Parallel-Group Controlled Trial of Surgery Versus Chemoradiotherapy in Patients With Stage I Esophageal Squamous Cell Carcinoma.

BACKGROUND & AIMS: Surgery is the standard of care for T1bN0M0 esophageal squamous cell carcinoma (ESCC), whereas chemoradiotherapy (CRT) is a treatment option. This trial aimed to investigate the noninferiority of CRT relative to surgery for T1bN0M0 ESCC. METHODS: Clinical T1bN0M0 ESCC patients were eligible for enrollment in this prospective nonrandomized controlled study of surgery versus CRT. The primary endpoint was overall survival, which was determined using inverse probability weighting with propensity scoring. Surgery consisted of an esophagectomy with 2- or 3-field lymph node dissection. CRT consisted of 2 courses of 5-fluorouracil (700 mg/m2) on days 1-4 and cisplatin (70 mg/m2) on day 1 every 4 weeks with concurrent radiation (60 Gy). RESULTS: From December 20, 2006 to February 5, 2013, a total of 368 patients were enrolled in the nonrandomized portion of the study. The patient characteristics in surgery arm and CRT arm, respectively, were as follows: median age, 62 and 65 years; proportion of males, 82.8% and 88.1%; and proportion of performance status 0, 99.5% and 98.1%. Comparisons were made using the nonrandomized groups. The 5-year overall survival rate was 86.5% in the surgery arm and 85.5% in the CRT arm (adjusted hazard ratio, 1.05; 95% confidence interval, 0.67-1.64 [<1.78]). The complete response rate in the CRT arm was 87.3% (95% confidence interval, 81.1-92.1). The 5-year progression-free survival rate was 81.7% in the surgery arm and 71.6% in the CRT arm. Treatment-related deaths occurred in 2 patients in the surgery arm and none in the CRT arm. CONCLUSIONS: CRT is noninferior to surgery and should be considered for the treatment of T1bN0M0 ESCC.

Gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer (JCOG0501): an open-label, phase 3, randomized controlled trial.

BACKGROUND: Specific treatment strategies are sorely needed for scirrhous-type gastric cancer still, which has poor prognosis. Based on the promising results of our previous phase II study (JCOG0210), we initiated a phase III study to confirm the efficacy of neoadjuvant chemotherapy (NAC) in type 4 or large type 3 gastric cancer. METHODS: Patients aged 20-75 years without a macroscopic unresectable factor as confirmed via staging laparoscopy were randomly assigned to surgery followed by adjuvant chemotherapy with S-1 (Arm A) or NAC (S-1plus cisplatin) followed by D2 gastrectomy plus adjuvant chemotherapy with S-1 (Arm B). The primary endpoint was overall survival (OS). RESULTS: Between October 2005 and July 2013, 316 patients were enrolled, allocating 158 patients to each arm. In Arm B, in which NAC was completed in 88% of patients. Significant downstaging based on tumor depth, lymph node metastasis, and peritoneal cytology was observed using NAC. Excluding the initial 16 patients randomized before the first revision of the protocol, 149 and 151 patients in arms A and B, respectively, were included in the primary analysis. The 3-year OS rates were 62.4% [95% confidence interval (CI) 54.1-69.6] in Arm A and 60.9% (95% CI 52.7-68.2) in Arm B. The hazard ratio of Arm B against Arm A was 0.916 (95% CI 0.679-1.236). CONCLUSIONS: For type 4 or large type 3 gastric cancer, NAC with S-1 plus cisplatin failed to demonstrate a survival benefit. D2 surgery followed by adjuvant chemotherapy remains the standard treatment.

Adherence to the guidelines and the pathological diagnosis of high-risk gastrointestinal stromal tumors in the real world.

