The preoperative geriatric nutritional risk index (GNRI) is an independent prognostic factor in elderly patients underwent curative resection for colorectal cancer.

The world is becoming longer-lived, and the number of elderly colorectal cancer patients is increasing. It is very important to identify simple and inexpensive postoperative predictors in elderly colorectal cancer patients. The geriatric nutritional risk index (GNRI) is a marker of systemic nutrition and is associated with poor survival in various kinds of cancers. A few reports have investigated recurrence factors using preoperative GNRI with CRC (colorectal cancer) patients. This study aimed to investigate whether preoperative GNRI is associated with recurrence-free survival (RFS) and overall survival (OS) in elderly patients with CRC. This study retrospectively enrolled 259 patients with Stage I-III CRC who were more than 65 years old and underwent curative surgery at a single institution in 2012-2017. We classified them into low GNRI (RFS: ≤ 90.5, OS ≤ 101.1) group and high GNRI (RFS: > 90.5, OS > 101.1) group. Multivariable analyses showed low GNRI group was an independent risk factor for 3-year RFS (P = 0.006) and OS (P = 0.001) in the patients with CRC. Kaplan-Meier analysis showed 3-year RFS and 3-year OS were significantly worse in the low GNRI group than in high GNRI group (p = 0.001, 0.0037). A low-preoperative GNRI was significantly associated with a poor prognosis in elderly CRC patients.

Predicting Overall Survival Using Preoperative Nutritional and Inflammation Status for Colorectal Cancer.

AIM: It has been shown that nutritional status and inflammation correlate with survival in patients with various cancer types. In this study, we evaluated several kinds of nutritional and inflammation parameters in preoperative blood samples and constructed new risk model predicting survival in patients with colorectal cancer. PATIENTS AND METHODS: We retrospectively examined 286 patients with stage I-III colorectal cancer who had undergone curative resection at Teikyo University Hospital. The association between overall survival (OS) and nutritional status and inflammation factors were examined using Kaplan-Meier curves and log-rank tests. RESULTS: Serum albumin, cholesterol and C-reactive protein concentration, neutrophil count and platelet count were shown to be correlated with OS. We constructed a new risk model (nutrition inflammation status, NIS) using these factors, and compared it with other nutrition and inflammation models. CONCLUSION: NIS was useful as a new model for predicting OS in patients undergoing curative resection for colorectal cancer, compared with known models.

Impact of subdivision of pathological stage I colorectal cancer.

AIM: Stage II-IV colorectal cancers are subdivided according to TNM categories. However, stage I cases are a single category, despite the inclusion of both T1 and T2 cases, which may have different outcomes. The aim of this study was to evaluate the usefulness of subdividing stage I colorectal cancers by T category. METHODS: From 1984 to 2015, 844 patients with stage I colorectal cancer (T1: 446, T2: 398) underwent colorectal resection with lymph node dissection at three hospitals. The long-term survival and recurrence rates were compared between T1 and T2. A Cox regression analysis was used to evaluate the risk factors associated with cancer recurrence. RESULTS: A comparison of the T1 and T2 groups revealed significant differences in 5-year overall (95.9% vs 91.4%, P = .008), recurrence-free (94.8% vs 87.1%, P = .0007), and cancer-specific survival (97.6% vs 93.6%, P = .004), and in the overall (2.5% vs 6.8%, P = .003), local (0.2% vs 1.5%, P = .04), and lymph node recurrence rates (0.2% vs 1.5%, P = .04). All local and lymph node recurrences were associated with lower rectal cancer, and this difference was significant. The Cox multivariate analysis identified male sex (P = .01, hazard ratio: 4.00, 95% confidence interval: 1.38-11.55), T2 (P = .02, hazard ratio: 2.98, 95% confidence interval: 1.17-7.60), and venous invasion (P = .03, hazard ratio: 2.38, 95% confidence interval: 1.12-5.10) as risk factors for recurrence. CONCLUSIONS: The subdivision of stage I colorectal cancer according to T category clearly reflected the long-term outcomes.

Long-term Outcomes of a Randomized Controlled Trial of Single-incision Versus Multi-port Laparoscopic Colectomy for Colon Cancer.

