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Ramucirumab (RAM) plus paclitaxel (PTX) therapy has shown promising results as a standard second-line treatment for advanced gastric cancer patients. Recently, combined docetaxel (DOC) plus S-1 (DS) therapy could be regarded as the new standard adjuvant chemotherapy for patients with curatively resected stage III gastric cancer. However, the efficacy and safety of RAM plus PTX therapy in patients treated previously with DOC-containing therapy remains unclear. This study assessed the clinical outcomes of RAM plus PTX therapy in advanced gastric cancer patients with or without a previous history of treatment with a DOC-containing regimen. In a series of 107 consecutive patients enrolled for this study, the median PFS and OS were 4.2 and 6.2 months, respectively. Fifty-five patients had a history of prior therapy with DOC and 52 did not. There was no significant difference between with and without DOC groups in the ORR (22.2% vs. 23.5%), PFS (4.2 vs. 5.3 months), or OS (7.2 vs. 6.4 months). In a comparison taking into account the interval from the DOC-containing therapy to the RAM plus PTX therapy, the number of treatment courses was significantly smaller and the PFS significantly shorter in the patient group with an interval of ≤ 6 months (median, 2 vs 4.5 courses, P = 0.033; 3.4 months vs. 5.1 months, P = 0.043). RAM plus PTX therapy in patients with advanced gastric cancer is effective even in patients who have previously received DOC-containing chemotherapy, especially if the interval is > 6 months.

The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system provided a specific ‘ypTNM’ stage grouping for patients with esophageal cancer. This study aimed to evaluate the clinical utility of the AJCC 8th edition ypTNM stage grouping for patients with esophageal squamous cell carcinoma (ESCC). We enrolled 152 patients with ESCC who underwent surgery after neoadjuvant cisplatin plus 5-fluorouracil (CF) therapy between June 2005 and December 2011. ypStage was evaluated according to the AJCC 7th and 8th editions. Predictive performance for disease-specific survival (DSS) and overall survival (OS) was compared between both editions. The prognostic significance of ypTNM stage grouping was evaluated using univariate and multivariate analyses. Revision of the AJCC 7th edition to the 8th edition was associated with a change in ypStage in 96 patients (63.2%). The AJCC 8th edition revealed a better predictive performance than the 7th edition in terms of DSS (Akaike’s information criterion [AIC] 499 vs. 513; Bayesian information criterion [BIC] 505 versus 519; concordance index [C-index] 0.725 versus 0.679) and OS (AIC 662 vs. 674; BIC 669 vs. 681; C-index 0.662 vs. 0.622). On univariate and multivariate analyses, ypStage in the 8th edition was an independent prognostic factor for both DSS and OS. ypTNM stage grouping in the AJCC 8th edition provided a better predictive performance for DSS and OS than that in the 7th edition. ypStage in the 8th edition was the most reliable prognostic factor for ESCC patients who underwent surgery after neoadjuvant CF therapy.

Pylorus-preserving gastrectomy (PPG) is widely used for early gastric cancer located in the middle third of the stomach. The minimization of the extent of gastrectomy may increase the risk of metachronous multiple gastric cancer (MGC). We report the findings of a study that was conducted to evaluate the prevalence of MGC after PPG. The clinical data of 533 patients who underwent PPG for gastric cancer between 1993 and 2018 were reviewed. The clinicopathological characteristics at the time of the primary treatment that were predictive of the development of MGC were explored. The median (range) observation period was 112.4 (8.1–290.7) months. Metachronous MGC was diagnosed in 33 of the 533 patients. The cumulative 5-year and 10-year event rates were 3.3% and 6.2%, respectively. The patient gender, presence/absence of synchronous MGC and the macroscopic type of the primary gastric cancer were significantly associated with the risk of development of metachronous MGC. Multivariate analysis identified the presence of synchronous MGC (hazard ratio [HR]: 4.828, 95% confidence interval [CI]; 1.611–12.30, p = 0.004) and Type 0-IIa primary gastric cancer (HR 2.810, 95% CI; 1.113–7.090, p = 0.029) as independent factors associated with the risk of development of MGC. All the patients could be treated by surgical or endoscopic resection for the metachronous MGC. Recurrence was observed in one patient. There was quite a few incidence of development of metachronous MGC after PPG. Nevertheless, PPG remains reasonable treatment option, if adequate postoperative surveillance can be ensured.

Clinical N category (cN) is generally assessed by measuring the nodal diameter by CT before the initiation of primary treatment in esophageal squamous cell carcinoma (ESCC). The short-axis diameter is recommended for evaluating treatment response in solid tumors by RECIST. This study aimed to elucidate the prognostic implication of the maximum short-axis diameter of lymph node (cN-size) before preoperative chemotherapy for ESCC. Methods We enrolled a total of 152 patients who underwent preoperative cisplatin/5-fluorouracil therapy (CF) followed by esophagectomy from 2005 to 2011. There were 127 men and 25 women with a median age of 65 years (range: 47–79 years). Clinically metastatic node was defined as follows; the node with cN-size ≥10 mm or that with 5 mm ≤ cN-size Results The number of patients with cN0 and cN1–3 was 60 and 92, respectively. Twenty-seven and 65 patients with cN1–3 were classified into cN-size Conclusion The maximum short-axis diameter of lymph node before preoperative chemotherapy is significantly associated with OS in patients with ESCC. Lymph node with 5 mm ≤ cN-size

