Textbook outcome contributes to long-term prognosis in elderly patients with esophageal squamous cell carcinoma.

Purpose: Textbook outcome (TO) is a composite quality measurement of outcomes for evaluating surgical procedures. We investigated whether TO can be used to predict outcomes after curative resection for esophageal squamous cell carcinoma (ESCC) in elderly patients. Methods: We retrospectively analyzed 105 patients who underwent curative esophagectomy for ESCC from 2005 to 2020. In accordance with previous reports, TO consisted of 10 parameters. The patients were divided into two groups: those who achieved TO (TO) and those who failed to achieve TO (non-TO). We evaluated the association between TO and long-term survival. Results: TO was achieved in 28 (26%) patients. The patients in the TO group were significantly older (p = 0.02). The parameter with the lowest achievement rate was "No hospital stay ≥21 days". The patients in non-TO group had significantly shorter overall survival than those in TO group (p = 0.03). Multivariable Cox regression analyses of overall survival revealed that lymph node metastasis (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.73-6.78; p < 0.0002) and non-TO (HR, 2.37; 95% CI, 1.05-5.65; p = 0.03) were significantly associated with poor overall survival. Conclusion: TO can be used to predict outcomes after curative esophagectomy in elderly patients with ESCC.

The difficulty of nuclear emergency prevention measures during natural disasters: ongoing challenges in Japan.

It is crucial to anticipate nuclear emergency scenarios and implement effective measures. Japan's climate and topography make it vulnerable to natural disasters; thus, it is necessary to address compounding and cascading disaster scenarios involving the simultaneous occurrence of natural and nuclear disasters. On 1 January 2024, an earthquake hit the Noto region of Ishikawa Prefecture, resulting in damage to the area around the Shika Nuclear Power Plant, located 90 km from the epicenter. This earthquake revealed that, in the event of a complex disaster, it is possible that residents living within 30 km of the Shika Nuclear Power Plant will be completely unprepared for a nuclear disaster. In the event of a complex disaster, it is crucial to implement appropriate countermeasures while balancing responses to both nuclear and natural disasters and optimizing radiation disaster prevention measures.

Laparoscopic versus open abdominal lymph node dissection for esophageal squamous cell carcinoma: a propensity score matching analysis.

PURPOSE: To compare the short- and long-term outcomes of laparoscopic and open abdominal lymph node dissection using propensity score matching (PSM) analysis. METHODS: The subjects of this retrospective analysis were 459 patients who underwent curative resection for esophageal squamous cell carcinoma (ESCC) between May, 2005 and December, 2019, at our hospital. Patients were divided into two groups: the Laparoscopic (Lap group) and the Open (Open group). Post-PSM, 139 patients from each group were selected for the analysis to compare the short- and long-term outcomes between the groups. RESULTS: The Lap group experienced fewer Clavien-Dindo (CD) Grade ≥ 2 complications (28.1% vs. 40.3%, P = 0.04) and lower rates of abdominal surgical site infections (SSI) (2.9% vs. 7.9%, P = 0.02) than the Open group. The number of lymph nodes harvested was similar in the Lap and Open groups (14.8 ± 7.5 vs. 15.7 ± 8.6, P = 0.34). There was no significant difference in 3-year overall survival rates (81.2% vs. 69.5%, P = 0.12) or relapse-free survival rates (61.1% vs. 58.2%, P = 0.54) between the groups. CONCLUSIONS: Laparoscopic abdominal lymph node dissection for ESCC can be performed safely and appears to be beneficial.

The relationship between the treatment course and prognosis of oligometastasis after esophageal squamous cell carcinoma resection.