OBJECTIVE: The aim of this study was to evaluate the long-term outcomes that were the secondary endpoints of a RCT of multi-port laparoscopic colectomy (MPC) versus SILC in colon cancer surgery. SUMMARY OF BACKGROUND DATA: The actual long-term outcomes, such as the 5-year RFS, OS, and recurrence patterns after surgery, have not been evaluated by a RCT. METHODS: Patients with histologically proven colon carcinoma located in the cecum, ascending, sigmoid or rectosigmoid colon clinically diagnosed as stage 0-III were eligible for this study. Patients were preoperatively randomized and underwent complete mesocolic excision. The 5-year RFS, OS, and recurrence patterns were analyzed (UMIN-CTR 000007220). RESULTS: Between March 1, 2012, and March 31, 2015, a total of 200 patients were randomly assigned to either the MPC arm (n = 100) or SILC arm (n = 100). The median follow-up for all patients was 61.0 months. An intention-to-treat analysis showed that the 5-year RFS was 91.0% [95% confidence interval (CI) 85.1%-96.9%] in the MPC arm and 88.0% (95% CI 82.1%-93.9%) in the SILC arm (hazard ratio: 1.37; 95% CI 0.58-3.24; P = 0.479). The 5-year OS was 95.0% (95% CI 91.1%-98.9%) in the MPC arm and 93.0% (87.1%-98.9%) in the SILC arm (hazard ratio: 1.39; 95% CI 0.44-4.39; P = 0.568). There were no significant differences in the recurrence patterns between the 2 arms. CONCLUSIONS: Even though the results of the 5-year OS and RFS in this trial were exploratory and underpowered, there were no statistically significant differences between the SILC and MPC arms. SILC may be an acceptable treatment option for select patients with colon cancer.

Impact of Colon Cancer Location on the Prognostic Significance of Nutritional Indexes and Inflammatory Markers.

BACKGROUND/AIM: The prognosis of colorectal cancer is reported to differ depending on the tumor site, and clinical differences depending on the site of occurrence have gained attention. The aim was to compare nutrition index and inflammatory markers according to the site of colon cancer. PATIENTS AND METHODS: We retrospectively analyzed 272 cases of stage I-III colon cancer (55% males, 45% females). The clinical characteristics, nutrition index and inflammatory markers were compared between patients with right colon cancer (RCC, n=119) and those with left colon cancer (LCC, n=153), and the relapse-free survival was then compared. RESULTS: RCC was associated with older age (p=0.03), female gender (p=0.003), higher T stage (p=0.01), elevated platelet/lymphocyte ratio (PLR) (p=0.009), and elevated CONUT score (p=0.028). The prognostic values differed between RCC and LCC (RCC: CONUT score, p=0.04, LCC: PLR, p=0.02). CONCLUSION: RCC was associated with an elevated CONUT score and PLR. In RCC, the CONUT score was an independent recurrence factor, and in LCC, the PLR was an independent recurrence factor.

Oncological outcomes of lateral lymph node dissection (LLND) for locally advanced rectal cancer: is LLND alone sufficient?

BACKGROUND: Lateral lymph node dissection (LLND) has been considered as the standard treatment strategy for locally advanced lower rectal cancer in Japan. Controversy remains around whether all patients require LLND. This study aims to examine the long-term outcomes of patients in which LLND was performed and clarify the value of LLND. METHOD: Consecutive 458 patients with lower rectal cancer who underwent total mesorectal excision (TME) plus LLND from 1992 to 2012 were included. The long-term outcomes and risk factors for recurrent in patients performed TME + LLND were examined. We assessed the impact of LLND on survival using an estimated therapeutic index. RESULTS: The incidence of LLNM was 15.5%. The 5-year RFS and OS rates of patients with LLNM were 40.9% and 47.7%, while patients without LLNM had a good prognosis. The 5-year local recurrence (LR) rate was 9.2%, and independent risk factors for LR were T4 and LLNM. The LR rate of patients with LLNM was high (22.8%). The LLNM rate of the groups with 0, 1, 2, 3, or 4 risk factors (male, tumor location < 4 cm from anal verge, T4, and MLNM) was 3.8%, 9.2%, 18.1%, and 50.0%. The 5-year OS of the groups was 96.2%, 86.1%, 69.7%, and 48.5%. CONCLUSION: Although patients with locally advanced lower rectal cancer who received LLND had a good prognosis, LLND alone was insufficient to control local recurrence in patients with metastatic lateral nodes.

Long-term results of a randomized study comparing open surgery and laparoscopic surgery in elderly colorectal cancer patients (Eld Lap study).

