Is Robotic Surgery Beneficial for Rectal Cancer Patients with Unfavorable Characteristic After Neoadjuvant Chemoradiotherapy?

BACKGROUND: The objective of this study was to compare long-term oncologic outcomes of robot and laparoscopic surgeries for patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by radical resection. METHODS: This study analyzed 3240 rectal cancer patients who underwent radical surgery from 2008 to 2019. Among them, 1204 patients who received nCRT (robotic, n = 316; laparoscopic, n = 888) were analyzed. The oncological outcome according to the number of unfavorable factors (male, body mass index ≥ 25, receiving CCRT) present in patients also was analyzed. We used 1:1 propensity score matching (PSM) to adjust for potential baseline confounders between groups. RESULTS: After PSM, two groups showed similar demographics and pathological results. After PSM analysis, the robotic group showed higher 5-year disease-free survival (DFS) and local recurrence-free survival rates than the laparoscopic group, whereas 5-year overall survival and distant recurrence-free survival rates were similar between the two groups. In addition, by comparing survival rates for each yp stage, it was found 5-year DFS and local recurrence-free survival of the robotic group in yp stage III were significantly higher than those of the laparoscopic group. Five-year DFS was conducted according to the number of unfavorable factors (male, body mass index ≥ 25 kg/m2, and undergoing nCRT) as a subgroup analysis. In patients with all three unfavorable factors, the robotic group showed significantly higher DFS than the laparoscopic group. CONCLUSIONS: Robotic approach for rectal cancer after nCRT, especially for patients with yp stage III and unfavorable factors, have the advantage of improving oncologic outcomes even for surgeons specializing in colorectal cancer.

Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer.

Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions. The CpG Island Methylator PhenotypeHigh (CIMP-H) exhibited notable enrichment of microsatellite instability-high (MSI-H). Additionally, our findings indicated a significant correlation between methylation of the MLH1 gene and MSI-H status. Furthermore, we found that the CIMP-H had a higher tendency to affect the right-side of the colon tissues and was slightly more prevalent among older patients. Through our methylome profile analysis, we successfully verified the thylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundation for exploring novel molecular insights and potential therapeutic targets for the treatment of CRC. [BMB Reports 2024; 57(2): 110-115].

Effectiveness of personalized treatment stage-adjusted digital therapeutics in colorectal cancer: a randomized controlled trial.

BACKGROUND: Colorectal cancer survivors often experience decline in physical performance and poor quality of life after surgery and during adjuvant therapies. In these patients, preserving skeletal muscle mass and high-quality nourishment are essential to reduce postoperative complications and improve quality of life and cancer-specific survival. Digital therapeutics have emerged as an encouraging tool for cancer survivors. However, to the best of our knowledge, randomized clinical trials applying personalized mobile application and smart bands as a supportive tool to several colorectal patients remain to be conducted, intervening immediately after the surgical treatment. METHODS: This study is a prospective, multi-center, single-blinded, two-armed, randomized controlled trial. The study aims to recruit 324 patients from three hospitals. Patients will be randomly allocated to two groups for one year of rehabilitation, starting immediately after the operation: a digital healthcare system rehabilitation (intervention) group and a conventional education-based rehabilitation (control) group. The primary objective of this protocol is to clarify the effect of digital healthcare system rehabilitation on skeletal muscle mass increment in patients with colorectal cancer. The secondary outcomes would be the improvement in quality of life measured by EORTC QLQ C30 and CR29, enhanced physical fitness level measured by grip strength test, 30-sec chair stand test and 2-min walk test, increased physical activity measured by IPAQ-SF, alleviated pain intensity, decreased severity of the LARS, weight, and fat mass. These measurements will be held on enrollment and at 1, 3, 6 and 12 months thereafter. DISCUSSION: This study will compare the effect of personalized treatment stage-adjusted digital health interventions on immediate postoperative rehabilitation with that of conventional education-based rehabilitation in patients with colorectal cancer. This will be the first randomized clinical trial performing immediate postoperative rehabilitation in a large number of patients with colorectal cancer with a tailored digital health intervention, modified according to the treatment phase and patient condition. The study will add foundations for the application of comprehensive digital healthcare programs focusing on individuality in postoperative rehabilitation of patients with cancer. TRIAL REGISTRATION: NCT05046756. Registered on 11 May 2021.

