess should be recorded as a predictor of better prognosis.

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.

Clinical impact of preoperative liver MRI in the evaluation of synchronous liver metastasis of colon cancer.

OBJECTIVES: To investigate whether additional MRI including gadoxetic acid enhancement is associated with survival rate (SR) in patients with synchronous liver metastasis of colon cancer (sCLM), compared with patients assessed only with CT. METHODS: Fifty-two patients underwent only CT (CT group) and 65 underwent additional MRI (CT+MRI group) for preoperative work-up of sCLM. In the CT+MRI group, the discrepancy between CT and MRI was analyzed. The 5-year SR was compared between the groups, and affecting factors were investigated. The inverse probability treatment weighting analysis (IPTW) adjusted by propensity scores was performed. RESULTS: In the CT+MRI group, 44 (67.7%) showed a discrepancy in the number of sCLMs between CT and MRI. MRI detected 39 additional sCLMs initially missed on CT in 26 patients. The number of detected sCLMs was better correlated with the pathologic findings in the CT+MRI group than in the CT group (p = 0.008). The estimated 5-year SR in the CT+MRI group was 70.8%, while that in the CT group was 48.1%. On adjusted multivariate analyses after the IPTW, the CT+MRI group showed a significantly lower risk of overall mortality than the CT group. CONCLUSION: Additional preoperative evaluation by MRI allowed us to more precisely detect sCLM and was associated with a better SR. KEY POINTS: • CT+MRI group showed significantly higher 5-year survival rates than CT group. • CT+MRI group was an independent prognostic factor of overall mortality. • MRI facilitates more accurate detection and better lesion characterization. • MRI selected better candidates for curative treatment. • The benefits of MRI were reflected by better survival.

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.

Microsatellite Instability was not Associated with Survival in Stage III Colon Cancer Treated with Adjuvant Chemotherapy of Oxaliplatin and Infusional 5-Fluorouracil and Leucovorin (FOLFOX).

BACKGROUND: The impact of microsatellite instability (MSI) on survival in stage III colon cancer treated with adjuvant 5-fluorouracil-oxaliplatin combination (FOLFOX) chemotherapy is not clear. We evaluated the association between MSI and survival in this population. METHODS: We analyzed 598 patients with curatively resected stage III colon cancer treated with adjuvant FOLFOX chemotherapy. We determined MSI status using polymerase chain reaction amplification; tumors were classified as high MSI (MSI-H, ≥2 unstable markers), low MSI (MSI-L, 1 unstable marker), or microsatellite stable (MSS, no unstable marker). RESULTS: Of 598 patients, 8.4% showed MSI-H. Tumors classified as MSI-H were more commonly located in the ascending colon (54.0 vs. 27.7%, p < 0.0001) and had poorly differentiated features (32.0 vs. 8.0%, p < 0.0001). After the median follow-up of 52.8 months, 5-year disease-free (DFS) and overall survival (OS) rates were 77.0 and 85.9%, respectively. In univariate analysis, pathologic T4 (pT4) and pathologic N2 (pN2) was associated with reduced DFS (p < 0.0001 and p < 0.0001, respectively) and OS (p = 0.002 and p = 0.001, respectively), whereas MSI status did not affect either DFS (p = 0.114) or OS (p = 0.525). In patients with pN2 tumors; however, MSI-H was associated with better survival compared with MSS/MSI-L; DFS and OS in patients with MSI-H/pN2 were comparable to those in patients with pN1 tumors. CONCLUSIONS: In patients with stage III colon cancer treated with adjuvant FOLFOX, pT4 and pN2 was associated with reduced survival, but MSI status alone did not affect survival.