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A 72-year-old woman with past medical history of rectal cancer resection (adenocarcinoma, pT3N1aM0) presented with a 2-month history of dysphagia. Imaging studies found a thoracic esophageal cancer, for which subtotal esophagectomy with gastric conduit reconstruction via retrosternal route followed by chemoradiotherapy were performed (squamous cell carcinoma, pT4N1M0, RM1). Seven months after the esophagectomy, a contrast-enhanced computed tomography (CT) demonstrated a new asymptomatic mass inside the right atrium. A thrombus or a tumorous lesion was suspected. Positron emission tomography (PET)/CT showed abnormal uptake in the mass. After a thorough discussion by a multidisciplinary oncology group, we performed 1-week anticoagulant therapy first, resulting in mass enlargement. Then tumorectomy was carried out. The final pathological findings revealed that the mass was squamous cell carcinoma, yielding the diagnosis of cardiac metastasis from esophageal cancer. The patient's postoperative course was unremarkable. PET/CT may help to estimate malignancy and to omit invasive heart surgery.

Gastric cancer (GC) is characterized by unique DNA methylation epigenotypes (MEs). However, MEs including adenocarcinomas of the esophagogastric junction (AEG) and background non-neoplastic columnar mucosae (NM) remain to be clarified.We analyzed the genome-wide DNA MEs of AEG, GC, and background NM using the Infinium 450 k beadarray, followed by quantitative pyrosequencing validation. Large-scale data from The Cancer Genome Atlas (TCGA) were also reviewed.Unsupervised two-way hierarchical clustering using Infinium data of 21 AEG, 30 GC, and 11 NM revealed four DNA MEs: extremely high-ME (E-HME), high-ME (HME), low-ME (LME), and extremely low-ME (E-LME). Promoter methylation levels were validated by pyrosequencing in 146 samples. Non-inflammatory normal mucosae were clustered into E-LME, whereas gastric or esophagogastric junction mucosae with chronic inflammatory changes caused by either Helicobacter pylori infection or reflux esophagitis were clustered together into LME, suggesting that inflammation status determined DNA MEs regardless of the cause. Three cases of Barrett's-related adenocarcinoma were clustered into HME. Among 94 patients whose tumors could be clustered into one of four MEs, 11 patients with E-LME cancers showed significantly shorter overall survival than that in the other MEs, even with the multivariate Cox regression estimate. TCGA data also showed enrichment of AEG in HME and a poorer prognosis in E-LME.E-LME cases, newly confirmed in this study, form a unique subtype with poor prognosis that is not associated with inflammation-associated elevation of DNA methylation levels. LME could be acquired via chronic inflammation, regardless of the cause, and AEG might preferentially show HME.

We sought to evaluate the feasibility of esophageal carcinoma (EC) surgery in cases requiring dialysis. Among 250 consecutive patients undergoing surgical resection for EC, three on maintenance dialysis were identified. We retrospectively analyzed their clinical characteristics. The three dialyzed patients were all males, 39-77 years old at EC surgery. The operations were thoracoscopic esophagectomy with nodal clearance (Case 1), cervical esophageal resection without thoracic procedures (Case 2), and thoracoscopic esophagectomy without reconstruction, emergently conducted for tumor bleeding (Case 3). Reoperation had been required for postoperative abdominal hematoma in Case 1. Postoperative tracheostomy had been performed due to severe pneumonia in Case 2. EC surgery for dialyzed patients, despite appearing to be feasible, might be associated with a high risk of life-threatening morbidities. To minimize surgical risk, therapeutic decision-making for such cases should be based on the balance between radicality and safety.

Gastric lymphangioma (GLA) is an extremely rare tumor without an established therapeutic strategy. Surgical resection is considered the mainstay of treatment, although there is a high risk of local recurrence if negative margins are not achieved. A 51-year-old man underwent routine abdominal ultrasonography, which incidentally detected a 20-mm tumor adjacent to the lesser curvature of the stomach. GLA was suspected based on its polycystic appearance. After a 16-month monitoring period, laparoscopic resection was performed because of tumor growth and involvement of the left gastric artery. Intraoperative indocyanine green (ICG) navigation system revealed lymphatic drainage from the tumor, which we used to help determine the optimal excision line and minimize the loss of gastric volume. Pathological examination confirmed complete resection with negative margins and supported a diagnosis of lymphangioma. We performed laparoscopic radical resection of GLA under guidance from intraoperative ICG fluorescence imaging, which allowed us to maximize residual gastric volume.

