CILP2 is a potential biomarker for the prediction and therapeutic target of peritoneal metastases in colorectal cancer.

Peritoneal metastases (PM) in colorectal cancer (CRC) is associated with a dismal prognosis. Identifying and exploiting new biomarkers, signatures, and molecular targets for personalised interventions in the treatment of PM in CRC is imperative. We conducted transcriptomic profiling using RNA-seq data generated from the primary tissues of 19 CRC patients with PM. Using our dataset established in a previous study, we identified 1422 differentially expressed genes compared to non-metastatic CRC. The profiling demonstrated no differential expression in liver and lung metastatic CRC. We selected 12 genes based on stringent criteria and evaluated their expression patterns in a validation cohort of 32 PM patients and 84 without PM using real-time reverse transcription-polymerase chain reaction. We selected cartilage intermediate layer protein 2 (CILP2) because of high mRNA expression in PM patients in our validation cohort and its association with a poor prognosis in The Cancer Genome Atlas. Kaplan-Meier survival analysis in our validation cohort demonstrated that CRC patients with high CILP2 expression had significantly poor survival outcomes. Knockdown of CILP2 significantly reduced the proliferation, colony-forming ability, invasiveness, and migratory capacity and downregulated the expression of molecules related to epithelial-mesenchymal transition in HCT116 cells. In an in vivo peritoneal dissemination mouse knockdown of CILP2 also inhibited CRC growth. Therefore, CILP2 is a promising biomarker for the prediction and treatment of PM in CRC.

Complete Obstruction, a Real Risk Factor: A Comprehensive Study on Obstruction in Stage IIA Colon Cancer With Propensity Score Matching Analysis.

MICROABSTRACT: This study evaluates the prognostic significance of obstructions in stage IIA colon cancer, distinguishing between partial and complete obstructions. It employs a retrospective review of 1914 patients with propensity score matching to analyze oncologic outcomes. Findings reveal complete obstruction as a significant risk factor for poorer outcomes, emphasizing the necessity for further research to refine treatment strategies, particularly regarding the efficacy of adjuvant chemotherapy across obstruction types. BACKGROUND: This study examined the prognostic impact of obstructions in stage IIA colon cancer. The analysis specifically differentiated partial and complete obstructions, analyzing their distinct influences of both on oncologic outcomes. MATERIALS AND METHODS: A retrospective review was conducted of stage IIA colon cancer cases with the presence of an obstruction. Patients were stratified by whether it was partial or complete based on the severity of obstruction. Propensity score matching was employed to control for confounders. RESULTS: Among 1914 consecutive patients diagnosed with stage IIA colon cancer, 758 patients (597 patients with partial obstruction, 161 patients with complete obstruction) exhibited obstruction, while 1156 patients had no obstruction. The median follow-up period was 126 months. Complete obstruction was associated with poorer disease-free survival (Hazard ratio (HR) = 1.785, P < .001) and overall survival (HR = 1.853, P = .001). This trend persisted after propensity score matching, patients with complete obstruction showing a worsened disease-free survival (HR = 1.666, P = .028) and overall survival (HR = 1.732, P = .041). Adjuvant chemotherapy showed improved outcomes overall, but its efficacy varied across obstruction types. CONCLUSION: Differentiating between complete and partial obstructions in stage IIA colon cancer is an important clinical distinction, as our findings suggest that complete obstruction is a significant risk factor for poorer oncologic outcomes. While adjuvant chemotherapy generally improves prognosis in stage IIA colon cancer, the correlation of obstruction type with its efficacy remains uncertain, necessitating further research to refine treatment strategies.

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn's disease.

BACKGROUND: Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn's disease (CD). Anti-tumor necrotic factor (TNF) therapy combined with drainage procedure is effective as well. However, previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure. AIM: This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn's perianal fistula (CPF) closure rates after stem cell transplantation with and without anti-TNF therapy, and to identify the factors affecting CPF closure and recurrence. METHODS: The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled. Clinical data were compared according to anti-TNF therapy and CPF closure. RESULTS: A total of 65 patients were included. The median age of females was 26 years (range: 21-31) and that of males was 29 (44.6%). The mean follow-up duration was 65.88 ± 32.65 months, and complete closure was observed in 50 (76.9%) patients. The closure rates were similar after stem cell transplantation with and without anti-TNF therapy (66.7% vs 81.6% at 3 year, P = 0.098). The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture (P = 0.027, 0.002, and 0.008, respectively). Clinical factors such as complexity, number of fistulas, presence of concurrent abscess, and medication were not significant for closure. The cumulative 1-, 2-, and 3-year closure rates were 66.2%, 73.8%, and 75.4%, respectively. CONCLUSION: Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation. However, both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy. Fistulous tract length, proctitis, and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

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.