Single-port laparoscopic versus single-port robotic right hemicolectomy: Postoperative short-term outcomes.

BACKGROUND: This study aimed to compare the short-term postoperative outcomes of single-port robotic (SPR) using da Vinci SP® system and single port laparoscopic (SPL) right hemicolectomy and determine whether the novel SPR system is safe and feasible. METHODS: From January 2019 to December 2020, a total of 141 patients (41 patients for SPR and 100 patients for SPL) who electively underwent right hemicolectomy for colon cancer performed by a single surgeon were included in the study. RESULTS: The time to the first bowel movement was 3 (range, 1-4) days after surgery in the SPR group and 3 (2-9, range) days in the SPL group (p = 0.017). However, there were no differences in pathologic outcomes or postoperative complications. CONCLUSIONS: SPR is a safe and feasible surgical technique and has an advantage in the time to first postoperative bowel movement over SPL with no other complications.

Association Between Distress at Diagnosis and Disease-free Survival Among Patients With Resectable Colon Cancer: A Large Cohort Study.

OBJECTIVE: This study aimed to evaluate the association between distress at initial diagnosis and disease-free survival in patients with resectable colon cancer. SUMMARY BACKGROUND DATA: Considerable research has examined the psychological impact of having a confirmed diagnosis of cancer, but relatively limited research has examined the impact of distress during the diagnostic phase on oncological outcomes. METHODS: This is a retrospective cohort study. We included newly diagnosed colon cancer patients who had resectable surgery and underwent distress screening between July 2014 and July 2021 (N=1,362). The Korean versions of the Distress Thermometer were used to assess distress and related problems. Patients were categorized into 3 groups based on distress score: low (<4), moderate (4-7), and severe (≥8). The primary outcome was disease-free survival. RESULTS: The mean distress was 5.1 (SD=2.4) and 61%, and 15% of patients had moderate and severe distress at diagnosis, respectively. The severe distress group was more likely to report fear, sadness, and concerns regarding insurance/finance, work, and childcare than the low distress group. Compared with the low distress group, the severe distress group had worse disease-free survival (Hazard Ratio=1.84, 95% CI=1.03, 3.29). The association was more evident in patients with stage IV disease (Hazard Ratio=2.53, 95% CI=1.02, 6.25). CONCLUSIONS: A substantial number of patients with colon cancer experience distress at diagnosis, and severe distress has a negative impact on oncologic outcomes. Active monitoring and appropriate management of distress at diagnosis should be adopted at clinical settings.

Revised Nodal Staging Integrating Tumor Deposit Counts With Positive Lymph Nodes in Patients With Stage III Colon Cancer.

OBJECTIVE: We evaluated the prognostic value of tumor deposit (TD) counts and incorporated them with the number of positive lymph nodes to develop a revised nodal staging. SUMMARY BACKGROUND DATA: The current American Joint Committee on Cancer (AJCC) staging on colon cancer includes the TDs only for nodenegative patients, as N1c, and their counts are not considered. METHODS: We included consecutive patients with stage III colorectal cancer who underwent curative resections between January 2010 and December 2019. The patients were grouped as TD 0, TD 1, TD 2, or TD ≥3 based on their TD counts. Disease-free survival and overall survival were compared. RESULTS: Of 2446 eligible stage III patients, 658 (26.9%) had TDs. Among them, 500 (76.0%) patients concurrently had positive lymph nodes (LNs). TD counts were significantly related to worse disease-free survival (DFS) and overall survival regardless of pT stages or the number of positive LNs. The patients were restaged based on the integrated number of TD counts and positive LNs. The N3 stage, which had ≥10 integrated TDs and positive LNs, was newly classified. Among the patients who completed 6 months of adjuvant chemotherapy, those upstaged to N2 from an initial stage of N1 experienced significantly worse DFS than those confirmed as N1 in the revised N staging. The newly N3-staged patients showed significantly worse DFS than the patients initially staged as N2. CONCLUSIONS: Revised N staging using the integrated number of TD counts and positive LNs could predict DFS more accurately than current staging. It would also draw greater attention to the patients with high-risk stage III colon cancer staged as N3.

Prognostic Impact of Lymphatic Invasion, Venous Invasion, Perineural Invasion, and Tumor Budding in Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy Followed by Total Mesorectal Excision.