Highlights • We performed extended DP-CAR with resection of the confluence of GDA and PHA. • The presence of r-RHA could reduce the risk of ischemic complications. • Further, r-RHA could be a practical choice to expand surgical margin in DP-CAR., Background While distal pancreatectomy with celiac axis resection (DP-CAR) contributes to R0 resection for pancreatic body cancer, arterial blood flow to the liver from gastroduodenal artery is essential. However, in the presence of replaced right hepatic artery (r-RHA), extended DP-CAR (Ex-DP-CAR) in which the right edge of pancreatic resection includes the confluence of gastroduodenal artery (GDA) and proper hepatic artery (PHA) may be feasible. Herein, we report a patient with r-RHA and perform Ex-DP-CAR without reconstruction of PHA. Case presentation A 39-year-old man with pancreatic cancer, cT4N0M0 (UICC 8th), underwent DP-CAR after neoadjuvant chemotherapy (NAC). After laparotomy, unlike the evaluation in preoperative imaging, the tumor was found to invade the confluence of GDA and PHA. After confirmation of arterial blood flow to the liver, GDA and PHA was ligated and Ex-DP-CAR was completed with R0 margin status. The postoperative course was uneventful, with no recurrence 18 months after the surgery. Conclusion We performed Ex-DP-CAR with resection of the confluence of GDA and PHA in the presence of r-RHA, which has a potential role in expanding the surgical indications for R0 resection by reducing the risk of ischemic complications without reconstruction of arterial blood supply to the liver.

Purpose Esophagectomy with extended lymph node (LN) dissection is a standard treatment for resectable esophageal cancer to prevent recurrence, but severe, potentially life-threatening postoperative complications are still important issues. Accurate diagnosis of LN metastases would enable the decision to dissect or leave the LNs in regions with high risk of complications. Advancements in intraoperative gamma probe and radioactivity detectors have made intraoperative navigation surgery possible using a radiotracer as a marker. F-FDG is one such candidate markers, and the diagnostic power of FDG through counting the radioactivity close to each LN should be elucidated. Materials and methods In 20 patients, 1073 LNs including 38 metastatic LNs were prospectively investigated. Preoperative FDG PET was performed on the same day before esophagectomy and visually surveyed in each LN station to identify abnormal uptake. The FDG radioactivity of each individual dissected LN was measured by a well-type counter, and the pathological diagnosis was compared with LN radioactivity on a one-by-one basis and with the preoperative FDG PET findings for each LN station. Results Lymph node station-based analysis showed a sensitivity and specificity of 28.6% and 96.7%, respectively. One-by-one LN-based analysis using a cutoff value obtained from the receiver operating characteristic curve showed a sensitivity and specificity of 94.7% and 78.7%, respectively, demonstrating higher accuracy compared with the use of LN weight or the shortest diameter. Conclusions The FDG uptake by each LN is a potentially useful marker for navigation surgery in esophageal cancer and has higher accuracy than LN weight or diameter.

Background: Gastric lymphangioma (GLA) is an extremely rare tumor without an established therapeutic strategy. Surgical resection is considered the mainstay of treatment, although there is a high risk of local recurrence if negative margins are not achieved. Thus, it would be useful to develop tools and strategies to achieve safe and complete resection. We describe our experience with the first case involving GLA resection under the intraoperative guidance of indocyanine green (ICG) fluorescence imaging, which allowed us to achieve limited but complete resection with negative margins.Case Presentation: A 51-year-old Japanese man with a history of alcoholic liver disease underwent routine abdominal ultrasonography, which incidentally detected a 20-mm tumor adjacent to the lesser curvature of the stomach. The mass was suspected to be GLA based on its polycystic appearance. After a 16-month monitoring period, the patient was referred to our hospital for further assessment because of tumor growth and involvement of the left gastric artery. We selected surgical resection to facilitate a pathological diagnosis and treatment of potential invasion to the surrounding organs. Intraoperative use of a ICG navigation system revealed lymphatic drainage from the tumor, which we used to help determine the optimal excision line and minimize the loss of gastric volume. Pathological examination confirmed complete resection with negative margins and supported a diagnosis of lymphangioma.Conclusions: We performed laparoscopic radical resection of GLA under guidance from intraoperative ICG fluorescence imaging, which allowed us to maximize residual gastric volume. Although further cases are needed to validate this strategy, it may be useful for guiding the resection of GLA.