Short- and long-term outcomes of surgical treatment in patients with intestinal Behcet's disease.

BACKGROUND: Behcet's disease (BD), a chronic vasculitic disorder affecting multiple organs, is characterized by recurrent oral and genital ulcers, arthritis, vasculitis, and intestinal ulcers. Although intestinal involvement of BD is common in East Asia, the efficacy and long-term outcomes of surgical treatment of intestinal BD still remain to be established. AIM: To evaluate the postoperative clinical course of intestinal BD and determine factors associated with its recurrence. METHODS: Data from patients who underwent surgical treatment for intestinal BD between January 2010 and August 2021 were retrospectively reviewed. Patients' demographics, clinical features, postoperative course, complications, and follow-up data were evaluated. RESULTS: We analyzed 39 surgeries in 31 patients. The mean patient age was 45.1 years, and the mean interval between the diagnosis of intestinal BD and surgical treatment was 4.9 years (range 1.0-8.0 years). The most common indication for surgery was medical intractability (n = 16, 41.0%), followed by fistula or abscess (n = 11, 28.2%). Laparoscopic approaches were used in 19 patients (48.7%), and 5 patients (12.8%) underwent emergency surgeries. The most common surgical procedure was ileocecal resection (n = 18, 46.2%), followed by right colectomy (n = 11, 28.2%). A diverting stoma was created in only one patient (2.6%). During a mean follow-up period of 45 (range 8-72) months, eight cases (20.5%) of recurrence in five patients required reoperation. The interval between operations was 12.1 months (range 6.3-17.8 mo). Four patients (10.3%) experienced recurrence within 1 year postoperatively, and all eight recurrences occurred within 2 years of the initial surgery. The reoperation rates at 1 and 3 years were 10.3% and 20.5%, respectively. A redo ileocolic anastomosis was performed in all recurrent cases. In multivariate Cox regression analysis, emergency surgery [hazard ratio (HR) 9.357, 95% confidence interval (CI): 1.608-54.453, P = 0.013] and elevated C-reactive protein (CRP) levels (HR 1.154, 95%CI: 1.002-1.328, P = 0.047), but not medication use, were predictors of recurrence. CONCLUSION: Surgical resection is a feasible treatment option for complicated BD. Reoperation is associated with severe inflammatory conditions, reflected by increased CRP levels and the requirement for emergency surgery.

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.

Transcriptomic Profiling and Cellular Composition of Creeping Fat in Crohn's disease.

BACKGROUND AND AIMS: Creeping fat [CF] is a poorly understood feature of Crohn's disease [CD], characterized by the wrapping of mesenteric adipose tissue [MAT] around the inflamed intestine. The aim of this study was to investigate the transcriptional profile and compositional features of CF. METHODS: We collected 59 MAT samples: 23 paired samples from patients with CD (CF [CD-CF] and MAT around the uninflamed intestine [CD-MAT]) and 13 MAT samples from non-CD patients [Con-MAT]. Differentially expressed gene [DEG], functional pathway, cell deconvolution, and gene co-expression network analyses were performed. RESULTS: By comparing three different MAT samples, we identified a total of 529 DEGs [|log2FoldChange| > 1.5; false discovery rate < 0.05]. Of these, 323 genes showed an incremental pattern from Con-MAT to CD-MAT, and to CD-CF, while 105 genes displayed a decremental pattern. Genes with an incremental pattern were related to immune cell responses, including B- and T-cell activation, while genes with a decremental pattern were involved in cell trafficking and migration. Cell deconvolution analysis revealed significant changes in cellular composition between the CD-CF and Con-MAT groups, with increased proportions of B-cells/plasma cells [p = 1.16 × 10-4], T-cells [p = 3.66 × 10-3], and mononuclear phagocytes [p = 3.53 × 10-2] in the CD-CF group. In contrast, only the B-cell/plasma cell component showed a significant increase [p = 1.62 × 10-2] in the CD-MAT group compared to Con-MAT. CONCLUSION: The distinct transcriptional profiles and altered cellular components of each MAT found in our study provide insight into the mechanisms behind CF and highlight its possible role in the pathogenesis of CD.