Thoracoscopic esophagectomy (TE) is considered the standard surgery for esophageal cancer because of its superiority over open esophagectomy (OE) in terms of short-term outcomes. However, few prospective multicenter studies have evaluated its long-term survival after TE. This study aimed to investigate whether the prognosis for patients with T1bN0M0 esophageal cancer after TE is not inferior to OE using data from the Japan Clinical Oncology Group Study (JCOG0502), a prospective multicenter trial comparing esophagectomy with chemoradiotherapy. Data of patients in JCOG0502 after esophagectomy were used to compare the overall survival (OS) and relapse-free survival (RFS) after OE versus TE. OE or TE was selected at the surgeon’s discretion. A hazard ratio and 95% confidence interval (CI) were calculated via Cox proportional-hazards model. Of the 210 patients who underwent esophagectomy, 109 underwent OE, whereas 101 underwent TE. The 5-year OS was 88.9% after OE and 85.0% after TE. The hazard ratio of TE for OS was 1.53 (95% CI, 0.84–2.78; p = 0.16) and 1.10 (95% CI, 0.52–2.35; p = 0.80) in the univariable and multivariable analyses, respectively. The 5-year RFS was 85.3% after OE and 79.1% after TE. The hazard ratio of TE for RFS was 1.39 (95% CI, 0.81–2.38; p = 0.23) and 0.88 (95% CI, 0.44–1.74; p = 0.70) in the univariable and multivariable analyses, respectively. The prognosis for patients with T1bN0M0 esophageal cancer after TE was not inferior to OE.

e13618Background: Approximately 5% of gastric cancer (GC) is associated with inherited cancer predisposition syndrome. Pathogenic germline BRCA1/2 mutations predispose, not only to breast and ovari...

A reddish depressed lesion was found in the corpus of the stomach of a 56-year-old man. Gastric biopsy showed no findings of mucosa-associated lymphoid tissue lymphoma, including lympho-epithelial lesions. A urea breath test, stool antigen test and serum IgG antibody to Helicobacter pylori test were negative. Magnifying endoscopy using narrow-band-imaging showed no malignant structures. Gastric biopsy specimens were subjected to immunohistochemistry and a polymerase chain reaction, which identified Helicobacter suis infection. Triple therapy with esomeprazole, metronidazole, and amoxicillin was administered for 10 days. Three months later, endoscopy showed the significant improvement of the lesion. H. suis infection should be considered in chronic gastritis patients without H. pylori infection.

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.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/mFrom 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.CRT is noninferior to surgery and should be considered for the treatment of T1bN0M0 ESCC.

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 (

Background:Metatarsalgia is frequently associated with hallux valgus. The aim of this study was to evaluate how the relative length and position of the first metatarsal head influenced metatarsalgia and plantar callosities beneath the lesser metatarsal heads.Methods:A retrospective analysis of the clinical data and radiographs of 102 cases was performed at a mean follow-up of 16 months after biplane interlocking osteotomies. Clinical evaluation was made using the Japanese Society for Surgery of the Foot (JSSF) hallux scale. Radiologic evaluation was made with standard weight-bearing anteroposterior radiographs, and the hallux valgus angle (HVA), intermetatarsal 1-2 angle (IMA), distal metatarsal articular angulation (DMAA), and the sesamoid position were evaluated. Relative first metatarsal length (RML) was determined according to Nilsonne/Morton’s technique.Results:The mean preoperative HVA decreased from 37 to 3 degrees, and the mean IMA from 17 to 4 degrees. The mean JSSF-hallux score improved from 56 to 96 points. The mean preoperative area of plantar callosities decreased from 3.1 to 1.5 mm2. Sixty percent of metatarsalgia cases improved, and 85% of painless callosities disappeared postoperatively. Among radiologic parameters, postoperative RML was most significantly associated with JSSF score ( P < .0001) and the presence of postoperative metatarsalgia ( P < .0001). Receiver operating characteristic analysis revealed that the RML cut-off point was −3 mm for avoiding metatarsalgia, with an area under the curve of 0.88, a specificity of 88%, and a sensitivity of 85%.Conclusion:Preservation of relative first metatarsal length during first metatarsal osteotomy was important to prevent postoperative metatarsalgia.Level of Evidence:Level IV, retrospective case series.

e16581 Background: Whereas radical resection for gastric cancer is only life-saving option, resulting host response have been suggested to trigger the outgrowth of previously disseminated foci at distant anatomical sites via alteration of anti-tumor immunity. The prognostic nutrition index (PNI) which was calculated as 10 × serum Alb concentration (g/dL) + 0.005 × peripheral total lymphocyte count (/µL) is a surrogate marker of inflammation related nutritional decline and the imbalance of T lymphocyte differentiation. The aim of study was to evaluate the impact of perioperative change of PNI. Methods: The medical record of 567 gastric cancer patients who matched with the following inclusion criteria, R0 resection between 2006 and 2018, no preoperative anticancer treatment, pStage IB-IIIC according to UICC TNM classification and no other organ cancer at surgery, was identified from the prospectively maintained database. The postoperative laboratory data was routinely evaluated at POD 1, 3, 7 and first visit after discharge (AD). The PNI was compared through the perioperative course. Then the predictive value of low PNI-AD which defined as PNI < 40 on the relapse free survival (RFS) after surgery was estimated by COX proportional hazards analysis. Results: The median value of PNI at base line, 1, 3, 7 POD and AD was 51.0, 35.9, 34.0, 38.3 and 48.2, respectively. The PNI as significantly decreased at 1, 3 and 7 POD. Though the PNI at AD had a proclivity to recover, which was still significantly lower than that at base line. During observation period after surgery, the recurrence was encountered in 80 patients. The 5-year RFS rate in patients of pStage IB (n = 164), II (n = 228) and III (n = 175) was 97.4%, 88.9% and 64.7%, respectively. The multivariate analysis identified female gender (HR: 1.715, 95%CI; 1.018-2.890, p = 0.04), pT3-4 (HR:3.620, 95%CI; 2.011-6.518, p < 0.01), pN1-3 (HR:2.741, 95%CI; 1.428-5.263, p = 0.02), vessel invasion (+) (HR:2.666, 95%CI; 1.681-4.229, p < 0.01), PNI-AD < 40 (HR:1.833, 95%CI; 1.002-3.352, p = 0.04) were independent predictors of recurrence. The low PNI-AD was significantly related to the recurrence in the population of pStage III, but not in pStage IB and II. Conclusions: The retardation of postoperative recovery of PNI might evoke the distant metastasis.