Background: Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. GC is a pathologically and molecularly heterogeneous disease. DNA hypermethylation in promoter CpG islands causes silencing of tumor-suppressor genes and thus contributes to gastric carcinogenesis. In addition, various molecular aberrations, including aberrant chromatin structures, gene mutations, structural variants, and somatic copy number alterations, are involved in gastric carcinogenesis. Summary: Comprehensive DNA methylation analyses revealed multiple DNA methylation patterns in GCs and classified GC into distinct molecular subgroups: extremely high-methylation epigenotype uniquely observed in GC associated with Epstein-Barr virus (EBV), high-methylation epigenotype associated with microsatellite instability (MSI), and low-methylation epigenotype. In The Cancer Genome Atlas classification, EBV and MSI are extracted as independent subgroups of GC, whereas the remaining GCs are categorized into genomically stable (GS) and chromosomal instability (CIN) subgroups. EBV-positive GC, exhibiting the most extreme DNA hypermethylation in the whole human malignancies, frequently shows CDKN2A silencing, PIK3CA mutations, PD-L1/2 overexpression, and lack of TP53 mutations. MSI, exhibiting high DNA methylation, often has MLH1 silencing and abundant gene mutations. GS is generally a diffuse-type GC and frequently shows CDH1/RHOA mutations or CLDN18–ARHGAP fusion. CIN is generally an intestinal-type GC and frequently has TP53 mutations and genomic amplification of receptor tyrosine kinases. Key Messages: The frequency and targets of genetic aberrations vary depending on the epigenotype. Aberrations in the genome and epigenome are expected to synergistically interact and contribute to gastric carcinogenesis and comprehensive analyses of those in GCs may help elucidate the mechanism of carcinogenesis.

Surveillance after curative surgery for gastric cancer is conventionally performed for 5 years. However, the appropriate follow-up period remains controversial. This study retrospectively compiled a clinicopathological database of patients who underwent curative gastrectomy between 1975 and 2010 at Toranomon Hospital and were reviewed until March 2020. Analyzing the follow-up rate and recurrence rate for each stage in each postoperative year, we set each follow-up endpoint when the subsequent recurrence rate fell below 1%. A total of 5235 patients were eligible for inclusion in the study. The rate of patients followed up for 5 years was 90.3%. The rates of follow-up were 52.7% at 10 years, 38.3% at 15 years, and 10.3% at 20 years. Recurrence was confirmed in 850 patients in total (16.2%) and in 50 patients beyond 5 years. The adequate follow-up endpoints according to stage (with

Adenocarcinoma of the esophagogastric junction (AEG) has heterogeneous carcinogenic process due to its location straddling the esophagogastric junction. We assessed background mucosal pathology and its correlation with clinicopathological features of each Siewert type of AEG. Clinicopathological and immunohistochemical analyses of 103 AEGs and 58 gastric cancers (GCs) were conducted. Background mucosal features were evaluated according to the updated Sydney System. Siewert classification divided 103 AEGs into three type I, 75 type II, and 25 type III tumors, respectively. Two type I, 9 type II AEGs, and none of type III AEGs were Barrett‐related and were excluded from further analysis. Background mucosa of type III AEGs more frequently showed moderate to marked degree of atrophy and intestinal metaplasia than those of type II AEGs and was very similar to those of GCs. Among type II AEGs, tumors with atrophic background were significantly associated with higher patient age and intestinal‐type histology. Type II AEGs with nonatrophic background, but not those with atrophic background, showed more frequent mismatch repair deficiency, TP53 overexpression, and less frequent intestinal phenotypic markers expression than type III AEG or GC. Type II AEGs with atrophic background involved suprapancreatic nodes more frequently than those without. We demonstrated that chronic atrophic gastritis was a major precancerous condition of AEG in the Japanese population, especially Siewert type III which had background mucosal pathology similar to that of GC. Type II AEGs with and without atrophic background showed some clinicopathological differences, and these observations might represent heterogeneous carcinogenic process within type II AEGs.