Short-term outcomes of da Vinci SP versus Xi for colon cancer surgery: a propensity-score matching analysis of multicenter cohorts.

Recent advancements in robotic systems have led to the introduction of the da Vinci SP system, which allows surgeons to perform colon cancer surgery through fewer ports. This study aimed to evaluate the perioperative outcomes of colon cancer surgeries conducted using the da Vinci SP and Xi systems. Patients who underwent robotic colon cancer surgeries between November 2020 and December 2022 at two tertiary referral centers were considered for inclusion. Following propensity-score matching, short-term outcomes between the two systems were retrospectively analyzed. Out of 189 patients included in the study, 106 from 53 propensity-score matched pairs were analyzed. Patients operated on with the SP system exhibited smaller incision lengths (5.0 cm vs. 9.4 cm, p < 0.001) experienced less pain at 8 h (3.0 vs. 3.5, p < 0.001) and at 24 h post-operation (2.9 vs. 3.3, p = 0.001) and had a shorter duration of hospital stay (5 days vs. 6 days, p = 0.002). The overall rate of postoperative complications was 10.4%, with no significant difference between the SP and Xi groups (7.5% vs. 13.2%). Robotic-assisted colon cancer surgery using the da Vinci SP system is feasible and demonstrates favorable short-term outcomes. Compared to the Xi system, the SP system offers advantages in terms of cosmesis, postoperative pain, and recovery duration for colon cancer patients.

Deciphering the DNA methylation landscape of colorectal cancer in a Korean cohort.

Aberrant DNA methylation plays a pivotal role in the onset and progression of colorectal cancer (CRC), a disease with high incidence and mortality rates in Korea. Several CRC-associated diagnostic and prognostic methylation markers have been identified; however, due to a lack of comprehensive clinical and methylome data, these markers have not been validated in the Korean population. Therefore, in this study, we aimed to obtain the CRC methylation profile using 172 tumors and 128 adjacent normal colon tissues of Korean patients with CRC. Based on the comparative methylome analysis, we found that hypermethylated positions in the tumor were predominantly concentrated in CpG islands and promoter regions, whereas hypomethylated positions were largely found in the open-sea region, notably distant from the CpG islands. In addition, we stratified patients by applying the CpG island methylator phenotype (CIMP) to the tumor methylome data. This stratification validated previous clinicopathological implications, as tumors with high CIMP signatures were significantly correlated with the proximal colon, higher prevalence of microsatellite instability status, and MLH1 promoter methylation. In conclusion, our extensive methylome analysis and the accompanying dataset offers valuable insights into the utilization of CRC-associated methylation markers in Korean patients, potentially improving CRC diagnosis and prognosis. Furthermore, this study serves as a solid foundation for further investigations into personalized and ethnicity-specific CRC treatments. [BMB Reports 2023; 56(10): 569-574].

Difference in prognostic impact of lateral pelvic lymph node metastasis between pre- and post-neoadjuvant chemoradiotherapy in rectal cancer patients.

Purpose: The prognostic significance and treatment of lateral pelvic lymph node metastasis (mLPLN) in rectal cancer patients receiving neoadjuvant chemoradiotherapy (nCRT) are not well understood. In this study, we evaluated the impact of mLPLN identified in imaging modality on outcomes. Methods: Between January 2008 and December 2016, 1,535 patients who underwent radical resection following nCRT were identified. The association between mLPLN and disease-free survival (DFS), overall survival (OS), local recurrence-free survival (LRFS), and pelvic recurrence-free survival (PRFS) was analyzed, along with risk factors associated with OS and DFS. Results: Overall, 329 (21.4%) of the 1,535 patients experienced disease recurrence; 71 (4.6%) had local recurrence, 25 (1.6%) had pelvic recurrence, and 312 (20.3%) had distant recurrence. The pre- and post-nCRT mLPLN (-) groups had better DFS, LRFS, PRFS, and OS than the (+) groups. LPLN sampling (LPLNs) was implemented in 24.0% of the pre-nCRT mLPLN (+) group and in 28.8% of the post-nCRT mLPLN (+) group. There was no significant difference in OS and LRFS between LPLNs group and no LPLNs group in pre- and post-nCRT mLPLN (+) groups. Pre-nCRT mLPLN was associated with poor OS (hazard ratio [HR], 1.43; P = 0.009) and post-nCRT mLPLN was associated with poor DFS (HR, 1.49; P = 0.002). Conclusion: Pre- and post-nCRT mLPLN (+) have different prognostic effects. Post-nCRT mLPLN appears to be more important for disease control. However, pre-nCRT mLPLN should not be disregarded when devising a treatment strategy since it is an independent risk factor for OS.

