Search

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.

The tumor-node-metastasis (TNM) staging system does not take the patient's physiological status into consideration, reportedly making it insufficient for predicting survival outcomes in frail cancer patients. We assessed the prognostic values of several nutrition- and inflammation-based markers in combination with pTNM stage in gastric carcinoma (GC) patients.In total, 1166 patients undergoing GC surgery were studied. The prognostic capabilities of 3 nutritional and 3 systemic inflammatory parameters were examined. We developed new staging systems by adding these markers, individually, to the pTNM stage. We then compared the prognostic capabilities of our new systems with that of pTNM stage alone. We also assessed the prognostic values of these systems by dividing our patient cohort into elderly (≥ 65 years) and non-elderly groups.Our novel staging systems had greater predictive capabilities for overall survival (OS) than pTNM alone. Most notably, survival discrimination was significantly increased for pTNM when it was combined with albumin-based nutritional indices (geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI)). Our new staging systems incorporating GNRI or PNI into pTNM had significantly better predictive capability for OS, especially non-GC mortality, than pTNM alone in elderly GC patients. In the non-elderly patients, the predictive capabilities of the new staging systems for OS differed minimally from that of pTNM.The predictive capability of pTNM stage was particularly enhanced when this parameter was combined with nutritional markers. Our new approach aids in predicting survival outcomes, especially non-GC-related death, in elderly GC patients.

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.

The progressive, systemic depletion of muscle mass is a poor prognostic factor for various types of cancers. However, the assessment of body composition for patients with esophagectomy remains unclear. Therefore, we evaluated the significance of the fat-free mass index (FFMI) and estimated the appropriate cutoff value.We compiled clinicopathological characteristics of patients who underwent curative operation for esophageal cancer between October 2013 and March 2018 at Toranomon Hospital and reviewed them until December 2020. We analyzed the short- and long-term outcomes, compared to conventional nutritional factors, and calculated the area under the receiver operating characteristic (ROC) curve.A total of 200 patients were eligible for inclusion. FFMI was ineffective in predicting postoperative complications, with no correlation with other nutritional biomarkers. Preoperative low FFMI led to poor overall survival (OS), and the lower cutoff values based on the time-dependent ROC analysis were 14.4 and 16.8 kg/mThe low FFMI was not predictive of postoperative complications but an independent prognostic factor in esophageal cancer with curative resection, having no correlation with other biomarkers. Our cutoff FFMI values could be useful in selecting the target for muscle improvement programs.

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.

Although gastric conduit cancer (GCC) arising after esophagectomy is increasingly being reported, therapeutic strategies for resectable GCC have yet to be optimized. We investigated clinicopathological features of patients undergoing endoscopic versus more invasive surgical treatments for GCC and compared their outcomes. Fifty-one patients, who had a history of esophagectomy with gastric conduit reconstruction for esophageal cancer and underwent resection for metachronous GCC, were identified. Their characteristics and outcomes were retrospectively reviewed. There were 48 males and three females, ranging in age from 46–86 years. Twelve patients underwent surgery for GCC (group S) and 39 underwent only endoscopic resection (group E). The most common cause of death was pneumonia (10/51, 19.6%). Neither overall survival nor cumulative incidence of pneumonia-caused death differed significantly between the two groups (P = 0.60, 0.84, respectively). In group S, partial gastrectomy was performed in four cases and total gastrectomy in seven. Partial resections, including three antrectomy without sternotomy or intrathoracic procedures, were completed with significantly shorter operative durations than total resections (median 208 vs 513 min, P = 0.012). GCC recurrence was experienced in two cases: one undergoing open approach partial resection of the corpus and the other thoracoscopic total gastrectomy. Even compared with endoscopic treatment, outcomes following surgery for GCC appeared to be acceptable. Open approach total gastric gastrectomy could be the most radical modality, while other less invasive alternatives, e.g., antrectomy, are also an option. Clinicians may select a treatment strategy balancing radicality and patient status, reflecting tolerance to invasive procedures.

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.

