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Little is known about the survival impacts of pretreatment cancerous stenosis on patients with esophageal carcinoma (EC).The clinicopathologic characteristics of patients who underwent surgery for EC between January 2010 and December 2018 were retrospectively reviewed. Esophageal stenosis was defined as present when a thin endoscope could not be passed through the tumor site. The impacts of stenosis on overall survival (OS) and cancer-specific survival (CSS) were evaluated using Cox hazards analysis.Of the 496 EC patients in this study, 51 (10.3 %) had pretreatment esophageal stenosis. Stenosis was associated with lower body mass index (P0.001) and higher pStage (P0.001). The 3-year OS rate for the patients with stenosis was significantly poorer than for the patients without stenosis (40.2 % vs 69.6 %; hazard ratio [HR], 2.19; P0.001). The survival outcomes, especially CSS, for the patients with stenosis were significantly poorer than for the patients without stenosis for both pStage II-III (P = 0.009) and pStage IV (P = 0.006) disease. The OS and CSS curves were well stratified by the presence of stenosis even in early-stage (pStage II) patients (P = 0.04 and P0.01, respectively). Multivariable analysis showed esophageal stenosis, pStage III-IV disease, and non-curative resection to be independently associated with poor OS (HR, 1.61; P = 0.02) and poor CSS (HR,1.67; P = 0.02). Higher pStage was an independent predictor of poor CSS for patients without stenosis, but not for those with stenosis.Esophageal carcinoma patients with pretreatment stenosis had significantly poorer survival outcomes, especially poorer CSS, than those without stenosis in both early- and advanced-stage diseases.

The intratumoral heterogeneity (ITH) of the tumor microenvironment (TME) has yet to be addressed in esophageal squamous cell carcinoma (ESCC). Here, we studied the ITH of CD8 and PD-L1 status in ESCC, and examined the potential of the tumor surface for representing the TME. Sixty-seven surgically resected clinical Stage II ESCC specimens were analyzed. The CD8 cell density, PD-L1 tumor proportion score (TPS) and combined positive score (CPS) were calculated in three (superficial, middle and deep) areas of each specimen. ITH was quantified by distance-standardized coefficient variations of the three values. The CD8 and PD-L1 status of each area was dichotomized, and tumor surface capabilities for predicting the entire tumor status were estimated. Variables were compared according to the presence of neoadjuvant chemotherapy (NAC). The ITH, especially PD-L1 heterogeneity, differed markedly among specimens. The concordance rates of CD8 and PD-L1 (CPS and TPS) status among the three different areas were 71.6%, 74.6% and 73.1%, respectively. The sensitivity and the specificity of the tumor surface for predicting the CD8 status of the whole tumor were high, especially in the NAC- group (both 1.0). The tumor surface also showed high capabilities for representing the whole PD-L1 status, while yielding moderate positive predictive values (0.70). The ITH degrees and predictive capabilities did not differ according to NAC. Taken together, the ITH of CD8 and PD-L1 differed among ESCC specimens, while not being markedly affected by NAC. The use of a biopsy specimen from the tumor surface might be feasible for TME evaluation.

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.

The long-term impacts of post-operative complications, especially pulmonary complications and anastomotic leakage, on health-related quality of life (HRQoL), nutritional status and body composition remain to be fully addressed in patients undergoing esophageal cancer surgery.Patients who underwent esophagectomy between 2015 and 2019 and survived without recurrence were eligible. HRQoL (European Organization for Research and Treatment of Cancer QLQ-C30 and the QLQ-OES18 questionnaires), nutritional and body composition data were prospectively evaluated before and at 3, 6, 12 and 24 months after surgery. Collected data were compared between patients with post-operative complications and those without.In total, 88 patients were included. Overall complications, anastomotic leakage and pulmonary complications developed in 48 (54.5%), 20 (20.7%) and 18 (20.5%) patients, respectively. Patients with pulmonary complications had significantly more reflux-related symptoms (dry mouth; P = 0.03, coughing; P = 0.047), and more difficulties with eating at 24 months after surgery, as compared to those without such complications. Anastomotic leakage increased pain, speaking problems and dysphagia up to 6 months after surgery. Patients with pulmonary complications had significantly lower prealbumin levels (P = 0.01, 0.02 and 0.008 at 6, 12 and 24 months after surgery, respectively) and lower prognostic nutritional index values over time after surgery than those without these complications. In contrast, anastomotic leakage was not associated with poor nutritional status post-operatively. Body composition was not affected by the occurrence of complications.Patients who developed post-operative complications, especially pulmonary complications, had long-lasting negative HRQoL outcomes and poor nutritional status after esophagectomy.

