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Background The “watch-and-wait” approach is a common treatment option amongst patients with locally advanced rectal cancer (LARC). However, the diagnostic sensitivity of clinical modalities, such as colonoscopy and magnetic resonance imaging to determine pathological response, is not high. We analysed the clinical utility of circulating tumour DNA (ctDNA) of patients with LARC to predict response to preoperative therapy and postoperative recurrence. Methods A serial ctDNA analysis of 222 plasma samples from 85 patients with LARC was performed using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with over 240 hotspots. Results ctDNA was detected in 57.6% and 22.3% of samples at baseline and after preoperative treatment, respectively, which was significantly different ( P  = 0.0003). Change in ctDNA was an independent predictor of complete response to preoperative therapy ( P  = 0.0276). In addition, postoperative ctDNA and carcinoembryonic antigen (CEA) were independent prognostic markers for risk of recurrence after surgery (ctDNA, P  = 0.0127 and CEA, P  = 0.0105), with a combined analysis having cumulative effects on recurrence-free survival ( P  = 1.0 × 10 –16 ). Conclusions Serial ctDNA analysis may offer clinically useful predictive and prognostic markers for response to preoperative therapy and postoperative recurrence in patients with LARC.

BackgroundAdvanced low rectal cancer has a non-negligible risk of lateral pelvic lymph node (LPLN) metastasis (LPLNM) and lateral local recurrence (LR) after neoadjuvant (chemo)radiotherapy and total mesorectal excision. LPLN dissection (LPLND) reduces LR but increases postoperative complications and sexual/urinary dysfunction.ObjectiveThe aim of this study was to develop a new radiomics-based prediction model for LPLNM in patients with rectal cancer.MethodsA total of 247 patients with rectal cancer and enlarged LPLNs treated by (chemo)radiotherapy and LPLND were enrolled in this retrospective, multicenter study. LPLN radiomic features were extracted from pretreatment portal venous-phase computed tomography images. A radiomics score of LPLN was constructed based on the least absolute shrinkage and selection operator regression in a primary cohort of 175 patients. Model performance was assessed in terms of discrimination, calibration, and decision curve analysis, and was externally validated in 72 patients.ResultsThe radiomics score showed significantly better discrimination compared with pretreatment short-axis diameter measurements in both the primary (area under the curve [AUC] 0.91 vs. 0.83, p = 0.0015) and validation (AUC 0.90 vs. 0.80, p = 0.0298) cohorts. Decision curve analysis also indicated the superiority of the radiomics score. In a subanalysis of patients with a short-axis diameter ≥ 7 mm, the radiomics nomogram, incorporating the radiomics score and LPLN shrinkage to ≤ 4 mm, had better discrimination compared with a model incorporating only LPLN shrinkage in both cohorts.ConclusionsRadiomics-based prediction modeling provides individualized risk estimation of LPLNM in rectal cancer patients treated with (chemo)radiotherapy, and outperforms measurements of pretreatment LPLN diameter.

BackgroundAmong numerous systemic inflammatory biomarkers, it remains unclear which is the most prognostic for patients with stage II/III colon cancer. We aimed to compare the prognostic significance of systemic inflammatory biomarkers among patients with stage II/III colon cancer.MethodsWe included 1303 patients with stage II/III colon cancer who underwent potentially curative resection from July 2004 to December 2013. Sixteen systemic inflammatory biomarkers—derived from combinations of neutrophils, lymphocytes, monocytes, platelets, C-reactive protein (CRP), and albumin—were compared to identify the biomarker most associated with overall survival (OS) and disease-free survival (DFS) using receiver operating characteristic (ROC) curve analysis.ResultsNine inflammatory biomarkers were predictive for OS, among which lymphocyte-to-CRP ratio (LCR), CRP-to-albumin ratio (CAR), neutrophil × CRP, monocyte × CRP, and platelet × CRP were also predictive for DFS. Among these five inflammatory biomarkers, the area under the curve (AUC) value was highest (0.630) for LCR, being significantly higher than that for neutrophil × CRP (P = 0.010), monocyte × CRP (P = 0.007), or platelet × CRP (P = 0.010) for OS. When the prognostic impact of LCR and CAR were analyzed by multivariate analysis, only LCR was an independent predictor of both OS [hazard ratio (HR), 1.77; 95% confidence interval (CI), 1.23–2.60; P = 0.002] and DFS (HR, 1.29; 95% CI, 1.00–1.66; P = 0.048).ConclusionsLCR may be the most useful predictive factor for OS and DFS in patients with stage II or III colon cancer.