PURPOSE: The concept of oligometastasis, which represents limited metastatic disease, has recently gained interest, accompanied by a more detailed classification. This study aims to investigate the relationship between the treatment course and prognosis in patients with a recurrence of esophageal squamous cell carcinoma (ESCC) after curative esophagectomy. METHODS: 126 patients with ESCC recurrence after curative resection were enrolled in this study. Oligometastasis was defined as fewer than five recurrences in a single organ. Patients were classified as having oligometastatic recurrence (OLR) or polymetastatic recurrence (PLR). Patients were further classified into four subgroups according to lesion progression: persistent oligorecurrence (PER-OLR), converted polyrecurrence (CON-PLR), induced oligorecurrence (IND-OLR), and persistent polyrecurrence (PER-PLR). We analyzed the relationship between the recurrence patterns and prognosis according to the progression of oligometastatic lesions. RESULTS: OLR was identified in 58 (46%) of 126 patients with recurrence. Patients with OLR had a significantly better prognosis than those with PLR (P < 0.0001). A further subgroup analysis revealed that patients who underwent IND-OLR had a similar prognosis to those who underwent PER-OLR. CONCLUSIONS: This study suggests that OLR is a prognostic factor after recurrence following resection of ESCC and that PLR can be converted to OLR by therapeutic intervention to achieve a long-term survival.

Cancer-Associated Fibroblast-Derived IL-8 Upregulates PD-L1 Expression in Gastric Cancer Through the NF-κB Pathway.

BACKGROUND: The expression of programmed death-ligand 1 (PD-L1) in tumor cells is a leading cause of tumor immune escape; however, the precise mechanism underlying the regulation of PD-L1 expression in gastric cancer (GC) cells remains unknown. In this study, we aimed to investigate the potential mechanism of cancer-associated fibroblasts (CAFs) regulating PD-L1 expression in GC cells. METHODS: We evaluated the immunomodulatory effects of CAFs in GC cells in vitro via the transwell co-culture system, cytometric bead array, and Western blotting. We detected the role of interleukin (IL)-8 in affecting underlying pathways in GC cells via transfecting IL-8 small-interfering RNA (siRNA), and the protection effects of CAFs on GC cells exposed to CD8+ T cells via cytotoxicity assays. RESULTS: The results revealed that CAFs upregulated PD-L1 expression of GC cells. IL-8 expression was increased after KATO III or MKN45 cells co-cultured with CAF. Additionally, CAF-derived IL-8 promoted PD-L1 expression in GC cells through the P38, JNK, and NF-κB pathways. Besides, repertaxin, an IL-8 receptors (CXCR1/2) inhibitor, reduced PD-L1 expression in GC cells by blocking the P38, JNK, and NF-κB pathways. Furthermore, the expressions of p-P38, p-JNK, and p-NF-κB decreased after GC cells co-cultured with siIL-8-treated CAF. Moreover, repertaxin attenuated the protection of CAFs to cancer cells that were resistant to CD8+ T-cell cytotoxicity, and improved the antibody effects of anti-PD-L1 facilitating CD8+ T-cell cytotoxicity by targeting IL-8. CONCLUSION: Targeting CAF-derived IL-8 may defeat PD-L1 upregulation-mediated immune resistance in GC cells, which provides a novel approach to improve the immunotherapeutic efficacies of patients with GC.

Relationship between the severity of emphysematous change in the lung and morbidity after esophagectomy for esophageal cancer: A retrospective study on a novel strategy for risk prediction.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) prevalence increases post-esophagectomy morbidity. However, the association between COPD severity and post-esophagectomy morbidity remains unclear because of the lack of an objective method to classify COPD severity. Low attenuation volume ratio (LAVR) estimated using Ziostation2 may reflect the extent of emphysematous changes in the lungs and COPD severity, thereby predicting post-esophagectomy morbidity. METHODS: A total of 776 patients who underwent curative McKeown esophagectomy for esophageal cancer between April 2005 and June 2021 were included. The patients were divided into high and low preoperative LAVR groups. Short-term outcomes between the groups were compared for patients who underwent open esophagectomy (OE) and minimally invasive esophagectomy (MIE). RESULTS: A total of 219 (28%) patients were classified into the high LAVR group. High LAVR was significantly associated with disadvantageous patient characteristics such as advanced age, heavy smoking, and impaired respiratory function. Patients with high LAVR had a significantly higher incidence of severe morbidity and pneumonia after OE. High LAVR was an independent risk factor for severe morbidity (odds ratio [OR], 2.52; 95% confidence interval [CI]: 1.237-5.143; p = 0.011) and pneumonia (OR, 2.12; 95% CI: 1.003-4.493; p = 0.049) after OE. Meanwhile, LAVR was not correlated with the incidence of post-MIE morbidity. CONCLUSIONS: LAVR may reflect COPD severity and predict severe morbidity and pneumonia after OE, but not after MIE. Less invasiveness of MIE may alleviate the effects of various disadvantageous backgrounds associated with high LAVR on worse short-term outcomes.