BACKGROUND: The diagnostic implications of lymphatic invasion, venous invasion, perineural invasion, and tumor budding in rectal cancer treated with neoadjuvant chemoradiotherapy are unknown. OBJECTIVE: This study aimed to identify the prognostic impact of lymphatic invasion, venous invasion, perineural invasion, and tumor budding in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at the Samsung Medical Center. Grouping was performed on the basis of lymphatic invasion, venous invasion, perineural invasion, and tumor budding status: no-risk group with 0 factor (n = 299), low-risk group with any 1 factor (n = 131), intermediate-risk group with any 2 factors (n = 75), and high-risk group with 3 or 4 risk factors (n = 32). PATIENTS: Patients who underwent neoadjuvant chemoradiotherapy, followed by radical operation for locally advanced rectal cancer, from January 2010 to December 2015 were included. MAIN OUTCOME MEASURES: The main outcome measures were disease-free and overall survival. RESULTS: Disease-free and overall survival varied significantly between the groups in stage III ( p < 0.001 and p < 0.001). Disease-free survival in stage I differed between the no-risk group and the intermediate-risk group ( p = 0.026). In stage II, disease-free and overall survival differed between the no-risk group and the intermediate-risk group ( p = 0.010 and p = 0.045). In multivariable analysis, risk grouping was an independent prognostic factor for both disease-free (p <0.001) and overall survival ( p < 0.001). LIMITATIONS: The inherent limitations are associated with the retrospective single-center study design. CONCLUSIONS: Lymphatic invasion, venous invasion, perineural invasion, and tumor budding are strong prognostic factors for disease-free and overall survival in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Therefore, adjuvant chemotherapy is strongly recommended in patients with positive lymphatic invasion, venous invasion, perineural invasion, and tumor budding. See Video Abstract at http://links.lww.com/DCR/B919 . IMPACTO PRONSTICO DE LA INVASIN LINFTICA, LA INVASIN VENOSA, LA INVASIN PERINEURAL Y LA GEMACIN TUMORAL EN EL CNCER DE RECTO TRATADO CON QUIMIORRADIOTERAPIA NEOADYUVANTE SEGUIDA DE ESCISIN TOTAL DEL MESORRECTO: ANTECEDENTES:Se desconocen las implicaciones diagnósticas de la invasión linfática, la invasión venosa, la invasión perineural y el crecimiento tumoral en el cáncer de recto tratado con quimiorradioterapia neoadyuvante.OBJETIVO:Este estudio fue diseñado para identificar el impacto pronóstico de la invasión linfática, la invasión venosa, la invasión perineural y la gemación tumoral en el cáncer de recto localmente avanzado tratado con quimiorradioterapia neoadyuvante.DISEÑO:Este estudio fue un estudio de cohorte retrospectivo.AJUSTES:Este estudio se realizó en el Centro Médico Samsung. La agrupación se realizó en función de la invasión linfática, la invasión venosa, la invasión perineural y el estado de crecimiento del tumor: grupo sin riesgo con 0 factores (n = 299), grupo de bajo riesgo con cualquier factor 1 (n = 131), grupo de riesgo intermedio con 2 factores cualquiera (n = 75), y un grupo de alto riesgo con 3 o 4 factores de riesgo (n = 32).PACIENTES:Se incluyeron un total de 537 pacientes que se sometieron a quimiorradioterapia neoadyuvante seguida de operación radical por cáncer de recto localmente avanzado desde enero de 2010 hasta diciembre de 2015.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la supervivencia libre de enfermedad y la supervivencia general.RESULTADOS:La mediana del período de seguimiento fue de 77 meses, y la supervivencia libre de enfermedad a los 5 años y la supervivencia general a los 5 años variaron significativamente entre los grupos en el estadio III (p < 0,001, p < 0,001). La supervivencia libre de enfermedad a los 5 años en el estadio I difirió entre el grupo sin riesgo y el grupo de riesgo intermedio (p = 0,026). En el estadio II, la supervivencia libre de enfermedad a 5 años y la supervivencia global a 5 años difirieron entre el grupo sin riesgo y el grupo de riesgo intermedio p = 0,010, p = 0,045). En el análisis multivariable, la agrupación de riesgo fue un factor pronóstico independiente tanto para la supervivencia libre de enfermedad (p < 0,001) como para la supervivencia global (p < 0,001).LIMITACIÓN:Las limitaciones inherentes están asociadas con el diseño de estudio retrospectivo de un solo centro..CONCLUSIÓN:La invasión linfática, la invasión venosa, la invasión perineural y la gemación tumoral son fuertes factores pronósticos para la supervivencia libre de enfermedad y la supervivencia general en el cáncer de recto localmente avanzado tratado con quimiorradioterapia neoadyuvante. Por lo tanto, se recomienda fuertemente la quimioterapia adyuvante en pacientes con invasión linfática positiva, invasión venosa, invasión perineural y tumor en en formacion. Consulte Video Resumen en http://links.lww.com/DCR/B919 . (Traducción-Dr Yolanda Colorado ).