Inhibition of the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis in combination with radiotherapy may be a promising approach to treat cancer. In the present study, we aimed to evaluate serum soluble PD-1/PD-L1 levels in patients with advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Serum soluble PD-L1 and PD-1 levels were measured using an enzyme-linked immunosorbent assay before and after CRT in 117 patients with low rectal cancer. Changes in the levels of sPD-L1/PD-1 after CRT, and the correlation between sPD-L1/PD-1 level and clinicopathological characteristics or disease-free survival (DFS) were evaluated. sPD-L1 levels significantly increased after CRT (p < 0.0001), whereas sPD-1 levels did not change significantly (p = 0.1050). High sPD-L1 before CRT was significantly associated with younger age (p = 0.044), and after CRT, with lymphovascular invasion (p = 0.021). High sPD-1 before and after CRT was significantly associated with a longer distance of the tumor from the anal verge (both p < 0.001). There was no correlation between sPD-L1 level and local PD-L1 expression on stromal immune cells. High sPD-L1 level after CRT tended to be associated with worse DFS (p = 0.0752). The multivariate analysis could not demonstrate an independent association for sPD-L1 levels after CRT with DFS. Significant increase of sPD-L1 levels after CRT suggests that anti-PD-L1 therapy might be a potential treatment strategy in combination with CRT in advanced rectal cancer.

BackgroundLateral pelvic node (LPN) dissection (LPND) is considered a promising technique for treating low rectal cancer; however, there is insufficient evidence of its prognostic value. Using centrally reviewed preoperative pelvic magnetic resonance (MR) images, this study aimed to find the patient population who has benefited from LPND.Patients and MethodsMR images of patients from 69 institutes with stage II–III low rectal cancer were reviewed by experienced radiologists. Recurrence-free survival (RFS), overall survival (OS), and short-term outcomes were measured.ResultsIn total, 731 preoperative MR images were reviewed (excluding patients with short-axis LPN ≥ 10 mm). Of these, 322 underwent total mesorectum excision (TME) without LPND (non-LPND group), and 409 underwent TME with LPND (LPND group). Preoperative treatment was performed for 40% and 25% of patients in the non-LPND and LPND groups, respectively. The incidence of postoperative complications was higher in the LPND group (44.5%) than in the non-LPND group (33.2%; P = 0.002). Among patients with LPNs < 5 mm, OS and RFS curves were not significantly different between the groups. Among patients with LPNs ≥ 5 mm, the LPND group had significantly higher 5-year OS and RFS than the non-LPND group (OS: 81.9% versus 67.3%; RFS: 69.4% versus 51.6%). On multivariate analysis of LPN ≥ 5 mm cases, LPND was independently associated with RFS.ConclusionsDespite the high incidence of postoperative complications, this study showed the prognostic impact of LPND on low rectal cancer patients with LPNs (≥ 5 mm, < 10 mm short axis) measured by experienced radiologists.Trial registration UMIN-ID: UMIN000013919

Conventional laparoscopic or robotic surgery for right-sided colon cancer often requires intraoperative repositioning and removal of the bowel. Changing positions during robotic surgery can be troublesome and robotic removal of the small intestine carries a risk of unexpected injury because robotic devices have a strong grasping force and no sense of touch. Herein, we introduce a novel mobilization of the medial approach without changing the position for robotic right hemicolectomy. Using this technique, mobilization is performed in counterclockwise succession, allowing all mobilizations and bowel removal to be completed sequentially, without positional change.

In the era of neoadjuvant chemoradiotherapy/radiotherapy and total mesorectal excision, overall oncological outcomes after curative resection of rectal cancer are excellent, with local recurrence rates as low as 5–10%. However, lateral nodal disease is a major cause of local recurrence after neoadjuvant chemoradiotherapy/radiotherapy and total mesorectal excision. Patients with lateral nodal disease have a local recurrence rate of up to 30%. The oncological benefits of lateral pelvic lymph node dissection (LPLND) in reducing local recurrence, particularly in the lateral compartment, have been demonstrated. Although LPLND is not standard in Western countries, technical improvements in minimally invasive surgery have resulted in rapid technical standardization of this complicated procedure. The feasibility and short- and long-term outcomes of laparoscopic and robotic LPLND have been reported widely. A minimally invasive approach has the advantages of less bleeding and providing a better surgical view of the deep pelvic anatomy than an open approach. With precise autonomic nerve preservation, postoperative genitourinary dysfunction has been reported to be minimal. We review recent evidence on the management of lateral nodal disease in rectal cancer and technical improvements of LPLND, focusing on laparoscopic and robotic LPLND.