Ryosuke Okamura

Laparoscopic Versus Open Lateral Lymph Node Dissection for Locally Advanced Low Rectal Cancer: A Subgroup Analysis of a Large Multicenter Cohort Study in Japan

BACKGROUND: Mesorectal excision with lateral lymph node dissection is the standard treatment for locally advanced low rectal cancer in Japan. However, the safety and feasibility of laparoscopic lateral lymph node dissection remain to be determined. OBJECTIVE: The purpose of this study was to evaluate the safety and feasibility of laparoscopic versus open lateral lymph node dissection for locally advanced low rectal cancer. DESIGN: This was a retrospective cohort study using an exact matching method. SETTING: We conducted a multicenter study of 69 specialized centers in Japan. PATIENTS: Patients with consecutive midrectal or low rectal adenocarcinoma cancer stage II to III who underwent mesorectal excision with curative intent between 2010 and 2011 were recruited. MAIN OUTCOME MEASURES: Short-term and oncological outcomes were compared between the laparoscopic and open-surgery groups. RESULTS: Of the 1500 eligible patients, 676 patients who underwent lateral lymph node dissection were analyzed, including 137 patients who were treated laparoscopically and 539 patients who were treated with open surgery. After matching, the patients were stratified into laparoscopic (n = 118) and open-surgery (n = 118) groups. Operative times in the overall cohort were significantly longer (461 vs 372 min) in the laparoscopic versus the open-surgery group. In the laparoscopic group, the blood loss volume was significantly smaller (193 vs 722 mL), with fewer instances of blood transfusion (7.3% vs 25.5%) compared with the open-surgery group. The postoperative complication rates were 35.8% and 43.6% for the laparoscopic and open-surgery groups (p = 0.10). The 3-year relapse-free survival rates were 80.3% and 72.6% for the laparoscopic and open-surgery groups (p = 0.07). LIMITATIONS: The study was limited by its retrospective design and potential selection bias. CONCLUSIONS: Laparoscopic lateral lymph node dissection is safe and feasible for cancer stage II to III low rectal cancer and is associated with similar oncological outcomes as open lateral lymph node dissection. See Video Abstract at http://links.lww.com/DCR/A334.

Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of CCR1+ Tumor-Associated Neutrophils through CCL15-CCR1 Axis

Purpose: We have reported loss of SMAD4 promotes expression of CCL15 from colorectal cancer to recruit CCR1+ myeloid cells through the CCL15-CCR1 axis, which contributes to invasion and liver metastasis. However, the molecular mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine whether similar mechanism is involved in the lung metastasis of colorectal cancer. Experimental Design: In a mouse model, we examined whether SMAD4 could affect the metastatic activity of colorectal cancer cells to the lung through the CCL15-CCR1 axis. We immunohistochemically analyzed expression of SMAD4, CCL15, and CCR1 with 107 clinical specimens of colorectal cancer lung metastases. We also characterized the CCR1+ myeloid cells using several cell-type–specific markers. Results: In a mouse model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1+ cells, promoting their metastatic activities to the lung. Immunohistochemical analysis of lung metastases from colorectal cancer patients revealed that CCL15 expression was significantly correlated with loss of SMAD4, and that CCL15-positive metastases recruited approximately 1.9 times more numbers of CCR1+ cells than CCL15-negative metastases. Importantly, patients with CCL15-positive metastases showed a significantly shorter relapse-free survival (RFS) than those with CCL15-negative metastases, and multivariate analysis indicated that CCL15 expression was an independent predictor of shorter RFS. Immunofluorescent staining showed that most CCR1+ cells around lung metastases were tumor-associated neutrophil, although a minor fraction was granulocytic myeloid-derived suppressor cell. Conclusions: CCL15-CCR1 axis may be a therapeutic target to prevent colorectal cancer lung metastasis. CCL15 can be a biomarker indicating poor prognosis of colorectal cancer patients with lung metastases. Clin Cancer Res; 23(3); 833–44. ©2016 AACR.