// Keisuke Matsusaka 1, 2 , Tetsuo Ushiku 3 , Masayuki Urabe 2, 3, 4 , Masaki Fukuyo 2 , Hiroyuki Abe 1 , Shumpei Ishikawa 3, 5 , Yasuyuki Seto 4 , Hiroyuki Aburatani 5 , Takao Hamakubo 6 , Atsushi Kaneda 2, 5 , Masashi Fukayama 1, 3 1 Division of Diagnostic Pathology, The University of Tokyo Hospital, Tokyo, Japan 2 Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan 3 Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 4 Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 5 Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan 6 Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan Correspondence to: Atsushi Kaneda, email: kaneda@chiba-u.jp Masashi Fukayama, email: mfukayama-tky@unin.ac.jp Keywords: gastric cancer, intratumoral heterogeneity, nodal metastases, CDH17, CLDN18 Received: April 22, 2016 Accepted: August 13, 2016 Published: August 26, 2016 ABSTRACT Patients with gastric cancer typically face gastrectomies even when few or no nodal metastases are reported. Current procedures poorly predict lymphatic metastases; thus, evaluation of target molecules expressed on cancer cell membranes is necessary for in vivo detection. However, marker development is limited by the intratumoral heterogeneity of gastric cancer cells. In this study, multiple gene expression arrays of 42 systemic normal tissue samples and 56 gastric cancer samples were used to investigate two adhesion molecules, cadherin 17 ( CDH17 ) and claudin 18 ( CLDN18 ), which are intestinal and gastric markers, respectively. Expression of CDH17 and CLDN18 was partially redundant, but overlapped in 50 of 56 cases (89.3%). Tissue microarrays constructed using primary lesions and nodal metastases of 106 advanced gastric cancers revealed CDH17 and CLDN18 expression in 98 positive cases of 106 (92%). Hierarchical clustering classified gastric cancers into three subgroups, CDH17(++)/CLDN18(+/-), CDH17(++)/CLDN18(++) or CDH17(+)/CLDN18(+), and CDH17(-)/CLDN18(++/+/-). Whole tissue sections displayed strong, homogeneous staining for CDH17 and CLDN18. Together, these results indicate that CDH17 and CLDN18 are useful target molecules; moreover, their coupling can aid in the comprehensive detection and localization of gastric cancer metastases in vivo to overcome challenges associated with intratumoral heterogeneity.

Solitary fibrous tumor (SFT) is one of the mesenchymal tumors, which rarely arises in the abdominal space. We report a very rare case of abdominal SFT, mimicking another mesenchymal tumor. A 52-year-old Japanese man was referred to our hospital for further evaluation and treatment of gallbladder polyp. Contrast-enhanced computed tomography (CT) showed an enhanced nodule within the gallbladder, and incidentally, also showed a well-circumscribed mass adjacent to the small intestine. The mass was depicted as slightly high density in plain CT, and with contrast-enhancement, the mass was partially stained in early phase and the stained area spread heterogeneously in delayed phase. Magnetic resonance imaging showed that the abdominal mass was depicted as slightly high intensity on T2-weighted imaging and low intensity on T1-weighted imaging. With double-balloon endoscopy and capsule endoscopy, we did not find any tumor inside the small intestine. These visual findings lead us to diagnose it as gastrointestinal stromal tumor of the small intestine with extraluminal growth. We planned to resect both the gallbladder polyp and the intraperitoneal tumor at the same time for pathologic diagnosis and treatment. When the operation was performed, we found a milk-white lobulated tumor on the greater omentum and the tumor was entirely resected. Microscopically, the gallbladder polyp was diagnosed as tubular adenoma, and the omental tumor was diagnosed as SFT. It is important to bear in mind that omental SFTs sometimes mimic other mesenchymal tumors and should be included in the differential diagnosis of abdominal tumor not revealed by endoscopy.