Learning curve for single-port robot-assisted colectomy.

Purpose: Since the introduction of robotic surgery, robots for colorectal cancer have replaced laparoscopic surgery, and a single-port robot (SPR) platform has been launched and is being used to treat patients. We analyzed the learning curve and initial complications of using an SPR platform in colorectal cancer surgery. Methods: We reviewed 39 patients who underwent SPR colectomy from April 2019 to October 2019. All surgeries were performed by the same surgeon using an SPR device. A learning curve was generated using the cumulative sum methodology to assess changes in total operation time (OT), docking time (DT), and surgeon console time (SCT). We grouped the patients into 3 groups according to the time period: the first 11 were phase 1, the next 11 were phase 2, and the last 17 were phase 3. Results: The mean age of the patients was 61.28±13.03 years, and they had a mean body mass index of 23.79±2.86 kg/m2. Among the patients, 23 (59.0%) were male, and 16 (41.0%) were female. The average OT was 186.59±51.30 minutes, the average SCT was 95.49±35.33 minutes, and the average DT (time from skin incision to robot docking) was 14.87±10.38 minutes. The SCT differed significantly among the different phases (P<0.001). Complications occurred in 8 patients: 2 ileus, 2 postoperation hemoglobin changes, 3 urinary retentions, and 1 complicated fluid collection. Conclusion: In our experience, the learning curve for SPR colectomy was achieved after the 18th case.

Efficacy of a local anesthetic gel infusion kit for pain relief after minimally invasive colorectal surgery: an open-label, randomized clinical trial.

Continuous wound infusion with local anesthesia is an effective method for reducing postoperative pain after laparoscopic colorectal surgery. However, most subcutaneous local anesthesia is delivered through continuous injection, which can be inconvenient for patients. This study compared the effectiveness of postoperative pain relief from the application of a local poloxamer 407-based ropivacaine hydrogel (Gel) to the incision site with continuous infusion-type ropivacaine administration (On-Q) in patients undergoing laparoscopic colorectal surgery. This prospective, randomized, non-inferiority study included 61 patients who underwent laparoscopic colorectal surgery with an incision length of 3-6 cm. All 61 patients were randomly assigned to the Gel group (poloxamer 407-based 0.75% ropivacaine, 22.5 mg) or the On-Q group (0.2% ropivacaine, 4 mg/hour for two days). Postoperative analgesia was induced in all patients with intravenous patient-controlled analgesia (IV-PCA). The outcome measures, which were assessed for 72 h after surgery, included the total amount of fentanyl consumed via IV-PCA (primary endpoint), and the amount of rescue analgesia (pethidine) and postoperative pain intensity assessed using a numeric rating scale (NRS) [secondary endpoints]. The Gel was administered to 31 patients and On-Q was used for 30 patients. There was no significant difference in the total usage of fentanyl between the two groups (Gel group, 1623.98 mcg; On-Q group, 1595.12 mcg; P = 0.806). There was also no significant difference in the frequency of analgesic rescue medication use (P = 0.213) or NRS scores (postoperative 6 h, P = 0.860; 24 h, P = 0.333; 48 h, P = 0.168; and 72 h, P = 0.655) between the two groups. The Gel, which continuously delivers a local anesthetic to operative sites, can thus be considered an effective device for analgesia and pain relief for midline incisions in laparoscopic colorectal surgery.

Neoadjuvant chemoradiotherapy determines the prognostic impact of anastomotic leakage in advanced rectal cancer.

