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International audience; Air traffic management (ATM) systems around the world are being modernized to accommodate shifts towards performance-and trajectory-based operations. These shifts will require new indices for safety, efficiency and complexity. The authors have been developing an index for evaluating air traffic control (ATC) difficulty that utilizes the relative positions and velocity vectors of aircraft pairs as input data. Prior to practical application of the index, it is necessary to understand the effects of input data error, i.e. errors in the positions and velocities of a pair of aircraft, on the estimated difficulty value. Two sensitivity analyses were therefore performed for a pair of aircraft cruising at constant speeds on intersecting linear tracks at the same altitude. Sensitivity analysis examines how uncertainty in inputs relates to uncertainty in outputs. Firstly, an analysis of propagation error was carried out. The formula of the propagation error at a certain point was derived based on the assumed input error, and the distribution of propagation error was investigated for all possible situations and compared with the distribution of difficulty values to clarify its characteristics. Secondly, a sensitivity analysis based on variance was carried out that evaluated the effect of each input parameter using a conditional variance value called the Sobol indices. Using a Monte Carlo method, we investigated the effect of each input parameter on the calculated difficulty value for all possible situations of aircraft pairs on intersecting trajectories. As a result, it was found that the parameter that most affects the difficulty value is the intersection angle of the trajectories.

Background Little is known about the survival outcomes of and predictive factors for survival in hemodialysis patients undergoing surgery for gastric cancer. Methods We performed a multicenter retrospective study from 9 institutions to investigate the survival outcomes of 75 hemodialysis patients with gastric cancer. Patient characteristics included demographic data, hemodialysis- and gastric cancer-related variables. Multivariate Cox hazards models were applied to determine independent predictors of poor overall survival and non-gastric cancer related death. Results Stage I disease was predominant (58.7%) in our series. The overall morbidity and the 30-day mortality rates were 25.3% and 1.3%, respectively. The 5-year overall survival rates of patients with pStages I, II, III, and IV disease were 59.2%, 42.9%, 32.3%, and 0%, respectively. Eleven (14.7%) patients died of gastric cancer, whereas many more (40.0%) died owing to causes other than gastric cancer. Non-gastric cancer-related death was especially prevalent in patients with pStages I (95.2%) and II (75.0%) disease. Multivariable analysis revealed advanced age, long duration of hemodialysis (> 5 years), total gastrectomy, and pStage IV disease to be independently associated with poor overall survival. Notably, advanced age, long duration of hemodialysis, and the presence of cardiovascular disease were all independent predictors of non-gastric cancer-related death. Patients with all 3 factors had very poor survival outcomes (3-year overall survival; 14.3%). Conclusion The survival outcomes of hemodialysis patients with gastric cancer, especially those with early-stage gastric cancer, were clearly poor, largely owing to the increased risk of non-gastric cancer-related death. Preoperative comorbidities and hemodialytic features were useful for predicting long-term outcomes of this vulnerable population.

Positive margins are reported in from 4.8 to 9.5% of all gastric cancer surgeries and they have a negative impact on the overall survival. Few cases with positive duodenal margins have been included in previous studies regarding the prognosis. This multi-institutional retrospective study included 115 gastric cancer patients with positive duodenal margins following gastrectomy between January 2002 and December 2017. The association between clinicopathological factors and the overall survival was evaluated by univariate and multivariate analyses. The three-year overall survival was 22% and the median survival was 13 months. A multivariate analysis found that distant metastasis, no postoperative chemotherapy, and non-Type 4 disease were significantly associated with a poor survival. Patients without distant metastasis who received postoperative chemotherapy had a 3-year overall survival of 56% and a median survival of 44 months. The patients who underwent post-operative chemotherapy showed a significantly better OS compared with those who did not undergo post-operative chemotherapy, regardless of the existence of distant metastasis. Postoperative chemotherapy may, therefore, improve the prognosis of surgically treated gastric cancer patients with positive duodenal margins.

A 78-year-old woman presenting with severe acute liver failure was admitted to our hospital. On screening for the etiology of acute liver failure, it was diagnosed as being due to idiopathic hypereosinophilic syndrome (eosinophil count reported as 4766/μL; 33.8% of the white blood cells). Her medical history included marked eosinophilia, as observed six months prior to this admission. Corticosteroid therapy was initiated. During the clinical course, duodenal perforation occurred but was managed promptly by appropriate surgery. A liver biopsy, following the initiation of corticosteroid therapy, revealed degenerating hepatic cells with mild eosinophilic infiltration. With corticosteroid therapy, the liver function improved.