Adenocarcinoma (AC) with neuroendocrine carcinoma (NEC) or enteroblastic (ENT) differentiation rarely develops in Barrett’s esophagus (BE). A 76-year-old man was diagnosed with Barrett’s AC (cT1bN0M0) and underwent thoracoscopic esophagectomy. A type 0-IIc + 0-Is lesion measuring 26 × 21 mm was macroscopically observed on a background of long segment BE (pT1bN0M0). The tumor comprised three different histological types of carcinoma (NEC, AC with ENT differentiation and moderately differentiated AC). NEC showed positivity for synaptophysin, chromogranin A and insulinoma-associated protein 1 with a Ki-67 index of 60.6%. ENT tumors were immunopositive for AFP and sal-like protein 4, and focally immunopositive for human chorionic gonadotrophin. The amounts of NEC, ENT and AC were 40%, 40% and 20%, respectively. p53 expression was positive throughout the tumor. Rb expression was negative at the NEC, but positive at the ENT and AC. CD4 and CD8 densities were lower in the NEC segment than in the AC and ENT segments, and PD-L1 expression was negative throughout the tumor. Early cancer arising in BE with a combination of tubular AC, ENT tumors and NEC is very rare. Our observations might contribute to understanding the carcinogenetic pathways and tumor microenvironment of NEC and ENT tumors.

Studies have revealed the impacts of various inflammatory and nutritional markers in patients with esophageal squamous cell carcinoma (ESCC). We evaluated the prognostic values of multiple inflammation- or nutrition-based markers, either alone or in combination with pStage, in ESCC patients.In total, 360 patients undergoing upfront surgery for ESCC were retrospectively reviewed. The prognostic capabilities of 7 inflammatory and 3 nutritional parameters were investigated. Furthermore, we devised new staging systems by adding these markers to pStage and examined the prognostic abilities of our new approach. Time-dependent receiver operating characteristic curves and the areas under the curve (AUCs) were estimated to compare prognostic capabilities among the parameters.The AUCs for predicting overall survival (OS) of the prognostic nutritional index (PNI), CRP to albumin ration (CAR), lymphocyte to CRP ratio (LCR) and the Naples prognostic score (NPS) were similar to that of pStage. Notably, CAR and LCR showed high predictive capabilities for OS (AUCs; 0.627 and 0.634 for 3-year OS, respectively). New staging systems combining inflammatory or nutritional markers with pStage provided higher AUCs for predicting OS than pStage alone. In particular, NPpStage (NPS and pStage) (P = 0.03), PNpStage (PNI and pStage) (P = 0.03) and LCpStage (LCR and pStage) (P = 0.05) showed significantly higher accuracy for predicting OS than pStage alone.Various inflammatory or nutritional markers, especially those derived from CRP, are useful for predicting survival outcomes of ESCC patients. The predictive capabilities of these indices were augmented when used in combination with pStage.

A 64-year-old man, who had previously undergone definitive chemoradiotherapy (dCRT) and endoscopic resections for metachronous multiple esophageal squamous cell carcinoma (ESCC) and had also received total pharyngolaryngectomy (TPL) for hypopharyngeal cancer, was diagnosed with ESCC in the middle thoracic esophagus (cT3N0M0). Salvage surgery was performed via thoracoscopy. Although the tumor was tightly adherent to the thoracic duct and both main bronchi, they were successfully mobilized. In order to maintain the blood supply to the trachea, we preserved the bilateral bronchial arteries and avoided prophylactic peritracheal lymph node dissection. Cervical end-to-side anastomosis between the jejunum and a gastric conduit was performed. Minor pneumothorax was managed conservatively, and the patient was discharged 44 days after the surgery. Overall, thoracoscopic salvage McKeown esophagectomy was safely performed in a patient with a history of TPL and dCRT. Surgeons should be very careful to prevent tracheobronchial ischemia by optimizing the extent of lymph node dissection.

Oncolytic virus therapy can increase the immunogenicity of tumors and remodel the immunosuppressive tumor microenvironment, leading to an increased antitumor response to immune-checkpoint inhibitors. Here, we investigated the therapeutic potential of G47Δ, a third-generation oncolytic herpes simplex virus type 1, in combination with immune-checkpoint inhibitors using various syngeneic murine subcutaneous tumor models. Intratumoral inoculations with G47Δ and systemic anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody administration caused an enhanced antitumor activity when combined and worked synergistically. Conversely, the efficacy of G47Δ in combination with anti-programmed cell death protein-1 (PD-1) antibody was equivalent to that of the anti-PD-1 antibody alone in all murine models examined. The combination of intratumoral G47Δ and systemic anti-CTLA-4 antibody was shown to recruit effector T cells into the tumor efficiently while decreasing regulatory T cells. Furthermore, a wide range of gene signatures related to inflammation, lymphoid lineage, and T cell activation was highly upregulated with the combination therapy, suggesting the conversion of immune-insusceptible tumors to immune susceptible. The therapeutic effect proved tumor specific and long lasting. Immune cell subset depletion studies demonstrated that CD4+ T cells were required for synergistic curative activity. The results depict the dynamics of immune modulation of the tumor microenvironment and provide a clinical rationale for using G47Δ with immune checkpoint inhibitors., Graphical abstract, G47Δ, a third-generation oncolytic HSV-1, works synergistically with CTLA-4 inhibition, but not PD-1, in murine tumor models. The combination therapy causes increased effector T cells, decreased Tregs, and upregulated gene signatures related to immunogenicity within tumors. The therapeutic effect proved tumor specific and long lasting and requires CD4+ cells for synergy.