4565 Background: Esophageal squamous cell carcinoma (ESCC) is associated with synchronous or metachronous cancer at other primary sites. Previous studies have suggested that patients (pts) with ESCC are still at a high risk of second primary malignancies after definitive therapies. In particular, early-stage ESCCs result in good prognosis, which is associated with a higher risk of second primary malignancies. Methods: The JCOG0502 was a phase III trial, which included a randomized and a non-randomized part and compared esophagectomy with definitive chemoradiotherapy in clinical T1bN0 ESCC. We additionally reviewed data of all pts enrolled in the JCOG0502 for second primary malignancies. Lugol-voiding lesions (LVLs) were assessed in the noncancerous esophageal mucosa before the treatments. Results: Among 379 enrolled pts, 213 pts received esophagectomy and the remaining received chemoradiotherapy. Patient characteristics of overall cohort were as follows: male, 85%; median age, 63 (range, 41–75) years; upper- /middle- /lower thoracic esophagus, 11/63/27%; alcohol consumption history, 79%; smoking history, 66%; prevalence of no LVLs/several LVLs/many LVLs/unknown, 45/36/8/11%. With a median follow-up of 7.1 years, a total of 118 second malignancies were observed in 99 pts (26%). Cumulative incidences of second malignancies after 3, 5, 10 years were 9, 15, 36%, respectively. Most common primary tumor sites were head and neck (35%), followed by stomach (20%) and lung (14%). In multivariable analyses, several LVLs [hazard ratio (HR): 2.24, 95% confidential interval (CI): 1.32–3.81, vs. no LVLs] and many LVLs (HR: 2.88, 95% CI: 1.27–6.52, vs. no LVLs) were significantly associated with the development of second malignancies. Regarding the three most common types of cancers, 62 out of the 77 cancers (81%) were diagnosed in clinical stage 0–I. Seventeen pts died due to second primary malignancies. There were 4 and 3 deaths from head and neck and lung cancer, respectively. Whereas, mortality caused by stomach cancer was not observed. Conclusions: In the JCOG0502, the incidence of second malignancies was high, indicating that careful follow-up is required for ESCC pts even after treatment completion. The presence of LVLs in esophagus was identified as an independent predictive factor for second primary malignancies, which may be useful for surveillance strategies. Clinical trial information: UMIN000000551 .

A number of training programs that seek to improve driving performance among older drivers are available accompanied by a growing interest in their effectiveness. The purpose of the present investigation was to examine the combined effect of (1) basic in-class training (BT); (2) on-road training with individualized feedback (OR); and (3) training on a driving simulator (S).Using a randomized controlled trial study design, 78 older drivers were randomly assigned to one of 3 groups (BT, BT + OR, or BT + OR + S). All participants completed a pre- and postintervention on-road driving evaluation on a standardized route. The driving evaluations were recorded using video and Global Positioning System (GPS) equipment and were scored by a blind assessor.The results indicated a significant reduction of approximately 30% in overall number of driving errors/omissions among participants in the BT + OR and the BT + OR + S groups in comparison to participants in the BT group.This study adds to the mounting evidence demonstrating the effectiveness of individualized driver training in improving safe driving among older adults.

7 Background: Esophagectomy (E) is the standard of care for stage I esophageal squamous cell carcinoma (ESCC), while chemoradiotherapy (CRT) is a treatment option. A parallel-group controlled trial including randomized arms to confirm the non-inferiority of CRT to E for stage IA ESCC was conducted. Methods: Patients (pts) with thoracic ESCC, adenosquamous cell, or basaloid cell carcinoma with stage IA (T1bN0M0), age 20 to 75, performance status 0 to 1, and adequate organ function were eligible. If pts accepted randomization, they were randomly allocated to E with 2-3 field lymph node dissection (arm A) or CRT (arm B). However, if pts had a preference and refused randomization, they were allocated to pts preference arm, E (arm C) or CRT (arm D). CRT consisted of cisplatin and 5-FU, with radiation at the dose of 60 Gy concurrently. The primary endpoint was overall survival (OS) of arm A and B, secondary endpoint included OS of arm C and D using inverse probability weighting with propensity score. The planned sample size in arm A and B was 114 pts in total with one-sided alpha of 10%, power of 75% and non-inferiority margin of HR as 1.78. The sample size in arm C and D was at least 156 pts in each arm with one-sided alpha of 2.5%, power of 85% and non-inferiority margin of HR as 1.78. Results: Between December 2006 and February 2013, 379 (Arm A: 4, B: 7, C: 209 C, D: 159) pts were enrolled. Primary endpoint was not calculated due to small number of randomized arms. Patients characteristics of arm C and D were as follows; median age: 62 and 65, male (%): 82.8 and 88.1, PS 0 (%): 99.5 and D 98.1. All histologic type was SCC except one basaloid cell carcinoma in arm C. The 3- and 5-year OS were 94.7% and 86.5% in arm C, and 93.1% and 85.5% in arm D (adjusted HR 1.05; 95% CI 0.67-1.64 [< 1.78]).Treatment related death were observed in two pts in arm C and none in arm D. Conclusions: Though the accrual of randomized arms was shortened, CRT showed trend toward non-inferiority compared to E in pts preference arms. CRT is considered as a treatment option for stage IA ESCC with organ preservation. Clinical trial information: UMIN000000551.