Interdot carrier and spin dynamics were studied in a two-dimensional array of high-density small quantum dots (SQDs) of InGaAs with an average diameter of 16 nm and a sheet density of 1.2 x 10(11) cm(-2), in which 24 nm diametric large QDs (LQDs) were embedded as local potential minima. We observed a delayed photoluminescence (PL) rise from the lower-lying LQD states and a considerably faster PL decay from the higher-lying SQD states, indicating carrier transfer from the two-dimensionally coupled SQDs into the LQDs. In addition, inverse carrier tunneling from the LQDs into the SQDs was thermally induced, which is characterized by the thermal activation energy between the LQDs and SQDs. Moreover, circularly polarized transient PL behavior from the SQD states exhibits a suppression of the spin polarization decay in the initial time region, depending on the excited spin density. This tentatively suppressed spin relaxation can be quantitatively explained by selective interdot transfer of minority-spin electrons from the SQDs into LQDs, when the majority spin states in both QDs are sufficiently populated by excited spins. These findings indicate that the high-density SQDs behave as the main emitters with suppressed spin relaxation, while the scattered LQDs with lower potential behave as the receivers of minority-spin electrons.

We demonstrate persistent high degrees of spin polarization (SPD) up to 70% during light emission in (In1-xGax) As quantum-dot-well (QD-QW) hybrid nanosystems, where QD excited states are laterally tunnel coupled through the adjacent two-dimensional QW potential depending on the QW thickness. Spinpolarized electrons are photo-excited by using circularly polarized light pulses. The decay time of spin relaxation, obtained by that of the SPD, is 70 times larger than the photoluminescence decay time. The temporally constant SPD is sustained by a selective transfer of minority spins among QDs after flipping from the majority spins, which is promoted by a moderate state filling of lower-energy spin sublevels in surrounding QDs. The spin transfer times are deduced as functions of the QW thickness and excited-spin density. These results can provide a precise control of lateral interdot spin-transfer dynamics and resultant suppression of spin relaxation in QD ensembles.

Interdot spin transfer dynamics is studied in a laterally coupled excited spin ensemble of high-density InGaAs quantum dots (QDs). We observe a rise time of the photoluminescence intensity of ∼100 ps and a simultaneous increase in the spin polarization of the excited spin ensemble, indicating spin injection from higher-energy levels in smaller QDs. Moreover, this coupled ensemble exhibits decay properties of the spin polarization that vary with the excited spin density. This phenomenon can be quantitatively understood by considering interdot spin transfer into lower-energy levels of the surrounding QDs, where the transfer rate depends on the degree of state filling of each QD level.Interdot spin transfer dynamics is studied in a laterally coupled excited spin ensemble of high-density InGaAs quantum dots (QDs). We observe a rise time of the photoluminescence intensity of ∼100 ps and a simultaneous increase in the spin polarization of the excited spin ensemble, indicating spin injection from higher-energy levels in smaller QDs. Moreover, this coupled ensemble exhibits decay properties of the spin polarization that vary with the excited spin density. This phenomenon can be quantitatively understood by considering interdot spin transfer into lower-energy levels of the surrounding QDs, where the transfer rate depends on the degree of state filling of each QD level.

Evaluating HER2 gene amplification is an essential component of therapeutic decision-making for advanced or metastatic gastric cancer. A simple method that is applicable to small, formalin-fixed, paraffin-embedded biopsy specimens is desirable as an adjunct to or as a substitute for currently used HER2 immunohistochemistry and in situ hybridization protocols. In this study, we developed a microfluidics-based digital PCR method for determining HER2 and chromosome 17 centromere (CEP17) copy numbers and estimating tumor content ratio (TCR). The HER2/CEP17 ratio is determined by three variables—TCR and absolute copy numbers of HER2 and CEP17—by examining tumor cells; only the ratio of the latter two can be obtained by digital PCR using the whole specimen without purifying tumor cells. TCR was determined by semi-automatic image analysis. We developed a Tumor Content chart, which is a plane of rectangular coordinates consisting of HER2/CEP17 digital PCR data and TCR that delineates amplified, non-amplified, and equivocal areas. By applying this method, 44 clinical gastric cancer biopsy samples were classified as amplified (n = 13), non-amplified (n = 25), or equivocal (n = 6). By comparison, 11 samples were positive, 11 were negative, and 22 were equivocally immunohistochemistry. Thus, our novel method reduced the number of equivocal samples from 22 to 6, thereby obviating the need for confirmation by fluorescence or dual-probe in situ hybridization to < 30% of cases. Tumor content chart-assisted digital PCR analysis is also applicable to multiple sites in surgically resected tissues. These results indicate that this analysis is a useful alternative to HER2 immunohistochemistry in gastric cancers that can serve as a basis for the automated evaluation of HER2 status.