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.

Interpretation and clinical utility of indocyanine-green fluorescence imaging (IFI) in robot-assisted anorectal-function saving operations (ASOs): A propensity-score matched analysis of 872 prospectively enroled patients undergoing IFI.

BACKGROUND: This study suggested a novel physiological evaluation of indocyanine-green fluorescence imaging (IFI), and its utility associated with anastomotic leakage/stricture (AL/AS) and prognosis. METHODS: This study focussed on the utility of IFI, comparing IFI + versus IFI- groups (n = 878 vs. 339), optimised by propensity-score matching. After intravenous injection of indocyanine green, maximal perfusion was separately assessed at the vasa recta (VR) and colonic wall (CW), by determining intensities at the VR (VRI) and CW (CWI) and respective time. RESULTS: Although IFI did not significantly reduce either AL or AS, which occurred approximately 3-fold frequently in patients with lower than higher intensity of VRI. IFI was found as an independent parameter for both disease-free [DFS: hazard ratio (HR) = 0.489; p = 0.002] and overall survival (OS: HR = 0.519; p = 0.021). CONCLUSIONS: Although IFI did not significantly reduce AL/AS, IFI independently reduced 5-year systemic recurrence and increased 5-year DFS and OS.

Partial mesorectal excision can be a primary option for middle rectal cancer: a propensity-score matched retrospective analysis.

Purpose: Although partial and total mesorectal excision (PME and TME) is primarily indicated for the upper and lower rectal cancer, respectively, few studies have evaluated whether PME or TME is more optimal for middle rectal cancer. Methods: This study included 671 patients with middle and upper rectal cancer who underwent robot-assisted PME or TME. The 2 groups were optimized by propensity-score matching of sex, age, clinical stage, tumor location, and neoadjuvant treatment. Results: Complete mesorectal excision was achieved in 617 of 671 patients (92.0%), without showing a difference between the PME and TME groups. Local (5.3% vs. 4.3%, P>0.999) and systemic (8.5% vs. 16.0%, P=0.181) recurrence rates also did not differ between the 2 groups, respectively, in patients with middle and upper rectal cancer. The 5-year disease-free survival (81.4% vs. 74.0%, P=0.537) and overall survival (88.0% vs. 81.1%, P=0.847) rates also did not differ between the PME and TME groups, confined to middle rectal cancer. Moreover, 5-year recurrence and survival rates were not affected by distal resection margins of 2 cm (P=0.112) to 4 cm (P>0.999), regardless of pathological stages. Postoperative complication rate was higher in the TME than in the PME group (21.4% vs. 14.5%, P=0.027). Incontinence was independently associated with TME (odds ratio [OR], 2.009; 95% confidence interval, 1.015-3.975; P=0.045), along with older age (OR, 4.366, P<0.001) and prolonged operation time (OR, 2.196; P=0.500). Conclusion: PME can be primarily recommended for patients with middle rectal cancer with lower margin of >5 cm from the anal verge.

Robot-assisted lateral pelvic lymph node dissection in patients with advanced rectal cancer: a single-center experience of 65 cases.

