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The number of patients who die from causes other than gastric cancer after R0 resection is increasing in Japan, due in part to the aging population. However, few studies have comprehensively investigated the clinicopathological risks associated with deaths from other causes after gastrectomy. This study aimed to build a risk score for predicting such deaths.We retrospectively reviewed clinical data for 3575 patients who underwent gastrectomy for gastric cancer at nine institutions in Japan between January 2010 and December 2014.The final study population of 1758 patients were assigned to Group A (n = 187): patients who died from other causes within 5 years of surgery, and Group B (n = 1571): patients who survived ≥ 5 years after surgery. Multivariate analysis identified nine characteristics as risk factors for poor survival: age ≥ 75 years, male sex, body mass index 22 kg/mThe risk score defined here may be useful for predicting deaths from other causes after curative gastrectomy.

Background Insufficient data are available on the prognostic significance of complications after resection of gastric cancer. Therefore, we aimed to assess this gap in our knowledge by studying patients with resectable gastric cancer. Methods A multi‐institutional retrospective database comprising clinical information of 3575 patients who received resection of gastric cancer from 2010 to 2014 at nine institutions. Grades 2 or greater complications of the Clavien‐Dindo classification were judged as clinically relevant postoperative complications, and their associations with postoperative survival were assessed. We assessed the effect of complications on times of initiation and continuation of postoperative adjuvant chemotherapy by S‐1. Results A total of 2954 patients were included in the analysis. Clinically relevant postoperative complications occurred in 664 (23%) patients. Patients’ recurrence‐free survival rate incrementally decreased as the grade of complications became greater. Patients with abdominal complications (eg, leakage of pancreatic fluids, intra‐abdominal abscess, and anastomotic leakage) and those with nonabdominal complications (eg, pneumonia) experienced worse recurrence‐free survival compared to those without complications. Patients who had complications were generally at greater risk of disease recurrence, except for those who underwent laparoscopic surgery and those with pathological stage I. Delayed initiation and shorter continuation of adjuvant S‐1 chemotherapy was experienced by patients with postoperative complications. Conclusions Postoperative complications adversely affected the prognosis in patients with resectable gastric cancer.

AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in stage II/III gastric cancer. METHODS From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions, data of 998 patients who underwent curative resection for stage II/III gastric cancer between 2010 and 2014 were retrieved and analyzed. The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels, the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy. RESULTS The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels. Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival. Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels, and patients with high levels of both markers showed significantly poorer prognosis than other patient groups. When we analyzed perioperative changes in serum CEA and CA19-9 levels, patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups. Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels, whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels. The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone, whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy. High postoperative CEA levels were significantly associated with an increased prevalence of liver, lung and bone recurrences, and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences. CONCLUSION The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy.

The prognostic significance of the number of retrieved lymph nodes (RLNs) in gastric cancer remains controversial. Therefore, we designed a multicenter collaborative database to investigate the correlation between the number of RLNs and prognosis of patients with advanced gastric cancer after curative resection. We retrospectively analyzed 1103 patients who underwent gastrectomy for stage II/III gastric cancer between 2010 and 2014. Lymph nodes, which were retrieved by surgeons from surgically resected specimens, were validated by pathologists. A target population and the optimal cutoff were determined using receiver operating characteristic (ROC) curve analysis. After propensity score matching of eight variables, including splenectomy and adjuvant chemotherapy, the prognostic significance of RLNs was evaluated. According to ROC curve analysis, the optimum cutoff score for predicting postoperative survival was 40. After matching, the backgrounds of patients in the RLN

Background The three dominant recurrence patterns of gastric cancer are peritoneal, hematogenous, and nodal recurrence. Correlation between initial recurrence site and prognosis is poorly understood, particularly after standardization of postoperative S‐1 adjuvant chemotherapy. Methods We analyzed a multi‐institutional database of 3484 patients who underwent gastrectomy for gastric cancer between 2010 and 2014. Patients who experienced recurrences after curative gastrectomy classified into peritoneal, hematogenous, or nodal recurrence groups, according to their initial recurrence sites, and their prognoses were compared. Results We included 313 patients in the analysis, of whom 190 patients (63%) were treated with postoperative adjuvant chemotherapy. Pathological disease states were stage I: n = 20 (6%), stage II: n = 62 (20%), and stage III: n = 231 (74%). Patients were categorized into groups by peritoneal (n = 127), hematogenous (n = 123), and nodal (n = 63) recurrence. The peritoneal recurrence group tended to have longer recurrence‐free survival, but shorter post‐recurrence survival, than the other two groups. Median disease‐specific survival after curative resection by group were peritoneal: 25.8 months, hematogenous: 29.0 months, and nodal: 27.8 months (peritoneal vs hematogenous, P = .152; hematogenous vs nodal, P = .955; peritoneal vs nodal, P = .213). Conclusions Prognoses after curative resection for gastric cancer were similar among patients with peritoneal, hematogenous, or nodal recurrences., We used a multi‐institutional dataset to see whether prognosis and site of initial recurrence after curative resection for gastric cancer were correlated. We found that prognoses were similar among patients with peritoneal, hematogenous, or nodal recurrences.

