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Late complications following gastric cancer surgery, including postgastrectomy syndromes, are complex problems requiring a solution. Reported risk factors for developing late complications include surgery-related factors, such as the surgical approach and the extent of resection and reconstruction. However, this has not been assessed in a prospective study with a large sample size. Therefore, this study aimed to evaluate associations between surgery-related factors and the development of late complications. Data from the JCOG0912 trial were used. It compared laparoscopy-assisted distal gastrectomy (LADG) to open distal gastrectomy (ODG) in clinical stage I gastric cancer patients.This study included 881/921 patients enrolled in the JCOG0912 trial. The incidence of late complications was compared between the ODG and the LADG arms. In addition, associations between surgery-related factors and the development of late complications were assessed by multivariable analyses using the proportional odds model to identify relevant risk factors.There was no difference in the type or number of patients with late complications between the LADG and the ODG arms. The multivariable analysis for each late complication revealed that the Billroth-I reconstruction (vs. R-en-Y or Billroth-II) had a lower risk of cholecystitis [odds ratio (OR) 0.187, 95% confidence interval (CI) 0.039-0.905, P = 0.037] or ileus (OR 0.116, 95%CI 0.033-0.406, P 0.001), and pylorus-preserving gastrectomy (vs. R-en-Y or Billroth-II) had a higher risk of reflux esophagitis (OR 3.348, 95% CI 1.371-8.176, P = 0.008). The surgical approach was not a risk factor for any late complications.Differences in surgical approaches did not constitute a risk for developing late complications after gastrectomy. Billroth-I reconstruction reduced the risk of ileus and cholecystitis, but pylorus-preserving gastrectomy carried a risk for reflux esophagitis.

We herein investigated the association between early tumor shrinkage (ETS) and depth of response (DpR) and clinical outcomes in patients with metastatic esophageal cancer treated with 2-weekly docetaxel combined with cisplatin plus fluorouracil (bDCF) using data from the JCOG0807, a phase I/II trial of bDCF as first-line chemotherapy for metastatic esophageal cancer.ETS was defined as a percent decrease in the sum of the target lesions' longest diameter after 8 weeks, whereas DpR was defined as a percentage of the maximal tumor shrinkage during the treatment course. Multivariable analyses were conducted to identify significant prognostic variables in progression-free survival (PFS) and overall survival (OS): one for ETS and covariates, and another for DpR and covariates.Among 53 patients, 35 patients with ETS ≥ 20% (66.0%) had longer PFS (7.5 vs. 3.4 months, hazard ratio [HR]: 0.26, 95% confidence interval [95% CI] 0.14-0.49), OS (13.8 vs. 6.1 months, HR 0.20, 95% CI 0.11-0.39), and PPS (6.4 vs. 2.8 months, HR 0.38, 95% CI 0.20-0.72) than those with ETS 20%. In addition, 37 patients with DpR ≥ 30% (69.8%) had longer PFS (7.5 vs. 2.9 months, HR 0.17, 95% CI 0.08-0.34), OS (13.8 vs. 6.0 months, HR 0.14, 95% CI 0.07-0.27), and PPS (6.8 vs. 2.8 months, HR 0.30, 95% CI 0.15-0.58) than those with DpR 30%. Multivariable analyses revealed that each ETS and DpR was an independent factor of longer PFS and OS.ETS and DpR might be associated with clinical outcomes in patients with metastatic esophageal cancer treated with bDCF.

The efficacy of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (GC) has recently been revealed. The use of tumor regression grade (TRG) has also been reported, where TRG has been positively correlated with prognosis. However, previous studies included several types of GC and treatments. The prognostic value of TRG in a specific population has not been well investigated. Therefore, a meta-analysis of studies on gastric adenocarcinomas treated with NAC that evaluate the prognostic impact of TRG on overall survival (OS) must be conducted to provide more accurate evidence.A meta-analysis of studies reporting gastric cancer/gastroesophageal junction (GC/GEJ) adenocarcinoma treated with NAC was performed. Studies that calculate the number of responders and non-responders were considered eligible. The risk ratio (RR) was obtained from the eligible studies, and a random-effects model was used for pooled analysis.Fourteen studies, which included a total of 1660 patients, were included in the current study. The responders showed better OS (RR: 0.53, 95% confidence interval (CI): 0.46-0.60, P 0.001). All subgroup analyses (Asian vs. non-Asian populations, different TRGs, GC/GEJ vs. GC) also revealed the statistical dominance of better TRG over better OS. However, the possibility of some publication bias remained.In this meta-analysis, better TRG was associated with better OS. However, the histology, configuration, and location of GC varied. Hence, a more subdivided analysis is recommended to obtain more solid evidence.

This study assessed lymph node metastasis characteristics to investigate the optimal treatment strategy for early and advanced remnant gastric cancer (RGC).Cases of completion gastrectomy for RGC were enrolled. The frequency of lymph node metastasis was investigated, and risk factors for metastasis were identified. The clinical significance of completion gastrectomy in early remnant gastric carcinoma cases was also examined. In advanced cases, 3-year survival was analysed to investigate the prognostic importance of lymph node dissection and splenectomy.Seventy-nine patients were included. Lymphatic invasion and pathological tumour depth were identified as risk factors for lymph node metastasis. There was no metastasis in the pT1 cases. In advanced cases, the incidence of lymph node #10 and jejunal lymph node metastasis was 8.3-10.0% and 17.6%, respectively. Prognosis was found to be unrelated with splenectomy.Lymphatic invasion and pathological T status were identified as risk factors for LN metastasis in RGC. Additional gastrectomy after ESD might not be mandatory for early RGC cases. For advanced RGC cases, splenectomy might not improve patient prognosis, however, lymph node dissection of jejunal and #10 lymph nodes should be considered due to its high incidence of metastasis.