BACKGROUND: We reported favorable short-term results of laparoscopic surgery in a randomized study comparing open and laparoscopic surgery for elderly patients with colorectal cancer (CRC). The purpose of this study is to clarify the long-term outcomes of the laparoscopic surgery for elderly patients with CRC. METHODS: The inclusion criteria were ≥ 75 years, adenocarcinoma, ≤ T4a, M0 and elective surgery. The patients were randomly allocated to open or laparoscopic surgery according to the tumor location. The survival rates, recurrence and reasons for death were compared. RESULT: One hundred patients (right colon 43, left colon 28, rectum 29) were included in each group. Eight patients who underwent open surgery and 2 patients who underwent laparoscopic surgery were excluded from the analysis because of metastatic diseases and other malignancies found during the operations. One hundred ninety patients (98 open, 98 laparoscopic) were analyzed. There was no difference in the backgrounds excluding more patients with vascular invasion in the laparoscopic rectal cancer. There were no differences in the 5-year overall survival rate (open vs. laparoscopic; 78.9% vs. 82.1%, p = 0.638), 5-year disease-free survival rate (70.5% vs. 62.8%, p = 0.276), 5-year recurrence-free survival rate (76.1% vs. 72.1%, p = 0.419), or 5-year cancer-specific survival rate (86.1% vs. 80.5%, p = 0.208). No differences in survival were detected in the analyses of stage and tumor location. There was no significant difference in the overall recurrence rate or recurrence site. However, distant lymph node metastases and local recurrences were more common after laparoscopic surgery than after open surgery. There was no difference in the cause of death. More than half of the patients died from other diseases in both groups (57.9% vs. 52.6%, p = 0.765). CONCLUSION: Laparoscopic surgery showed similar long-term results compared to open surgery in elderly patients with CRC. Laparoscopic surgery is an effective surgical procedure for elderly patients with CRC.

The comparison of health-related quality of life and patient satisfaction between single-incision and multiport laparoscopic colectomy for cancer: A sub-study of a randomized, prospective clinical trial.

AIM: The present study clarified the effect on the health-related quality of life and patient satisfaction of single-incision laparoscopic colectomy compared with multiport laparoscopic colectomy for colorectal cancer. METHODS: We conducted a multicenter, randomized, control trial comparing single-incision and multiport laparoscopic colectomy for colon cancer. We performed a pre-planned secondary analysis of health-related quality of life and patient satisfaction data of 200 patients. Health-related quality of life was evaluated using the Japanese 36-item Short Form Health Survey (SF-36) version 2.0 before surgery and at 1 month after surgery. Patient satisfaction was compared using seven questionnaires at 1 month after surgery. RESULTS: One hundred patients were assigned to each group. After excluding 18 patients (9.0%) who did not complete the SF-36, 182 patients (91.0%) were included in the analysis (92 cases of single-incision laparoscopic colectomy and 90 cases of multiport laparoscopic colectomy). The SF-36 scores at 1 month after surgery were not significantly different between the two arms. The role physical, bodily pain, vitality and physical component summary were significantly lower at 1 month after surgery than before in both groups. However, the role emotional was significantly lower after surgery than before only in the single-incision laparoscopic colectomy group. In terms of patient satisfaction at 1 month after surgery, there were no significant differences in any of the seven items on the questionnaire. CONCLUSIONS: Single-incision laparoscopic colectomy was similar to multiport laparoscopic colectomy in terms of health-related quality of life and patient satisfaction. However, single-incision laparoscopic colectomy may be inferior than multiport laparoscopic colectomy in terms of the role emotional.

The pretreatment Controlling Nutritional Status (CONUT) score is an independent prognostic factor in patients undergoing resection for colorectal cancer.

The Controlling Nutritional Status (CONUT) score is a marker of nutrition and is associated with poor survival in various kinds of cancers. However, no reports have yet compared risk factors for colorectal cancer recurrence using a nutritional index. We assessed the predictive value of the CONUT score compared with the modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) in colorectal cancer (CRC) patients. We performed a retrospective cohort study of the medical records of 336 consecutive patients with stage I-I I I CRC who underwent curative resection at a single institution in 2012-2017. Univariate and multivariate analyses were conducted to identify prognostic factors associated with relapse-free survival (RFS) and overall survival (OS). The low CONUT score group exhibited higher RFS and longer OS compared to the high CONUT score group (82.2% vs. 63.3%, p = 0.002 and 95.5% and 86.2%, p = 0.005, respectively). The Akaike's information criterion values of each index for RFS and OS were superior in CONUT score (723.71 and 315.46, respectively) compared to those of PNI (726.95 and 316.52) and mGPS (728.15 and 318.07, respectively). The CONUT score was found to be a good predictor of RFS and OS in patients with resectable CRC.