BACKGROUND: A multidisciplinary approach based on guidelines and pathological diagnosis by specialized pathologists are important for improving the prognosis and QoL of GIST patients. This study examined the adherence to the guidelines and the concordance of the pathological diagnosis of high-risk GISTs. PATIENTS AND METHODS: Among 541 patients with high-risk GISTs recruited to the prospective registry between Dec. 2012 and Dec. 2015, 534 patients were analyzed after central pathology with KIT and DOG1 IHC and genotyping of KIT and PDGFRA. RESULTS: Of the 534 patients, 432 (81%) received imatinib adjuvant therapy at a starting dose of 400 or 300 mg/day. Multivariate analysis indicated that age (HR 0.71; 95% CI 0.58-0.88), tumor size (HR for > 10 cm vs < 5 cm, 3.87; 95% CI 1.72-8.74), mitosis (HR for > 10 vs < 5, 3.54; 95% CI 1.84-6.79), tumor rupture (HR 3.69; 95% CI 1.43-9.52) and performance status (HR 0.55; 95% CI 0.31-0.99) were independently related to adjuvant therapy. Among the 534 high-risk GISTs diagnosed locally, 19 tumors (3.6%) were diagnosed as non-GISTs, and the other 93 (18.1%) GISTs were reclassified into lower risk categories by central pathology. Among 10 patients with non-GISTs and 8 patients with PDGFRA D842V mutations, 4 (40%) and 3 (38%) patients, respectively, continued the therapy after receiving the central pathology results. CONCLUSIONS: The adherence to guidelines and the concordance of pathological diagnoses were comparatively good for high-risk GISTs. Central pathology may contribute to improved diagnosis, but further refinements may be required.

Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer, the short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG0501).

BACKGROUND: The prognosis of patients with linitis plastica (type 4) and large (≥ 8 cm) ulcero-invasive-type (type 3) gastric cancer is extremely poor, even after extended surgery and adjuvant chemotherapy. Given the promising results of our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (JCOG0210), we performed a phase III study to confirm the efficacy of NAC in these patients, with the safety and surgical results are presented here. METHODS: Eligible patients were randomized to gastrectomy plus adjuvant chemotherapy with S-1 (Arm A) or NAC followed by gastrectomy + adjuvant chemotherapy (Arm B). The primary endpoint was the overall survival (OS). This trial is registered at the UMIN Clinical Trials Registry as C000000279. RESULTS: From February 2007 to July 2013, 300 patients were randomized (Arm A 149, Arm B 151). NAC was completed in 133 patients (88%). Major grade 3/4 adverse events during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). Gastrectomy was performed in 147 patients (99%) in Arm A and 139 patients (92%) in Arm B. The operation time was significantly shorter in Arm B than in Arm A (median 255 vs. 240 min, respectively; p = 0.024). There were no significant differences in Grade 2-4 morbidity and mortality (25.2% and 1.3% in Arm A and 15.8% and 0.7% in Arm B, respectively). CONCLUSIONS: NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing the morbidity or mortality.

Impact of laparoscopy on the prevention of pulmonary complications after thoracoscopic esophagectomy using data from JCOG0502: a prospective multicenter study.

BACKGROUND: Postoperative pulmonary complications (PPCs) are the most common causes of serious morbidity after esophagectomy, which involves both thoracic and abdominal incisions. Although the thoracoscopic approach decreases PPC frequency after esophagectomy, it remains unclear whether the frequency is further decreased by combining it with laparoscopic gastric mobilization. This study aimed to determine the impact of laparoscopy on the prevention of PPCs after thoracoscopic esophagectomy using data from the Japan Clinical Oncology Group Study 0502 (JCOG0502). METHODS: JCOG0502 is a four-arm prospective study comparing esophagectomy with definitive chemo-radiotherapy. The use of thoracoscopy and/or laparoscopy was decided at the surgeon's discretion. PPCs were defined as one or more of the following postoperative morbidities grade ≥2 (as per Common Terminology Criteria for Adverse Events v3.0): pneumonia, atelectasis, and acute respiratory distress syndrome. RESULTS: A total of 379 patients were enrolled in JCOG0502. Of these, 210 patients underwent esophagectomy via thoracotomy with laparotomy (n = 102), thoracotomy with laparoscopy (n = 7), thoracoscopy with laparotomy (n = 43), and thoracoscopy with laparoscopy (n = 58). PPC frequency was reduced to a greater extent by thoracoscopy than by thoracotomy (thoracoscopy 15.8%, thoracotomy 30.3%; p = 0.015). However, following thoracoscopic esophagectomy, laparoscopy failed to further decrease the PPC frequency compared with laparotomy (laparoscopy 15.5%, laparotomy 16.3%; p = 1.00). Univariable analysis showed that thoracoscopy (shown above) and less blood loss (<350 mL 16.3%, ≥350 mL 30.2%; p = 0.022) were associated with PPC prevention, whereas laparoscopy showed a borderline significant association (laparoscopy 15.4%, laparotomy 26.9%; p = 0.079). Multivariable analysis also showed that thoracoscopy and less blood loss were associated with PPC prevention. CONCLUSION: Thoracoscopic approach to esophagectomy significantly reduced PPC frequency with minimal additional effect from laparoscopic gastric mobilization.

