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Despite recent advances in the development of therapeutic antibodies, the prognosis of unresectable or metastatic gastric cancer (GC) remains poor. Here, we searched for genes involved in the malignant phenotype of GC and investigated the potential of one candidate gene to serve as a novel therapeutic target. Analysis of transcriptome datasets of GC identified natriuretic peptide receptor 1 (NPR1), a plasma membrane protein, as a potential target. We employed a panel of human GC cell lines and gene-specific small interfering RNA-mediated NPR1 silencing to investigate the roles of NPR1 in malignancy-associated functions and intracellular signaling pathways. We generated an anti-NPR1 polyclonal antibody and examined its efficacy in a mouse xenograft model of GC peritoneal dissemination. Associations between NPR1 expression in GC tissue and clinicopathological factors were also evaluated. NPR1 mRNA was significantly upregulated in several GC cell lines compared with normal epithelial cells. NPR1 silencing attenuated GC cell proliferation, invasion, and migration, and additionally induced the intrinsic apoptosis pathway associated with mitochondrial dysfunction and caspase activation via downregulation of BCL-2. Administration of anti-NPR1 antibody significantly reduced the number and volume of GC peritoneal tumors in xenografted mice. High expression of NPR1 mRNA in clinical GC specimens was associated with a significantly higher rate of postoperative recurrence and poorer prognosis. NPR1 regulates the intrinsic apoptosis pathway and plays an important role in promoting the GC malignant phenotype. Inhibition of NPR1 with antibodies may have potential as a novel therapeutic modality for unresectable or metastatic GC.
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Receptores do Fator Natriurético Atrial , Neoplasias Gástricas , Humanos , Camundongos , Animais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Apoptose , Proliferação de Células , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Abnormal activation of the coagulation system is associated with malignant tumor progression. Although neoadjuvant treatment (NAT) for resectable esophageal squamous cell carcinoma (ESCC) is the standard of care, the correlation between coagulation status and prognosis of patients undergoing preoperative treatment is insufficiently understood. METHODS: Patients (n = 200) who underwent radical subtotal esophagectomy after preoperative treatment for ESCC between January 2012 and December 2021were included in the analysis. Plasma D-dimer and fibrinogen levels and their combined indices (non-hypercoagulation; D-dimer and fibrinogen levels within the upper normal limit, or hypercoagulation; D-dimer or fibrinogen levels above the upper normal limit) were determined before and after NAT and correlated to clinicopathological factors and prognosis. RESULTS: The nonhypercoagulation group achieved superior overall survival (OS) than the hypercoagulation group (5-year OS rates = 89% vs. 55%; hazard ratio 3.62, P = 0.0008) when determined according to coagulation status after NAT. Multivariate analysis showed that hypercoagulation after NAT served as an independent factor for poor postoperative OS (hazard ratio 3.20; P = 0.0028). The nonhypercoagulation group achieved significantly better disease-free survival (76% vs. 54%; P = 0.0065) than the hypercoagulation group that experienced a significantly higher rate of hematogenous metastasis as an initial recurrence (P = 0.0337). CONCLUSIONS: Hypercoagulation state after NAT served as a valid indicator correlating with postoperative outcomes of patients with ESCC who underwent NAT followed by radical subtotal esophagectomy.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas/cirurgia , Esofagectomia , Terapia Neoadjuvante , Estudos Retrospectivos , PrognósticoRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis despite advances in multidisciplinary treatments and immune checkpoint inhibitors. We previously reported that neural pentraxin receptor (NPTXR), a transmembrane protein mainly expressed in the brain and involved in synaptic transmission, is implicated in gastric cancer malignancy. This study evaluated the expression and function of NPTXR in ESCC, the therapeutic potential of monoclonal antibody (mAb) against NPTXR, and its prognostic value in ESCC patients. METHODS: The study involved analyzing the NPTXR expression in 21 ESCC cell lines and total 371 primary ESCC tissue samples using quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. The impact of NPTXR on the malignant behavior of ESCC was examined using small interfering RNA-mediated knockdown and a subsequent assessment of cell proliferation, apoptosis, and adhesion. This study further investigated the efficacy of anti-NPTXR mAb in vitro and associations between the expression of NPTXR messenger RNA (mRNA) and protein with clinicopathological factors and the prognosis. RESULTS: NPTXR was overexpressed in several ESCC cell lines and primary ESCC tissues. Knockdown of NPTXR in ESCC cells resulted in reduced proliferation, increased apoptosis, and decreased cell adhesion. The mAb against NPTXR significantly inhibited ESCC cell proliferation in vitro. A high NPTXR expression in patient tissues was correlated with a worse overall survival, suggesting its potential as a prognostic biomarker. CONCLUSIONS: NPTXR influences the malignant behavior of ESCC cells. Anti-NPTXR mAb may be a promising therapeutic agent, and its expression in ESCC tissues may serve as a prognostic biomarker.