Background Extranodal extension (ENE) is a prognostic factor for several types of malignant tumors, including esophageal cancer. Although the prognostic value of ENE has been investigated in esophageal cancer, its clinical utility warrants further investigation. Materials and methods This retrospective single-center study evaluated 105 patients who underwent esophagectomy and had histologically node-positive metastasis between January 2007 and June 2017. The abilities of ENE to predict overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and log-rank test, as well as Cox proportional hazard models. Subgroup analyses of ENE's prognostic value were performed according to each pathological tumor-node-metastasis category. Results Significant differences according to ENE status were observed in the Kaplan-Meier analyses of OS (p = 0.001) and DFS (p = 0.001), as well as in the Cox proportional hazards models for OS (p = 0.009) and DFS (p = 0.012). Relative to patients without ENE, patients with ENE had significantly poorer OS if they also had pT3 status, pN1 status, or pathological stage III disease. However, no significant differences were observed in the subgroup analyses of pN3 status and pathological stage IV disease. Conclusions Among patients with esophageal cancer, ENE status can predict a poor prognosis and may be useful for patient stratification. However, the prognostic value of ENE status may be limited to patients with specific pathological factors.

381 Background: Postoperative S-1 (80 mg/m2/day for 4 weeks and 2 weeks rest in one course) for 1 year corresponding to 8 courses is a standard adjuvant chemotherapy for pathological stage (pStage) II gastric cancer. To shorten the duration of S-1 chemotherapy, we conducted a phase III trial to confirm non-inferiority in relapse-free survival (RFS) of 4 courses of S-1 to 8 courses of S-1 for pStage II gastric cancer. When 590 patients were enrolled, the study was closed at the first interim analysis because of futility. The RFS at 3 years was 89.8% for 4-courses and 93.1% for 8-courses (HR 1.84, 95% confidence interval (CI) 0.93-3.63). This is a final 5-year follow-up results of this study. Methods: Key eligibility criteria were pStage II except for T1 and T3N0 (7th edition of TNM), ECOG performance status 0-1, R0 resection with D2 lymph node dissection for >clinical stage (cStage) II or D1+ lymph node dissection for cStage I, within 7 weeks after surgery, and age between 20 and 80 years. The total sample size was determined to be 1,000 with a 3-year RFS of 85% in both arms and non-inferiority margin of hazard ratio (HR) of 1.37, with one-sided alpha of 5% and 80% power. Results: Between Feb 2012 and Mar 2017, 590 patients, 295 for each arm, were enrolled. When closing the study, the patients who were allocated to the 4-courses arm were informed of the primary results and the recommendation to continue S-1 until 8 courses as an off-protocol when they were receiving S-1. The cut-off date for the final follow-up data was March 22, 2022 with a median follow-up period for surviving patients of 6.0 years (IQR; 5.0-7.2). In 4-courses arm, 27 patients were receiving S-1 when the study was closed at the interim analysis. Among them, 22 patients expressed their will to continue until 8 courses. The RFS at 3/5 years was 90.1%/85.6% for 4-courses and 92.2%/87.7% for 8-courses (HR 1.27, 95% CI 0.85-1.89). The overall survival at 3/5 years was 93.2%/88.6 for 4-courses and 94.9%/89.7 for the 8-courses (HR 1.12, 95% CI 0.72-1.75). The HR of the cumulative incidence of the recurrence was 1.38 (95% CI 0.85-2.24) for the 4-courses against 8-courses. Recurrence was frequently observed in patients who received up to 4 courses of S-1 (38 for 4-courses vs. 28 for 8 courses). The HR of the cumulative incidence of the peritoneal recurrence was 1.54 (95% CI 0.82-2.89) for the 4-courses against 8-courses. Conclusions: This final follow-up data confirmed the primary results presented at the interim analysis. S-1 adjuvant chemotherapy for 1 year for pStage II gastric cancer is highly recommended. Clinical trial information: 000007306 .

Gastric cancer (GC) patients with peritoneal metastasis are defined as stage IV in the Japanese classification of GC. For patients with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) and/or localized peritoneal metastasis (P1a), gastrectomy followed by S1 monotherapy is one of the most widely accepted therapeutic strategy in Japan. This study investigated the efficacy of preoperative chemotherapy as initial treatment in GC patients with CY1 and/or P1a. We retrospectively reviewed GC patients diagnosed with CY1 and/or P1a at 34 institutions in Japan between 2008 and 2012. Selection criteria were: adenocarcinoma, no distant metastasis except CY1 or P1a, and no prior treatment. The subjects were divided into an Initial-Chemotherapy group and an Initial-Surgery group, according to the initial treatment. A total of 824 patients were collected and 713 eligible patients were identified for this study. As the initial treatment, 150 patients received chemotherapy (Initial-Cx), and 563 patients underwent surgery (Initial-Sx). Initial-Cx regimens were cisplatin plus S1/docetaxel plus cisplatin plus S1/others (n = 90/37/23). Both overall survival (OS) and progression-free survival (PFS) were similar between the Initial-Cx and Initial-Sx groups (median OS 24.8 and 24.0 months, HR 1.07, 95% CI 0.87–1.3; median PFS 14.9 and 13.9 months, HR 1.04, 95% CI 0.85–1.27). The 5-year OS rates were 22.3% in the Initial-Cx group and 21.5% in the Initial-Sx group. Although, the preoperative chemotherapy did not show a survival benefit for GC patients with CY1 and/or P1a, initial-Cx showed favorable survival in patients who converted to P0 and CY0.