Hand grip strength as a predictor of postoperative complications in esophageal cancer patients undergoing esophagectomy.

BACKGROUND: Radical esophagectomy remains the primary treatment option for resectable esophageal cancer. However, it sometimes induces postoperative complications due to its invasive nature. Recently, the impact of loss of muscle mass on postoperative complications and survival among cancer patients has been highlighted. This study aimed to identify the impact of low hand grip strength (HGS) on postoperative complications after esophagectomy. METHODS: A total of 188 patients (male: 166, female: 22) who underwent radical esophagectomy with gastric tube reconstruction between 2008 and 2014 were included. The correlation between HGS and age was analyzed using Pearson's correlation coefficient. Due to the small patient numbers, only male patients were stratified into two groups according to age (<70 years: non-elderly group, ≥70 years: elderly group). Receiver operating characteristic curve analysis was performed for each group using postoperative complication occurrence as the endpoint to determine an optimal HGS cutoff value. RESULTS: Postoperative complications occurred in 60.9% of the elderly group and 47.4% of the non-elderly group. When the cutoff values were set at 30.5 and 37 kg for the elderly and non-elderly group, respectively, low HGS was an independent predictive factor of postoperative complications on multivariate analysis only in the elderly group (p = 0.008). In the elderly group, the incidence of postoperative pneumonia was 39.5% among patients with low HGS vs. 3.8% among patients with high HGS. CONCLUSION: Preoperative HGS is an independent predictive factor of postoperative complications, especially postoperative pneumonia, for elderly male patients with esophageal cancer treated with radical esophagectomy.

Short-term surgical outcomes from a phase III study of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric cancer: Japan Clinical Oncology Group Study JCOG0912.

BACKGROUNDS: No confirmatory randomized controlled trials (RCTs) have evaluated the efficacy of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG). We performed an RCT to confirm that LADG is not inferior to ODG in efficacy. METHODS: We conducted a multi-institutional RCT. Eligibility criteria included histologically proven gastric adenocarcinoma in the middle or lower third of the stomach, clinical stage I tumor. Patients were preoperatively randomized to ODG or LADG. This study is now in the follow-up stage. The primary endpoint is relapse-free survival (RFS) and the primary analysis is planned in 2018. Here, we compared the surgical outcomes of the two groups. This trial was registered at the UMIN Clinical Trials Registry as UMIN000003319. RESULTS: Between March 2010 and November 2013, 921 patients (LADG 462, ODG 459) were enrolled from 33 institutions. Operative time was longer in LADG than in ODG (median 278 vs. 194 min, p < 0.001), while blood loss was smaller (median 38 vs. 115 ml, p < 0.001). There was no difference in the overall proportion with in-hospital grade 3-4 surgical complications (3.3 %: LADG, 3.7 %: ODG). The proportion of patients with elevated serum AST/ALT was higher in LADG than in ODG (16.4 vs. 5.3 %, p < 0.001). There was no operation-related death in either arm. CONCLUSIONS: This trial confirmed that LADG was as safe as ODG in terms of adverse events and short-term clinical outcomes. LADG may be an alternative procedure in clinical IA/IB gastric cancer if the noninferiority of LADG in terms of RFS is confirmed.

Role of metastasectomy for recurrent/metastatic gastrointestinal stromal tumors based on an analysis of the Kinki GIST registry.