Few well-controlled studies have compared postoperative complications between Billroth I (B-I) and Roux-en-Y (R-Y). The aim of the present study was to compare the incidence of overall and severe postoperative complications by reconstruction method after distal gastrectomy. We performed a multi-institutional dataset study of patients who underwent distal gastrectomy with B-I or R-Y reconstruction from 2010 to 2014. Using propensity scores to strictly balance the significant variables, we compared postoperative complications between the techniques. After matching, we enrolled 1014 patients (n = 507 in each group). The incidence of postoperative complications in the R-Y group was significantly higher vs the B-I group (29% vs 17%, P

This study aimed to evaluate whether the timing of initiating postoperative chemotherapy with S-1 monotherapy affects gastric cancer patients’ prognosis. A multi-institution dataset identified patients with pStage II or III gastric cancer who received S-1 monotherapy for over 6 months after curative resection between 2010 and 2014. Patients were divided into three groups based on the timing of S-1 monotherapy initiation. Prognostic factors for relapse-free survival (RFS) were investigated. We classified 401 patients into groups as follows: S-1 administered within 6 weeks (n = 247), between 6 and 8 weeks (n = 95), and after 8 weeks (n = 59). The RFS times were not significantly different in the within 6 weeks group and the between 6 and 8 weeks group, but the after 8 weeks group had a shorter RFS time compared with the other two groups (within 6 weeks group vs. after 8 weeks group; P = 0.0044). By disease stage, this trend was the same. The multivariable analysis showed that a larger tumor size (≥ 50 mm), pStage III, and the after 8 weeks group were independent prognostic factors for RFS (after 8 weeks group: hazard ratio, 2.05; P = 0.0069). The prevalence of hematogenous metastasis as the initial recurrence site increased by delayed initiation of S-1. A forest plot revealed that delayed administration after 8 weeks was associated with a greater risk of recurrence in most subgroups. Postoperative chemotherapy with S-1 monotherapy for gastric cancer is recommended to begin within 8 weeks after surgery.

Anastomotic leakage is a major cause of prolonged hospitalization after gastrectomy and sometimes leads to fatal complications, such as abdominal abscess and sepsis. Arginine, glutamine, and β-hydroxy-β-methylbutyrate (HMB) are indispensable for biosynthesis of collagen, which plays an important role in the process of wound healing. However, treatment effects of amino acid supplements containing HMB on the healing process of anastomotic leakage after gastrectomy remain unclear. We designed an open-label, multicenter, phase II clinical trial to evaluate the therapeutic efficacy of an enteral amino acid supplement consisting of arginine, glutamine, and HMB (Abound, Abbott Japan Co., Ltd., Tokyo, Japan) in patients with anastomotic leakage after gastrectomy. Patients who are diagnosed with anastomotic leakage within 14 days after gastrectomy are eligible for this trial and the target sample size is 20. A pack of Abound is administered twice a day for 2 weeks. The primary objective of this clinical trial is to determine the length of time between diagnosis and cure of anastomotic leakage. The secondary endpoints include the safety of Abound, duration of drainage placement and fasting, postoperative hospital stay, surgical procedure, and blood test data. Variables are compared between enrolled patients and a historical control consisting of 20 patients who underwent gastrectomy between 2004 and 2016 at Nagoya University Hospital. We herein describe the study design and the concept in this protocol paper.