The comprehensive review of gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) from diagnosis and treatment.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) was first proposed by Wothley et al. in 2012 as a rare familial gastric cancer syndrome associated with an autosomal dominant form of inheritance. GAPPS is characterized by gastric basal gland polyposis from the hilum to the body of the stomach. Li et al. in 2016 showed that the cause of the disease is a point mutation in the promotor 1B region of the APC gene, and genetic testing was used to confirm the diagnosis. If the patient has already developed gastric cancer, treatment should be based on the usual treatment for gastric cancer. If no distant metastases exist, a good prognosis can be expected by performing a total gastrectomy. On the other hand, patients with distant metastasis have a poor prognosis. In the case of dysplasia, prophylactic total gastrectomy is recommended, but because it is highly invasive and postoperative postgastrectomy syndrome must be considered, the decision should be made with careful consideration of the patient's background. Therefore, there are no guidelines for screening for GAPPS, the timing of prophylactic total gastrectomy, or methods of endoscopic surveillance. Because GAPPS is a rare disease, its natural history is still unclear. Further case series are needed to elucidate the molecular biology and clinicopathological features of GAPPS and to establish clinical management, including diagnosis, treatment, and surveillance. In this review, we provide an overview of GAPPS, its clinical management, and its problems, which will be useful for the treatment of GAPPS.

Textbook outcome contributes to long-term prognosis in older adults with gastric cancer.

PURPOSE: Textbook outcome (TO) is a composite quality measurement of short-term outcomes for evaluating surgical procedures. We investigated whether TO can be used to predict outcomes after curative gastric cancer (GC) surgery in older adults. METHODS: We retrospectively analyzed 492 consecutive patients who underwent curative gastrectomy for GC from 2005 to 2017. Among these, 141 advanced-age patients were eligible. The patients were divided into two groups: those who achieved TO (a-TO group) and those who failed to achieve TO (f-TO group). In accordance with previous reports, TO consisted of eight metrics. We evaluated the association between TO and long-term survival. RESULTS: TO was achieved 73 (52%) patients. The patients in the f-TO group had a significantly higher body mass index (P = 0.01), longer surgery time (P = 0.03), and more blood loss (P = 0.001). The metric with the lowest achievement rate was "no postoperative severe complication." The patients in the f-TO group had significantly shorter overall survival than those in the a-TO group (P = 0.03). Multivariable Cox regression analyses of overall survival revealed that an American Society of Anesthesiologists physical status classification of 3 (hazard ratio [HR], 3.28; 95% confidence interval [CI], 1.79-5.98; P < 0.0001) and f-TO (HR, 1.92; 95% CI, 1.09-3.39; P = 0.02) were significantly associated with poor overall survival. CONCLUSION: TO can be used to predict outcomes after curative GC surgery in patients of advanced age.

Prognostic value of 18F-fluorodeoxyglucose uptake in the bone marrow on pretreatment positron emission tomography/computed tomography in patients with esophageal cancer who underwent esophagectomy.