Background Real‐world outcomes of nivolumab treatment for gastric cancer and associated prognostic factors remain unclear; the present study aimed to evaluate both items. Methods A total of 278 consecutive patients treated with nivolumab for gastric cancer during 2017‐2019 were enrolled in this multi‐institutional retrospective cohort study. The impact of laboratory findings, immune‐related adverse events (irAEs), and clinicopathological factors on long‐term survival was evaluated using the Cox proportional hazards model. Results The response rate was 11.7% in patients with measurable lesions. The overall and progression‐free survival estimates were 6.77 and 2.53 months, respectively. The incidence of irAEs was 30.6% (6.8% for grade ≥3). There were no treatment‐related deaths. Multivariate analysis revealed that C‐reactive protein level of ≤0.5 mg/dL (hazard ratio = 0.476, P 3.5 g/dL (hazard ratio = 0.688, P = .045), performance status 0 (hazard ratio = 0.711, P = .028), lymphocyte count >1000/μL (hazard ratio = 0.686, P = .027), and differentiated histological type (hazard ratio = 0.740, P = .046) were independently associated with improved survival. The median survival of patients with four or more good prognostic factors was 18.3 months. Conclusion Nivolumab showed safety and survival benefits in patients with previously treated unresectable or recurrent gastric cancer. Low C‐reactive protein level, irAE occurrence, high albumin level, high lymphocyte count, and differentiated histological type may affect outcomes. The presence of four or more good prognostic factors may help identify likely long‐term survivors., Multi‐institutional retrospective cohort study of nivolumab treatment for unresectable or recurrent gastric cancer revealed that the median overall and progression‐free survival estimates were 6.77 and 2.53 months, respectively. Low C‐reactive protein level, immune‐related adverse events, high albumin level, performance status 0, high lymphocyte count, and differentiated pathological type were associated with improved survival.

Aim This study aimed to compare the efficacy of taxane-based and platinum-based regimens in patients with early recurrent gastric cancer after radical surgery with S-1 adjuvant chemotherapy. Methods The medical records of 118 patients from six institutes with early recurrent stage II/III gastric cancer, who developed recurrence during adjuvant S-1 or within 6 months after completion of adjuvant therapy between January 2006 and December 2017, were retrospectively analyzed. Patients treated with second line chemotherapy were enrolled and followed to the end of December 2019. The impact of two regimens, taxane-based (n = 46) versus platinum-based (n = 31), on treatment outcome were evaluated using multivariate analysis. Results Median overall survival was 9.0 months and median progression-free survival was 4.1 months. No difference was observed in overall survival between taxane-based and platinum-based regimens (P = 0.64). Although not significant, the response rate of platinum-based regimens was better than that of taxane-based regimens (16% vs. 6.5%, P = 0.26). Multivariate analysis identified performance status (P = 0.040), multiorgan metastases (P = 0.029), and undifferentiated histological type (P = 0.018) as independent poor prognostic factors. In undifferentiated histological type, multiorgan metastases (P = 0.013) and taxane-based regimens (P = 0.018) were independent prognosis factors characterized by multivariate analysis. Conversion rate to third-line chemotherapy or more was 51% in undifferentiated histological type and 65% in differentiated histological type (P = 0.26). Conclusion Platinum-based regimens may be recommended for undifferentiated early recurrent gastric cancer after S-1 adjuvant chemotherapy.

Congestion is a major cause of inefficiency in air transportation. A question is whether delays during the arrival phase of a flight can be absorbed more fuel-efficiently in the future. In this context, we analyze Japan’s flow strategy empirically and use queueing techniques in order to gain insight into the generation of the observed delays. Based on this, we derive a rule to balance congestion delays more efficiently between ground and en-route. Whether fuel efficiency can be further improved or not will depend on the willingness to review the concept of runway pressure.