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.

Chemoradiotherapy is an alternative to surgery for esophageal cancer, with a putatively equivalent outcome. However, disease recurrence after a complete response is common and if follow-up surveillance detects recurrence, salvage treatments for potentially curable disease must follow. We conducted a nation-wide questionnaire survey of institutions in Japan certified by the Japanese Esophageal Society to investigate outcomes of primary thoracic esophageal cancer patients initially treated by chemoradiotherapy with complete response diagnoses. The primary endpoint was overall survival, the secondary endpoint disease recurrence. Outcomes of patients who had undergone salvage treatments were also investigated. Cases were excluded from analysis if endoscopic study, endoscopic biopsy, or computed tomography data were lacking. At 41 institutes 544 case records were collected; valid data on 392 patients were obtained; 5-year survival was 74.8%, 5-year disease-free survival, 66.8%. Clinical staging before treatment significantly affected both overall and disease-free survival rates, but differences between adjoining stages were unexpectedly small. The primary relapse site was classified as primary site (n = 58), regional lymph nodes (n = 36), or distant disease (n = 34). Salvage treatments with curative intent (surgery, endoscopic treatments, and additional radiation) were performed on 38, 23, and 4 cases; 5-year survival after esophagectomy (n = 22), endoscopic treatment (n = 23), and lymphadenectomy (n = 9) was 47.4%, 70.9%, and 33.3%, respectively. A quarter of patients developed recurrent disease, mostly locoregional, after complete response. Complete response patients with originally advanced stage disease had fair clinical outcomes; salvage treatments after locoregional recurrence achieved modest long-term survival.

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

We aimed to evaluate the prognostic impact of pulmonary dysfunctions and their relationships with other possible prognostic factors, especially sarcopenia, in elderly patients with gastric carcinoma (GC). In total, 402 elderly GC patients (≥ 75 years) who underwent radical gastrectomy were retrospectively reviewed. Restrictive and obstructive pulmonary dysfunction were defined as %VC

Assessment of preoperative physiological status is crucial for optimizing clinical outcomes in patients undergoing surgery for esophageal carcinoma (EC). We aimed to evaluate the prognostic impact of pulmonary dysfunctions and their relationships with other physiological factors, especially sarcopenia, in EC patients receiving esophagectomy. In total, 411 EC patients who underwent esophagectomy between 2006 and 2016 were retrospectively reviewed. Preoperative pulmonary functions were evaluated based on %vital capacity (%VC) and forced expiratory volume (FEV) 1.0%. The thresholds were set as the lowest quartile (99% for %VC and 68.6% for FEV1.0%) in this cohort. One hundred and two patients (24.8%) had low %VC (%VC

Purpose: The long-term impacts of postoperative complications, especially pulmonary complications and anastomotic leakage, on health-related quality of life (HRQoL), nutritional status and body composition remain to be fully addressed in patients undergoing esophageal cancer surgery.Methods:Patients who underwent esophagectomy between 2015 and 2019 and survived without recurrence were eligible. HRQoL (European Organization for Research and Treatment of Cancer QLQ-C30 and the QLQ-OES18 questionnaires), nutritional and body composition data were prospectively evaluated before and at 3, 6, 12 and 24 months after surgery. Collected Data was compared between patients with postoperative complications and those without.Results: In total, 88 patients were included. Overall complications, anastomotic leakage and pulmonary complications developed in 48 (54.5%), 20 (20.7%) and 18 (20.5%) patients, respectively. Patients with pulmonary complications had more reflux-related symptoms (dry mouth; P = 0.03, coughing; P = 0.047, reflux; P = 0.1), and more problems with eating (nausea/vomiting; P = 0.051, eating difficulties; P = 0.06) at 24 months after surgery, as compared to those without such complications. Anastomotic leakage increased pain, speaking problems and dysphagia up to 6 months after surgery. Patients with pulmonary complications had significantly lower prealbumin levels and lower prognostic nutritional index values over time after surgery than those without these complications. In contrast, anastomotic leakage was not associated with poor nutritional status postoperatively. Body composition was not affected by the occurrence of complications.Conclusion: Postoperative complications, especially pulmonary complications, exert long-lasting negative effects on HRQoL, leading to poor nutritional status after esophagectomy.