A 76-year-old man was referred to our hospital for treatment of a submucosal tumor in the esophagus. The patient had a history of superficial esophageal cancer treated by endoscopic resection and radiation. Positron emission tomography showed intense localized uptake of fluorodeoxyglucose on the esophageal mass. Transthoracic esophagectomy and reconstruction with a gastric tube were performed. Histopathological examination revealed that the tumor consisted of a proliferation of atypical spindle cells with infiltration of many inflammatory cells. The spindle cells were positive for vimentin, alpha smooth muscle actin, and anaplastic lymphoma kinase immunostaining. The Ki-67 labeling index was 10–20 %. The tumor was finally diagnosed as inflammatory myofibroblastic tumor. Late phase inflammation caused by radiation potentially had an effect on the occurrence of the tumor in this case. For tumors of the irradiated esophagus, especially, careful pretreatment examination and treatment strategies with consideration of the radiation damage are important to obtaining a favorable outcome.

To evaluate the sites and frequencies of overall and initial lymph node (LN) metastases (LNMs) of clinical T1N0 esophageal cancer.The sites and frequencies of initial LNMs and sentinel LNs (SLNs) of esophageal cancer remain unclear.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.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%.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.

The optimal treatment for early stage carcinoma of the thoracic esophagus is undecided and remains debatable. This report documents the results of a series of patients with clinical stage IA carcinoma of the thoracic esophagus treated at our institute with esophagectomy and two-field lymphadenectomy (2FL). We analyzed 70 patients with clinical stage IA carcinoma who underwent radical esophagectomy with 2FL. The overall 5-year survival rate of the 70 patients was 81 %. Seventeen of the 70 patients (24 %) had lymph node metastasis. The overall 5-year survival rate of the 53 patients with no metastatic nodes (87 %) was significantly better than that of the 17 patients with positive nodes (65 %; p = 0.022). The operative morbidity was 44 %. Recurrence was recognized in 17 patients (24 %). The median disease-free interval (DFI) until recurrence was 20.5 months. With respect to the initial tumor recurrence, among the 16 patients with a recurrence, there were 9 with a cervical lymph node recurrence, 3 with a hematogenous recurrence, 2 with a combined recurrence, 1 with an abdominal lymph node recurrence in the paraaortic site, and 1 in the anastomotic site. The median DFI and survival times of the patients with a cervical lymph node recurrence were 26 and 55 months, respectively. Of the 9 patients with a cervical lymph node recurrence, 3 disease-free patients survived: 2 received surgery and 1 received radiotherapy. Two-field lymphadenectomy might be enough for patients with clinical stage IA carcinoma of the middle and lower thoracic esophagus in regard to prognosis, but close follow-up for lymph node recurrence, especially at the cervical site, should be conducted.

Background The 8th edition of the American Joint Committee on Cancer staging (AJCC-8th) of esophageal cancer presents independent stage grouping for patients who underwent neoadjuvant therapy followed by esophagectomy (ypTNM). The aim of this study is to elucidate the clinical utility of ypTNM stage grouping in Japanese patients with esophageal squamous cell carcinoma (ESCC). Methods A total of 146 patients (121 men and 25 women, with a median age of 65 years) who underwent curative esophagectomy following neoadjuvant chemotherapy with cisplatin and 5-fluorouracil (CF) for ESCC between 2005 and 2011 were enrolled in this retrospective study. We compared the distribution of patients and disease-specific survival after esophagectomy (DSS) stratified by ypStage between AJCC-7th and 8th. Additionally, we evaluated the association between clinicopathological features including ypStage in AJCC-8th and DSS. Results The number of patients classified into ypStage 0/IA/IB/IIA/IIB/IIIA/IIIB/IIIC/IV was 5/1/14/11/35/40/18/18/4 in AJCC-7th, and that classified into ypStage I/II/IIIA/IIIB/IVA/IVB was 27/18/21/58/18/4 in AJCC-8th. According to the revision from AJCC-7th to 8th, ypStage of 85 and 7 patients was up- and down-graded, respectively. Up-grading of ypStage was observed in 83% of patients with ypT4 tumor and in 78% of patients with ypN1–3. The 5-year DSS of ypStage 0/IA/IB/IIA/IIB/IIIA/IIIB/IIIC/IV was 100/100/93/91/75/62/50/28/50% in AJCC-7th, and that of ypStage I/II/IIIA/IIIB/IVA/IVB was 96/83/68/58/28/50% in AJCC-8th. The 5-year DSS of ypStage III was 61% in AJCC-8th comparing to 51% in AJCC-7th, and that of ypStage IV was 31% in AJCC-8th comparing to 50% in AJCC-7th. Univariate analyses identified ypT-8th (P = 0.028), ypN-8th (P Conclusion ypTNM stage grouping in AJCC-8th can more accurately stratify the prognosis of patients who underwent neoadjuvant CF therapy for ESCC, by classifying patients with residual tumor invasion to adjacent structures and regional lymph node metastasis into more unfavorable prognostic group than that in AJCC-7th. ypStage according to AJCC-8th is the most reliable prognosticator for this disease. Disclosure All authors have declared no conflicts of interest.