BACKGROUND The survival impact of the geriatric nutrition risk index (GNRI) has yet to be investigated in patients undergoing gastric carcinoma (GC) surgery. METHODS In total, 1166 GC patients who underwent radical gastrectomy were retrospectively reviewed. The predictive and discrimination abilities for overall survival (OS) were compared among GNRI, nutrition indices, and systemic inflammatory markers. Patients were dichotomized by GNRI (GNRI

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.

Percutaneous endoscopic gastrostomy (PEG) is a minimally invasive procedure providing nutritional benefits to malnourished patients. Although a past history of celiotomy is not a contradiction for PEG construction, this procedure is rarely undertaken in post-esophagectomy patients, for two reasons: anatomically limited gastric spaces and high susceptibility to pulmonary aspiration. To overcome these limitations, we developed an original method of introducing PEG with jejunal extension for esophagectomized patients with retrosternal gastric pull-up reconstruction. The procedures were as follows: (1) confirmation of endoscopic transillumination of the antrum; (2) test puncture of the antral wall and subsequent gastropexy using a double-needle device; (3) insertion of a needle jejunostomy catheter into the antrum; (4) direct catheter cannulation to the pylorus and introduction of a feeding tube into the jejunum. We successfully carried out this procedure in three male patients (70-78 years old): two suffering from repetitive aspiration pneumonia and one with extensive recurrence of esophageal carcinoma. The operative times ranged 15-50 min. There were no PEG-associated complications. Of note, none of the patients experienced aspiration pneumonia after PEG construction. Our novel method appears to be a promising approach to managing esophagectomized patients because of its feasibility and the potential to prevent postoperative pulmonary aspiration.

Diaphragmatic herniation (DH) is a rare but potentially fatal event after total gastrectomy (TG). Despite being life-threatening, risk factors for postoperative DH have yet to be elucidated. We conducted a retrospective analysis to identify clinical characteristics of patients developing DH after TG, along with a comprehensive review of the published literature. Among 1361 consecutive patients undergoing TG for esophagogastric cancer between 1985 and 2013 in Toranomon Hospital, those requiring surgical intervention for postoperative DH were included. We also conducted a PubMed literature search on DH following TG. Five patients (four males, one female), with a median age of 68 at DH surgery, were identified. Intervals between TG and DH repair ranged from 2.9 to 189.0 (median, 78.1) months. Four patients had needed emergency surgery. Three patients had undergone open TG and two others laparoscopic TG, suggesting a significantly higher incidence of DH after laparoscopic TG (3/1302 vs. 2/59, p = 0.017). The diaphragmatic crus incision, creating the space for esophagojejunostomy, had been performed in all cases. The literature yielded seven relevant publications (16 patients). Intervals between TG and DH reduction ranged from 2 days to 36 months. All operations for DH had been carried out emergently. The risk of DH persisted after TG. DH is potentially a very late complication of TG, presenting as a surgical emergency. Laparoscopic TG was suggested to be a risk factor for postgastrectomy DH. Incising the crus might also be a predictor of DH. Measures to prevent DH, e.g., appropriate closure of the crus, would be recommended in minimally invasive TG.

Predicting lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) is critical for selecting appropriate treatments despite the low accuracy of computed tomography (CT) for detecting LNM. Variation in potential nodal sizes among locations or patients' clinicopathological background factors may impact the diagnostic quality. This study explored the optimal criteria and diagnostic ability of CT by location.We retrospectively reviewed preoperative CT scans of 229 patients undergoing curative esophagectomy. We classified nodal stations into six groups: Cervical (C), Right-upper mediastinal (UOptimal cut-offs were 6.5 mm (M), 6 mm (C, L, and A), and 5 mm (UOptimal criteria and diagnostic abilities for predicting LNM in ESCC varied among locations, and poor differentiation might contribute to failure to detect LNM.