The prognosis of esophageal cancer has improved, but the incidence of gastric conduit cancer has increased. Gastric conduit cancer is difficult to treat because current treatment options are highly invasive; in particular, surgical procedures have high mortality and modality. Treatment through the retrosternal route usually requires sternotomy, which often causes lethal osteomyelitis. To prevent lethal complications and reduce invasiveness, we used the laparoscopic mediastinal approach. Here, we report a successful case using the laparoscopic mediastinal approach for the treatment of gastric conduit cancer through the retrosternal route. Despite a few concerns, this approach can be a treatment option for gastric conduit cancer through the retrosternal route.

A multicenter phase 2 trial analysed chemoselection with docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy (ICT) and subsequent conversion surgery (CS) for locally advanced unresectable esophageal cancer. This study presents updated 3-year analyses to further characterize the impact of DCF-ICT followed by CS. Esophageal cancer patients with clinical T4 disease, unresectable supraclavicular lymph node metastasis, or both were eligible for this study. The treatment starts with DCF-ICT, followed by CS if the cancer is resectable, or by concurrent chemoradiation if it is not resectable. This updated analysis presents 3-year overall survival (OS), 3-year progression-free survival (PFS), and pattern of relapse. The median follow-up period for the patients surviving without death was 39.3 months. The estimated 1-year OS was 66.7%, and the lower limit of the 80% confidence interval (CI) was 54.6%. The estimated 3-year OS was 46.6% (95% CI 34.2–63.5%). The OS for the patients who underwent R0 resection (n = 19) was significantly longer than for those who did not (3-year OS: 71.4% vs. 30.1%). The estimated 1-year PFS was 50.6%, and the 3-year PFS was 39.6%. The PFS for R0 was significantly longer than for non-R0 (3-year PFS: 61.3% vs 25.0%). Recurrence or progression at the primary site was observed in 31% of the non-R0 group. The rate of distant metastasis did not differ significantly between the non-R0 and R0 groups (21% vs 16%). Long-term follow-up evaluation confirmed that DCF chemoselection aimed at CS is feasible and promising in terms of survival for patients with locally advanced esophageal cancer.

Background: The standard treatment for locally advanced unresectable squamous cell carcinoma (SCC) of the oesophagus is chemoradiation with cisplatin and 5-fluorouracil (CF-RT). This multicentre phase II trial assessed the safety and efficacy of chemoselection with docetaxel plus cisplatin and 5-fluorouracil (DCF) induction chemotherapy (ICT) and subsequent conversion surgery (CS) for initially unresectable locally advanced SCC of the oesophagus. Methods: Patients with clinical T4 and/or unresectable supraclavicular lymph node metastasis were eligible. Treatment started with three cycles of DCF-ICT, followed by CS if resectable, or by CF-RT if unresectable. The resectability was re-evaluated at 30–40 Gy of CF-RT, followed by CS if resectable, or by completion of 60 Gy of CF-RT. If resectable after CF-RT, CS was performed. The primary end point was 1-year overall survival (OS). Results: From April 2013 to July 2014, 48 patients were enrolled. CS was performed in 41.7% (n=20), including DCF-CS (n=18), DCF-CF-RT40Gy-CS (n=1), and DCF-CF-RT60Gy-CS (n=1). R0 resection was confirmed in 19 patients (39.6%). Grade ⩾3 postoperative complications included one event each of recurrent laryngeal nerve palsy, lung infection, wound infection, pulmonary fistula, and dysphagia; but no serious postoperative complications were observed in patients undergoing CS. Clinical complete response after CF-RT was confirmed in 4 patients (8.3%). The estimated 1-year OS was 67.9% and lower limit of 80% confidence interval was 59.7%. There was one treatment-related death in patient receiving DCF-CF-RT60Gy. Conclusions: Chemoselection with DCF-ICT followed by CS as a multidisciplinary treatment strategy showed promising signs of tolerability and efficacy in patients with locally advanced unresectable SCC of the oesophagus.