Long-term survival outcomes following laparoscopic surgery for clinical stage 0/I rectal carcinoma.

AIM: To clarify and evaluate the long-term outcomes of laparoscopic surgery for clinical stage 0/I rectal carcinoma patients. METHODS: This single-arm phase II trial involved accredited surgeons from 43 Japanese institutions. Patients were registered preoperatively. The planned sample size was 490. The primary endpoint was overall survival, and long-term outcomes were evaluated. RESULTS: A total of 495 patients were registered between February 2008 and August 2010. Eight patients (1.6%) required conversion to open surgery. Sphincter-preserving procedures were performed in 477 (97%) patients. Positive radial resection margin was found in two (0.4%) patients. Of 490 patients, 22, 314, 38, 115, and one patient had final pathological stages (p-stage) 0, I, II, III, and IV, respectively. Pathologically, 31.4% (154/490) of the patients did not have p-stage 0/I. The 5-year overall survival (OS) rates in p-stages 0, I, II, and III were 100%, 98%, 97%, and 94%, respectively. The 5-year OS of all patients at 96.6% (95% CI 94.6-97.9) was significantly better than the expected 5-year OS of 81.1% (P < .0001). The 5-year relapse-free survival in p-stages 0, I, II, and III were 100%, 93%, 81%, and 79%, respectively. The 5-year relapse-free survival of all patients was 90.1%. Fifty patients (10.2%) had recurrence; lung recurrence was found in 22 patients, local recurrence in 14, liver in seven, distant lymph node in nine, and bone in three. CONCLUSIONS: Laparoscopic surgery for clinical stage 0/I rectal carcinoma has feasible long-term outcomes. (ClinicalTrials.gov No.NCT00635466.).

The effect of TJ-28 (Eppikajutsuto) on the prevention of hand-foot syndrome using Capecitabine for colorectal cancer: The Yokohama Clinical Oncology Group Study (YCOG1102).

BACKGROUND: Eppikajututo (TJ-28, a Kampo medicine) is effective against rheumatoid arthritis and eczema. We conducted a randomized comparative trial to assess the efficacy of TJ-28 for preventing hand-foot syndrome (HFS) as a complication of adjuvant chemotherapy using capecitabine. METHODS: The present study was a multi-institutional randomized-controlled trial (UMIN000005899). Colorectal cancer patients scheduled to receive capecitabine chemotherapy as adjuvant therapy were randomly assigned to receive TJ-28 (7500 mg/day) or oral pyridoxine (60 mg/day). Patients were monitored for the development of grade ≥ 2 HFS according to the National Cancer Institute Common Toxicity Criteria until chemotherapy completion. RESULTS: Twenty-two patients were enrolled in this study. The relative dose intensity of capecitabine was 76.2% in the TJ-28 group and 68.2% in the pyridoxine group. Grade ≥ 2 HFS developed in 6 (50.0%) of 12 TJ-28 patients and in 4 (40.0%) of 10 pyridoxine patients. Chemotherapy treatment failure was observed in seven patients, mainly due to HFS, liver dysfunction, diarrhea, and neutropenia. Chemotherapy treatment failure due to HFS occurred in none of the TJ-28 group and 2 patients (20.0%) in the pyridoxine group (p = 0.114). CONCLUSION: Capecitabine-associated HFS was not markedly prevented by TJ-28 compared with pyridoxine. However, TJ-28 might support the continuation of chemotherapy with capecitabine. Further studies are warranted to clarify the benefits of TJ-28.

Transitional impact of short- and long-term outcomes of a randomized controlled trial to evaluate laparoscopic versus open surgery for colorectal cancer from Japan Clinical Oncology Group Study JCOG0404.