BackgroundPrimary malignant melanoma of the esophagus is a rare tumor with a poor prognosis; the optimal treatment strategy has yet to be established. This study aimed to clarify clinical features, courses, and outcomes of patients undergoing surgical resection of primary malignant melanoma of the esophagus.MethodsSix patients with primary malignant melanoma of the esophagus, in whom the absence of other primary melanomas had been confirmed, were selected from the medical database maintained in Toranomon Hospital. Their clinicopathological characteristics and long-term outcomes were retrospectively reviewed and analyzed.ResultsAll 6 patients (five males and one female) underwent radical esophagectomy with three-field regional lymphadenectomy, and none received neoadjuvant therapy. Tumor invasion was classified into T1 in 5 (83%) cases and T3 in one (17%). Four (67%) patients had nodal metastases (one N1, one N2 and two N3). No distant metastatic lesions were detected preoperatively in any of our cases. Postoperative surveillance revealed recurrence in all 6 patients, and 5 (83%) died of the disease. The median overall survival was 24 months. One patient with a T3N3M0 tumor was treated after surgery with a dacarbazine-nimustine-vincristine regimen followed by irradiation for bone recurrence and survived for 87 months postoperatively. Another patient with a T1N3M0 tumor who survived for 27 months after liver and bone recurrence was treated with nivolumab, ipilimumab, and dacarbazine.ConclusionAlthough the courses of patients with primary malignant melanoma of the esophagus were consistently unfavorable, surgical resection with multidisciplinary therapeutic modalities may prolong survival in some cases.

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.

Although surgical resection is a mainstay in the management of esophageal carcinoma (EC), its postoperative outcomes remain unsatisfactory. To optimize surgical strategies for EC, a simple method of stratifying patients according to risk factors is desired. Controlling nutritional status (CONUT), the prognostic nutritional index (PNI), transthyretin and transferrin are nutritional parameters used to predict the long-term outcomes of EC patients. We aimed to comparatively evaluate the prognostic significance of these four markers, measured preoperatively, in patients with operable EC. In total, 224 patients undergoing surgical resection for EC were retrospectively reviewed. Overall/cancer-specific survivals (OS/CSS) were estimated applying the Cox proportional hazard model to univariate and multivariate analyses. PNI, transthyretin and transferrin levels were treated as continuous variables in these analyses. Preoperative CONUT had significant associations with tumor location, depth and preoperative irradiation. The other three markers all showed significant relationships with age and tumor depth. On univariate Cox regression analysis, preoperative CONUT, PNI, transthyretin and transferrin all correlated significantly with OS and CSS. On multivariate Cox regression analysis, the preoperative transthyretin level was identified as an independent predictor of OS (HR 0.51 per 10 mg/dL increase, 95% CI 0.29–0.88, p = 0.017) and CSS (HR 0.50, 95% CI 0.27–0.91, p = 0.027) as well as tumor depth, nodal metastasis and preoperative irradiation, while the other three parameters were not. Preoperative transthyretin, as a continuous variable, independently predicted both OS and CSS in resectable EC patients, appearing to be the best prognosticator among conventional nutrition-related parameters.

The age-dependent survival impact of body mass index (BMI) remains to be fully addressed in patients with gastric carcinoma (GC). We investigated the prognostic impacts of BMI in elderly (≥70 years) and non-elderly patients undergoing surgery for GC.In total, 1168 GC patients were retrospectively reviewed. Patients were stratified into 3 groups according to BMI; low (20), medium (20-25) and high (25). The effects of BMI on overall survival (OS) and cancer-specific survival (CSS) were assessed using univariate and multivariate Cox hazards models.There were 242 (20.7%), 685 (58.7%) and 241 (20.6%) patients in the low-, medium- and high-BMI groups, respectively. The number of patients with high BMI but decreased muscle mass was extremely small (n = 13, 1.1%). Patients in the low-BMI group exhibited significantly poorer OS than those in the high- and medium-BMI group (P 0.001). Notably, BMI classification significantly demarcated OS and CSS curves (both P 0.001) in non-elderly patients, while did not in elderly patients (OS; P = 0.07, CSS; P = 0.54). Furthermore, the survival discriminability by BMI was greater in pStage II/III disease (P = 0.006) than in pStage I disease (P = 0.047). Multivariable analysis focusing on patients with pStage II/III disease showed low BMI to be independently associated with poor OS and CSS only in the non-elderly population.BMI-based evaluation was useful for predicting survival and oncological outcomes in non-elderly but not in elderly GC patients, especially in those with advanced GC.