PURPOSE: To define the role of surgery for metastatic/recurrent lesions after resection of primary gastrointestinal stromal tumors (GISTs). METHODS: Based on data obtained from the Kinki GIST registry, patients with recurrence or metastasis were divided into a surgical treatment group (ST group), comprised those treated with surgery in addition to tyrosine kinase inhibitor (TKI) therapy; and a drug treatment group (DT group), comprised those treated with TKI therapy alone. We compared the baseline characteristics and survival outcomes of the groups. RESULTS: Metastasis or recurrence developed in 93 of the 737 patients with GISTs treated between 2003 and 2007, 50 (53.8 %) of whom were assigned to the ST group and 43 (46.2 %) to the DT group. In the ST group, the 5-year overall survival rate was significantly higher for patients who underwent R0/R1 resection than for those who underwent R2 resection (82.2 vs. 47.0 %, p = 0.018). Survival time after recurrence was correlated with the duration of total TKI therapy in both the ST and DT groups (r = 0.766 and r = 0.932, respectively, p < 0.001). CONCLUSIONS: Continuous TKI therapy appears to be important primarily for the prognostic improvement of patients with recurrent/metastatic GISTs. R0/R1 resection may have benefits when combined with TKI therapy for patients with stable disease or disease responsive to TKI therapy, less than four metastatic lesions, and lesions <100 mm in total.

The Prevalence of Overall and Initial Lymph Node Metastases in Clinical T1N0 Thoracic Esophageal Cancer: From the Results of JCOG0502, a Prospective Multicenter Study.

OBJECTIVE: To evaluate the sites and frequencies of overall and initial lymph node (LN) metastases (LNMs) of clinical T1N0 esophageal cancer. BACKGROUND: The sites and frequencies of initial LNMs and sentinel LNs (SLNs) of esophageal cancer remain unclear. METHODS: The Japan Clinical Oncology Group JCOG0502 trial was a 4-arm prospective study that compared esophagectomy with chemoradiotherapy for clinical T1N0 esophageal cancer in both randomized and patient-preference arms. The preoperative diagnostic accuracy was evaluated for patients assigned to the surgery arm. Patients who withdrew consent and who were not treated were excluded. All patients underwent esophagectomy with D2 or greater LN dissection. From the pathologic findings, sites and frequencies of LNMs and SLNs were assessed and the frequency of skip LNMs was calculated. RESULTS: In total, 211 patients underwent LNM and SLN analysis. Regarding N-factor accuracy, 57 (27.0%) of 211 clinical N0 cases had pathologic LNMs. The upper mediastinal and mediastinal/abdominal regions were frequent sites of LNMs in upper and lower thoracic cases, respectively. However, in middle thoracic cases, LNMs were observed in the neck, mediastinal, and abdominal regions, and pathologic SLN spread to all 3 fields. The frequency of skip LNMs was 36.7%. CONCLUSIONS: A clinical diagnosis of T1N0 is not sufficiently accurate, and therefore, it is unacceptable to omit LN dissection or minimize the prophylactic radiation field. SLNs, which are not location restricted, should be surveyed in all 3 fields.

Primary surgery as a frontline treatment for synchronous metastatic gastrointestinal stromal tumors: an analysis of the Kinki GIST registry.

PURPOSE: To investigate the outcomes of a combined treatment regimen comprising primary surgery and tyrosine kinase inhibitor (TKI) therapy for synchronous metastatic gastrointestinal stromal tumors (GIST). METHODS: We analyzed retrospectively 14 cases of synchronous metastatic GIST from the Kinki GIST registry between 2003 and 2007. RESULTS: The primary tumor was located in the stomach, small intestine, and rectum in seven, six, and one patients, respectively. Metastatic tumors developed in the liver, peritoneum, other sites, and multiple organs in three, six, two, and three patients, respectively. The R0 resection rate was 42.9 % and the 5-year overall survival rate was 69.3 %. There was no significant difference in the 5-year overall survival rate between patients who underwent R0/R1 and those who underwent R2 resection (71.4 vs. 68.6 %). There was a strong correlation between survival time from diagnosis and the duration of imatinib therapy (Pearson's correlation coefficient, 0.86; p < 0.001). CONCLUSIONS: Although the role of surgery in the treatment of synchronous metastatic GIST is still unclear, primary surgery as the sole frontline treatment may not have a survival benefit: Continuous TKI therapy is more important for prolonging survival.

A phase III study of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric Cancer (JCOG0912).

A Phase III study was started in Japan to evaluate the non-inferiority of overall survival of laparoscopy-assisted distal gastrectomy with open distal gastrectomy in patients with clinical IA (T1N0) or IB [T1N1 or T2(MP)N0] gastric cancer. This study followed the previous Phase II study to confirm the safety of laparoscopy-assisted distal gastrectomy (JCOG0703) and began in March 2010. A total of 920 patients will be accrued from 33 institutions within 5 years. The primary endpoint is overall survival. The secondary endpoints are relapse-free survival, proportion of laparoscopy-assisted distal gastrectomy completion, proportion of conversion to open surgery, adverse events, short-term clinical outcomes, postoperative quality of life. Only a credentialed surgeon can be responsible for both open distal gastrectomy and laparoscopy-assisted distal gastrectomy.