Multicenter analysis of transanal tube placement for prevention of anastomotic leak after low anterior resection

Anastomotic leak (AL) is a serious complication of low anterior resection (LAR). This study aimed to evaluate the effect of transanal tube placement for prevention of AL.

Open versus Laparoscopic Surgery for Advanced Low Rectal Cancer: A Large, Multicenter, Propensity Score Matched Cohort Study in Japan

Background: Laparoscopic surgery for rectal cancer is widely performed all over the world and several randomized controlled trials have been reported. However, the usefulness of laparoscopic surgery compared with open surgery has not been demonstrated sufficiently, especially for the low rectal area. Objective: The aim of this study was to investigate the hypothesis that laparoscopic primary tumor resection is safe and effective when compared with the open approach for locally advanced low rectal cancer. Patients and Methods: Data from patients with clinical stage II to III low rectal cancer below the peritoneal reflection were collected and analyzed. The operations were performed from 2010 to 2011. Short-term outcomes and long-term prognosis were analyzed with propensity score matching. Results: Of 1608 cases collated from 69 institutes, 1500 cases were eligible for analysis. The cases were matched into 482 laparoscopic and 482 open cases. The mean height of the tumor from the anal verge was 4.6 cm. Preoperative treatment was performed in 35% of the patients. The conversion rate from laparoscopic to open surgery was 5.2%. Estimated blood loss during laparoscopic surgery was significantly less than that during open surgery (90 vs 625 mL, P < 0.001). Overall, the occurrence of complications after laparoscopic surgeries was less than that after open surgeries (30.3% vs 39.2%, P = 0.005). Three-year overall survival rates were 89.9% [95% confidence interval (95% CI) 86.7–92.4] and 90.4% (95% CI 87.4–92.8) in the laparoscopic and open groups, respectively, and no significant difference was seen between the 2 groups. No significant difference was observed in recurrence-free survival (RFS) between the 2 groups (3-year RFS: 70.9%, 68.4 to 74.2 vs 71.8%, 67.5 to 75.7). Conclusion: Laparoscopic surgery could be considered as a treatment option for advanced, low rectal cancer below the peritoneal reflection, based on the short-term and long-term results of this large cohort study (UMIN-ID: UMIN000013919).

A cadaveric demonstration of visualization of the urethra using a lighted stent during transanal intersphincteric resection

Urethral injury is one of the crucial intraoperative complications during transanal total mesorectal excision (taTME) for male patients with low rectal cancer. Urethral injury can occur during the anterior dissection around the inferior lobe of the prostate and the membranous urethra. A tool to visualize the urethra around this area would be useful to avoid urethral injury. We report a cadaveric demonstration of visualization of the urethra using a lighted stent during transanal intersphincteric resection. The lighted stent (InfraVision Ureteral Kit, Stryker) was placed through the irrigation channel of a clear three-way urinary catheter. After the anterior dissection, the visibility of the lighted stent was investigated under the three laparoscopic light conditions: (1) normal intensity; (2) low intensity; and (3) turned-off. In the proper dissection plane that led to preservation of the urethra, the lighted stent was hardly visible under the normal-intensity condition, but it was clearly visible under the turned-off condition. In the improper dissection plane that led to urethral injury, the lighted stent was clearly visible under both the normal-intensity and the turned-off conditions. Visualization of the urethra using the lighted stent under the turned-off condition of the laparoscopic light can be useful to avoid inadvertent urethral injury during the anterior dissection of male taTME. Clear visibility of the lighted stent under the normal-intensity condition can indicate that the dissection plane is too close to the urethra.