196 Background: The phase III trial (JCOG1104), comparing between 4- (6 months) and 8-course (1 year) of S-1 as the adjuvant chemotherapy for pathological stage II gastric cancer, registered a total of 590 patients between Feb. 2012 and Mar. 2017 until the study was terminated due to futility at the interim analysis (relapse-free survival at 3 years: 93.1% in the 8-course group and 89.8% in the 4-course group). Non-inferiority of the 4-course to the 8-course was not shown, highlighting a continuation of S-1 adjuvant chemotherapy for one year. This preplanned exploratory study investigated the risk factors for time to treatment failure (TTF). Methods: TTF was defined as the time from randomization to the date of termination of S-1 before the planned treatment period, relapse, or any cause of death, whichever came first, and censored on the last date of contact for a surviving patient after completing the planned treatment or the last date of S-1 in the patients under the protocol treatment when the trial was closed. The risk factor of TTF was analyzed by Cox proportional hazard model using the variables of the planned treatment period, PS, age, sex, body weight loss (percentile of the body weight loss at the registration compared with that before surgery: BWL), albumin, lymphocyte count, creatinine clearance (Ccr), extent of gastrectomy (total gastrectomy vs. others), surgical approach (open vs. laparoscopic approach), and blood loss during surgery. As TTF did not reach 50%, proportion of treatment completion was compared. Results: Among 590 registered patients, this study included 530 patients (273 in the 8-course group and 257 in the 4-course group) by excluding 24 ineligible patients, 7 patients who did not start the protocol treatment, and 29 patients with unavailable data for variables. Proportion of treatment completion at 6 months estimated by Kaplan-Meier method were 89.2% in the 4-course group and 84.6% in the 8-course group ( P=0.1204), and that at 1 year was 73.6% in the 8-course group. Risk factors of TTF before 6M identified by multivariable analysis with stepwise selection method including both groups, in which all patients completed treatment were censored at 6 months, were the planned treatment period (4-courses vs. 8-course, HR 0.611, 95% Confidence interval (CI) 0.375-0.996, P=0.0482), age (continuous value, HR 1.039, 95% CI 1.004-1.074, P=0.0266), and Ccr (80 ml/min, HR 1.943, 95% CI 1.105-3.415, P=0.0211). As for the TTF in the 8-course group, BWL (>10% vs 80 ml/min, HR 1.900, 95% CI 1.186-3.045, P=0.0076) were independent risk factors. Conclusions: Compared to 8-course, 4-course of S-1 adjuvant chemotherapy was associated with a higher 6-month proportion of treatment completion. When planning the adjuvant chemotherapy with S-1 for one year, BWL (>10%) and low Ccr (

Preoperative chemoradiotherapy (CRT) is a standard treatment for stage II/III esophageal cancer. Preoperative chemotherapy is also considered a standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in patients who undergo radical lymph node dissection. We conducted a feasibility study of preoperative CRT with cisplatin plus 5-fluorouracil (CF) and elective lymph node irradiation followed by esophagectomy with radical lymph node dissection in patients with stage II/III ESCC. Patients with clinical stage II/III, excluding T4, ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy comprised two courses of CF infusion repeated after 4-weeks. Radiation therapy was concurrently administered to the primary tumor, metastatic lymph nodes, and regional lymph nodes at a dose of 41.4 Gy. After the completion of CRT, transthoracic esophagectomy with 2–3 fields lymphadenectomy was performed. The primary endpoint was the completion rate of protocol treatment with R0 resection. Thirty-one eligible patients were enrolled. During CRT, the most common grade 3 or 4 toxicities were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%) and hyponatremia (16%). Thirty patients (96.8%) underwent surgery. One patient received palliative chemotherapy because of appearance of lung metastasis during CRT. The completion rate of protocol treatment was 93.5% (29/31). There was one treatment-related death after surgery. Pathological complete response was achieved in 42% (13/30). Preoperative CRT with CF and elective lymph node irradiation showed an acceptable toxicity and promising activity especially in ESCC.

Background A multicenter phase II trial revealed that docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy (IC) and subsequent conversion surgery (CS) was tolerable and effective in patients with locally advanced unresectable esophageal cancer (LAUEC) (Br J Cancer 2016;115:1328–1334). Here, we report updated 3-year analyses to further characterize the impact of DCF-IC followed by CS. Methods Esophageal cancer patients with clinical T4 disease and/or unresectable supraclavicular lymph node metastasis were eligible. The treatment starts with 3 cycles of DCF-IC, followed by CS if resectable, or by concurrent radiation plus chemotherapy with 5-fluorouracil and cisplatin (CF-RT) if not resectable. This updated analysis represents 3-year overall survival (OS), 3-year progression free survival (PFS), location of relapse, and subsequent therapy. Results As of October 11, 2017, 25 patients were dead. The median follow-up period in patients surviving without death was 39.3 months (95%CI: 38.7 - 41.7months). The estimated 1-year OS was 66.7% and lower limit of 95% confidence interval was 54.6%. The estimated 3-year OS was 46.6% (95% CI; 34.2 - 63.5%). The OS for patients who underwent R0 resection (n = 19) was significantly longer than those who did not undergo R0 resection (3-year OS: 71.4% vs. 30.1%). The estimated 1-year PFS was 50.6% (95%CI: 38.1 - 67.3%) and the estimated 3-year PFS was 39.6% (95%CI: 27.7 - 56.6%). The PFS for patients who underwent R0 resection (n = 19) was significantly longer than those who did not undergo R0 resection (3-year PFS: 61.3% vs. 25%). The recurrence or progression in primary site was observed in 31% of non R0 group. There was no significant difference in the rates of distant metastasis between the two groups (non R0 group vs. R0 group; 21% vs. 16%). The subsequent therapy after protocol therapy included chemotherapy (n = 18), radiotherapy (n = 11), and surgery (n = 5). Conclusion This longer follow up of DCF-IC followed by CS strategy for patients with LAUEC revealed promising OS and PFS. Based on this phase 2 trial, JCOG1510, a prospective randomized controlled trial to compare chemoselection with DCF-IC followed by CS versus CF-RT as a standard treatment is in preparation for LAUEC. Disclosure All authors have declared no conflicts of interest.