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Apoptose , Biomarcadores Tumorais , Proliferação de Células , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/tratamento farmacológico , Prognóstico , Masculino , Feminino , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Taxa de Sobrevida , Pessoa de Meia-Idade , Células Tumorais Cultivadas , Anticorpos Monoclonais/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Seguimentos , Movimento Celular , Adesão Celular , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , RNA Mensageiro/genética , Idoso , Proteína C-ReativaRESUMO
BACKGROUND: Advanced gastric cancer (GC) has a poor prognosis. This study aimed to identify novel GC-related genes as potential therapeutic targets. METHODS: Killer cell lectin-like receptor G2 (KLRG2) was identified as a candidate gene by transcriptome analysis of metastatic GC tissues. Small interfering RNA-mediated KLRG2 knockdown in human GC cell lines was used to investigate KLRG2 involvement in signaling pathways and functional behaviors in vitro and in vivo. Clinicopathological data were analyzed in patients stratified according to tumor KLRG2 mRNA expression. RESULTS: KLRG2 knockdown in GC cells decreased cell proliferation, migration, and invasion; caused cell cycle arrest in G2/M phase; induced apoptosis via caspase activation; suppressed JAK/STAT and MAPK-ERK1/2 pathway activities; and upregulated p53 and p38 MAPK activities. In mouse xenograft models of peritoneal metastasis, the number and weight of disseminated GC nodules were decreased by KLRG2 knockdown. High tumor levels of KLRG2 mRNA were significantly associated with lower 5-year overall survival (OS) and relapse-free survival (RFS) rates in patients with Stage I-III GC (5-year OS rate: 64.4% vs. 80.0%, P = 0.009; 5-year RFS rate: 62.8% vs. 78.1%, P = 0.030). CONCLUSIONS: KLRG2 knockdown attenuated the malignant phenotypes of GC cells via downregulation of JAK/STAT and MAPK-ERK1/2 pathway activity and upregulation of p38 MAPK and p53. Targeted suppression of KLRG2 may serve as a new treatment approach for GC.
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Janus Quinases , Neoplasias Gástricas , Humanos , Animais , Camundongos , Janus Quinases/genética , Janus Quinases/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia , Sistema de Sinalização das MAP Quinases , Proteína Supressora de Tumor p53/genética , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Proliferação de Células/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , RNA Mensageiro/metabolismo , Receptores Semelhantes a Lectina de Células NK/genética , Receptores Semelhantes a Lectina de Células NK/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Large type 3 (diameter ≥ 8 cm) and type 4 gastric cancers have been arbitrarily combined in Japan as a single entity. However, whether these two types are oncologically similar remain unclear. This study aimed to clarify this issue. METHODS: In this retrospective study, we analyzed a database of 3,575 patients from nine institutions who underwent gastrectomy between 2010 and 2014. Using propensity scores to balance significant variables, we compared prognoses and tumor recurrences. RESULTS: Of patients with clinical T3/T4 who underwent R0 resection, 75 and 73 had large type 3 and 4 tumors, respectively. Patients with type 4 tumors had significantly lower overall survival rates than those of patients with large type 3 tumors (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.14-2.74). However, among the large type 3 tumors, a remarkable difference in prognosis was observed between the differentiated and undifferentiated histological types. A comparison was made between large type 3 with undifferentiated phenotype and type 4, each with 39 patients after propensity score matching. Outcomes in both groups were similar in terms of overall survival (HR 1.28; 95% CI 0.73-2.25) and relapse-free survival (HR 1.34; 95% CI 0.80-2.27). No statistically significant differences were observed in the incidence of peritoneal recurrence (35.9% vs. 46.1%, P = 0.36) and lymph node recurrence (25.6% vs. 12.8%, P = 0.15). CONCLUSIONS: Large type 3 tumors with undifferentiated phenotype and type 4 tumors were oncologically similar. This subgroup could be considered as a new entity for future clinical trials.
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BACKGROUND: Proximal gastrectomy (PG) has become an increasingly preferred procedure for treating early cancer in the upper third of the stomach. However, advantages of PG in postoperative quality of life (QOL) over total gastrectomy (TG) has not fully proven. METHODS: We conducted a multi-institutional prospective observational study (CCOG1602) of patients who undergo TG or PG for cStage I gastric cancer. We used the PGSAS-37 and EORTC-QLQ-C30 to evaluate the changes in body weight and QOL over a 3-year postoperative period. The primary endpoint was the weight loss rate 3 years after surgery. RESULTS: We enrolled 109 patients from 18 institutions and selected 65 and 19 patients for inclusion in the TG and PG groups, respectively. Mean postoperative weight loss rates were 16.0% and 11.7% for the TG and PG groups, respectively (p = 0.056, Cohen's d 0.656) during postoperative year 1% and 15.0% and 10.8% for TG and PG (p = 0.068, Cohen's d 0.543), respectively, during postoperative year 3, indicating that the PG group achieved a better trend with a moderate effect size. According to the PGSAS-37, the PG group experienced a better trend in the indigestion subscale (p < 0.001, Cohen's d -1.085) and total symptom score (p = 0.050, Cohen's d -0.59) during postoperative year 3 compared with the TG group. In contrast, the EORTC-QLQ-C30 detected no difference between the groups at any time point during 3-year postoperative period. CONCLUSIONS: This prospective study demonstrates that PG tended to be more favorable compared with TG with respect to postoperative weight loss and QOL, particularly regarding indigestion.