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.

The survival impacts of the prognostic nutritional index (PNI) and sarcopenia have been separately investigated in patients with gastric carcinoma (GC), while the prognostic impact of the combination of them remains to be addressed.In total, 1166 GC patients undergoing radical gastrectomy were retrospectively reviewed. A new prognostic score (PNIS) was developed based on preoperative PNI and sarcopenia; patients with both low PNI (≤44.8) and sarcopenia were allocated a score of 2, and those with only one or neither of these abnormalities were assigned a score of 1 or 0, respectively.A lower PNI was independently associated with sarcopenia (P = 0.007). There were 704 (60.4%), 356 (30.5%) and 106 (9.1%) patients in the PNIS 0, 1 and 2 groups, respectively. A higher PNIS was associated with advanced age (P 0.001) and a higher incidence of postoperative complications (P = 0.01). Patients with PNIS 2 showed significantly poorer overall survival (OS) than those with PNIS 1 or 0 (5-year OS; 57.8% vs. 79.2% vs. 91.6%, P 0.001). Multivariate Cox hazards analysis showed PNIS 2 to be a powerful predictor of poor OS (HR 5.73, P 0.001) in patients with pStage I disease, while not being independently associated with OS in those with pStage II/III disease. Patients with PNIS 2 had a markedly higher prevalence of non-GC-related death than those with scores of 0-1.The scoring system combining PNI and sarcopenia is useful for predicting survival outcomes, especially non-GC-related death, in patients with early GC, a population with basically good oncological outcomes.

Trastuzumab-based chemotherapy is now a standard approach for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. However, histopathologic changes after treatment have yet to be elucidated. This study aims to characterize the histologic response of gastric cancer to trastuzumab treatment and its correlation with HER2 status. Twenty-one advanced HER2-positive gastric cancers treated with trastuzumab-based chemotherapy, including 10 surgically resected specimens and 11 biopsy samples from patients with inoperable tumors, were evaluated for the histologic responses and HER2 status of residual cells. We also reviewed, as controls, 10 cases undergoing surgical resection of tumors after chemotherapy without trastuzumab. Complete and partial histologic responses were obtained in 2 and 8 of the surgical cases, respectively. HER2-positive neoplastic cells were recognized at least focally in the 8 cases. Notably, the proportion of HER2-positive cells was always higher in superficial (mucosal/submucosal) layers than in deeper layers. Three specimens contained HER2-positive neoplastic cells exclusively in the superficial area or intravascular space, whereas deeply invasive or metastatic components almost completely disappeared or were HER2 negative when still present. In contrast, HER2-negative cells or residual tumor cells in control cases tended to survive as well or better in deeply invasive areas or in metastases than in superficial areas. Biopsy samples from nonoperative patients remained HER2 positive after treatment in 8 of 11 patients. Our observations suggest that HER2-positive neoplastic cells tend to survive within superficial areas or intravascular spaces after trastuzumab therapy, even when deeply invasive or metastatic lesions responded well to therapy.

// 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.

A 63-year-old man presented with a protruded tumor in the middle thoracic esophagus demonstrated by endoscopy. The tumor showed diffuse submucosal infiltrations, and the biopsy yielded a pathological diagnosis of adenocarcinoma. As an initial treatment, definitive chemoradiotherapy was performed. Although subsequent evaluations by endoscopy showed a good response, the lesion presented stenotic change. Positron emission tomography showed abnormally increased accumulation of 18F-fluorodeoxyglucose in the primary lesion suspicious for remnant disease. Therefore, the patient underwent salvage esophagectomy. On the resected specimen, the tumor was localized within the middle third of the esophagus: Its anal side was lined by non-cancerous squamous cell epithelium. The tumor was pathologically diagnosed as moderate to poorly differentiated adenocarcinoma. The tumor accompanied a circular stricture and a prominent fibrosis, a histologic finding known as scirrhous-type growth. Here, we report a case of scirrhous-like adenocarcinoma arising from middle thoracic esophagus successfully operated on after definitive chemoradiotherapy.