The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) as preoperative treatment for esophageal squamous cell carcinoma (ESCC) has not been investigated. We carried out a multicenter phase II feasibility study of preoperative chemotherapy with DCF for ESCC. Patients with clinical stage II/III ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy consisted of i.v. docetaxel (70-75 mg/m(2)) and cisplatin (70-75 mg/m(2)) on day 1, and continuous infusion of fluorouracil (750 mg/m(2)/day) on days 1-5. Antibiotic prophylaxis on days 5-15 was mandatory. This regimen was repeated every 3 weeks with a maximum of three cycles allowed. After completion of chemotherapy, esophagectomy with extended lymphadenectomy was carried out. The primary endpoint was the completion rate of protocol treatment. Forty-two eligible patients were enrolled. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (83%), anorexia (7%), and stomatitis (5%). Forty-one (98%) patients underwent surgery. The completion rate of protocol treatment was 90.5% (38/42). No treatment-related death was observed and the incidence of operative morbidity was tolerable. According to RECIST, the overall response rate after the completion of DCF was 64.3%. Pathological complete response was achieved in 17%. The estimated 2-year progression-free survival and overall survival were 74.5% and 88.0%, respectively. Although these data are preliminary, preoperative DCF was well tolerated. Antitumor activity was highly promising and warrants further investigation. This trial was registered with University Hospital Medical Information Network (no. UMIN000002396).

Background & Aims: The early detection of colorectal cancer is desired because this cancer can be cured surgically if diagnosed early. The purpose of the present study was to determine the feasibility of a new methodology for isolating colonocytes from naturally evacuated feces, followed by cytology or molecular biology of the colonocytes to detect colorectal cancer originating from any part of the colorectum. Methods: Several simulation studies were conducted to establish the optimal methods for retrieving colonocytes from any portion of feces. Colonocytes exfoliated into feces, which had been retrieved from 116 patients with colorectal cancer and 83 healthy volunteers, were analyzed. Part of the exfoliated colonocytes was examined cytologically, whereas the remainder was subjected to DNA analysis. The extracted DNA was examined for mutations of the APC, K-ras, and p53 genes using direct sequence analysis and was also subjected to microsatellite instability (MSI) analysis. Results: In the DNA analysis, the overall sensitivity and specificity were 71% (82 of 116) of patients with colorectal cancer and 88% (73 of 83) of healthy volunteers. The sensitivity for Dukes A and B was 72% (44 of 61). Furthermore, the sensitivity for cancers on the right side of the colon was 57% (20 of 35). The detection rate for genetic alterations using our methodology was 86% (80 of 93) when the analysis was limited to cases in which genetic alterations were present in the cancer tissue. Conclusions: We have developed a new methodology for isolating colonocytes from feces. The present study describes a promising procedure for future clinical evaluations and the early detection of colorectal cancers, including right-side colon cancer.

Purpose. The face scale has not been used as a global parameter of quality of life (QOL). The aims of this study were to assess the QOL of patients after esophagectomy for cancer and to examine whether a face scale is useful as a global parameter of QOL. Method. Seventy-one patients without postoperative recurrence after curative esophagectomy answered the questionnaire with the face scale and food intake. We calculated the QOL score (its full mark: 85) and examined the correlation between the QOL score and other parameters including the face scale. Result. The duration of the postoperative period ranged from 8 to 253 months (median 87 months). Gastric pullups at the left cervix were selected in 66 patients. The retrosternal route was performed in 55 patients. The mean QOL score was 64.2 (range 33–84). There was the significant positive correlation between QOL score and the face scale (P < 0.0001). The quantity of meal intake decreased in 55 patients (77.55%) by more than 50% compared with their healthy state. About a half of the subjects still suffered from the swallowing problems and a decreased food intake. Conclusion. The face scale is correlative with the total QOL score after an esophagectomy and is useful as a global parameter of the QOL.

We carried out a phase I/II trial of adding 2-weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2-weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2-weekly docetaxel (30 mg/m(2) [dose level (DL)1] or 40 mg/m(2) [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m(2) cisplatin, day 1; 800 mg/m(2) fluorouracil, days 1-5) repeated every 4 weeks. The primary endpoint was dose-limiting toxicity (DLT) in phase I and central peer review-based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty-two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P0.0001; 95% confidence interval, 48-75%); median overall survival and progression-free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment-related death in one patient. The 2-weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737.

4021Background: This multicenter phase II trial assessed the safety and efficacy of docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy (IC) and subsequent conversion surgery (...

Establishment of a sensitive, reliable and non-invasive method for the diagnosis of early-stage colorectal cancer is necessary, because colorectal cancer can be cured surgically if diagnosed early. The aim of the present study was to evaluate the feasibility of using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis of the DNA extracted from the colonocytes isolated from naturally evacuated feces, in order to detect colorectal cancer.Colonocytes exfoliated into feces, retrieved from 33 patients with colorectal cancer and 63 healthy volunteers, were analyzed for the presence of mutations in their DNA. The DNA extracted from the colonocytes was examined for mutations of the APC, K-ras and p53 genes using direct sequence analysis, and also subjected to PCR-SSCP analysis.Genetic alterations were detected in the colonocytes isolated from the feces of 12 out of 33 patients with colorectal cancer (36.4%) by direct sequence analysis. PCR-SSCP analysis using the same DNA samples revealed abnormal signals in 18 of the 33 patients (54.5%). However, 3 and 7 among the 63 healthy volunteers were also found to have abnormal genetic alterations by direct sequence and PCR-SSCP analysis, respectively.The present study indicated the feasibility of using PCR-SSCP analysis for the detection of mutations in the DNA extracted from colonocytes isolated from naturally evacuated fecal samples.