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Dispepsia , Neoplasias Gástricas , Humanos , Qualidade de Vida , Estudos Prospectivos , Neoplasias Gástricas/cirurgia , Dispepsia/cirurgia , Gastrectomia/métodos , Período Pós-Operatório , Redução de Peso , Resultado do TratamentoRESUMO
PURPOSE: While regarded as function-preserving gastrectomy, few prospective longitudinal clinical trials have addressed the postoperative quality of life (QOL) after pylorus-preserving gastrectomy (PPG). We prospectively compared chronological changes in postoperative body weight and the QOL between PPG and distal gastrectomy (DG) for pathological Stage I gastric cancer (GC). METHODS: We conducted a multi-institutional prospective study (CCOG1601) to evaluate patients who underwent DG and PPG. The QOL was examined using the European Organization for Research and Treatment of Cancer Quality of life questionnaire-C30 (EORTC QLQ-C30) and the Post-Gastrectomy Syndrome Assessment Scale-37 (PGSAS-37). A total of 295 patients were enrolled from 15 institutions, and propensity score matching was performed to adjust for the essential variables for comparison analyses. RESULTS: After propensity score matching, 25 pairs of patients were identified. In the first postoperative month, DG achieved a superior nausea and vomiting score (EORTC QLQ-C30) and meal-related distress, indigestion, and dumping scores (PGSAS-37). No significant differences were noted between DG and PPG in the long-term QOL. Postoperative body weight loss was similar in both groups. CONCLUSIONS: This prospective observational study failed to demonstrate the superiority of PPG over DG in terms of postoperative body weight changes and the QOL.
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BACKGROUND: In the chain of survival for Out-of-hospital cardiac arrest (OHCA), each component of care contributes to improve the prognosis of the patient with OHCA. The SARS-CoV-2 (COVID-19) pandemic potentially affected each part of care in the chain of survival. The aim of this study was to compare prehospital care, in-hospital treatment, and outcomes among OHCA patients before and after the COVID-19 pandemic. METHODS: We analyzed data from a multicenter prospective study in Kanto area, Japan, named SOS-KANTO 2017. We enrolled patients who registered during the pre-pandemic period (September 2019 to December 2019) and the post-pandemic period (June 2020 to March 2021). The main outcome measures were 30-day mortality and the proportion of favorable outcomes at 1 month, and secondary outcome measures were changes in prehospital and in-hospital treatments between the pre- and post-pandemic periods. RESULTS: There were 2015 patients in the pre-pandemic group, and 5023 in the post-pandemic group. The proportion of advanced airway management by emergency medical service (EMS) increased (p < 0.01), and EMS call-to-hospital time was prolonged (p < 0.01) in the post- versus pre-pandemic group. There were no differences between the groups in defibrillation, extracorporeal membrane oxygenation, or temperature control therapy (p = 0.43, p = 0.14, and p = 0.16, respectively). Survival rate at 1 month and favorable outcome rate at 1 month were lower (p = 0.01 and p < 0.01, respectively) in the post- versus pre-pandemic group. CONCLUSION: Survival rate and favorable outcome rate 1 month after return of spontaneous circulation of OHCA worsened, EMS response time was prolonged, and advanced airway management by EMS increased in the post- versus pre-pandemic group; however, most prehospital and in-hospital management did not change between pre- and post-COVID-19 pandemic.