Relationships among body composition indices assessed by various modalities remain to be addressed in patients with esophageal squamous cell carcinoma (ESCC), in whom being underweight is more strikingly prevalent than in those with other malignancies. We investigated the relationships of body composition parameters with the sarcopenia prevalence of ESCC patients.In this prospective study, we analyzed preoperative data obtained from 75 ESCC patients undergoing esophagectomy. Body composition data included body mass index (BMI), skeletal muscle index (SMI) assessed by computed tomography, and parameters calculated by bioelectrical impedance analysis (skeletal muscle mass (SMM), body fat mass). Muscle strength was evaluated by handgrip strength (HGS). Sarcopenia was defined as having both low SMI and low HGS.The median BMI value was 22.5 (range 15.2-28.7) in our ESCC cohort. BMI correlated significantly with fat mass (r = 0.84, P 0.001), SMM (r = 0.57, P 0.001) and SMI (r = 0.49, P 0.001). Similarly, SMI showed a significant correlation with SMM (r = 0.45, P 0.001). Meanwhile, HGS was highly correlated with SMM (r = 0.67, P 0.001), while showing significant but weak associations with both BMI and SMI (r = 0.33, 0.34, respectively, P 0.001). Notably, sarcopenia prevalence differed markedly according to BMI category; 28.6%, 12.2%, and 0% in the low ( 20), medium (20-25), and high ( 25) BMI groups, respectively.BMI reflects comprehensive information on body composition in ESCC patients, although its correlation with muscle mass and muscle strength was moderate. Decreased BMI might serve as an indicator for sarcopenia in this population, in which the presence of sarcopenic obesity is rare.

We investigated the synthesis of polyfluorene with a pinacol boronate (PinB) moiety at one end and with controlled molecular weight by means of Suzuki–Miyaura coupling polymerization of pinacol (7‐bromo‐9,9‐dioctyl‐9H‐fluoren‐2‐yl)boronate (1) with a palladium(0) precatalyst in the presence of pinacol 4‐trifluoromethylphenylboronate (2) as a chain terminator and CsF/18‐crown‐6 as a base. When we used AmPhos Pd G2, which has a propensity for intramolecular catalyst transfer on a π‐electron face, polyfluorene with the PinB moiety at one end and PhCF₃ (derived from 2) at the other end was obtained, and the molecular weight increased in proportion to the feed ratio of [1]₀/[catalyst]₀, though the molecular weight distribution was broad. Since the molecular weight also linearly increased with respect to the conversion of 1 until the middle stage of polymerization, the polymerization appears to involve chain‐growth polymerization through intramolecular catalyst transfer from the Pd catalyst inserted into the CBr bond of 1. The broad molecular weight distribution might be mainly due to slow initiation and slow termination with 2, rather than polymer–polymer coupling. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2498–2504

The good short-term and oncological outcomes of robot-assisted radical esophagectomy have been demonstrated, although its impact on long-term health-related quality of life (HRQoL) remains to be investigated. This study aimed to assess long-term HRQoL in patients after robot-assisted radical transmediastinal esophagectomy (TME), which is characterized as non-transthoracic esophagectomy comprising a robotic transhiatal approach and a video-assisted cervical approach, and transthoracic esophagectomy (TTE). The European Organization for Research and Treatment of Cancer generic and disease-specific modules (QLQ-C30 and QLQ-OES18), nutritional status and body composition data were prospectively collected in patients undergoing TME or TTE before and at 3, 6, 12, 18, and 24 months after surgery. The results of long-term (≥ 2 years) survivors without recurrence were compared between the two groups. A total of 37 patients (TME; n = 18, TTE; n = 19) were included for analysis. Longitudinal survey of function scales revealed scores of physical, role, social, and emotional function to be significantly better in the TME group than in the TTE group at many points postoperatively. Markedly, the symptoms of general pain, esophageal pain, and dry mouth greatly worsened after surgery in the TTE group, but did not deteriorate in the TME group. In contrast, symptoms relating to eating difficulties, body composition data, and nutritional status did not differ between the groups over time. At 24 months after surgery, TME provided significantly higher scores of global QOL (P = 0.01) and emotional function (P = 0.01) and also resulted in significantly fewer problems of fatigue (P = 0.04), general pain (P = 0.04), insomnia (P = 0.02), and dry mouth (P = 0.03), as compared to TTE. This study indicates that TME can provide better long-term HRQoL outcomes than TTE.

Background Multidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC. Methods Eligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included. Results In total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide. Conclusions Recent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.