We recently developed a new methodology for isolating colonocytes from fecal samples. We then applied a DNA-based analysis to the isolated colonocytes to detect colorectal cancer cells originating from any part of the colorectum. The purpose of the present study was to determine how long after defecation and at what temperature the fecal samples should be stored to isolate the colonocytes successfully.Fecal samples were collected from 6 patients with colorectal cancer and 6 healthy volunteers soon after defecation at the National Cancer Center Hospital. The fecal samples were stored at 4 degrees C, room temperature or 40 degrees C for 0, 24 or 48 hours. Colonocytes were then isolated from the fecal samples, and the DNA was purified. Finally, PCR for p53, K-ras and APC was conducted to determine whether the corresponding PCR products could be obtained.The colonocyte recovery rate was not reduced, when compared with the data for successful PCR amplification, if the fecal samples were kept at 4 degrees C after defecation and if the colonocytes were isolated within 48 hours after defecation.The present data provided important clinical knowledge regarding the storage of fecal samples for future mass screening tests.

The early detection of colorectal cancer originating from any part of the colorectum is desirable because this cancer can be cured surgically if diagnosed early. We searched for marker genes for a fecal RNA-based colorectal cancer screening method by comparison of genome-wide expression profiles among cancerous and non-cancerous tissues, and healthy volunteer- and cancer patient-derived colonocytes from the feces, and the peripheral blood. Of 14,564 genes, only 3 (PAP, REG1A, and DPEP1) were selectable as final candidates which were expressed frequently at any stage of this cancer and were suppressed in non-cancerous tissues and also in the peripheral blood and colonocytes of healthy volunteers. Next, we directly compared fecal RNA-expression profiles between colorectal cancer patients and healthy volunteers, and found that most of the genes (92%) expressed in the colonocytes of the cancer patients were not expressed in those of the healthy volunteers. Six genes (SEPP1, RPL27A, ATP1B1, EEF1A1, SFN, and RPS11) selected randomly from 85 cancer patient-derived colonocyte-specific genes were evaluated. In total, reverse transcription-polymerase chain reaction or focused microarray of all those 9 genes detected 18 (78%) of 23 curable colorectal cancers (Dukes stages A-C), 9 or 10 (64% or 71%) of 14 early cancers with no lymph node metastasis (Dukes stage A or B) and 4 (80%) of 5 right-sided cancers. Our extensive gene list provides other markers for fecal RNA-based colorectal cancer screening.

155 Background: Although the impact of postoperative complications, especially infectious complications (IC), on long-term survival after transthoracic esophagectomy remains controversial to date, we hypothesized that postoperative IC may affect tumor recurrence and survival of the patients (pts) undergoing transthoracic esophagectomy. Methods: The data from JCOG9907 (Ando N; Ann Surg Oncol 2012) was used to estimate the influence of IC on the outcome of current standard preoperative chemotherapy followed by surgery for clinical stage II/III squamous cell carcinoma of the thoracic esophagus. IC were classified into three: pneumonia, anastomotic leakage, and the others. OS and PFS were estimated by landmark method at 6 months from randomization. Univariate and multivariate analyses using Cox proportional hazard model were performed to assess the impact of postoperative complications on the survival after right-transthoracic esophagectomy with extended lymphadenectomy. Results: Among the 152 analyzed pts, the incidence of overall IC was 36%, among which pneumonia and anastomotic leakage were observed both in 14%. OS of pts with any IC (n=54) was shorter than that of pts without IC (HR 1.66, 95%CI [1.02-2.71]) and PFS also tended to be shorter in pts with any IC (HR 1.44, [0.92-2.23]). OS of pts with pneumonia (n=22) was shorter than that of pts without pneumonia (HR 1.82, [1.01-3.29]), and PFS also tended to be shorter in pts with pneumonia (HR 1.50, [0.85-2.62]). OS of pts with anastomotic leakage (n=21) were nearly identical to that for pts without leakage (HR 1.06, [0.52-2.13]) and PFS was slightly shorter in pts with leakage (HR 1.28, [0.71-2.32]). Multivariate analysis revealed that pneumonia tended to compromise OS and PFS (HR 1.66, [0.87-3.17] and HR 1.37, [0.75-2.51]). Conclusions: This study reveals that postoperative morbidity, especially pneumonia may deteriorate the survival of pts undergoing esophagectomy after preoperative chemotherapy. Achieving esophagectomy without postoperative complications might prolong OS and PFS. Clinical trial information: NCT00190554.