BACKGROUND: The JCOG0404 randomized controlled trial conducted to compare laparoscopic surgery (LAP) with open surgery (OP) for stage II/III colon cancer showed better short-term outcomes and equal long-term outcomes of LAP versus OP. Technical instrumentation of surgery and anticancer agents given during the registration period might have affected the outcomes. AIM: To evaluate outcomes according to the registration periods. METHODS: The overall registration period was divided into three periods (first: 2004-2005, second: 2006-2007 and third: 2008-2009). Short-term and long-term outcomes were compared between registration periods. RESULTS: In total, 1057 patients were registered. Numbers of patients undergoing each approach for each of the three periods (1st/2nd/3rd) were 528 for OP (106/244/178) and 529 for LAP (106/246/177). Operation time (minutes) did not change between the periods for OP (160/156/161) or LAP (205/211/219). Blood loss (mL) gradually decreased in the latter two periods: (119/80/75) for OP and (35/28/25) for LAP. Incidence of complications (%) decreased in the latter periods for OP (27.6/20.3/21.3), whereas that for LAP remained consistently low (14.3/14.8/13.6). There was no particular trend in 5-year overall survival and recurrence-free survival depending on the period regardless of treatment. D3 dissection rates were 95% or more for all periods in both groups. CONCLUSIONS: Operation time and survival rates did not change over time, whereas blood loss in OP improved in the latter periods. Quality control applied in this trial might have been effective in producing such safe endpoints. (ClinicalTrials.gov, number NCT00147134, UMIN Clinical Trials Registry, number C000000105.).

Randomized controlled trial to evaluate laparoscopic versus open surgery in transverse and descending colon cancer patients.

BACKGROUND: The safety and efficacy of laparoscopic surgery for transverse and descending colon cancer remain controversial. This study aimed to evaluate the short- and long-term outcomes of this procedure. METHODS: We conducted a single-institutional randomized controlled trial. Patients with transverse or descending colon cancer were randomly allocated to receive laparoscopic surgery (LAC) or conventional open surgery (OC). The primary endpoint was the overall complication rate between the two groups. The secondary endpoints were the length of the postoperative hospital stay, the health-related quality of life (HRQOL) score (at 1, 6, and 12 months after surgery), the 5-year relapse-free survival (RFS), and the 5-year overall survival (OS). RESULTS: Between August 2008 and October 2012, a total of 66 patients were enrolled (33 in the LAC group and 33 in the OC group). The patient characteristics showed no significant differences between the two groups. The complication rates (≥ grade 3) were 6.1% in the LAC group and 12.1% in the OC group (p = 0.392). The length of postoperative stay was not significantly different between the two groups. Regarding the HRQOL, the physical functioning, role physical, bodily pain, social functioning, mental health, and role component summary at 1 month after surgery and the social functioning and mental health at 6 months after surgery were better in the LAC group than in the OC group. The 5-year RFS and OS rates were similar between the LAC and OC groups (RFS 90.5% and 87.3%, respectively, p = 0.752; OS 93.3% and 100.0%, respectively, p = 0.543). CONCLUSIONS: The short- and long-term outcomes of laparoscopic surgery for transverse and descending colon cancer are almost equal to those of open surgery. Laparoscopic resection is a better choice than open surgery for managing this cancer with regard to the short- and mid-term QOL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01861691 .

Short-term and long-term results of a randomized study comparing high tie and low tie inferior mesenteric artery ligation in laparoscopic rectal anterior resection: subanalysis of the HTLT (High tie vs. low tie) study.

BACKGROUND: In rectal anterior resection, a clear consensus regarding the optimal level of inferior mesenteric artery (IMA) ligation does not exist because of a lack of randomized trials. We conducted a randomized trial to determine if the IMA should be tied at the origin (high tie, HT) or distal to the left colic artery (low tie, LT) (HTLT study). This study is a subanalysis of HTLT study for laparoscopic surgery. METHODS: All candidates were randomly divided into the HT or LT groups. The lymph node dissection around the origin of the IMA was performed in the LT group. The stratified factor was the approach (open or laparoscopy). Evaluation parameters were operative factors, short-term and long-term results. In the present study, laparoscopic surgeries were examined as subgroup analysis. RESULTS: From June 2006 to September 2012, 331 patients were registered. Two hundred and fifteen patients (107 for HT: 108 for LT) underwent laparoscopic surgeries. There was no difference between the groups in background. The incidence of anastomotic leakage (HT: LT %) showed no significant differences for grade 2 or higher (11.2:9.3), and grade 3 or higher (2.8:4.6). There were no differences in operative time (200:205 min), blood loss (15:15 ml), number of dissected lymph nodes (22:20), and postoperative hospital stay (10:10 days). The incidence of bowel obstruction in HT was significant (3.7 vs. 0%, p = 0.043). There were no significant differences in overall survival (5-year: 91.3 vs. 90.2%, p = 0.850) and disease-free survival (5-year: 83.2 vs. 78.0%, p = 0.525). There were no differences in the first recurrent site and death reason between both groups. The risk factors for leakage were being male and an anastomotic level in a multivariate analysis by logistic regression. CONCLUSION: The IMA ligation level was unrelated to anastomotic leakage. No significant difference was detected in long-term results between HT and LT.