Chemoradiotherapy is an alternative to surgery for esophageal cancer, with a putatively equivalent outcome. However, disease recurrence after a complete response is common and if follow-up surveillance detects recurrence, salvage treatments for potentially curable disease must follow.We conducted a nation-wide questionnaire survey of institutions in Japan certified by the Japanese Esophageal Society to investigate outcomes of primary thoracic esophageal cancer patients initially treated by chemoradiotherapy with complete response diagnoses. The primary endpoint was overall survival, the secondary endpoint disease recurrence. Outcomes of patients who had undergone salvage treatments were also investigated. Cases were excluded from analysis if endoscopic study, endoscopic biopsy, or computed tomography data were lacking.At 41 institutes 544 case records were collected; valid data on 392 patients were obtained; 5-year survival was 74.8%, 5-year disease-free survival, 66.8%. Clinical staging before treatment significantly affected both overall and disease-free survival rates, but differences between adjoining stages were unexpectedly small. The primary relapse site was classified as primary site (n = 58), regional lymph nodes (n = 36), or distant disease (n = 34). Salvage treatments with curative intent (surgery, endoscopic treatments, and additional radiation) were performed on 38, 23, and 4 cases; 5-year survival after esophagectomy (n = 22), endoscopic treatment (n = 23), and lymphadenectomy (n = 9) was 47.4%, 70.9%, and 33.3%, respectively.A quarter of patients developed recurrent disease, mostly locoregional, after complete response. Complete response patients with originally advanced stage disease had fair clinical outcomes; salvage treatments after locoregional recurrence achieved modest long-term survival.

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.

Neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy is a well-established standard of care for patients with locally advanced esophageal carcinoma (EC) (1). Although trimodal therapy provides significantly better survival outcomes than surgery alone, the long-term outcomes of patients with locally advanced EC remain unsatisfactory with 5-year overall survival rates ranging from 25% to 47% (2,3).

Background The current eighth tumor node metastasis lymph node category pathologic lymph node staging system for esophageal squamous cell carcinoma is based solely on the number of metastatic nodes and does not consider anatomic distribution. We aimed to assess the prognostic capability of the eighth tumor node metastasis pathologic lymph node staging system (numeric-based) compared with the 11th Japan Esophageal Society (topography-based) pathologic lymph node staging system in patients with esophageal squamous cell carcinoma. Methods We retrospectively reviewed the clinical records of 289 patients with esophageal squamous cell carcinoma who underwent esophagectomy with extended lymph node dissection during the period from January 2006 through June 2016. We compared discrimination abilities for overall survival, recurrence-free survival, and cancer-specific survival between these 2 staging systems using C-statistics. Results The median number of dissected and metastatic nodes was 61 (25% to 75% quartile range, 45 to 79) and 1 (25% to 75% quartile range, 0 to 3), respectively. The eighth tumor node metastasis pathologic lymph node staging system had a greater ability to accurately determine overall survival (C-statistics: tumor node metastasis classification, 0.69, 95% confidence interval, 0.62–0.76; Japan Esophageal Society classification; 0.65, 95% confidence interval, 0.58–0.71; P = .014) and cancer-specific survival (C-statistics: tumor node metastasis classification, 0.78, 95% confidence interval, 0.70–0.87; Japan Esophageal Society classification; 0.72, 95% confidence interval, 0.64–0.80; P = .018). Rates of total recurrence rose as the eighth tumor node metastasis pathologic lymph node stage increased, while stratification of patients according to the topography-based node classification system was not feasible. Conclusion Numeric nodal staging is an essential tool for stratifying the oncologic outcomes of patients with esophageal squamous cell carcinoma even in the cohort in which adequate numbers of lymph nodes were harvested.

BACKGROUND Patients with oesophageal squamous cell carcinoma (ESCC) generally have distinctive body compositions; being underweight is highly prevalent and sarcopenic obesity is rare. We investigated the survival impacts of body mass index (BMI) in elderly (≥65 years) and non-elderly patients undergoing surgery for ESCC. METHODS In total, 379 ESCC patients were retrospectively reviewed. Patients were divided into 3 groups according to BMI; low (

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.