Helicobacter pylori has been considered to be non-invasive and to rarely infiltrate the gastric mucosa, even though there is an active Th1 immune response in the lamina propria of the H. pylori-infected stomach. To elucidate whether H. pylori invades the lamina propria and translocates to the gastric lymph nodes, we examined H. pylori in formalin-fixed and paraffin-embedded tissue sections of stomach and gastric lymph nodes obtained from 51 cancer patients using real-time PCR and immunohistochemistry (IHC) with a novel anti-H. pylori monoclonal antibody that recognizes lipopolysaccharides. Fresh gastric lymph nodes were used to culture for H. pylori. In 46 patients with H. pylori in the stomach, the bacterium was found in the lymph nodes from 21 patients by culture, 37 patients by PCR, and 29 patients by IHC. H. pylori captured by macrophages was found in the lamina propria of 39 patients. In the lymph nodes, the bacterium was found in many macrophages and a few interdigitating dendritic cells at the paracortical areas. H. pylori was also found in the intracellular canaliculi of parietal cells in 21 patients, but intracytoplasmic invasion into gastric epithelial cells was not identified. When compared to the commercially available anti-H. pylori antibodies, the novel antibody showed the highest sensitivity to detect H. pylori-positive macrophages, whereas no difference was found for H. pylori in the mucous layer. The H. pylori-positive macrophages in the lamina propria correlated with chronic gastritis as well as translocation of such cells to the lymph nodes. These results suggest that H. pylori-induced gastric epithelial damage allows the bacteria to invade the lamina propria and translocate to the gastric lymph nodes, which may chronically stimulate the immune system. The bacteria captured by macrophages, whether remaining alive or not, may contribute to the induction and development of H. pylori-induced chronic gastritis.

Background/Aims: C-reactive protein (CRP) was recently identified as a prognostic factor for patients with hepatocellular carcinoma (HCC) after surgical resection. We investigated the relationship between the serum levels of high sensitivity CRP (H-CRP) and the prognosis of HCC patients. Method: We conducted a cohort study of 90 HCC patients enrolled from 1997 to 1998. All patients were treated and followed for a mean period of 3.2 years. Clinical variables were compared between patients positive for H-CRP (serum H-CRP levels ≥3.0 mg/L, n=47) and those negative for H-CRP (serum H-CRP levels

Background/Aims: This study aimed to evaluate the usefulness of 18F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) and PET plus computed tomography (CT) fusion images for the detection of extrahepatic metastases of hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (combined HCC/CC). Methods: Twenty-one patients with HCC and combined HCC/CC were enrolled in the study from December 2004 to February 2005. In all patients, PET and CT of the chest to pelvis region were performed. The sensitivity of PET plus CT fusion images was compared with the sensitivity of PET, CT, and bone scintigraphy. Results: In 14 patients, a total of 58 extrahepatic metastases were diagnosed. The detection rate of PET plus CT fusion images, PET, CT, and bone scintigraphy was 98.2% (57 of 58 metastases), 89.6% (52 of 58 metastases), 91.2% (52 of 57 metastases), and 68.7% (11 of 16 bone metastases), respectively. No extrahepatic metastases were detected in the other seven patients. The detection rate of PET was 10/18 (55.6%) for intrahepatic lesions of HCC and combined HCC/CC. Conclusions: The fusion of PET plus CT images is useful in detecting extrahepatic metastases in HCC and combined HCC/CC patients.

症例は56歳,男性.平成13年9月,直腸癌に対し高位前方切除術,リンパ節郭清術を施行,中分化腺癌,深達度ss, リンパ節転移を認めずstage IIと診断した.その後外来経過観察中の平成14年10月,腫瘍マーカーは正常であったが,腹部CT検査で右副腎に25mmの鵬を認めた.平成15年1月CEAの上昇と腹部CT検査での副腎鵬の増大を認め,直腸癌の転移性副腎腫瘍を疑い平成15年2月右副腎腫瘍摘出術を行った.病理組織学的に,副腎髄質を主体に原発巣に類似した高分化から中分化腺癌像を認め,他に転移がみられないため直腸癌の右副腎転移と診断した.転移巣切除後13カ月経過し再発の徴候は認めない. 転移性副腎腫瘍は特徴的な臨床所見が少なく,早期に診断され治療される症例は少なく.血中CEAおよびCT検査を定期的に行うことで早期に発見でき,切除しえた直腸癌術後の孤立性副腎腫瘍について報告した.

当センターで胃癌に対して胃切除術を施行し, follow up 中に残胃の癌が発見され切除を施行した症例は15例であった.このうち噴門側胃切除術後の残胃の癌切除症例4例を詳細に分析した.これらは同時期に施行した噴門側胃切除術症例の2.8%であった.発見までの介在期間は11か月から4年2か月, 平均2.9年であった.発生部位は全例非断端部であった.全例早期癌であったが4例中3例は未分化型のSM浸潤癌であった.1例にリンパ節転移を認めたが観察期間4-125か月で全例無再発生存, 予後良好であった.初回術式は全例, 食道胃吻合術がなされており残胃の内視鏡での観察が容易であった.本邦における自験例を除く噴門側胃切除術後の残胃の癌24例の集計では, 介在期間の平均は7.0年, 組織型は分化型が多く, 残胃進行癌が多かった.以上の特徴を念頭におき, 計画的な経過観察により早期発見・治療に努めることが重要であると考えた.