The treatment of lateral pelvic lymph node (LPLN) metastasis of rectal cancer has evolved because of technical difficulties from open surgery to laparoscopy and, recently, robot-assisted surgery. This study aimed to evaluate the technical feasibility and short- and long-term outcomes of robot-assisted LPLN dissection (LPND) following total mesorectal excision (TME) in advanced rectal cancer. Clinical data of 65 patients who underwent robotic-assisted TME with LPND from April 2014 to July 2022 were reviewed. Data regarding operative details, postoperative morbidity (within 90 postoperative days) for short-term outcomes and lateral recurrence as long-term outcomes were analyzed. Among the 65 patients with LPND, preoperative chemoradiotherapy was performed in 49 (75.4%). The mean operative time was 306.8 (range 191-477) min, and the mean time of unilateral LPND was 38.6 (range 16-66) min. LPND was bilaterally performed in 19 (29.2%) patients. The mean number of each side of harvested LPLNs was 6.8. Lymph node metastasis was observed in 15 (23.0%) patients, and 10 (15.4%) patients had postoperative complications. Lymphocele (n = 3) and pelvic abscess (n = 3) were the most common, followed by voiding difficulty, erectile dysfunction, obturator neuropathy, and sciatic neuropathy (all n = 1). During the 25 months of median follow-up, no lateral recurrence of the LPND site was noted. Robot-assisted LPND following TME is safe and feasible and showed acceptable short- and long-term outcomes. Despite some study limitations, we may be able to apply this strategy more widely through subsequent prospective controlled studies.

Reduced expression of alanyl aminopeptidase is a robust biomarker of non-familial adenomatous polyposis and non-hereditary nonpolyposis colorectal cancer syndrome early-onset colorectal cancer.

BACKGROUND: Early-onset colorectal cancer (EOCRC) has been increasing in incidence worldwide but its genomic pathogenesis is mostly undetermined. This study aimed to identify robust EOCRC-specific gene expression patterns in non-familial adenomatous polyposis (FAP) and non-hereditary nonpolyposis colorectal cancer syndrome (HNPCC) EOCRC. METHOD: We first performed gene expression profiling analysis using RNA sequencing of discovery cohort comprised of 49 EOCRC (age <50) and 50 late-onset colorectal cancer (LOCRC) (age >70) specimens. To obtain robust gene expression data from this analysis, we validated differentially expressed genes (DEGs) through TCGA cohort (EOCRC:59 samples, LOCRC:229 samples) and our validation cohort (EOCRC:72 samples, LOCRC:43 samples) using real-time RT-PCR. After the validation of DEGs, we validated the selected gene at protein levels using Western blotting. To identify whether genomic methylation regulates the expression of a particular gene, we selected methylation sites using The Cancer Genome Atlas (TCGA) datasets and validated them by pyrosequencing in our validation cohort. RESULTS: The EOCRC patients included in this study had significantly more prominent family history of cancer than the LOCRC patients (23 [46.9%] vs. 13 [26%], p = 0.050). Alanyl aminopeptidase (ANPEP) was significantly downregulated in the EOCRC tissues (FC = 1.78, p = 0.0007) and was also commonly downregulated in the TCGA cohort (FC = -1.08, p = 0.0021). Moreover, the ANPEP mRNA and protein expression levels were significantly downregulated in the EOCRC tissues of our validation cohort (p = 0.037 and 0.027). In comparisons of the normal and tumor tissues in public datasets, the ANPEP level was significantly lower in the tumor tissue in the TCGA dataset (p < 2.2 × 10-16 ) and GSE196006 dataset (p = 0.0005). Furthermore, the ANPEP expression level did not show a decreasing tendency at a young age in the normal colon tissue of the GTEx dataset. Lastly, the hypermethylation of cg26222247 in ANPEP was identified to be weakly associated with reduced ANPEP expression in our EOCRC cohort. CONCLUSION: The reduced expression of ANPEP was identified as a novel biomarker of non-FAP and non-HNPCC EOCRC.

Pathologic Implications of Magnetic Resonance Imaging-detected Extramural Venous Invasion of Rectal Cancer.