A randomised-controlled trial of 1-year adjuvant chemotherapy with oral tegafur-uracil versus surgery alone in stage II colon cancer: SACURA trial.

BACKGROUND: Efficacy of adjuvant chemotherapy in patients with stage II colon cancer is still controversial. The SACURA trial is a randomised-controlled study evaluating the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer. METHODS: Patients were randomly assigned to the surgery-alone group or UFT group (UFT at 500-600 mg/day for 5 days, followed by 2-day rest, for 1 year). The primary end-point was disease-free survival (DFS). Target sample size was 2000, determined with one-sided alpha of 0.05, power of 0.9 and assumed hazard ratio (HR) 0.729. RESULTS: A total of 1982 patients (997 in the surgery-alone group and 985 in the UFT group) were analysed. Median follow-up was 69.5 months, median age was 66 years and for stage IIA/IIB/IIC, the distribution was 84%/13%/3%. The 5-year DFS rate was 78.4% in the surgery-alone group and 80.2% in the UFT group. The HR for DFS was 0.91 (95% confidence interval [CI], 0.75-1.10; p = 0.31); superiority of UFT was not demonstrated. Approximately 9% of patients experienced second cancers, which consist 40.7% of the DFS events. The 5-year relapse-free and overall survival rates of the surgery-alone and UFT group were 84.6% and 87.2% (HR, 0.82; 95% CI, 0.65-1.04) and 94.3% and 94.5% (HR, 0.93; 95% CI, 0.66-1.31), respectively. Subgroup analysis failed to disclose superiority in prognosis of adding UFT to the patients with risk factors for recurrence. CONCLUSIONS: Superiority of 1-year adjuvant UFT over surgery alone was not demonstrated in stage II colon cancer. Patients with risk factors for recurrence did not benefit from UFT. TRIAL REGISTRATION: ClinicalTrials. Gov. #NCT00392899.

Absorptive anti-adhesion barrier for the prevention of bowel obstruction after laparoscopic colorectal cancer surgery.

OBJECTIVES: The protective efficacy of an absorptive adhesion prevention product (SeprafilmⓇ) against bowel obstruction (BO) during open surgery was demonstrated in a large-scale randomized controlled clinical trial in Europe and America. However, the efficacy of Seprafilm against BO in laparoscopic surgery remains uncertain. The objective of this study was to clarify the protective efficacy of Seprafilm against BO after laparoscopic surgery for colorectal cancer. METHODS: From 2009 to 2016, 1328 laparoscopic colorectal resections were performed for colorectal cancer. From 2009, Seprafilm was used for preventing BO in laparoscopic colorectal surgery. The incidence of BO and short-term results were compared between the Seprafilm and non-Seprafilm groups after propensity score matching. RESULTS: Propensity scoring generated 270 matched patients per group for the comparisons between the Seprafilm and non-Seprafilm groups. The two groups showed no significant differences regarding patients' backgrounds. Among all patients, 73.1% (19/26) of BO occurred within 30 days after the surgery. Significantly lower incidences of all grade (2.6% vs. 7.0%; p = 0.016) and grade 2 + 3a (1.5% vs. 5.2%; p = 0.017) BO were observed in the Seprafilm group than in the non-Seprafilm group; no significant difference regarding grade 3b BO (1.1% vs. 1.9%; p = 0.476) was found. A significant difference in BO within 30 days was also noted between the two groups (1.9% vs. 5.2%, p = 0.036). There were no significant differences between the groups regarding anastomotic leakage and deep surgical site infection. CONCLUSIONS: Seprafilm was useful for preventing BO, requiring decompression therapy of the bowel, after laparoscopic colorectal surgery without increasing adverse events.

Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial.