Survival outcomes of patients with cT4 esophageal squamous cell carcinoma (ESCC) remain extremely poor. We aimed to investigate long-term outcomes and identify prognostic factors in patients treated by definitive chemoradiotherapy (dCRT) alone or with dCRT plus salvage surgery (SALV) for cT4 ESCC. In total, 73 patients completing dCRT were analyzed. Patients achieving clinical complete response (CR) received follow-up evaluations thereafter. For patients diagnosed with clinical partial response (PR), potentially curative SALV was generally performed. Possible prognostic factors included demographic data, tumor staging, blood chemistry profiles, and esophageal stenosis. The 1- and 3-year overall survival (OS) rates of the 73 patients were 67.1% and 40.8%, respectively. Twenty-one patients (29%) achieved clinical CR with dCRT alone. Among 35 patients (48%) with clinical PR, 31 underwent SALV and 4 opted for non-surgical treatments. In the dCRT-alone group (n = 42), patients with clinical CR-PR (n = 25) showed significantly better 3-year OS than those who responded poorly to dCRT (stable or progressive) (n = 17) (67.5% vs. 0%, P

Although both sarcopenia and systemic inflammation reportedly affect long-term outcomes of esophageal carcinoma (EC) patients, their reciprocal associations with survival outcomes have yet to be investigated. This study aimed to evaluate the survival impact of sarcopenia combined with the neutrophil-to-lymphocyte ratio (NLR) in EC patients undergoing esophagectomy.In total, 378 EC patients were retrospectively reviewed. The cutoff value for NLR was set at the NLR median of the cohort. Sarcopenia was determined based on decreased skeletal muscle index calculated from computed tomography obtained before surgery. Univariate and multivariate Cox hazards models were applied to determine independent predictors of poor overall survival and cancer-specific survival.Sarcopenia was more common in the high-NLR group (2.57 or greater) than in the low-NLR group (less than 2.57; P = .01). In the high-NLR group, patients with sarcopenia had significantly poorer overall and cancer-specific survival than those without sarcopenia (P.001). In contrast, there was no survival impact of sarcopenia in the low-NLR group. Patients with both high NLR and sarcopenia exhibited poor overall and cancer-specific survival (5-year overall survival = 44.4%, 5-year cancer-specific survival = 57.0%). Sarcopenia was independently associated with poor overall survival (hazard ratio = 1.95; P = .007) and poor cancer-specific survival (hazard ratio = 2.66; P = .002) as well as pathological stage III disease and noncurative resection in the high-NLR group.The survival and oncological impact of sarcopenia was noteworthy only when present with elevated NLR. The combination of 2 factors is rational for identifying EC patients likely to have poor survival outcomes.

The survival impact of the preoperative prognostic nutritional index (PNI) has been investigated in older patients with gastric carcinoma (GC), while that of the postoperative PNI has yet to be addressed. We evaluated the significance of PNI before and after surgery in older GC patients (≥75 years).In total, 309 older GC patients undergoing radical gastrectomy between 2006 and 2016 were retrospectively reviewed. The PNI was evaluated before and at six months after gastrectomy. Patients were divided into low (45) and high (≥45) PNI groups. The impact of low PNI on overall survival (OS), cancer-specific survival (CSS), and non-GC-related death were investigated.Low PNI was present in 134 patients (43.4%) preoperatively and 121 (39.2%) postoperatively. Low pre-PNI was independently associated with poor overall survival (P .001). Similarly, OS was significantly stratified by post-PNI (P .001). The significant survival difference according to post-PNI was present only in pStage I disease (P .001). Low post-PNI independently increased the risk of non-GC-related death in a multivariable analysis (P = .002). In contrast, CSS was not stratified by post-PNI (P = .45). In the high pre-PNI group, total gastrectomy and super-older age (≥80 years) independently increased the risk of low post-PNI, which was significantly associated with poor survival outcomes.Pre- and post-operative PNI are useful for predicting long-term outcomes in older patients with GC. Low postoperative PNI is a powerful determinant of mortality due to other diseases. Optimal perioperative management is required for those at high risk of malnutrition postoperatively.

The impact of lymph node (LN) dissection on long-term outcomes for patients with colorectal cancer (CRC) perforation remains unclear. We aim to investigate factors associated with poor prognosis and recurrence in patients with CRC, with special reference to cancer perforation and LN dissection. The subjects comprised 550 patients who underwent colorectal surgery for CRC at Stage II or III (TNM classification) between February 2006 and November 2013. Short- and long-term outcomes of patients with or without CRC perforation were evaluated. We also sought risk factors on poor prognosis, focusing on LN dissection in patients with CRC perforation. A total of 508 underwent surgery for CRC without perforation (the non-perforation group) and 39 for CRC with perforation (the perforation group). Both overall survival and recurrence-free survival rates were significantly lower in the perforation group than in the non-perforation group (overall survival, P = 0.009; recurrence-free survival, P