BACKGROUND: Increased 18F-fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) clinically reflects increased BM metabolism owing to systemic inflammation, bacterial infection, anemia, and cytokine-producing tumors. The association between FDG uptake in the BM and prognosis after esophagectomy for esophageal cancer has not been investigated. METHODS: This study included 651 patients who underwent PET/CT before any treatment and McKeown esophagectomy for esophageal cancer between June 2007 and August 2021. The pretreatment degree of FDG uptake in the BM was evaluated using a visual assessment criterion. Patients were divided into low- and high-FDG uptake groups. We retrospectively investigated whether the degree of FDG uptake in the BM was associated with clinicopathological and surgical backgrounds, blood parameters, and prognosis. RESULTS: High FDG uptake in the BM was significantly associated with elevated white blood cell and neutrophil counts, increased C-reactive protein levels, decreased hemoglobin, serum albumin, and total cholesterol levels. High FDG uptake in the BM was an independent predictor of worse overall survival in clinical stages 0-II esophageal cancer (hazard ratio, 2.27; 95% confidence interval, 1.097-4.695; P = 0.027). Worse overall survival was also associated with advanced age, low American Society of Anesthesiologists physical status, an advanced clinical stage, and high intraoperative blood loss. CONCLUSION: Increased FDG uptake in the BM on pretreatment PET/CT may be a surrogate indicator of various clinically disadvantageous backgrounds and may act as a predictor of poor prognosis after esophageal cancer surgery.

Roles of octopamine neurons in the vertical lobe of the mushroom body for the execution of a conditioned response in cockroaches.

Aminergic neurons mediate reward signals in mammals and insects. In crickets, we showed that blockade of synaptic transmission from octopamine neurons (OANs) impairs conditioning of an odor (conditioned stimulus, CS) with water or sucrose (unconditioned stimulus, US) and execution of a conditioned response (CR) to the CS. It has not yet been established, however, whether findings in crickets can be applied to other species of insects. In this study, we investigated the roles of OANs in conditioning of salivation, monitored by activities of salivary neurons, and in execution of the CR in cockroaches (Periplaneta americana). We showed that injection of epinastine (an OA receptor antagonist) into the head hemolymph impaired both conditioning and execution of the CR, in accordance with findings in crickets. Moreover, local injection of epinastine into the vertical lobes of the mushroom body (MB), the center for associative learning and control of the CR, impaired execution of the CR, whereas injection of epinastine into the calyces of the MB or the antennal lobes (primary olfactory centers) did not. We propose that OANs in the MB vertical lobes play critical roles in the execution of the CR in cockroaches. This is analogous to the fact that midbrain dopamine neurons govern execution of learned actions in mammals.

Gastric cancer with a giant lymph node metastasis: a case report and review of the literature.

A 78-year-old man presented with a large abdominal mass detected by ultrasonography during a regular checkup. Even if the mass was > 10 cm in diameter, he was asymptomatic. Computed tomography detected an oval-shaped mass, with a maximum diameter of 12 cm, adjacent to the greater curvature of the stomach. Esophagogastroduodenoscopy revealed a 20 mm slightly depressed (type 0-IIc) lesion on the posterior wall of the gastric antrum, which was confirmed to be adenocarcinoma. Three cycles of combination chemotherapy with S-1 and oxaliplatin were administered as neoadjuvant chemotherapy. After neoadjuvant chemotherapy, the patient underwent distal gastrectomy, and a histopathological study identified the 12 cm giant mass as a lymph node metastasis. The postoperative course was uneventful, and thus far, the patient has completed adjuvant chemotherapy without relapse. Cases of gastric cancer with a giant lymph node metastasis are extremely rare. In this study, we report the present case and review the previous literature.

Dynamic Alteration in HLA-E Expression and Soluble HLA-E via Interaction with Natural Killer Cells in Gastric Cancer.