Purpose: The prognostic impact of anastomotic leakage (AL) in rectal cancer remains uncertain. We investigated the prognostic significance of AL in rectal cancer patients who underwent curative surgery, especially in terms of chemoradiotherapy. Methods: A total of 1,818 rectal cancer patients who underwent radical surgery from 2011 to 2015 were retrospectively evaluated. We categorized patients according to AL and compared survival outcomes between the groups before and after matching. In locally advanced rectal cancer patients, we classified patients according to neoadjuvant chemoradiotherapy (nCRT) or adjuvant chemotherapy (aCTx) and analyzed survival outcomes according to AL in each group. Results: Before matching, overall survival (OS) was significantly worse in the AL (+) group compared to the AL (-) group (P = 0.004). In matched patients, there were no differences in disease-free survival (DFS) and OS between groups (P = 0.423 and P = 0.083, respectively). In subgroup analysis for locally advanced rectal cancer, patients were classified as follows: nCRT (+) and aCTx (+) group; nCRT (+) and aCTx (-) group; nCRT (-) and aCTx (+) group; and nCRT (-) and aCTx (-) group. In the nCRT (-) and aCTx (+) group, patients with AL exhibited significantly worse DFS than patients without AL (P = 0.040). In the other 3 groups, there were no differences in DFS according to AL. Conclusion: In locally advanced rectal cancer, AL had an adverse effect on oncologic outcome in patients receiving aCTx without nCRT but not in patients receiving nCRT.

Elevated Carcinoembryonic Antigen at the Time of Recurrence as a Poor Prognostic Factor in Colorectal Cancer: A Propensity Score Matching Analysis.

There are few studies on the prognostic impact of CEA level at the time of recurrence in recurrent colorectal cancer. The objective of this study was to evaluate the prognostic value of serum CEA levels at the time of recurrence in patients with recurrent colorectal cancer. Between 2007 and 2014, 962 consecutive recurrent patients for colorectal cancer were analyzed. These patients were divided into two groups according to CEA level at the time of recurrence (r-CEA): high r-CEA (≥5 ng/ml) (n = 428) and normal r-CEA (<5 ng/ml) (n = 534). The prognostic effects of r-CEA were evaluated by one-to-one propensity score matching (PSM) to adjust factors between groups. After matching, a total of 778 patients, 389 per group, were analyzed. After matching, the 5-year disease-free survival rate for the high r-CEA group was significantly lower than that for the normal r-CEA group. The 5-year overall survival rate was 56.5% in the high r-CEA group and 66.0% in the normal r-CEA group (p = 0.008). The 5-year cancer-specific survival rate was 61.7% in the high group and 67.5% in the normal group (p = 0.035). In a multivariate analysis of prognostic factors, high preoperative CEA level at the time of recurrence, poor histologic grade, and lymphatic invasion were associated with poorer overall survival. The high r-CEA level group showed significantly poorer prognosis than the normal r-CEA group. Therefore, the r-CEA level can be used as a prognostic factor in recurrent colorectal cancer. Aggressive adjuvant treatment needs to be considered for patients with an initially high CEA level and lymph node positivity who are prone to recurrence.

Comparison of Oncologic Outcomes Between Incomplete Obstructive Colon Cancer and Non-Obstructive Colon Cancer by Tumor Location.

Introduction: Obstruction in colon cancer is a well-known risk factor for worse oncologic outcomes. However, studies on differences in survival of patients with incomplete obstructive colon cancer (IOCC) by tumor location are insufficient. Thus, the aim of this study was to compare oncologic outcomes between IOCC and non-obstructive colon cancer (NOCC) according to tumor location. Methods: From January 2010 to December 2015, a total of 2,004 patients diagnosed with stage II or stage III colon adenocarcinoma who underwent elective colectomy were included (IOCC, n = 405; NOCC, n = 1,599). Incomplete obstruction was defined as a state in which colonoscopy could not pass through the cancer lesion but did not require emergent surgery, stent insertion, or stoma formation because the patient was asymptomatic without problem in bowel preparation. Kaplan-Meier method and log-rank tests were used to compare survival between IOCC and NOCC. Multivariable analysis was performed to determine which factors affected survivals. Results: Stage III IOCC patients showed significantly lower overall survival (OS) and recurrence-free survival (RFS). Stage II IOCC patients and stage III NOCC patients had similar survival curves. IOCC patients with tumors on the right side showed worse OS than other patients. In multivariable analysis, incomplete obstruction was an independent risk factor for worse OS and RFS in all stages. Tumor located at the right side in stage III was an independent risk factor for RFS (HR: 1.40, p = 0.030). Conclusions: Patients with IOCC showed significantly worse survival outcomes than those with NOCC. Stage II IOCC patients and stage III NOCC patients showed similar survival. Patients with stage III IOCC located at the right side showed significantly worse oncologic outcomes than those located at the left side. These results confirm that prognosis is different depending on the presence of incomplete obstruction and the location of the tumor, even in the same stage.