BACKGROUND: Adjuvant chemotherapy with oral fluoropyrimidine alone after D3/D2 lymph node dissection improves disease-free survival and overall survival in patients with stage III colon cancer. Adjuvant S-1 has been shown to be non-inferior to uracil and tegafur plus leucovorin in terms of disease-free survival. This study aims to confirm the non-inferiority of S-1 compared with capecitabine as adjuvant treatment in patients with stage III colorectal cancer. METHODS: This study was an open-label, non-inferiority, randomised, phase 3, multicentre trial done in 56 Japanese centres to assess the non-inferiority of S-1 to capecitabine as adjuvant chemotherapy. Eligible patients were aged 20-80 years with stage III colorectal adenocarcinoma, as defined by the presence of an inferior margin of the primary tumour above the peritoneal reflection; R0 resection; and colectomy with D3 or D2 lymph node dissection. Patients were randomly assigned (1:1) to receive eight courses of capecitabine (1250 mg/m2 orally twice daily, days 1-14, every 21 days) or four courses of S-1 (40 mg/m2 orally twice daily, days 1-28, every 42 days). Randomisation was done via phone call, fax, or web-based systems to the Japan Clinical Oncology Group Data Center and used a minimisation method with a random component adjusted by institution, tumour location (colon vs rectosigmoid and upper rectum), number of positive lymph node metastases (≤3 vs ≥4), and surgical technique (conventional vs non-touch isolation). The primary endpoint was disease-free survival with a non-inferiority margin for the hazard ratio (HR) set at 1·24, analysed by intention to treat. This trial was registered with UMIN Clinical Trial Registry, number UMIN000003272. FINDINGS: Between March 1, 2010, and Aug 23, 2013, 1564 patients were randomly assigned to capecitabine (n=782) or S-1 (n=782), all of whom were included in the efficacy analysis; 777 patients in the capecitabine group and 768 in the S-1 group were included in the safety analysis. At the prespecified second interim analysis after final accrual, 258 (48%) of 535 required events were reported, and the Data and Safety Monitoring Committee recommended early publication because S-1 could not show non-inferiority compared with capecitabine for disease-free survival. With a median follow-up of 23·7 months (IQR 14·1-35·2), 3-year disease-free survival was 82·0% (95% CI 78·5-85·0) for the capecitabine group and 77·9% (74·1-81·1) for the S-1 group (HR 1·23, 99·05% CI 0·89-1·70; one-sided pnon-inferiority=0·46). The most frequent grade 3 or higher adverse events in the capecitabine group were hand-foot skin reactions (123 [16%] of 777 patients), and in the S-1 group were diarrhoea (64 [8%] of 768 patients) and neutropenia (61 [8%]). There was one (<1%) treatment-related death in each group. INTERPRETATION: Adjuvant capecitabine remains one of the standard treatments for stage III colorectal cancer in Japan; S-1 is not recommended. FUNDING: National Cancer Center and Ministry of Health, Labour and Welfare of Japan.

Survival outcomes following laparoscopic versus open D3 dissection for stage II or III colon cancer (JCOG0404): a phase 3, randomised controlled trial.

BACKGROUND: Although benefits of laparoscopic surgery compared with open surgery have been suggested, the long-term survival of patients undergoing laparoscopic surgery for colon cancer requiring Japanese D3 dissection remains unclear. We did a randomised controlled trial to establish non-inferiority of laparoscopic surgery to open surgery. METHODS: We did an open-label, multi-institutional, randomised, two-arm phase 3 trial in 30 hospitals in Japan. Patients aged 20-75 years who had histologically proven colon cancer; tumours located in the caecum or ascending, sigmoid, or rectosigmoid colon; T3 or deeper lesions without involvement of other organs, node stages N0-2, and metastasis stage M0; and tumour size of 8 cm or smaller were included. Only accredited surgeons did surgery as an operator or instructor. Patients were randomly assigned (1:1) preoperatively to undergo D3 resection either by an open route or a laparoscopic route, via phone call or fax to the Japan Clinical Oncology Group (JCOG) Data Center. Randomisation used a minimisation method with a biased-coin assignment according to tumour location (caecum, ascending vs sigmoid, rectosigmoid) and institution. The primary endpoint was overall survival and was analysed by intention to treat. The non-inferiority margin for the hazard ratio (HR) was set at 1·366. This study is registered with UMIN Clinical Trials Registry, number C000000105, and ClinicalTrials.gov, number NCT00147134. FINDINGS: Between Oct 1, 2004, and March 27, 2009, 1057 patients were randomly assigned to either open surgery (n=528) or laparoscopic surgery (n=529). 5-year overall survival was 90·4% (95% CI 87·5-92·6) for open surgery and 91·8% (89·1-93·8) for laparoscopic surgery. Laparoscopic D3 surgery was not non-inferior to open surgery for overall survival (HR 1·06, 90% CI 0·79-1·41; pnon-inferiority=0·073). 65 (13%) patients in the open surgery group and 53 (10%) patients in the laparoscopic surgery group had grade 2-4 adverse events. Grade 2-4 adverse events included diarrhoea (15 [3%] in the open surgery group vs 14 [3%] in the laparoscopic surgery group), paralytic ileus (six [1%] vs nine [2%]), and small intestine bowel obstruction (16 [3%] vs 11 [2%]). Two treatment-related deaths occurred in the open surgery group: one patient died 7 days after surgery (probably due to myocardial infarction), and one patient died from febrile neutropenia, pneumonia, diarrhoea, and gastrointestinal haemorrhage during postoperative chemotherapy. INTERPRETATION: Laparoscopic D3 surgery was not non-inferior to open D3 surgery in terms of overall survival for patients with stage II or III colon cancer. However, because overall survival in both groups was similar and better than expected, laparoscopic D3 surgery could be an acceptable treatment option for patients with stage II or III colon cancer. FUNDING: National Cancer Center Research and Development Fund, Grant-in-Aid for Cancer Research, and Health and Labour Sciences Research Grant for Clinical Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