BACKGROUND: Some reports showed the immune tolerance of soluble human leukocyte antigen E (HLA-E), but the role that soluble HLA-E plays in gastric cancer (GC) is unknown. We aimed to clarify the molecular mechanism and clinical significance of soluble HLA-E in GC. METHODS: We examined the expression of HLA-E on GC cells and soluble HLA-E under co-culture with natural killer (NK) cells in a time-dependent manner. Changes in NK cell activity were investigated using anti-NK group 2 member A (NKG2A) antibodies in the presence of soluble HLA-E. Expression of soluble HLA-E in the serum of GC patients was determined. RESULTS: Whereas HLA-E expression on GC cells peaked with interferon (IFN)-γ secretion by NK cells in a time-dependent manner, soluble HLA-E was upregulated in conditioned medium. Pre-incubation with anti-NKG2A antibodies increased the activation of NKG2A+ NK cells in the presence of soluble HLA-E. Expression of soluble HLA-E in the serum of GC patients correlated with disease progression. CONCLUSIONS: HLA-E expression dynamically changes on GC cells and in conditioned medium. Furthermore, soluble HLA-E can contribute to immune escape in GC cell lines, which may have significance in clinical practice. Moreover, soluble HLA-E may be a potential prognostic biomarker.

C-Reactive Protein Levels After Esophagectomy are Associated with Increased Surgical Complications and Poor Prognosis in Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND: C-reactive protein (CRP) levels are reported to predict complications and survival after surgery in various cancers. However, the relationship between postoperative CRP levels and short- and long-term outcomes of esophageal squamous cell carcinoma (ESCC) patients after esophagectomy is unclear. METHOD: We reviewed the records of 543 ESCC patients who underwent subtotal esophagectomy with gastric conduit reconstruction at Kumamoto University Hospital between August 2010 and July 2021. Blood tests for CRP were done on postoperative days (PODs) 1, 3, 5 or 6, and 7 or 8. RESULTS: The mean CRP levels on day 1, day 3, day 5/6, and day 7/8 were 6.68 ± 0.13 mg/dL, 11.49 ± 0.27 mg/dL, 7.48 ± 0.26 mg/dL, and 5.38 ± 0.22 mg/dL, respectively. Mean CRP levels were highest on day 3, and CRP levels after day 3 correlated with grade >2 complications based on the Clavien-Dindo classification. Receiver operating characteristic curve analysis established the optimal cut-off value for CRP day 3 levels to be 12.19 mg/dL. Multivariate logistic regression analyses found that high CRP day 3 levels significantly correlated with grade >2 complications (odds ratio [OR] 3.77, 95% confidence interval [CI] 2.56-5.35; p < 0.001). Moreover, high day 7/8 CRP levels (>3.52) correlated with postoperative survival, and based on multivariate logistic regression analyses, were significantly associated with poor prognosis (hazard ratio 1.67, 95% CI 1.14-2.43; p = 0.008). CONCLUSION: Our findings suggest CRP day 3 levels as a potential biomarker for predicting postoperative complications and that CRP day 7/8 levels have potential prognostic value for ESCC patients after esophagectomy.

Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer.

BACKGROUND: The NKG2A/HLA-E pathway functions as an immune checkpoint with potential for inhibition using therapeutic antibodies. Through this pathway, immune cells lose activity, which allows cancers to progress. We aimed to determine whether HLA-E expression combined with NK cell status serves as a prognostic biomarker for gastric cancer (GC). METHODS: We enrolled patients (n = 232) with advanced GC who underwent curative gastrectomy. Immunohistochemical analyses of global HLA-E expression, and the expression of CD56 and CD3 to identify NK cells were performed. Survival analysis was performed to evaluate the significance of HLA-E expression and NK status. RESULTS: Patients with HLA-E-positive was 104 (41.3%) and had significantly worse prognosis of relapse-free survival (RFS) compared with those with HLA-E-negative. Moreover, patients with NK Low status had worse prognoses for RFS compared with those with NK High status. Statistical analysis of RFS demonstrated that HLA-E expression was a significant independent factor for poor prognosis (HR 1.57, 95% CI 1.04-2.36, P = 0.031). Furthermore, HLA-E-positive patients with low NK low status experienced the shortest RFS, particularly those in the upper GC group. CONCLUSIONS: HLA-E served as a prognostic factor after curative resection of GC, and HLA-E expression combined with NK status served as a sensitive prognostic biomarker for advanced GC.