Clinical prediction model of pathological response following neoadjuvant chemoradiotherapy for rectal cancer.

Patients with pathologic complete response (pCR) achievement can consider local excision or "watch and wait" strategy instead of a radical surgery. This study analyzed the predictive factors of pCR in rectal cancer patients who underwent radical operation after neoadjuvant chemoradiotherapy (nCRT). This study also analyzed the recurrence patterns in patients who achieved pCR and the oncologic outcomes and prognostic factors by ypStage. Between 2000 and 2013, 1,089 consecutive rectal cancer patients who underwent radical resection after nCRT were analyzed. These patients were classified into two groups according to pCR. The clinicopathologic and oncologic outcomes were analyzed and compared between the two groups. Multivariate analysis was conducted on factors related to pCR. The proportion of patients achieving pCR was 18.2% (n = 198). The pCR group demonstrated earlier clinical T and N stages, smaller tumor size, better differentiation, and a lower percentage of circumferential resection margin (CRM) involvement than did the non-pCR group. The prognostic factors associated with poorer disease-free survival were high preoperative carcinoembryonic antigen levels, non-pCR, poor histology, lymphatic/perineural invasion, and involvement of CRM. Multivariate analysis revealed that clinical node negativity, tumor size < 4 cm, and well differentiation were significant independent clinical predictors for achieving pCR. Patients with pCR displayed better long-term outcomes than those with non-pCR. The pCR-prediction model, based on predictive factors, is potentially useful for prognosis and for prescribing a treatment strategy in patients with advanced rectal cancer who need nCRT.

Can CCRT/RT Achieve Favorable Oncologic Outcome in Rectal Cancer Patients With High Risk Feature After Local Excision?

Purpose: The oncologic outcome of concurrent chemoradiotherapy (CCRT) after local excision in patients with high-risk early rectal cancer as compared with radical operation has not been reported. The aim of this study is to compare the oncologic outcome between radical operation and adjuvant CCRT after local excision for high-risk early rectal cancer. Materials and Methods: From January 2005 to December 2015, 266 patients diagnosed with early rectal cancer and treated with local excision who showed high-risk characteristics were retrospectively analyzed. Propensity score matching was applied in a ratio of 1:4, comparing the CCRT/radiotherapy (RT) (n = 34) and radical operation (n = 91) groups. Univariate and multivariate analyses were performed to identify prognostic factors for survival. Results: The median follow-up period was 112 months. The 5-year disease-free survival rate and the 5-year overall survival of the radical operation group were significantly higher than those of the CCRT/RT group after propensity score matching (96.7% vs. 70.6%, p <0.001; 100% vs. 91.2%, p = 0.005, respectively). In a multivariate analysis, salvage therapy type and preoperative carcinoembryonic antigen (CEA) were prognostic factors for 5-year disease-free survival (p <0.001 and p = 0.021, respectively). The type of salvage therapy, the preoperative CEA, and the pT were prognostic factors for 5-year overall survival (p = 0.009, p = 0.024, and p = 0.046, respectively). Conclusions: Patients who undergo radical operations after local excision with a high-risk early rectal cancer had better survival than those treated with adjuvant CCRT/RT. Therefore, radical surgery may be recommended to high-risk early rectal cancer patients who have undergone local excision for more favorable oncologic outcomes.

Determining Which Patients Require Preoperative Pelvic Radiotherapy Before Curative-Intent Surgery and/or Ablation for Metastatic Rectal Cancer.