Advancing of age apparently influences the behavior of colorectal cancer (CRC). The pattern of activation and expression of Wnt target genes may influence the behavior of the cancer. In the present study, the level of activation of some elements of Wnt signaling was evaluated and correlated with the patient's age and clinicopathological characteristics of the tumor. Beta-catenin and c-Myc mRNA expressions were evaluated by semiquantitative real-time PCR, and subcellular localization of the beta-catenin protein was evaluated by immunohistochemistry. Patients aged 70-84 tended to have locally advanced disease more frequently than younger patients. The same group of patients also more frequently had high nuclear expression of beta-catenin protein and higher expression of c-Myc mRNA. Beta-catenin mRNA had a rather constant expression with advancing of age. High nuclear expression of beta-catenin and high expression of c-Myc were apparently also correlated with locally advanced disease. We concluded that the level of Wnt signaling activation might influence the behavior of the disease in different age groups.

The incidence of cancer increases with advancing age, but the biological behavior of cancer is known to be less aggressive in elderly people. Thus, the proliferative activity and extent of apoptosis of cancer cells were assessed in samples from 163 cases of colorectal cancer focusing on the age of patients, using Ki-67 labeling index (LI) and apoptotic index (AI) by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick end labeling method and staining for activated caspase-3. The Ki-67 LI of colorectal cancer ranged from 2.33 to 80.4% (mean 32.2%), while the AI ranged from 0.00 to 14.8% (mean 3.57%). Concerning the aging effect, linear and positive correlations were found for the Ki-67 LI of cancer with age (p0.05) and the AI of cancer with age (p0.05). However, in normal colorectal mucosa, aging of patients revealed a significant correlation only with the AI but not with the Ki-67 LI. The AI in earlier stages of cancers (stages 0 and 1) revealed a significant difference between younger cases (age65) and more elderly cases (age/=65) (p0.05), however, the Ki-67 LI did not exhibit a significant difference. Therefore, an increased frequency of apoptosis in colorectal cancer tissues, especially in the earlier stages, may possibly explain the slower growth of colorectal cancers in the elderly. Next, the expressions of several regulatory molecules for the proliferation/apoptosis of tumor cells were determined. The results demonstrated a tendency for stronger and more frequent expressions of c-myc, Bak and Bax despite a rather weaker expression of Bcl-2 in cancer tissues from the elderly compared with those from the younger patients. The potential roles of these regulatory molecules on age-change in the proliferation/apoptosis of colorectal cancers are discussed.

A case of lymphoid hyperplasia arising in the large intestine of a 54-year-old woman is described. Barium enema X-ray and colonoscopic examination revealed multiple small polyps in the right side of the colon. Pathological findings from forceps biopsy revealed similar features to a mucosa-associated lymphoid tissue (MALT) lymphoma. A right hemicolectomy with mesenteric lymph node dissection was carried out. Histological sectioning demonstrated hypertrophic lymphoid follicles with well-formed germinal centers. Occasionally, lymphocytes infiltrated the crypts, in a way similar to that found in lymphoepithelial lesions, which was suggestive of a MALT lymphoma diagnosis. Cryptitis was also observed in the lamina propria. Immunohistochemically, proliferating lymphocytes were positive for CD20 (L26) and negative for CD45RO (UCHL-1). Analyses of immunoglobulin gene (IgHJH) rearrangement could not detect any monoclonality in these cells. These findings suggested that the present case should be categorized as lymphoid hyperplasia rather than lymphoma.

We describe herein the case of an extremely unusual composite carcinoid-adenocarcinoma tumor of the stomach, most of which was found to be carcinoid. The carcinoid tumor component exhibited argyrophilic granules, immunohistochemical localization of chromogranin, and serotonin immunoreaction. Conversely, none of the adenocarcinoma component reacted with argyrophilia, chromogranin, or serotonin. DNA flow cytometric analysis revealed a near-diploid pattern in the carcinoid element and an aneuploid pattern in the adenocarcinoma element. The transitional zone and continuity between the two tumor components were observed. These findings suggest that the tumor originated from the endocrine system, although part of it showed nonendocrine differentiation. The patient died approximately 6 months after the onset of symptoms and an autopsy could not be performed.