Background Advanced gastric cancer frequently recurs even after radical resection followed by adjuvant chemotherapy. The aim of this study was to evaluate the relationship between pathological infiltrative pattern (INF) and initial recurrence patterns in patients with stage II/III gastric cancer using a large multicenter database. Methods We retrospectively analyzed 1098 eligible patients who underwent curative gastrectomy for stage II/III gastric cancer at nine institutions between 2010 and 2014. Patients were categorized into the INF‐a/b and INF‐c groups and adjusted using propensity score matching. Results After propensity score matching, 686 patients (343 for each) were classified in the INF‐a/b and INF‐c groups. There were no significant differences in overall and disease‐free survival between the two groups. In the INF‐a/b group, frequencies of recurrence at the peritoneum, lymph node, and liver were equivalent. In contrast, the peritoneum was the most frequent site and accounted for 60% of the total recurrences in the INF‐c group. The cumulative peritoneal recurrence rate was significantly higher in the INF‐c group than in the INF‐a/b group (hazard ratio 2.47). INF‐c was a significant risk factor for peritoneal recurrences in most subgroups including age, sex, macroscopic type, tumor differentiation, and disease stage, and whether the postoperative treatment was given. Multivariate analysis identified INF‐c as an independent risk factor for peritoneal recurrences. The cumulative liver recurrence rate was significantly higher in the INF‐a/b group than in the INF‐c group (hazard ratio 3.44). Conclusions INF may represent an important predictor of recurrence patterns after curative resection of stage II/III gastric cancer.

Aneurysm formation is a potential complication of granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis. It is a very rare complication, but immediate diagnosis and therapy should be performed because an aneurysm can be life-threatening if it ruptures. An accessory left gastric artery (ALGA) is also a rare variant gastric artery that may obtain its blood supply from the left hepatic artery and left gastric artery. We herein describe a 57-year-old Japanese man who was diagnosed with GPA complicated by aneurysm rupture in an ALGA. Emergency surgery was performed after failure of arterial coil embolization to interrupt blood flow in the ALGA. The patient underwent partial resection of the lesser omentum, which contained all aneurysms. During partial resection of the lesser omentum, both the left gastric artery and ALGA were ligated because they were thought to be feeders of the aneurysms. Postoperative recovery was uneventful; no bleeding or recurrence of the aneurysms occurred. Immediate diagnosis and therapy should be performed for patients with GPA with symptoms of vascular ischemia or aortitis. Endovascular intervention is the first-choice therapy especially for hemodynamically stable patients with ruptured aneurysms or aneurysms located on variant arteries, which may have multiple blood supplies. In the present case, although endovascular treatment failed, the approach described herein was helpful during open surgery.

Purpose Patients with pathological stage T1N+ or T2-3N0 gastric cancer may experience disease recurrence following curative gastrectomy. However, the current Japanese Gastric Cancer Treatment Guidelines do not recommend postoperative adjuvant chemotherapy for such patients. This study aimed to identify the prognostic factors for patients with pT1N+ or pT2-3N0 gastric cancer using a multi-institutional dataset. Materials and methods We retrospectively analyzed the data obtained from 401 patients with pT1N+ or pT2-3N0 gastric cancer who underwent curative gastrectomy at 9 institutions between 2010 and 2014. Results Of the 401 patients assessed, 24 (6.0%) experienced postoperative disease recurrence. Multivariate analysis revealed that age ≥70 years (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.09-7.23; P=0.030) and lymphatic and/or venous invasion (lymphovascular invasion (LVI): HR, 7.88; 95% CI, 1.66-140.9; P=0.005) were independent prognostic factors for poor recurrence-free survival. There was no significant association between LVI and the site of initial recurrence. Conclusions LVI is an indicator of poor prognosis in patients with pT1N+ or pT2-3N0 gastric cancer.

症例は61歳の女性で，53歳時より原発性胆汁性肝硬変・シェーグレン症候群・膜性腎症にて加療中である．今回，右季肋部痛を主訴に受診し，腹部CTで肝左葉外側区域に径9 cmの腫瘍を指摘された．身体検査所見では掻痒感を認めるも黄疸はなく，血液生化学検査で胆道系酵素・IgMの上昇，抗ミトコンドリア抗体陽性を認めた．肝炎ウィルスマーカーおよび腫瘍マーカーは陰性であった．画像検査所見にて腫瘍は被膜様構造を伴う境界明瞭な腫瘤として描出された．内部は脂肪成分に富み造影による早期濃染を認めた．鑑別診断として大型の高分化型肝細胞癌と肝血管筋脂肪腫が考えられたが，確定診断はつかず肝左葉切除術を施行した．摘出標本の病理組織学的検査にて肝血管筋脂肪腫と診断された．術後1年経過した現在のところ明らかな再発所見を認めていない．今回，原発性胆汁性肝硬変の経過中に急速に増大した肝血管筋脂肪腫の1例を経験したので報告する．

症例は21歳，女性．約1年前に子宮外妊娠の疑いにて左付属器摘出術を施行され，病理結果で卵巣癌と診断された．術後に血中hCG高値を認め，化学療法が施行されていたが，CTにて右ドーム部に増大傾向にある約3cm大の腫瘤を認めたため，播種性転移を疑い手術を施行した．術中所見は，右横隔膜にヘルニア嚢を有する径3cm大の筋層欠損部を認め，同部より胸腔へ突出する肝を認めるのみであり，術中超音波検査でも肝内に腫瘤は認めず，ヘルニア門を縫合閉鎖し手術終了とした．成人の右側Bochdalek孔ヘルニアは非常に稀な疾患であり，今回われわれは，その経時的な変化を画像で捉えた症例を経験したため若干の文献的考察を加えて報告する．