BACKGROUND: The aim of this study is to determine the optimal indications for preoperative pelvic radiotherapy (RT) in patients with metastatic rectal cancer who underwent curative-intent surgical resection and/or ablation. METHODS: Between January 2000 and October 2019, 246 patients who met our inclusion criteria were enrolled. Preoperative RT was performed in 22 patients (8.9%). Lower margin below the peritoneal reflection (p < 0.001), mesorectal fascia (MRF) invasion (p = 0.02), and lateral pelvic lymph node (LPLN) involvement (p = 0.005) were more frequent in the preoperative RT group. RESULTS: During the median follow-up period of 13.3 months (interquartile range [IQR]: 6.0-36.3 months), local recurrence (LR) was identified in 60 patients (24.4%). It was the first site of recurrence in 45 of them (18.3%). Among them, three patients were in the preoperative RT group. On multivariable analysis, lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, carcinoembryonic antigen (CEA) level ≥ 10 ng/mL before treatment, and preoperative RT were significant prognostic factors for LR-free survival (LRFS). In the patient group without any risk factors, the 2-year LRFS rate was 94.9% without preoperative RT. In the patient group with one or more risk factors, the 2-year LRFS was 64.4% without and 95.2% with preoperative RT. CONCLUSION: LR developed in about 25% of patients within 2 years. Preoperative RT should be considered, especially in patients with a risk factor for LR, including lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, or CEA ≥ 10 ng/mL before treatment.

Oncologic outcomes of pathologic T4 and T3 colon cancer patients diagnosed with clinical T4 stage disease using preoperative computed tomography scan.

BACKGROUND: The diagnostic accuracy of computed tomography (CT) for colon cancer is low, and the preoperative risk factors for locally advanced colon cancer are unknown. This study aimed to evaluate the correlation between preoperative CT scan findings and oncologic outcomes and to identify risk factors associated with locally advanced colon cancer. MATERIALS AND METHODS: Patients diagnosed with clinical stage (cT) 4 colon cancer based on preoperative CT scan findings who underwent curative surgery between January 2005 and December 2015 were retrospectively studied. Patients were divided according to pathologic stage (pT) into pT3 (n = 114) and pT4 (n = 102). RESULTS: The disease-free survival rate was significantly different between the pT3 and pT4 groups (88.6% vs. 68.6%, p < 0.001). The overall survival rate of the pT3 group was significantly higher than that of the pT4 group (91.2% vs. 76.5%, p = 0.002). Perineural invasion and tumor budding were identified as preoperative risk factors predisposing to pT4 staging (p = 0.044, p = 0.001). CONCLUSION: The survival rate of pT3 patients was significantly higher than that of pT4 patients with a preoperative cT4 diagnosis. This suggests that when planning for neoadjuvant chemotherapy in locally advanced colon cancer, preoperative CT scan findings may overestimate clinical staging and lead to inappropriate treatment. Thus, there is a need for a new modality to evaluate local advancement in colon cancer.

Learning curve for single-port robot-assisted rectal cancer surgery.

Purpose: We analyzed the learning curve of single-port robotic (SPR)-assisted rectal cancer surgery. Methods: Fifty-seven consecutive SPR-assisted rectal cancer surgery cases performed by the same surgeon were considered in surgical interventions for rectal cancer. Total operation time (OT), docking time (DT), and surgeon console time (SCT) measured during surgery were used to parametrize the learning curve. The parameters representing the learning curve were evaluated using the cumulative sum (CUSUM). Results: The mean value of total OT was 241.8 ± 91.7 minutes, the mean value of DT was 20.6 ± 19.1 minutes, and the mean value of SCT was 135.9 ± 66.7 minutes. The learning curve was divided into phase 1 (initial 16 cases), phase 2 (second 16 cases), and phase 3 (subsequent 25 cases). The peak on the CUSUM graph occurred in the 21st case. The longest OT among phases was in phase 2. Complications were most frequent in phase 2. However, complications of Clavien-Dindo (CD) grade IIIb were most frequent in phase 3 with 2 patients. The most common complications were fluid collection and urinary retention (7 patients each). Complications of CD grade IIIb required one stomal revision due to stoma obstruction and one irrigation and loop ileostomy due to anastomosis leakage. Conclusion: Improvement in surgical performance of SPR assisted rectal cancer operation was achieved after 21 cases. The three phases identified in the cumulative sum analysis showed a significant decrease in operative time after the middle stage of the learning curve without an increase in the complication rate.

Proteomic identification of arginine-methylated proteins in colon cancer cells and comparison of messenger RNA expression between colorectal cancer and adjacent normal tissues.