e16068Background: Defective homologous recombination (HR) due to genetic aberrations of HR genes contributes to a high response of platinum therapy in ovarian and breast cancers. The aim of this st...

Background: The relationship between Helicobacter pylori infection and iron metabolism has not been well studied in Japan. We examined the association of H. pylori infection and its eradication to iron metabolism. Methods: A total of 654 adults who completed a health survey in 2012 were enrolled. H. pylori stool antigen was tested and serum antibody titer and serum iron, ferritin and pepsinogen levels were estimated. Subjects reported on their daily intake of the diets to calculate daily intake of iron and vitamin C. Among the H. pylori-infected patients surveyed in 2012, 177 patients completed the same health survey in 2014. For these patients, the change of daily intake of iron and vitamin C and serum iron and ferritin levels were examined. Results: In 2012, 244 subjects (37.3%) were considered as infected with H. pylori. In male subjects aged 35–64 years, serum level of ferritin was 77.5 (SD 53.1) ng/mL in infected patients and 130.6 (114.3) ng/mL in non-infected subjects (p

A case of carcinosarcoma arising from the area of intraepithelial spread of relapsed esophageal squamous cell carcinoma (SCC) after definitive chemoradiotherapy (CRT) is reported herein. A 71-year-old man was referred to our hospital because of a superficial esophageal carcinoma. Definitive CRT was performed because the patient refused surgical treatment. Complete response was recognized after CRT, but tumor relapse was diagnosed 3 months later. The relapsed tumor initially revealed a minimal depression with a small white nodule. This nodule developed to a sessile elevated mass after 1 month and finally to a polypoid tumor 3.2 × 2.3 × 1.5 cm in size within 125 days. A subtotal esophagectomy with two-field lymph node dissection was performed. Histologically, the polypoid tumor was composed mainly of spindle-shaped sarcomatous cells and invaded the muscularis propria of the esophageal wall. An area of intraepithelial spread of SCC was found at the base of its stalk. No lymph node metastases were found. The postoperative course was uneventful, and the patient has remained free of disease for 45 months. To our knowledge, this is the only reported case of esophageal carcinosarcoma arising from an area of intraepithelial spread of relapsed SCC that showed such rapid growth by serial endoscopies.

はじめに：大腸癌取扱い規約第7版（以下，第7版）では，腫瘍下縁がRSまたはRaの癌で3 cm，腫瘍下縁がRbの癌で2 cmの肛門側切離が必要であるとされている．直腸癌における肛門側癌進展（distal spread；以下，DS）に関する病理組織学的検討から直腸癌の肛門側切離範囲について検討した．方法：対象は直腸S状部癌および直腸癌213例．直腸間膜を含めた全割標本から，腸管壁内DSと直腸間膜内DSを検出し，それぞれの危険因子について検討した．また，第7版の定める肛門側切離範囲を超えるDSを高度DSとし，その特徴を明らかにした．結果：213例中31例（15％）にDSを認めた．内訳は，腸管壁内DSのみが20例，直腸間膜内DSのみが5例，腸管壁内DSと直腸間膜内DSの両者が6例であった．多変量解析では，腸管壁内DSの危険因子は組織型（tub2，por）と遠隔転移であり，直腸間膜内DSの危険因子は遠隔転移であった．高度DSは213例中3例（1.4％）に認め，全例がリンパ節転移を4個以上有するpN2症例であり，また3例中2例が遠隔転移を有していた．考察：遠隔転移を有する症例はDSを念頭においた手術が必要である．第7版の定める肛門側切離範囲は大部分の症例において妥当であるが，pN2症例や遠隔転移を有する症例の中には，高度DSを有する症例もあり，注意が必要である．

症例は60歳の男性で, 家族歴として, 一卵性双生児の兄が家族性大腸腺腫症で加療中である. 1974年, 家族性大腸腺腫症と診断され, 結腸全摘術, 回腸直腸吻合術を施行された. 1991年, 残存直腸の多発ポリープに対し残存直腸切除, 回腸. 肛門吻合術を施行された. 2000年, 多発胃癌に対し, 幽門側胃切除術を施行, 2002年, 残胃癌に対し内視鏡的粘膜切除術, 2006年, 局所切除術を施行された. 2007年3月, 上部消化管内視鏡検査で食道胃接合部直下に0-IIa病変を認め, また十二指腸に密生する多発ポリープを認めた. いずれも生検で高分化腺癌と診断された. 5月下旬, 胃局所切除術, 膵頭温存十二指腸全摘術を施行した. 病理組織学的診断は, 胃は高分化腺癌, 十二指腸は高分化腺癌および腺腫の混在する病変で, いずれも粘膜内癌であった. 術後, 縫合不全, 膵液瘻, 胆汁瘻などの合併症なく順調に経過し, 第11病日に退院した.