Proposal of a stage-specific surveillance strategy for colorectal cancer patients: A retrospective analysis of Japanese large cohort

BACKGROUND Frequency and duration of postoperative surveillance for colorectal cancer patients remain debatable, and follow-up data regarding stage I or resected stage IV patients are limited. METHOD Cohort data from 22 institutions were retrospectively analyzed; 18,841 patients who underwent curative surgery for stage I to IV cancer were included. The cumulative incidence of recurrence, recurrence rate over surveillance period, and risk of recurrence each year after surgery were assessed. RESULTS Recurrence rates in stages I, II, III, and IV were 4.2%, 14%, 32%, and 75%, respectively. Over 80% of recurrences occurred within the first 2 years in stage IV, and 3 years in stages II and III, whereas 86.8% of recurrences occurred in 5 years in stage I. Among patients with 5-year recurrence-free survival, 2.2% in stage III and 7.0% in stage IV still experienced recurrence after the 5-year postoperative period. When the duration is extended to 6 years in stage III and 8 years in stage IV, approximately 1% over the surveillance period would be achieved. In stage I, the risk of recurrence each year after surgery was consistently low, whereas the risks in stages II, III, and IV were high in the early postoperative phase. The risk of recurrence each year in stages III and IV patients were over 2-fold and 6-fold higher than that in stage II, respectively. CONCLUSIONS Recurrence patterns were markedly different according to cancer stages. These results suggest that a stage-specific approach to postoperative surveillance may improve the efficiency of detecting recurrences.

Local control of sphincter-preserving procedures and abdominoperineal resection for locally advanced low rectal cancer: Propensity score matched analysis

Sphincter‐preserving procedures (SPPs) for surgical treatment of low‐lying rectal tumors have advanced considerably. However, their oncological safety for locally advanced low rectal cancer compared with abdominoperineal resection (APR) is contentious. We retrospectively analyzed cohort data of 1500 consecutive patients who underwent elective resection for stage II‐III rectal cancer between 2010 and 2011. Patients with tumors 2‐5 cm from the anal verge and clinical stage T3‐4 were eligible. Primary outcome was 3‐year local recurrence rate, and confounding effects were minimized by propensity score matching. The study involved 794 patients (456 SPPs and 338 APR). Before matching, candidates for APR were more likely to have lower and advanced lesions, whereas SPPs were carried out more often following preoperative treatment, by laparoscopic approach, and at institutions with higher case volume. After matching, 398 patients (199 each for SPPs and APR) were included in the analysis sample. Postoperative morbidity was similar between the SPPs and APR groups (38% vs 39%; RR 0.98, 95% CI 0.77‐1.27). Margin involvement was present in eight patients in the SPPs group (one and seven at the distal and radial margins, respectively) and in 12 patients in the APR group. No difference in 3‐year local recurrence rate was noted between the two groups (11% vs 14%; HR 0.77, 95% CI 0.42‐1.41). In this observational study, comparability was ensured by adjusting for possible confounding factors. Our results suggest that SPPs and APR for locally advanced low rectal cancer have demonstrably equivalent oncological local control.

Reply to "How should we define the no. 3b lesser curvature lymph node?"

We thank Yamashita et al. for responding to our recently published article, in which we showed that the rate of metastasis and the therapeutic index of no. 3b lymph nodes (LNs) were extremely low when the distal tumor border ended in the upper third of the stomach, suggesting that proximal gastrectomy with the exclusion of no. 3b lymphadenectomy could be an indication for treating most advanced gastric cancers localized to the upper third of the stomach [1]. Yamashita et al. have concerns regarding the definition of the border between nos. 3a and 3b [2]. In 2011, the Japanese Gastric Cancer Association (JGCA) redefined the no. 3 station by separating it into no. 3a [along the left gastric artery (LGA)] and no. 3b [along the right gastric artery (RGA)] substations [3]. However, as Yamashita et al. pointed out, the border between 3a and 3b is sometimes vague due to anastomosis of the branches of the LGA and the RGA. The LGA usually divides into two branches, an anterior branch distributing to the anterior surface and a posterior branch distributing to the posterior surface of the stomach. In most cases, the posterior branch anastomoses with the RGA, which gives branches to the distal part of the lesser curvature [4]. Indeed, this anastomosis was observed in 88 of the 90 (97.8%) cases in our series. In the same way that the right gastric vein and the left gastric vein form the coronary vein, the RGA and the posterior branch of the LGA form the coronary artery along the lesser curvature. Nevertheless, it is not practical to further subclassify no. 3a into an ‘‘anterior’’ no. 3a and a ‘‘posterior’’ no. 3a, and it is not possible to accurately distinguish no. 3b from ‘‘posterior’’ no. 3a. Furthermore, as Yamashita et al. mentioned, it is rarely feasible to identify a solely ‘‘posterior’’ no. 3b. Therefore, we assumed that the boundary line between nos. 3a and 3b was along the anterior terminal branch of the LGA. Unfortunately, in the current edition of the Japanese classification of gastric cancer, a figure illustrating the locations of LN stations did not show the most common variant of the vascular anatomy of the lesser curvature [3]. We propose a revision of that figure. Finally, Yamashita et al. suggest that the cross-section of the tumor comprising the different parts of the stomach (i.e., anterior or posterior wall, depending on the dominant area of invasion) may influence the indication for proximal gastrectomy, due to differences in lymphatic flow between the anterior and posterior surfaces of the lesser curvature. In our series, 2 of the 4 no. 3b-positive tumors had the distal border located in the lesser curvature, and the others were involved circumferentially, whereas no tumors were predominantly located in the anterior or posterior walls [1]. Thus, we cannot clearly elucidate on this matter. However, considering that the lymphatics along the RGA may provide only a minor lymphatic stream from the lesser curvature of the lower stomach [1], a cross-section of the tumor may not be able to provide additional perspectives to consider when performing proximal gastrectomy. This reply refers to the article available at doi:10.1007/s10120-0160638-9.