Prophylactic laparoscopic total gastrectomy for gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): the first report in Asia.

A 41-year-old woman was admitted to our hospital for epigastralgia. She had been admitted to another hospital for fundic gland polyposis (FGP) without any symptoms, and no malignancy had been noted in her previous endoscopy. However, a biopsy performed at our hospital revealed adenocarcinoma, and computed tomography (CT) revealed multiple liver and peritoneal metastases. We clinically suspected gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and indicated genetic testing. The point mutation in exon 1B of APC was revealed. She was diagnosed with GAPPS with multiple liver metastases and underwent systemic chemotherapy. She has two older brothers who also have FGP. The same genomic mutation was observed in both brothers and their mother, and they were also diagnosed with GAPPS. The brothers underwent prophylactic laparoscopic total gastrectomy with D1 lymph-node dissection.

Leukotriene C4 synthase is a novel PPARγ target gene, and leukotriene C4 and D4 activate adipogenesis through cysteinyl LT1 receptors in adipocytes.

Leukotriene (LT) C4 synthase (LTC4S) catalyzes the conversion from LTA4 to LTC4, which is a proinflammatory lipid mediator in asthma and other inflammatory diseases. LTC4 is metabolized to LTD4 and LTE4, all of which are known as cysteinyl (Cys) LTs and exert physiological functions through CysLT receptors. LTC4S is expressed in adipocytes. However, the function of CysLTs and the regulatory mechanism in adipocytes remain unclear. In this study, we investigated the expression of LTC4S and production of CysLTs in murine adipocyte 3T3-L1 cells and their underlying regulatory mechanisms. Expression of LTC4S and production of LTC4 and CysLTs increased during adipogenesis, whereas siRNA-mediated suppression of LTC4S expression repressed adipogenesis by reducing adipogenic gene expression. The CysLT1 receptor, one of the two LTC4 receptors, was expressed in adipocytes. LTC4 and LTD4 increased the intracellular triglyceride levels and adipogenic gene expression, and their enhancement was suppressed by co-treatment with pranlukast, a CysLT1 receptor antagonist. Moreover, the expression profiles of LTC4S gene/protein during adipogenesis resembled those of peroxisome proliferator-activated receptor (PPAR) γ. LTC4S expression was further upregulated by treatment with troglitazone, a PPARγ agonist. Promoter-luciferase and chromatin immunoprecipitation assays showed that PPARγ directly bound to the PPAR response element of the LTC4S gene promoter in adipocytes. These results indicate that the LTC4S gene expression was enhanced by PPARγ, and LTC4 and LTD4 activated adipogenesis through CysLT1 receptors in 3T3-L1 cells. Thus, LTC4S and CysLT1 receptors are novel potential targets for the treatment of obesity.

Long-term survival after multidisciplinary treatments for advanced esophagogastric junction cancer.

Stage IV Gastric/Esophagogastric junction cancer (G/EGJ) has an unfavorable prognosis and poor curability. In this study, we report the case of long-term survival after multidisciplinary treatments for advanced esophagogastric junction cancer. A 53-year-old male patient was diagnosed with HER2 positive advanced esophagogastric junction cancer and mediastinal and paraaortic lymph node metastasis. After systemic chemotherapy for 1 year, minimally invasive esophagectomy was conducted as conversion surgery. However, peritoneal and liver metastasis was observed on 3 months after curative surgery. 2 years after operation, solitary brain metastasis was detected and stereotactic radiosurgery (SRS) using a gamma knife was underwent. After 1 year, despite the continuous administration of Nivolumab, the paraaortic lymph node increased in size again and radiation therapy was conducted. Currently, he is alive and undergoing chemotherapy.