今回, 我々は極めてまれとされている残胃に発生した悪性リンパ腫と癌腫の衝突腫瘍症例を経験したので報告する. 症例は79歳の男性で, 67歳時に十二指腸悪性リンパ腫 (Non Hodgkin lymphoma, diffuse, small B cell type) にて幽門側胃切除術, Billroth II法再建を施行された. 2005年5月, 糖尿病の治療目的で入院した際の上部消化管内視鏡検査で残胃吻合部後壁に2型胃癌を指摘された. 2005年6月, 当科にて残胃全摘術, D1リンパ節郭清を施行された. 病理組織学的診断の結果, 悪性リンパ腫 (Non Hodgkin lymphoma, diffuse, small B cell type, 深達度fSM) と低分化腺癌 (深達度fMP) との衝突腫瘍と診断された. リンパ節転移は認めなかった. 術後, 肺炎および全身衰弱のため長期の入院加療を要した. 退院後は悪性リンパ腫, 癌腫ともに明らかな再発を認めずに経過したが, 術後2年目に重症肺炎にて死亡した.

Objective There is little information about the patterns of care for elderly esophageal squamous cell carcinoma patients, and a standardized strategy has not been established. Therefore, we conducted a questionnaire survey about the patterns of care for these patients. Methods On September 2014, the questionnaires were sent to all 43 institutions of the Japan Esophageal Oncology Group, which comprised five parts: (i) definition of 'elderly' (age, method), (ii) basic treatment strategy according to stage and elderly status (fit/vulnerable/frail), (iii) patterns of care in each stage, (iv) considerations about conducting future clinical trials and (v) other information about geriatric oncology concerning esophageal squamous cell carcinoma. Results All answers were obtained by January 2015. Nearly half institutions (47%) considered the chronological definition of elderly to be over 80 years old. Among 43 institutions, 36 (84%) reported that the type of comorbidity and performance status were important factors for decision-making; no institution selected geriatric scale as an indicator. The most selected treatment strategy in fit healthy elderly patients was the same as the standard treatment of non-elderly patients. Radiation alone was considered the main treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Most of the institutions answered that clinical trials for the elderly are warranted. Most institutions (70%) chose Stage II/III (non-T4) esophageal squamous cell carcinoma as an important investigational target. Conclusions Fit healthy elderly were considered the same as non-elderly patients, although there are no established treatment selection criteria. Radiation alone plays most important role in the treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Stage II/III (non-T4) disease is attractive and warranted for future investigations.

The relationship between ascites, as detected by preoperative computed tomography (CT), and peritoneal metastasis of gastric cancer requires clarification because of its likely significance for clinical outcome.A retrospective analysis of 293 patients with advanced gastric cancer investigated the association between preoperative CT findings of ascites and surgical findings of peritoneal washing cytology and peritoneal metastasis.Forty-five of 293 patients (15%) presented with ascites on preoperative CT. Positive ascites on CT predicted the presence of free tumor cells with 40% sensitivity and 97% specificity, and peritoneal metastasis with 51% sensitivity and 97% specificity. Ascites on CT was an independent prognostic factor by univariate (P.001) and multivariate (relative risk, 2.03; 95% confidence interval, 1.39-2.96; P.001) analyses. The median survival time was 6.0 months in patients with positive ascites on CT.The presence of ascites on CT suggests the presence of peritoneal metastasis and indicates a poor prognosis. The presence of peritoneal metastasis should be confirmed by diagnostic laparoscopy in gastric cancer patients with ascites.

We here report on the clinicopathological characteristics of three cases of esophageal composite tumor showing tirpartite differentiation toward distinct squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. All tumors had in situ squamous cell carcinoma components and the deeply invasive parts of adenocarcinoma and small cell carcinoma components, which showed positive immunoreactivity for neuroendocrine markers and intracytoplasmic argyrophil granules. All three patients suffered disseminated tumor recurrence soon after esophagectomy and died of the disease within 14 months after operation. The metastatic tumors were predominantly composed of small cell carcinoma, and serum levels of neuron-specific enolase (NSE) were abnormally elevated at the time of recurrence in all cases. Esophageal composite tumors with tripartite differentiation are extremely aggressive; this aggression is primarily the result of the small cell carcinoma component, indicating the necessity for clinicians to treat such tumors as small cell carcinoma.

Patients with advanced esophageal carcinoma including clinical T4 tumor, extensive lymph node metastasis, or intramural metastasis have a dismal prognosis, despite recent multimodality treatments. The aim of this study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy using fluorouracil, doxorubicin, and cisplatin or nedaplatin (FAP/N) in these patients.Twenty-six patients were enrolled in this study. The first 9 patients received 600 mg/m2 fluorouracil on days 1-7 and days 29-35, and 30 mg/m2 doxorubicin and 60 mg/m2 cisplatin on days 1 and 29 (FAP). The next 17 patients received modified FAP, in which 50 mg/m2 nedaplatin was given instead of cisplatin (FAN).Grade 3 or 4 toxicities developed in 6 patients (23.1%) during chemotherapy, but there was no discontinuation of treatment. The clinical response rate was 46.2%. Twenty-one patients (80.8%) underwent esophagectomy, and R0 resection was achieved in 16 patients (61.5%). The 1-year survival rates of 26 patients, 21 patients with resectable tumor, 16 with R0 resection, and 12 clinical responders, were 31.3%, 32.1%, 33.3%, and 45.5%, respectively, each with a median survival time of 9 months. The median progression-free survival time of 26 patients was 6 months; in 16 patients with R0 resection progression-free survival was 6.5 months. There was no correlation between the recurrence pattern and tumor spread before treatment.FAP/N was found to have acceptable toxicities and the ability to control locoregional tumors, but made little contribution to patient survival. The efficacy of this treatment for patients with advanced esophageal carcinoma, however, may not yet be apparent.