Polymorphisms of the UDP-glucuronosyl transferase 1A genes are associated with adverse events in cancer patients receiving irinotecan-based chemotherapy.

A prodrug, irinotecan (CPT-11), is a semisynthetic derivative of camptothecin. It inhibits topoisomerase I and is used for treatment of lung, stomach, and colon cancers in Japan. The active form of CPT-11, SN-38, causes the adverse events such as neutropenia and diarrhea. Since SN-38 is metabolized to non-toxic SN-38-glucuronide by hepatic uridine diphosphate glucuronosyl transferase (UGT) 1A enzymes, UGT1A enzyme activities may influence adverse events of CPT-11. UGT1A enzymes consist of three isozymes (1A1, 1A7, 1A9), and their genes are characterized by polymorphisms. Here, to identify the genetic factors that affect the adverse events of CPT-11, we determined the polymorphism in three UGT 1A isozyme genes in 45 inpatients with lung, colon, or stomach cancer. The univariate and multivariate analysis of patients' physiological and genetic factors revealed that one or more genotypes of UGT1A1*6/*28, UGT1A7*3/*3, and UGT1A9*1/*1 may enhance the adverse events. Each of the first two genotypes is expected to generate the enzyme with low catalytic activity. The UGT1A9*1 represents the wild-type allele, which however provides the lower catalytic activity, compared to the UGT1A9*22 variant that is common in this study population. Indeed, four (67%) out of six patients who carry one or more of the above-mentioned genotypes suffered from adverse events, leading to the discontinuation of chemotherapy or the decreased dose of CPT-11. By contrast, only six (15%) out of 39 patients with other genotypes suffered from adverse events. In conclusion, UGT1A1*6/*28, UGT1A7*3/*3, and UGT1A9*1/*1 should be taken into consideration as markers for preventing severe adverse events of CPT-11 administration.

Combination chemotherapy with S-1 plus cisplatin for gastric cancer that recurs after adjuvant chemotherapy with S-1: multi-institutional retrospective analysis.

BACKGROUND: It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy. METHODS: We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy. RESULTS: In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1 months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4 months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8 months, and the median overall survival (OS) was 12.2 months. Compared with patients with an RFI of <6 months (n = 25), patients with an RFI of ≥6 months (n = 27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2 months, respectively), and longer overall survival (7.3 vs. 16.6 months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6 months was still significantly associated with PFS and OS. CONCLUSIONS: S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of ≥6 months.

[Pharmacists in community medicine: especially in cancer treatment].

It is important for clinics and hospitals to cooperate in treating cancer patients in the community health. We are treating cancer patients in cooperation with five general hospitals in Shizuoka and about 100 clinics in the same community. In this system, it is required that pharmacists in the community should have knowledge about beneficial effects and adverse events of anticancer drugs as do hospital pharmacists, and furthermore they should have good communication with cancer patients. The expectation for pharmacists is great in community medicine especially in the treatment of cancer patients.

Cumulative incidence of venous thromboembolism in patients with advanced cancer in prospective observational study.

Venous thromboembolism (VTE) is frequently observed in patients with advanced cancer. The objective of this prospective observational study was to estimate, based on intensive screening, using computed tomography, lower-extremity ultrasonography, and D-dimer testing, the prevalence of VTE in patients with advanced cancer. Patients with metastatic or locally advanced cancer without anticoagulant therapy, who were planning to receive chemotherapy during 4 weeks, were eligible. Evaluations of VTE were performed at pretreatment, 12 weeks, and 24 weeks after the start of chemotherapy. Primary endpoint was cumulative incidence of VTE for 24 weeks. Secondary endpoints included incidence of VTE (pretreatment, 12 weeks, and 24 weeks after the start of chemotherapy), VTE according to primary cancer site, symptomatic VTE, pulmonary thromboembolism (PE), and treatment of VTE. We enrolled 860 patients with a median age of 68 years, including 34% female and 71% lung cancer. Cumulative incidence of VTE for 24 weeks was 22.6% (95% confidence interval: 19.8%-25.5%) (194 of 860 patients). Incidence of VTE was 11.3% pretreatment, 16.8% 12 weeks, and 14.1% 24 weeks. Symptomatic VTE was observed in 4.0% and PE in 1.0% of patients. By multivariate analysis, sex, D-dimer level, and platelet count were independent risk factors of VTE for 24 weeks. This large prospective observational study showed that cumulative incidence of VTE was high in advanced cancer patients, mainly lung cancer. Although most patients showed asymptomatic VTE, intensive screening of VTE may be considered in advanced cancer patients, especially in women with high level of D-dimer and decreased platelet count (UMIN000015243).