Salvage esophagectomy (SALV) is potentially beneficial for patients with residual or relapsed esophageal carcinoma after definitive chemoradiotherapy (dCRT), although preoperatively identifying good candidates for SALV remains difficult. We investigated the prognostic impacts of inflammatory and nutritional status in patients undergoing SALV after dCRT. Forty-seven SALV patients were retrospectively reviewed, of whom 46 (98%) had squamous cell carcinoma and 1 (2%) adenocarcinoma. Possible prognostic factors included patients' demographic data, physical status, blood chemistry profiles, and clinical/pathological tumor features. The Glasgow prognostic score (GPS) was derived from preoperative C-reactive protein (CRP) and albumin values. Thirty (64%), 11 (23%), and 6 (13%) patients were classified into the GPS 0, 1, and 2, respectively, groups. None of the possible prognostic factors showed significant correlations with GPS. Patients with GPS 0 had better outcomes than those with GPS 1 or GPS 2 (Median survivals: 37.8, 15.9, and 5.1 months, respectively, P < 0.001). In the multivariable Cox proportional hazards model, GPS 1 (HR 5.62, 95% CI 1.94-16.4, P = 0.002), GPS 2 (HR 9.10, 95% CI 2.60-31.8, P < 0.001), R1/2 resection (HR 16.3, 95% CI 3.62-86.7, P < 0.001) and incomplete response to dCRT (HR 3.53, 95% CI 1.12-12.5, P = 0.03) were all independent risk factors for a poor outcome. Preoperative GPS is potentially useful for predicting outcomes in esophageal cancer patients undergoing SALV.

Background The outcome of definitive chemoradiotherapy (dCRT) for patients with cT4b esophageal carcinoma (EC) remains poor. Also, few studies focused on the prognostic factors in cT4b EC patients undergoing dCRT. Methods 80 patients undergoing dCRT for cT4b EC between 2006 and 2016 were retrospectively reviewed. All were in ECOG-PS 0–1. For evaluation of the pretreatment status, we employed demographic data, BMI, inflammatory marker (CRP), nutritional marker (Alb, prognostic nutritional index (PNI)) and tumor factors (clinical staging, pretreatment stenosis, tumor marker). Results There were 62 men with a mean age of 65 years (range, 41–83 years). 77 patients were squamous cell carcinoma, while 3 were adenocarcinoma. There were 12 (15%) patients with cM1 (lym) status. 36 (45.0%) patients had esophageal stenosis. 70 patients had cN + before dCRT, while 22 had cN + after dCRT. 30 patients (37.5%) had a CRP > 10 mg/l before dCRT, while 15 patients (18.8%) were in poor-nutritional status (PNI Conclusion The outcome of dCRT for cT4b EC is acceptable. Pretreatment inflammatory status significantly influences the prognosis of patients undergoing dCRT. Disclosure All authors have declared no conflicts of interest.

Background Although the incidence of postoperative complications is higher than typical surgery, salvage esophagectomy for esophageal squmous cell cancer(ESCC) is expected to achieve good prognosis when it resutles in R0 resection. At our hospital, definitive chemo radiotherapy(dCRT) consists of irradiation(50.4 Gy/28 Fr) with concurrent chemotherapy(Nedaplatin/TS-1, or 5FU continuous administration). Salvage surgery is performed 4 weeks after the end of dCRT in case of residual disease. Methods Among 55 patients of salvage surgery after dCRT in our hospital between 2006 and 2016, 47 patients underwent salvage esophagectomy. These cases are retrospectively reviewed in terms of factors related to short and long term outcome and survival. Results The clinical T factor was 4/2/116/25 in cT1/T2/T3/T4 respectively. Clinical evaluation after dCRT was non-CR/SD in 18 cases(38%), SD in 14 (30%), PDin 2(4.3%) and recurrence after CR in 13(28%). R0 resection rate was 75%. Postoperative complications occurred in 64%. The incidence of complications exceeding Clavien-Dindo class Grade3 were 45% and all in-hospital mortality was 8.5% (4 cases). Pathological therapeutic effects were Grade1a (30%) in 14 cases and Grade3 (32%) in 15. Pathologic lymphnode metastasis was detected in 4 cases among these 15. The median overall survival (OS) time was 20.3 months and 3 year and 5 year OS rate were 39 and 22% respectively. Univariate analysis showed R1/2 cases, clinically positive lymphnode metastasis after dCRT, and pathological Grade 0/1/2 and pT3/4 was risk factors for overall survival rate. In multivariate analysis, R1/2 resected cases (HR 7.38, 95% CI 2.42–24.6, P Conclusion It is necessary to reduce the surgical insult of salvage esophagectomy with minimal invasive procedure and postoperative treatment. Salvage esophagectomy is highly recommended as long as it achieves R0 resection resulting in good prognosis. Disclosure All authors have declared no conflicts of interest.