小腸大量切除施行後の縫合不全の為,長期間経口摂取ができない甲状腺全摘後の症例に対し,経直腸的に坐薬として甲状腺ホルモン剤(チラージンS,甲状腺末)の投与を行った.当初,内服と同じ量のチラージンSを粉末にし坐薬の形で使用したが,血中のf-T4, f-T3濃度は上昇しなかった.そこで甲状腺末200mgから300mgを坐薬とし使用したところ,血中f-T4, f-T3濃度は上昇してきた.坐薬挿入前後に急な血中濃度の変化は無かった.本症例では,術前T4(チラージンS®)として150μgを使用しeu-thyroidを保っていたが,今回経直腸的には甲状腺末が200～300mg必要であった.この量は,チラージンS 150μgの2～3倍に相当する.経直腸的に比較的大量の甲状腺ホルモン剤が必要であったのは薬剤の吸収がただ単に悪いというだけではなく,時折,便秘と下痢を繰り返す状況にあったこともその吸収において影響したものと思われる.

The prognosis of pathological T4 (pT4) esophageal carcinoma is still dismal, however, the current TNM classification categorizes some pT4 cancers (pT4M0) as stage III. The purpose of this study was to evaluate of the relevance of this classification.One hundred and thirty-five patients who underwent esophagectomy for pathological stage III (n = 85) and IV (n = 50) esophageal tumors were enrolled in the study. The outcomes and prognostic factors for these patients were examined. After the reclassification that pT4M0 tumors were categorized as stage IV, the two survival curves were compared between new stage III and IV.The 5-year survival rates for stage III and IV were 14.6%, 19.1%, respectively (P = 0.9). The 5-year survival rates for pT3N1M0 and pT4M0 were 21.1%, 0%, respectively (P0.0001). After the reclassification, the overall 5-year survival rates for new stage III and IV were 24.0%, 14.2%, respectively (P = 0.004). Curative resection (P = 0.002), radiotherapy (P = 0.001), depth of tumor invasion (pT3; P = 0.0004, pT1; P = 0.04) were the significant prognostic factors for stage III and IV carcinomas. Thirty-one (83.8%) of 37 patients with pT4 tumor had received non-curative esophagectomy.All pathological T4 esophageal carcinomas should be categorized as stage IV in the TNM classification.

The face scale has not been used as a global parameter of quality of life (QOL). The aims of this study were to assess the QOL of patients after esophagectomy for cancer and to examine whether a face scale is useful as a global parameter of QOL.Seventy-one patients without postoperative recurrence after curative esophagectomy answered the questionnaire with the face scale and food intake. We calculated the QOL score (its full mark: 85) and examined the correlation between the QOL score and other parameters including the face scale.The duration of the postoperative period ranged from 8 to 253 months (median 87 months). Gastric pullups at the left cervix were selected in 66 patients. The retrosternal route was performed in 55 patients. The mean QOL score was 64.2 (range 33-84). There was the significant positive correlation between QOL score and the face scale (P0.0001). The quantity of meal intake decreased in 55 patients (77.55%) by more than 50% compared with their healthy state. About a half of the subjects still suffered from the swallowing problems and a decreased food intake.The face scale is correlative with the total QOL score after an esophagectomy and is useful as a global parameter of the QOL.

129 Background: Neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered the standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory and neoadjuvant chemoradiotherapy (NeoCRT) may improve the outcome of stage II/III ESCC patients. We conducted a feasibility study of NeoCRT with CDDP plus 5-FU and elective nodal irradiation in patients with stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, a Performance status (PS) of 0-1, and age of 20–75 years. Chemotherapy consisted of 2 courses of 5-FU infusion (1000 mg/m2, days 1–4) and a 2-h CDDP infusion (75 mg/m2, day 1), with a 4-week interval. Radiotherapy was concurrently administered to the primary tumor, metastatic lymph nodes, and regional lymph nodes (total dose of 41.4 Gy in 23 fractions. After completion of NeoCRT, transthoracic esophagectomy with extensive lymphadenectomy (>D2) was performed. The primary endpoint was the completion rate of NeoCRT with R0 resection. Results: Thirty-three patients were enrolled in this study between July 2010 and June 2011 and 2 were determined to be ineligible. Characteristics of the 31 eligible patients included, a median age of 63 years (range, 40–73 years), male/female: 28/3, PS 0/1: 19/12, and cStage IIA/IIB/III: 2/10/19. Median observation time was 30.0month. In total, 29 patients (93.5%) underwent NeoCRT with R0 resection. Among the patients who underwent surgery, there was 1 treatment-related death, and the incidence of operative morbidity was similar to that in previous studies. According to RECIST, the overall response rate was 78% (14/18) after CRT. Pathological complete response was achieved in 13 patients (42%) who underwent esophagectomy. The 2 years recurrence free survival rate 69.8%, and 2 years survival rate was77.4%, respectively. Conclusions: NeoCRT was well tolerated and found to be highly promising. A randomized controlled trial (JCOG1109) comparing with neoadjuvant chemotherapy was started. Clinical trial information: UMIN000004223.