Background Extended radical esophagectomy with three-field lymphadenectomy for patients with thoracic esophageal cancer has been shown to be effective. But even if this operation is performed, some patients still experience relapse of the disease. The purpose of this study was to clarify the pattern and timing of recurrence after extended radical esophagectomy. Study design Recurrence of esophageal squamous cell carcinoma was examined in 171 of 174 patients who underwent extended radical esophagectomy with three-field lymphadenectomy. Recurrence patterns were classified as locoregional (at the site of the primary tumor, the anastomotic site, or the lymph nodes), hematogenous, and other (pleura or site of gastrostomy). Factors associated with recurrence were identified using univariate and multivariate statistical methods for survival analysis. Results The overall 5-year survival rate was 55.6%. Recurrence was recognized in 74 patients (43.3%). The median disease-free interval until recurrence was 11 months. Thirty patients (17.5%) developed a locoregional recurrence, and 24 (14.0%) developed a hematogenous recurrence. Five patients (2.9%) developed both recurrences simultaneously and were classified as hematogenous recurrences. Of 30 patients with cervical lymph node metastasis, recurrent disease was recognized in 19 patients (63.3%). In multivariate analysis of 160 patients, the depth of invasion and pM-lym (cervical or celiac lymph node metastasis) were significant factors for locoregional recurrence; the depth of invasion and number of lymph node metastases at operation were significant factors for hematogenous recurrence. Survival time for patients with hemotogenous recurrence (median 16 months) was significantly shorter than that of patients with locoregional recurrence (median 25.5 months). Conclusions Locoregional recurrence is associated mainly with the extent of the local tumor and lymph node metastasis; hematogenous recurrence is not only associated with tumor stage but also with the tumor's oncologic behavior.

扁桃悪性リンパ腫の精査中に発見された早期胃癌と胃悪性リンパ腫の衝突腫瘍の1例を経験したので報告する. 症例は62歳の男性で, 2002年7月, 左扁桃腫脹を主訴に当院耳鼻咽喉科を受診し, 左扁桃悪性リンパ腫 (diffuse large B cell type) と診断された. 全身検索のために施行した上部消化管内視鏡検査にて胃体下部後壁に早期胃癌を発見され, 2002年9月10日, 当科にて幽門側胃切除, D2 リンパ節郭清を施行した. 病理診断の結果, 病変は高分化型腺癌 (深達度m) と悪性リンパ腫 (diffuse large B cell type, 深達度sm2) の衝突腫瘍を形成しており, リンパ節転移は認めなかった. 術後, 2002年10月18日より左扁桃悪性リンパ腫に対して, 当院関連病院内科にてCyclOBEAP療法を6コース施行し, 完全寛解を得た. 現在までに胃悪性リンパ腫, 胃癌および扁桃悪性リンパ腫の再発を認めていない.

The role of cervical lymphadenectomy for thoracic esophageal cancer is controversial. This study evaluated the impact of cervical lymphadenectomy on the cervical lymph node metastasis (LNM) and survival rates of patients with esophageal cancer. We analyzed 199 patients who received radical esophagectomy with three-field lymphadenectomy. The overall 5-year survival rate was 49.4%. Cervical LNM was found in 36 (18.1%) out of the 199 patients. The 5-year survival rates of the patients with cervical LNM from upper and mid-esophageal cancers were 71.4% and 35.9%, respectively. However, none of the patients with cervical LNM from lower esophageal cancer survived more than 4 years after esophagectomy. The overall survival of patients with five or more metastatic nodes (5.9%) was significantly worse than that of patients with less than five positive nodes (45.5%). Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus, and with less than five positive nodes.

BACKGROUND: Adequate extent of surgical resection of simultaneous primary esophageal and extraesophageal carcinomas is controversial. STUDY DESIGN: Clinicopathologic records and treatment outcomes of 57 patients undergoing simultaneous resection of both synchronous esophageal and extraesophageal carcinomas (SC group) were reviewed and compared with those of 316 patients receiving esophagectomy for solitary esophageal carcinoma (EC group). RESULTS: Mortality and morbidity rates were 3.5% and 45.6% in the SC group, and 3.2% and 44.3% in the EC group, respectively. No significant difference was detected in either of the rates between the two patient groups. The overall 5-year survival rate of the SC group was 40%. Survival of the patients undergoing curative resection of both esophageal and extraesophageal tumors (n = 30) was significantly better than that of the patients receiving palliative resection of at least one of the two tumors in the SC group (n = 27)(5-year survival, 54.2% versus 19.9%, respectively)(p CONCLUSIONS: Simultaneous resection of synchronous esophageal and extraesophageal carcinomas can be safely performed, and complete tumor clearance of both tumors is needed for favorable longterm results.