BACKGROUND: Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. Recent advances in magnetic resonance imaging (MRI) allow for the detection of EMVI before surgery. This study aimed to analyze the correlations between MRI-detected EMVI (MR-EMVI) and pathologic parameters in patients with rectal cancer. MATERIALS AND METHODS: This study retrospectively analyzed 721 patients who underwent radical resection for locally advanced rectal cancer between 2018 and 2019 at the Asan Medical center. All patients underwent an MRI before surgery. The lesions of patients who received neoadjuvant chemoradiation therapy (CRT) were evaluated by MRI before and after the neoadjuvant CRT. RESULTS: Of the 721 patients, 118 (16.4%) showed a positive MR-EMVI, which significantly correlated with advanced pathologic T-category and N-category, extranodal extension, poor differentiation, lymphatic invasion, venous invasion, and perineural invasion. In addition, MR-EMVI was an independent factor for predicting the pathologic nodal status (OR 3.476, 95% CI, 2.186-5.527, P < .001). Patients with a positive MR-EMVI had a sensitivity of 28.0% and specificity of 91.9% for predicting regional lymph node metastasis, whereas the MR-N category had a sensitivity of 88.7% and specificity of 30.6%. Patients whose MR-EMVI changed from positive to negative after neoadjuvant CRT had no significant differences in pathologic parameters except for lymphatic invasion with patients who were negative before and after neoadjuvant CRT. CONCLUSION: MR-EMVI correlated with aggressive pathologic features, which indicated a poor prognosis. MR-EMVI may be a complementary imaging biomarker for predicting nodal status and evaluating tumor response to neoadjuvant CRT.

Technical, functional, and oncological validity of robot-assisted total-intersphincteric resection (T-ISR) for lower rectal cancer.

BACKGROUND: Few studies fairly compared anorectal function and prognostic outcomes between patients undergoing abdominoperineal resection (APR) and anorectal-function-saving operations (ASO) under the equivalent conditions. By contrast, surgeons used to be somewhat hesitant to conduct total intersphincteric resection (T-ISR) as maximal ASO, due to its technical complexity and potential anorectal dysfunction. METHODS: Propensity-score matched cohorts undergoing robot-assisted R0 surgery [T-ISR vs APR vs partial-subtotal ISR (PS-ISR)/lower anterior resection (LAR)] for rectal cancer (n = 1361) were included. Operative outcomes, recurrence, and disease-free/overall survival (DFS/OS) were analyzed. Anorectal function was evaluated based on fecal incontinence score and high-resolution manometry between the T-ISR and other ASO groups. RESULTS: Few differences were detected between the T-ISR and APR groups. More patients undergoing APR had T4 stage disease, while the lowest tumor margin was the same in both groups (mean, 1.5 cm from anal verge). Prognostic outcomes did not differ between the T-ISR and APR groups, including local (5.1% vs 7.7%, p = 1) or systemic (15.4% vs 25.6%, p = 0.401) recurrence, and 5-year DFS (78.7% vs 61.5%, p = 0.1) and OS (89% vs 82.1%, p = 0.434) rates, nor were there differences between the T-ISR and PS-ISR/LAR groups. The PS-ISR group generally showed less anorectal dysfunction than the T-ISR group, but maximal tolerance volume did not differ between these two groups and was within the range for the healthy population. CONCLUSIONS: T-ISR can replace most traditional APR, except for advanced T4 disease with aggressive infiltration into the levator-sphincters, and can provide tolerable anorectal dysfunction.

Efficacy of preoperative chemoradiotherapy in patients with cT2N0 distal rectal cancer.

PURPOSE: This study was designed to determine the feasibility of preoperative chemoradiotherapy (PCRT) in patients with clinical T2N0 distal rectal cancer. METHODS: Patients who underwent surgery for clinical T2N0 distal rectal cancer between January 2008 and December 2016 were included. Patients were divided into PCRT and non-PCRT groups. Non-PCRT patients underwent radical resection or local excision (LE) according to the surgeon's decision, and PCRT patients underwent surgery according to the response to PCRT. Patients received 50.0 to 50.4 gray of preoperative radiotherapy with concurrent chemotherapy. RESULTS: Of 127 patients enrolled, 46 underwent PCRT and 81 did not. The mean distance of lesions from the anal verge was lower in the PCRT group (P=0.004). The most frequent operation was transanal excision and ultralow anterior resection in the PCRT and non-PCRT groups, respectively. Of the 46 patients who underwent PCRT, 21 (45.7%) achieved pathologic complete response, including 15 of the 24 (62.5%) who underwent LE. Rectal sparing rate was significantly higher in the PCRT group (11.1% vs. 52.2%, P<0.001). There were no significant differences in 3- and 5-year overall survival and recurrence-free survival regardless of PCRT or surgical procedures. CONCLUSION: PCRT in clinical T2N0 distal rectal cancer patients increased the rectal sparing rate via LE and showed acceptable oncologic outcomes. PCRT may be a feasible therapeutic option to avoid abdominoperineal resection in clinical T2N0 distal rectal cancer.