はじめに：P0CY1症例の臨床病理組織学的因子，予後について検討し，P1症例と比較した．方法：当院で1996年から2005年までに手術を施行した656例の胃癌症例のうち，開腹時に腹腔洗浄細胞診（以下，CY）を施行した339例を対象とした．CYはPapanicolaou染色にて判定し，ClassVをCY1と診断した．結果：P0は281例でそのうちCY1は33例（11.7％）であった．P0CY1全例が深達度T3もしくはT4で，リンパ節転移陽性であり，P0CY0と比較してT因子，N因子の進展を認めた．生存期間を比較すると，P0CY0，P0CY1，P1の順に不良であった．腹膜播種陽性例を胃癌取扱い規約第12版に従い，P1，P2，P3に分類してP0CY1も含め比較したところ，P0CY1，P1はP3に比べ生存期間は長かった．また，P0CY1の腹腔洗浄細胞診における癌細胞数の多寡による比較を行うと，癌細胞数少数例のほうが多数例に比べ生存期間は長かった．胃切除，リンパ節郭清を行ったP0CY1のうち，有意差はないがMSTはD2群が497日，D0，D1群が264日という結果であった．考察：CY1は予後不良因子であるが，P1より生存期間は長い．腹腔洗浄細胞診における癌細胞数の多寡は予後予測因子になりうると考えられた．

はじめに: 上部胃癌の手術術式の選択にあたり, 噴門側胃切除が至適術式として採用できるか否かをリンパ節郭清の程度も含め, 壁深達度とリンパ節転移の状況に基づき検討した. 方法: 1973年から2005年に行われたH0P0M0のU領域, 初発単発胃癌切除例401例を対象とし, No.4d, 5, 6, 10, 11のリンパ節の転移の特徴, 臨床病理組織学的因子につき検討した. 結果: 深達度SSまでのNo.10転移例は郭清例126例中5例 (4.0%) であり, 全例病変の占居部位は胃上部左半にあった. 4例は腫瘍径が40mm以上であり, 1群リンパ節転移を伴っていた. No.11転移例は郭清例126例中8例 (6.3%) で, そのうちNo.11dの転移例は3例のみであり, 全例病変の占居部位は胃上部左半にあり, 1群リンパ節転移を伴っていた. そのうち, 2例は腫瘍径が40mm以上であった. No.4d転移例は郭清例189例中3例 (1.6%) で, 全例腫瘍径は40mm以上, 病変の占居部位は胃上部左半にあった. No.5, 6リンパ節転移例は認めなかった. 深達度SE, SIではそれぞれのリンパ節転移率は高率となる傾向であった. 結語: 深達度SSまでで占居部位が小彎に限局, あるいは腫瘍径が40mm未満もしくは1群リンパ節転移を認めない場合, No.4d, 5, 6, 10, 11dのリンパ節転移例はごくまれであった. したがって, 上部胃癌では上記の条件を満たす場合, 噴門側胃切除術, D1+No.7, 8a, 9, 11pのリンパ節郭清は至適術式と考えてよいと思われた.

Underphosphorylated retinoblastoma (Rb) protein inhibits progression around the cell cycle by binding to transcription factors like E2F; subsequent hyperphosphorylation of Rb protein releases E2F from the complex so that it can then drive the cell into S phase. We immunolocalized Rb protein in human cells during the cell cycle. Rb protein translocated into nucleoli after DNA replication completed, and the nucleolar Rb was shown to be in the hyperphosphorylated form by immunoblotting. This form, but not its underphosphorylated counterpart, interacted with the nucleolar protein nucleophosmin/B23. The two formed a salt-resistant complex in vitro, and the two could be immunoprecipitated together from nucleolar extracts. These results suggest that hyperphosphorylated Rb protein is imported into nucleoli late in S or G2 phase with nucleophosmin/B23. Analysis of the nucleolar location of Rb protein using various deletion mutants tagged with the green fluorescent protein implicated pocket A of Rb protein as the region responsible for nucleolar targeting; this region also interacted with nucleophosmin/B23. Nucleolar translocation of Rb mutant was inhibited by introducing nucleophosmin/B23 antisense oligomer. These results suggest that nucleolar translocation of Rb protein is promoted by the binding with nucleophosmin/B23 via the pocket A region.