Pantothenate kinase from the thermoacidophilic archaeon Picrophilus torridus.

Pantothenate kinase (CoaA) catalyzes the first step of the coenzyme A (CoA) biosynthetic pathway and controls the intracellular concentrations of CoA through feedback inhibition in bacteria. An alternative enzyme found in archaea, pantoate kinase, is missing in the order Thermoplasmatales. The PTO0232 gene from Picrophilus torridus, a thermoacidophilic euryarchaeon, is shown to be a distant homologue of the prokaryotic type I CoaA. The cloned gene clearly complements the poor growth of the temperature-sensitive Escherichia coli CoaA mutant strain ts9, and the recombinant protein expressed in E. coli cells transfers phosphate to pantothenate at pH 5 and 55 degrees C. In contrast to E. coli CoaA, the P. torridus enzyme is refractory to feedback regulation by CoA, indicating that in P. torridus cells the CoA levels are not regulated by the CoaA step. These data suggest the existence of two subtypes within the class of prokaryotic type I CoaAs.

Multicenter, phase II, placebo-controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin.

Aprepitant is a new neurokinin-1 (NK(1) ) receptor antagonist developed as a treatment for chemotherapy-induced nausea and vomiting (CINV). To evaluate the efficacy and safety of aprepitant used in combination with standard therapy (granisetron and dexamethasone), we conducted a multicenter, phase II, placebo-controlled, double-blind, randomized study in Japanese cancer patients who received cancer chemotherapy including cisplatin (≥70mg/m(2) ). Aprepitant was administered for 5days. A total of 453 patients were enrolled. In the three study groups, (i) standard therapy, (ii) aprepitant 40/25mg (40mg on day 1 and 25mg on days 2-5) and (iii) aprepitant 125/80mg (125mg on day 1 and 80mg on days 2-5), the percentage of patients with complete response (no emesis and no rescue therapy) was 50.3% (75/149 subjects), 66.4% (95/143 subjects) and 70.5% (103/146 subjects), respectively. This shows that efficacy was significantly higher in the aprepitant 40/25mg and 125/80mg groups than in the standard therapy group (χ(2) test [closed testing procedure]: P=0.0053 and P=0.0004, respectively) and highest in the aprepitant 125/80mg group. The delayed phase efficacy (days 2-5) was similar to the overall phase efficacy (days 1-5), indicating that aprepitant is effective in the delayed phase when standard therapy is not very effective. In terms of safety, aprepitant was generally well tolerated in Japanese cancer patients. (ClinicalTrials.gov number, NCT00212602.)

Video-assisted esophagectomy using a port-free organ retractor for the prevention of laryngeal nerve paralysis.

INTRODUCTION: Recurrent laryngeal nerve (RLN) paralysis is a major complication of esophageal cancer surgery. The free jaw clip (FJ clip) was developed as an organ-retracting device, and it can also reduce the number of ports required during surgery. Here, we describe a new technique for lymphadenectomy along the left RLN using the FJ clip. MATERIALS AND SURGICAL TECHNIQUE: After the middle and lower mediastinal lymph nodes were dissected, the upper esophagus and other tissues, including the lymph nodes and left RLN, were retracted by cutting the tracheal arteries between the esophagus and trachea and then pulling the upper esophagus to the dorsal side with the FJ clip. The esophagus was transected at the upper mediastinum, and the proximal esophagus was drawn by the FJ clip. This technique helped provide a good field of view during lymphadenectomy along the left RLN. The data of nine consecutive patients who underwent video-assisted esophagectomy in the left lateral decubitus position by the same surgeon were reviewed. Postoperative left RLN paralysis occurred in only one patient in whom the RLN could not be preserved. DISCUSSION: Given the excellent short-term outcomes with respect to left RLN paralysis, lymphadenectomy along the left RLN using the FJ clip was safe and feasible.