This retrospective analysis compared the cost outcomes for both patients and hospitals, as well as the short-term outcomes, for laparoscopic hepatectomy (LH) and open hepatectomy (OH).The subjects comprised 70 patients who underwent LH or OH. The total hospital charge was calculated using the Japanese lump-sum payment system according to the diagnosis procedure combination.Of the 70 patients, 10 in the LH group and 16 in the OH group underwent primary single limited/anatomic resection or left lateral sectoriectomy. The operation time, blood loss, and postoperative complications did not differ significantly between the two groups. The median [range] time of inflow occlusion was significantly longer [120 (50-194) vs. 57 (17-151) min, P = 0.03] and the postoperative hospital stay was significantly shorter [5 (4-6) vs. 9 (5-12) days, P 0.01] in the LH group than in the OH group, respectively. The mean ± standard deviation surgical costs (1307 ± 596 vs. 1054 ± 365 US$, P = 0.43) and total hospital charges (12046 ± 1174 vs. 11858 ± 2096 US$, P 0.99) were similar in the LH and OH groups, respectively, although the charges per day were significantly higher in the LH group than in the OH group (1388 ± 217 vs. 1016 ± 134 US$, P 0.01).The costs to patients for LH are similar to those for OH. However, LH provides a financial advantage to hospitals due to a reduced hospital stay and comparable surgical costs.

論文(Article), The perturbations of a water column at the deepest part of Lake Onogawa by a local heavy rainfall were analyzed. Mixing throughout the water column (18.8-m deep) was indicated by changes in the distribution of water temperature. This mixing perturbed the hypolimnetic seasonal distributions of dissolved components. All particulate components peaked at 10m, suggesting a center of inflowing water. Compared with background levels, particulate nitrogen (PN), particulate carbon (PC), particulate phosphorus (PP), and suspended solids (SS) increased from 16-fold for PN to 100-fold fos SS. Soluble reactive phosphorus was the only dissolved component that formed a clear maximum at 10m, as did the particulate components. Assuming that SS consists mainly of mineral particles, SS can be classified into three categories: (1) A rapidly sinking fraction, the main body of the loaded SS, with a sinking rate exceeding 1m day~-1 and radii exceeding 2-3μm. (2) A slowly sinking fraction with a sinking speed of about 10cm day~-1 and radii of 0.7-0.9μm; this fraction is calculated to be about 4% of the total loaded SS at most. (3) A fraction that was essentially retained in the water column. The maximum estimate of this fraction was 0.5% of the total. Key words : Heavy allochthonous load・Material distribution・Ventilation・SS sinking rate

論文(Article), The concentration of dissolved oxygen in waters 0.5-0.6m above the bottom of Lake Hibara, a dimictic lake, was zero in early spring of 1994 and 1997. The concentrations in early spring of 1992, 1993, 1995, 1996, and 1998 ranged from 3.75 to 10.1mg1~-1. The depth profiles of water temperature suggest that water had not circulated prior to the sample collections of 1994 and 1997, but it had done so in the cases of the other years, suggesting that winter conditions were well preserved in the former years. On the other hand, the dissolved oxygen in the same strata decreased severely in summer. However, more or less titratable amounts of dissolved oxygen still remained (0.01-0.73mg1~-1) at the final stages of summer stratification from 1992 to 1998. These facts show that a completely anoxic condition is not formed in this lake in summer but is sometimes formed in winter. It is interesting to note that in spite of unfavorable winter conditions for oxygen consumption, i.e., shorter duration and lower water temperature, oxygen is exhausted. These facts suggest that ventilation to the depths is much greater in summer than in winter. Key words : Dissolved oxygen・Ventilation・Oxygen consumption

論文(Article), The first record of depth-time profiles for some physicochemical and biological parameters of Lake Bishamon-numa based on periodic observations during the ice-free season of 1996 are reported. Throughout the observed period, the thermocline was either absent or very weak. In accordance with this structure of water temperature, the dissolved oxygen was distributed uniformly in the water column at above a 90% saturation level. The average and standard deviation of transparency was 5.1 ± 1.1 m. On the assumption that the trophogenic zone is from the surface to a depth of twice the transparency, the whole water body of the east basin in which the sampling station is located, constitutes the trophogenic zone. pH was fairly constant from July to December with an average and standard deviation of 6.2 ± 0.1. Compared with past data, the pH of Lake Bishamon-numa has changed greatly within a relatively short time period in the past and has lately stabilized around pH 6. The concentrations of Na, K, Mg, and Ca were in the order of m mol 1~-1, while those of Fe and Mn were of μmol 1~-1. Ranked in descending order of concentrations, they are Na, Ca, Mg, K, Mn and Fe. The annual maximum of Chl. a was 1.5 μg 1~-1 in May. Though there were slight maxima and minima, the Chl. a concentration was below 1 μg 1~-1 in most seasons and averaged 0.51 μg 1~-1. This Chl. a level corresponds to those of other oligotrophic lakes. Nano-phytoplankton ranging from 2 to 20 μm predominated, and macro-phytoplankton greater than 20 μm were relatively scarce. Key words : Goshiki-numa Lake Group, depth-time profiles, metals seasonal trend