PURPOSE: Identification of type I protein arginine methyltransferase (PRMT) substrates and their functional significance during tumorigenesis is becoming more important. The present study aimed to identify target substrates for type I PRMT using 2-dimensional (2D) gel electrophoresis (GE) and 2D Western blotting (WB). METHODS: Using immunoblot analysis, we compared the expression of type I PRMTs and endogenous levels of arginine methylation between the primary colorectal cancer (CRC) and adjacent noncancerous tissues paired from the same patient. To identify arginine-methylated proteins in HCT116 cells, we carried out 2D-GE and 2D-WB with a type I PRMT product-specific antibody (anti-dimethyl-arginine antibody, asymmetric [ASYM24]). Arginine-methylated protein spots were identified by mass spectrometry, and messenger RNA (mRNA) levels corresponding to the identified proteins were analyzed using National Center for Biotechnology Information (NCBI) microarray datasets between the primary CRC and noncancerous tissues. RESULTS: Type I PRMTs and methylarginine-containing proteins were highly maintained in CRC tissues compared to noncancerous tissues. We matched 142 spots using spot analysis software between a Coomassie blue (CBB)-stained 2D gel and 2D-WB, and we successfully identified 7 proteins that reacted with the ASYM24 antibody: CACYBP, GLOD4, MAPRE1, CCT7, TKT, CK8, and HSPA8. Among these proteins, the levels of 4 mRNAs including MAPRE1, CCT7, TKT, and HSPA8 in CRC tissues showed a statistically significant increase compared to noncancerous tissues from patients using the NCBI microarray datasets. CONCLUSION: Our results indicate that the method shown here is useful in identifying arginine-methylated proteins, and significance of arginine modification in the proteins identified here should be further identified during CRC development.

Is a cutoff value of 12 still useful in stage II right-sided colon cancer without risk factors?

Purpose: Various clinical practice guidelines recommend at least 12 regional lymph nodes should be removed for resected colon cancer. According to a recent study, the lymph node yield (LNY) in colon cancer surgery in the last 20 years has tended to increase from 14.91 to 21.30. However, it is unclear whether these guidelines adequately reflect recent findings on the number of harvested lymph nodes in colon cancer surgery. The aim of this study is to assess the impact of an LNY of more than 25 on survival in right-sided colon cancer. Methods: We included 285 patients who underwent a right hemicolectomy during the period from January 2010 through December 2015. Patients were divided into two groups (<25 nodes and ≥25 nodes). Primary endpoints included 5-year and 10-year survival including disease-free and overall. Results: We found that survival outcomes of patients with a harvest of ≥25 nodes were not significantly different compared with a <25 group. Large tumor size (5 cm) is significantly associated with poor 5-year and 10-year overall survival. Conclusion: Survival outcomes of patients with a harvest of ≥25 nodes were not significantly different compared with the <25 group in stage II colon cancer with no risk.

Sphincter-saving surgery versus abdominoperineal resection in low rectal cancer following neoadjuvant treatment with propensity score analysis.

BACKGROUND: Sphincter-saving operation is the treatment of choice in patients with lower rectal cancer, although abdominoperineal resection (APR) is necessary in some cases for adequate oncological outcomes. This study compared the oncologic outcomes of patients with low rectal cancer undergoing APR and intersphincteric resection (ISR) after neoadjuvant chemoradiotherapy (nCRT). METHODS: We compared 104 patients who underwent ISR for lower rectal cancer between 2008 and 2014 with 79 patients who underwent APR during the same period. Cases in which tumors involved the levator ani muscle or the external anal sphincter, as well as those in which surgeons were unable to obtain a negative distal margin via sphincter-saving operation were excluded. Fifty-two patients who underwent ISR were matched via propensity scoring with 52 patients who underwent APR. The analyzed variables included patient and tumor characteristics and long-term outcomes before and after 1:1 propensity score matching (PSM). RESULTS: After matching, there were no significant differences between the two groups in clinical stage and tumor distance from anal verge. Short- and long-term outcomes were similar between the two groups. The 5-year disease-free survival rate was 76.3% in the ISR group and 57.8% in the APR group (p = 0.080). The 5-year cancer-specific survival rate was 89.5% in the ISR group and 85.4% in the APR group (p = 0.383). CONCLUSIONS: This reveals that ISR and APR have similar oncologic outcomes following nCRT in patients with advanced low rectal cancer adjusted for background variables.