Usefulness of virtual enteroscopy for the detection of small polypoid lesion in the small bowel, a case report.

INTRODUCTION: Virtual enteroscopy (VE) has been developed to explore the entire small bowel. We have previously reported that VE can reveal elevated lesions measuring >10 mm in diameter. However, data on the existence of smaller polypoid lesions is scarce. This study aimed to report a case of pyogenic granuloma in the ileum detected by VE. PRESENTATION OF CASE: A 55-year-old woman presented to our hospital with iron deficiency anemia. Esophagogastroduodenoscopy, colonoscopy, and abdominal contrast-enhanced computed tomography did not indicate any bleeding sources. Video capsule endoscopy revealed a small polypoid lesion in the small bowel. VE was subsequently performed and a polypoid lesion was detected at 119 cm from the ileocecal valve. Its size was estimated to be 6 mm. Based on VE findings, laparoscopic-assisted surgery for the small bowel tumor was performed. During surgery, the polypoid lesion, at 120 cm from the end of the ileum, was barely palpable. The resected specimen showed a 5.5 × 5.0 mm polypoid lesion. Microscopically, the polypoid lesion was diagnosed as pyogenic granuloma. DISCUSSION: We detected a 5.5 × 5.0 mm polypoid lesion in the small bowel, and this is the minimum size of the lesion visualized on VE. This imaging technique provides surgeons with data on the location, number, and size of polypoid lesions. CONCLUSION: VE is a new useful tool for the preoperative collection of data on small polypoid lesions in the small bowel.

Survival outcomes after laparoscopy-assisted distal gastrectomy versus open distal gastrectomy with nodal dissection for clinical stage IA or IB gastric cancer (JCOG0912): a multicentre, non-inferiority, phase 3 randomised controlled trial.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) is increasingly being used as an alternative to open distal gastrectomy (ODG) for gastric cancer treatment. Retrospective studies have shown equivalent survival with the two procedures, but these studies are limited by selection bias because LADG is more technically difficult than ODG. We aimed to evaluate whether LADG was non-inferior to ODG in terms of long-term survival outcomes. METHODS: We did an open-label, multicentre, non-inferiority, phase 3 randomised controlled trial at 33 institutions in Japan. Patients aged 20-80 years with histologically confirmed gastric adenocarcinoma (T1N0, T1N1, or T2[MP]N0), clinical stage I, in the middle or lower third of the stomach, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with a body-mass index of less than 30 kg/m2, were randomly assigned (1:1) to receive ODG or LADG. Randomisation was done by telephone, fax, or with a web-based system in the Japan Clinical Oncology Group Data Center; a minimisation method with a random component was used to adjust for institution and clinical stage (IA or IB). Only study-accredited surgeons performed ODG and LADG. The primary endpoint was relapse-free survival and was analysed according to the intention-to-treat principle. The non-inferiority margin (LADG vs ODG) was set at a hazard ratio (HR) of 1·54. The trial was registered with the UMIN Clinical Trials Registry, UMIN000003319. FINDINGS: Between March 15, 2010, and Nov 29, 2013, 921 patients were enrolled and randomly assigned to receive ODG (n=459) or LADG (n=462). 912 (99%) participants had the assigned surgery. 5-year relapse-free survival was 94·0% (95% CI 91·4-95·9) in the ODG group and 95·1% (92·7-96·8) in the LADG group. LADG was non-inferior to ODG for relapse-free survival (HR 0·84 [90% CI 0·56-1·27]), p=0·0075). The most common grade 3 or 4 adverse event was bowel obstruction, occurring in 11 (2%) of 455 patients in the ODG group and five (1%) of 457 patients in the LADG group. There were no treatment-related deaths. INTERPRETATION: This trial supports the non-inferiority of LADG compared with ODG for clinical stage I gastric cancer relapse-free survival, suggesting that LADG should be considered a standard treatment option when performed by experienced surgeons. FUNDING: Japan National Cancer Center, Ministry of Health, Labour and Welfare of Japan, Japan Agency for Medical Research and Development.