e15592 Background: Molecular heterogeneity represents a significant hurdle in realizing precision medicine for gastric cancer (GC). Large-scale whole exome sequencing projects have identified distinct molecular subtypes to help define the heterogeneity of GC. However, it remains unclear whether the targeted gene panel-based sequencing can provide optimum targeted therapies and clinical utility in GC. The aim of this study is to generate comprehensive genomic profiling data and classify Japanese GC into actionable clusters associated with targeted therapies. Methods: FFPE tumor tissues were obtained from surgical or biopsy specimens of 207 Japanese patients with GC. Extracted DNA was subjected to genomic sequencing for 435 cancer related genes including 69 druggable genes with FDA approved targeted therapies. Somatic mutations, copy number alterations (SCNA), microsatellite instability (MSI) and Epstein-Barr virus (EBV) infection were evaluated using sequencing data. Results: Genomic sequencing identified at least one alteration of 435 genes in 194 pts (94%), and that of 69 druggable genes in 141 pts (68%). The most frequently altered druggable gene was ERBB2 (14%), following BRCA2 (11%) and ATM (10%). We successfully classified 207 tumors into four molecular subtypes, similar to the previously report; EBV (4%), MSI (8%), chromosomal instability (58%) and genomically stable subtype (30%). Frequent alterations of druggable genes ( > 5%) were widely observed through these subtypes. To discover the novel classifications associated with targeted therapies, we classified 207 tumors using mutation rate and hierarchical clustering. We identified a hypermutated group (n = 32), and a remaining non-hypermutated group (n = 175) which were sub-divided into six clusters including five actionable ones; ERBB2 (n = 25), CDKN2A and CDKN2B (n = 10), KRAS (n = 10), BRCA2 (n = 9) and ATM cluster (n = 12). Interestingly, we experienced a case of unresectable GC with a remarkable response for anti-HER2 therapy in the ERBB2 cluster. Conclusions: Genomic sequencing using a 435-gene panel has the potential to provide the information of optimum targeted therapies for upcoming precision medicine in Japanese GC.

e23191 Background: Microsatellite instability-high status (MSI-H) and alterations in the DNA mismatch repair pathway associate with the efficacy of 5-FU and immune checkpoint inhibitors in patients with gastrointestinal cancers. The activin type II receptor (ACVR2) that binds to the transforming growth factor beta superfamily of ligands is frequently mutated in MSI-H colorectal cancer. However, the incidence of ACVR2 mutations in gastric cancer patients remains unclear. The aim of this study is to reveal the incidence and to examine the association between the MSI-H and ACVR2A mutations in gastric cancer patients. Methods: 124 archived FFPE gastric cancer tissues (stage I-IV), who were operated at Niigata University Medical and Dental Hospital or Niigata Cancer Center Hospital, were analyzed for ACVR2A mutation and MSI status with the NGS-based comprehensive genomic test platform. Clinicopathological characteristics of the patients were also examined. Results: All 124 gastric cancer patients were successfully analyzed. 13 out of 124 patients (10.4%) showed MSI-H status. Interestingly, 10 of 13 MSI-H patients (76.9%) showed ACVR2A mutation, where none (0%) was found among patients with microsatellite stable status (P < 0.001), indicating the strong association between ACVR2A mutation and MSI status in gastric cancer patients. In the ACVR2A mutated group, there was a female predominance (P < 0.05), and cancers of the lower part of the stomach were more common (P < 0.05), compared with the wild type group. Only one of 10 patients with ACVR2A mutation died, and the patients with ACVR2A mutation show a 5-year overall survival rate of 90%. No statistically significant difference in survival was achieved between patients with ACVR2A mutation and wild type; this is probably due to the small number of patients. Conclusions: 10 of 13 MSI-H patients showed ACVR2A mutation. Our results indicate a strong association between ACVR2A mutation and MSI-H in gastric cancer patients.

Objective The Japanese health insurance system approved the use of proton pump inhibitors (PPIs) for the prevention of peptic ulcers in patients using low-dose aspirin (LDA) and/or non-steroidal anti-inflammatory drugs (NSAIDs). However, many orthopedists and physicians do not prescribe PPIs to elderly patients with atrophic gastritis. The aim of this study was to determine whether PPIs are effective in preventing gastrointestinal mucosal injury in elderly Japanese patients with atrophic gastritis. Methods We examined the associations between the use of antiulcer drugs and endoscopic findings in elderly Japanese patients using LDA or NSAIDs. Patients We evaluated 100 patients using LDA and 58 patients using non-aspirin NSAIDs 65 years of age or older. All patients underwent upper GI endoscopy to detect the presence of open ulcers and hemorrhagic lesions and assess the extent of atrophic gastritis. Results Among the patients using LDA, the prevalence of open ulcers was significantly lower in the patients using PPIs than in those using mucosal protective agent only and those not receiving antiulcer treatment (p

Background. Currently, there is only limited information regarding tumor angiogenesis and its clinical implications in cases of esophageal carcinoma. The purpose of this study was to clarify which clinicopathologic parameters correlate with tumor angiogenesis; furthermore, the study was conducted to evaluate whether tumor angiogenesis is an independent prognostic factor in cases of esophageal carcinoma. Methods. Intratumoral microvessel density (MVD) and thymidine phosphorylase (dThdPase) expression were immunohistochemically studied after extended radical esophagectomy in 103 cases of esophageal carcinoma. Results. Increased MVD significantly correlated with the depth of tumor invasion, the frequency of intramural metastasis, and the stage of tumor advancement (P