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), modified Glasgow prognostic score (mGPS) and prognostic nutritional index (PNI) are simple indices determined employing laboratory data alone and have been used to predict the clinical outcomes of patients with esophagogastric tumors. However, prior results were generally based on analyzing dichotomous data with arbitrary cutoff values. This retrospective study aims to assess prognostic utilities of preoperative NLR, PLR, LMR, mGPS and PNI, as continuous variables, in gastric cancer (GC) and adenocarcinoma of esophagogastric junction (AEG). Preoperative data from 1363 patients who underwent surgery for GC/AEG were retrospectively examined. Survival time was evaluated applying the Cox proportional hazard model to both univariate and multivariate estimates of clinicopathological factors and the aforementioned indices as continuous variables. Preoperatively, each index value was significantly associated with T and N stages, as well as lymphatic involvement and venous involvement. On univariate Cox regression analysis, preoperative NLR, PLR, LMR and PNI were significantly associated with overall survival (OS) and relapse-free survival (RFS). Preoperative mGPS was associated only with RFS. On multivariate Cox regression analysis, preoperative PNI was independently associated with OS and RFS (hazard ratio [HR] 0.62 per 10-unit increase, 95% CI 0.47–0.82, p

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 have studied GaAs and AlGaAs barriers for the purpose of improving spin-transport performance in spin-polarized light-emitting diodes (LEDs) based on self-assembled quantum dots (QDs) of InGaAs. In the spin-LED utilizing a spin-functional optical active layer of In-based self-assembled QDs, growth temperatures of top barriers of GaAs and AlGaAs were reduced to suppress indium diffusion from the QDs into the barriers after forming the QDs. We show a significant improvement of spin-transport property as well as of carrier-transport one with increasing growth temperature of the Al 0.1 Ga 0.9 As barrier from 580 to 640 °C, while luminescent spectral energy and shape of the QDs are not markedly affected.

We have grown ultrahigh-density self-assembled quantum dots (QDs) of InGaAs with sheet densities up to 2.5×1011 cm−2 and lateral diameters down to 10 nm, where the dot density increases with increasing As pressure during dot growth under optimum growth conditions. A ground-state photoluminescence (PL) spectrum shows a spectral width of 47 meV for the highest-density sample. Optical excitation-density dependences of the PL intensity and time profile are studied. The PL intensity from QD excited states increases with increasing excitation power, originating from a state-filling effect in QDs, which is directly confirmed by a plateau-like behavior on the PL decay curve. We find that the filling effect is significantly suppressed in the above ultrahigh-density dot ensemble, which suggests potential applications to superior energy-saving lasing and spin-functional optical devices.

Electric-field control of spin states has been studied in InGaAs-based coupled nanostructures composed of quantum dots (QDs) and wells (QWs), where electron spins optically excited in the QW can be transferred into the QDs via tunneling depending on the strength of applied electric field. The photoluminescence (PL) intensity in the QDs and the circular polarization, reflecting the electron-spin states after the injection, are found to be largely dependent on the electric field. The spin dynamics responsible for the field-dependent PL properties is discussed in terms of the potential-driven spin injection via tunneling and subsequent energy spin relaxation in the QDs.

We have made transient photoluminescence (PL) study on electron-spin dynamics in InGaAs-based coupled nanostructures of quantum dots (QDs) with quantum wells (QWs). Self-assembled InGaAs QDs were grown integrated with an InGaAs QW through a GaAs tunneling barrier or embedded in a GaAs QW. Time-resolved circularly polarized PL in the QDs was measured as a function of temperature after optical spin excitation selectively in the QW, reflecting electron-spin polarization injected from the QW into QDs. We show the spin injection dynamics induced by spin tunneling and subsequent energy relaxation from the QW into QDs in the former coupled QDs. Spin relaxation at excited states in the QDs after the dynamical spin injection is shown as a function of temperature. These coupled QD samples exhibit thermally persistent spin polarization up to 200 K, originating from ultrafast and thus efficient spin injection as well as longer spin-relaxation times compared to radiative decay times in the QDs after the injection.