e15016 Background: Thougha triplet chemotherapy with D plus CF (DCF) has shown promising activity, high incidence of adverse events (AEs) especially in febrile neutropenia (FN) was observed in previous studies for head and neck cancer (TAX323, 324) and gastric cancer (TAX325). To reduce its AEs with keeping activity, we conducted a multicenter open-label phase I/II study of biweekly D plus CF for AEC. Methods: Eligibility criteria included histologically proven AEC with measurable disease, age 20 to 75, non-resectable or recurrent disease, performance status (PS) 0 to 1. Pts received escalating doses of D (dose level (DL) 1: 30 mg/m2, DL 2: 40 mg/m2, on days 1, 15) in combination with fixed dose of CF (cisplatin 80 mg/m2 on day 1, fluorouracil 800 mg/m2on days 1-5) repeated every 4 weeks with 3+3 design in phase I part (P-I). The primary endpoint of P-I was dose limiting toxicity (DLT) and that of phase II part (P-II) was response rate (RR) defined by central peer review. Based on a SWOG two stage design (p0=35%, p1=50%; one-sided a=0.1, β =0.2) at least 22 responders among 50 eligible pts should be observed to satisfy the primary endpoint. Results: Between Feb 2009 and Mar 2010, 62 pts were enrolled for P-I and P-II. In P-I, 10 pts were enrolled with DLT of 0/3 in DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended dose for P-II was determined as DL1. Thus, 3 (P-I) and additional 52 pts (P-II) were analyzed: 53 for efficacy (excluded 2 ineligible pts) and 55 for safety. Pts characteristics were as follows: male/female 49/6, age median 61 (range 44 to 75), PS 0/1 39/16. The RR was 62% (95% confidence interval, 48-75%, p2) combined with CF showed promising activity and tolerability. A phase III study comparing CF with DCF is warranted. Clinical trial information: UMIN000001737.

TPS4152 Background: Based on the results of JCOG9907, preoperative cisplatin plus 5- fluorouracil (CF) followed by esophagectomy with D2-3 lymphadenectomy has become standard care for advanced esophageal cancer in Japan, while the standard therapy in Western countries is preoperative chemoradiotherapy. A new clinical question has thus arisen of whether CF plus docetaxel (DCF) or CF plus radiotherapy (CF-RT) shows a survival benefit over preoperative CF even with intensive surgery. Methods: Eligibility criteria include histologically proven thoracic esophageal squamous cell carcinoma with stage IB/II/III (excluding T4) based on the 7th UICC-TNM, age 20 to 75, and performance status 0 to 1. No prior chemotherapy, radiotherapy, or hormonal therapy is allowed. Adequate organ function and written informed consent are required. Patients are randomized into any of the following three arms by a minimization method balancing the arms in terms of institution and tumor depth (T1–2 versus T3). Patients in arm A (CF) receive two courses of cisplatin at 80 mg/m2 on day 1 and fluorouracil at 800 mg/m2 on days 1–5, repeated every three weeks. Patients in arm B (DCF) receive three courses of docetaxel at 70 mg/m2, cisplatin at 70 mg/m2 on day 1, and fluorouracil at 750 mg/m2 on days 1–5, repeated every three weeks. Patients in arm C (CF-RT) receive two courses of cisplatin at 75 mg/m2 on day 1 and fluorouracil at 1000 mg/m2 on days 1–4, repeated every four weeks concurrently with radiotherapy at 41.4Gy/23fr. This trial is designed to demonstrate the superiority of preoperative DCF and/or CF-RT over CF in terms of overall survival. We assumed three-year survival with preoperative CF to be 63% and expected a 10% increase in three-year survival for DCF and CF-RT. The sample size was calculated as a total of 501 patients (167 patients per arm) with a study-wise one-sided alpha level of 5%, power of 70% for each pair comparison, an accrual period of 6.25 years, and a follow-up period of three years. This trial was registered as UMIN000009482 and started in December 2012. Clinical trial information: UMIN000009482.

Background Based on the JCOG 9907 trial results, neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered a standard treatment of stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory and neoadjuvant chemoradiotherapy (NeoCRT) may improve the outcome of stage II/III ESCC patients. We conducted a feasibility study of NeoCRT with CDDP plus 5-FU and elective nodal irradiation for stage II/III ESCC. Methods Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, PS 0-1, and age 20–75 years. Chemotherapy consisted of two courses of 5-FU infusion (1000 mg/m2, days 1–4) and a 2-h CDDP infusion (75 mg/m2, day 1), with a 4-week interval. Radiotherapy was concurrently administered to a total 41.4 Gy in 23 fractions for primary tumor, metastatic lymph nodes (LNs) and regional LNs. Esophagectomy with extensive lymphadenectomy (≥D2) was carried out 42–56 days after NeoCRT. The primary end point was the completion rate of NeoCRT and R0 resection. Results Thirty-three patients were enrolled, including 2 ineligibles. In 31 eligible patients, the median age was 63 years (range, 40–73); PS0/1: 19/12; cStage IIA/IIB/III: 2/10/19. The completion rate of protocol treatment was 93.5% (29/31). During CRT, the most common grade 3 or 4 toxic effects were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%), hyponatremia (16%). One treatment-related death was observed. The incidence of operative morbidity was similar to that in previous studies but incidence of anastomotic leakage was observed more frequently (27%). According to RECIST, the overall response rate was 78% (14/18) after CRT. Pathological complete response was achieved in 42% (13/31). Conclusions NeoCRT was tolerable and active. The randomized, controlled trial compared with neoadjuvant chemotherapy is needed and we plan it.

4060 Background: The results of JCOG 9907 randomized trial of neoadjuvant chemotherapy with cisplatin plus 5-fluorouracil (CF) vs. adjuvant CF for stage II/III esophageal squamous cell carcinoma (E...