A New Prediction Model for Local Recurrence After Curative Rectal Cancer Surgery: Development and Validation as an Asian Collaborative Study

BACKGROUND: Local recurrence is one of the remaining problems in rectal and rectosigmoid cancer, and it is sometimes difficult to treat. OBJECTIVE: This study aimed to explore various factors that are highly related to local recurrence and to develop a new prediction model for local recurrence after curative resection. DESIGN: This is a retrospective cohort study SETTINGS: This study was conducted at 2 academic hospitals in Japan and Korea. PATIENTS: A total of 2237 patients with stage I to III rectal and rectosigmoid cancer who underwent a curative operation with a negative circumferential margin were selected. INTERVENTIONS: Surgical treatment was the intervention. MAIN OUTCOME MEASURES: Local recurrence was the primary outcome measure. RESULTS: A total of 1232 patients were selected, and rectosigmoid cancer with rare local recurrence (2/221) was excluded. A different set of 792 patients with rectal cancer were chosen for validation. Multivariate analysis showed the following factors as significant for local recurrence: poorly differentiated tumor (HR, 11.2; 95% CI, 4.5–28.0), tumor depth (HR, 5.0), lymph node metastasis (HR, 4.1), operative procedure (HR, 3.2), postoperative complications (HR, 2.9), tumor location (HR, 2.6), and CEA level (HR, 2.4); a new prediction score was created by using these factors. A poorly differentiated tumor was assigned 2 points, and all other factors were assigned 1 point each. Patients who scored more than 5 points (n = 21) were judged as “high risk,” with a 2-year local recurrence rate of 66.5%. The new predictive model could also separate the patients into different risk groups in the validation set. The high-risk group had higher recurrence rates than medium- and low-risk groups (2-year local recurrence rate: 41%, 15%, and 2.1%). LIMITATIONS: This study was limited by its retrospective nature and potential for selection bias. CONCLUSIONS: Seven factors were shown to be significantly correlated with the local recurrence of rectal cancer, and the usefulness of this new prediction model was demonstrated. See Video Abstract at http://links.lww.com/DCR/A429.

Evidence of Laparoscopic Surgery for Colorectal Cancer

Laparoscopic surgery for colorectal cancer is widely spread all over the world. In this chapter, the history of colorectal surgery and evidences of laparoscopic colorectal surgery were described. In these 200 years, colorectal cancer surgery has dramatically changed. In the last two decade, laparoscopic surgery appeared and greatly changed the history of colorectal cancer treatment. Many evidences have reported and many inventions are being developed in the laparoscopic surgical field. A combination of great knowledge and skilled technique with novel devices will lead to an excellent outcome for colorectal cancer patients.