Midterm follow-up of a randomized trial of open surgery versus laparoscopic surgery in elderly patients with colorectal cancer.

BACKGROUND: Laparoscopic surgery has been widely accepted for the treatment of colorectal cancer; however, long-term outcomes in elderly patients remain controversial. The midterm results of a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer are presented. METHODS: This was a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer. The primary outcome was complication rate, and secondary outcomes included 3-year recurrence-free survival and overall survival. A total of 200 patients were randomly assigned to open surgery or laparoscopic surgery between 2008 and 2012. The main study objective was to compare the midterm outcomes of open surgery with those of laparoscopic surgery in elderly patients with colorectal cancer. This trial is registered with Clinical Trials.gov (NCT01862562). RESULTS: There were no differences between the laparoscopic surgery group and open surgery group in the 3-year overall survival rate (91.5% for laparoscopic surgery vs. 90.6% for open surgery, p = 0.638) or the 3-year recurrence-free survival rate (84.8% for laparoscopic surgery vs. 88.2% for open surgery, p = 0.324). The local recurrence rate was significantly higher in the laparoscopic surgery group than in the open surgery group in rectal cancer (13.8% for laparoscopic surgery vs. 0% for open surgery, p = 0.038). In subgroup analysis according to tumor location, there were no significant differences in the 3-year overall survival rate or 3-year recurrence-free survival rate between the two treatment groups. CONCLUSION: The midterm outcomes of laparoscopic surgery are similar to those of open surgery in elderly patients with colorectal cancer.

Systematic review of laparoscopic vs open surgery for colorectal cancer in elderly patients.

AIM: To verify the safety and validity of laparoscopic surgery for the treatment of colorectal cancer in elderly patients. METHODS: A meta-analysis was performed of a systematic search of studies on an electronic database. Studies that compared laparoscopic colectomy (LAC) in elderly colorectal cancer patients with open colectomy (OC) were retrieved, and their short and long-term outcomes compared. Elderly people were defined as 65 years old or more. Inclusion criteria were set at: Resection of colorectal cancer, comparison between laparoscopic and OC and no significant difference in backgrounds between groups. RESULTS: Fifteen studies were identified for analysis. LAC was performed on 1436 patients, and OC performed on 1810 patients. In analyses of short-term outcomes, operation time for LAC was longer than for OC (mean difference = 34.4162, 95%CI: 17.8473-50.9851, P < 0.0001). The following clinical parameters were lower in LAC than in OC: Amount of estimated blood loss (mean difference = -93.3738, 95%CI: -132.3437 to -54.4039, P < 0.0001), overall morbidity (OR = 0.5427, 95%CI: 0.4425-0.6655, P < 0.0001), incisional surgical site infection (OR = 0.6262, 95%CI: 0.4310-0.9097, P = 0.0140), bowel obstruction and ileus (OR = 0.6248, 95%CI: 0.4519-0.8638, P = 0.0044) and cardiovascular complications (OR = 0.4767, 95%CI: 0.2805-0.8101, P = 0.0062). In analyses of long-term outcomes (median follow-up period: 36.4 mo in LAC, 34.3 mo in OC), there was no significant difference in overall survival (mean difference = 0.8321, 95%CI: 0.5331-1.2990, P = 0.4187) and disease specific survival (mean difference = 1.0254, 95%CI: 0.6707-1.5675, P = 0.9209). There was also no significant difference in the number of dissected lymph nodes (mean difference = -0.1360, 95%CI: -4.0553-3.7833, P = 0.9458). CONCLUSION: LAC in elderly colorectal cancer patients had benefits in short-term outcomes compared with OC except operation time. The long-term outcomes and oncological clearance of LAC were similar to that of OC. These results support the assertion that LAC is an effective procedure for elderly patients with colorectal cancer.