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COVID-19 , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Humanos , Japão/epidemiologia , Pandemias , COVID-19/epidemiologia , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/terapia , Estudos Prospectivos , SARS-CoV-2 , Hospitais , Resultado do TratamentoAssuntos
Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Prognóstico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Proteína C-Reativa , Proteínas do Tecido NervosoRESUMO
Aim: Prescription drug and over-the-counter (OTC) drug overdose is a major problem in emergency departments in Japan, and some need advanced care which is more than observation. We aimed to identify the prehospital risk factors for the need of advanced care among overdose patients. Methods: This was a single-center retrospective cohort study. We included overdoses patients of prescription drugs or OTC drugs, who admitted to our hospital between 2016 and 2021. We grouped them into advanced care and non-advanced care. The main outcome was the need for advanced care. We performed a multiple logistic regression analysis, calculated the PAV score (Paracetamol use, Alcohol use, abnormal Vital signs on scene) and performed a receiver operating characteristic (ROC) analysis. Results: There were 229 subjects. The logistic regression analysis revealed that alcohol, paracetamol, and the abnormal vital signs on scene were associated with advanced care (alcohol-odds ratio [OR]: 2.95; 95% confidence interval [CI]: 1.29-6.75; paracetamol-OR: 5.47; 95% CI: 2.18-13.71; abnormal vital signs-OR: 4.61, 95% CI: 2.07-10.27). The rate of advanced care in the high PAV score (2 and 3) group was statistically higher than that in the low PAV score (0-1) group (p = 0.04). Area under the ROC curve of the PAV score was 0.72 (95% CI, 0.65-0.80). Conclusion: Alcohol, paracetamol use and abnormal vital signs on scene might be risk factors for advanced care among prescription drugs or OTC drugs overdose patients, and the PAV score may predict the need for advanced care.
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Background: Agonal breathing is a relatively common symptom that follows cardiac arrest when the brainstem function is preserved. Agonal breathing is associated with favorable survival in patients experiencing out-of-hospital cardiac arrest (OHCA). While previous studies focused on agonal breathing observed in the pre-hospital setting for all study subjects, we focused on agonal breathing observed upon hospital arrival. In this multicenter prospective study, we aimed to assess the prognosis of patients exhibiting agonal breathing upon hospital arrival were compared. We hypothesized that agonal breathing at hospital arrival would be associated with favorable neurological outcomes among patients with OHCA. Methods: The data on incidence of agonal breathing were prospectively collected for all evaluable participants in a multicenter, observational study in Japan (SOS-KANTO [Survey of Survivors after Out-of-Hospital Cardiac Arrest in Kanto Area] 2017 Study). Groups with and without agonal breathing were compared upon hospital arrival. Propensity-score with inverse probability of treatment weighting (IPTW) analysis was performed to adjust for confounding factors. The primary outcome was a favorable neurological outcome (Cerebral Performance Category 1-2) at 1 month. Results: A total of 6,457 participants out of the 9,909 registered in SOS-KANTO 2017 (in which 42 facilities participated) were selected for the current study. There were 128 patients (2.0%) in the with-agonal breathing group and 6,329 (98.0%) in the withoutagonal breathing group. The primary outcome was 1.1% in the with-agonal breathing group and 0.6% in the without-agonal breathing group (risk difference, 0.55; 95% confidence interval, 0.23-0.87) after IPTW analysis. Conclusion: In this multicenter prospective study, agonal breathing at hospital arrival was significantly associated with better neurological outcomes and increased survival at 1 month. Thus, agonal breathing at hospital arrival may be a useful prognostic predictor for patients experiencing OHCA.
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Purpose Infant vision assessment often relies on grating acuity; however, its objectivity and convenience must be improved. A calibration-free eye-tracking system, even in preverbal children, enables easy and precise gaze analysis. This pilot study aimed to develop a reliable automated monocular vision screening. Methods Participants (n=118) underwent a grating visual acuity test using the eye-tracking system. Correlations between the grating acuity, uncorrected visual acuity, and refractive error were analyzed across different cutoff values of fixation duration percentage. Results Strong correlations were found between the grating acuity and refractive error at 69% and 88% thresholds. Similar correlations with uncorrected visual acuity were noted at 70% and 89% thresholds. False-negatives around the 70% threshold were noted, indicating potential overestimation of acuity in cases of low visual acuity/high refractive error. Discussion The results highlight the feasibility of calibration-free eye-tracking system-based monocular vision screening with an optimal screening threshold of 90%.
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Enterovesical fistula (EVF) in Crohn's disease (CD) often does not improve with medical treatment and requires surgical treatment. The surgical treatment strategy for EVF in CD is definitive resection of the intestinal tract side, and performing a leak test using dye injection into the bladder after EVF dissection to determine the appropriate surgical procedure for the bladder side. This study aimed to evaluate the outcomes of surgical treatment for EVF in CD. Twenty-one patients who underwent surgery for EVF between 2006 and 2021 were included and retrospectively evaluated for clinical background, surgical procedures, and postoperative complications. The most common origin of EVF was the ileum (17 cases; 81%), and the most common site of EVF formation was the apex (12; 57%). Surgical approaches were laparotomy in 11 (52%) cases and laparoscopy in 10 (48%). Surgical procedures on the bladder side were fistula dissection in 13 (62%) cases and sutured closure of fistula in 8 (38%). A comparison of approaches revealed no significant difference in operative time, but the amount of blood loss was significantly less in the laparoscopy (p < 0.01). There was no significant difference in the occurrence of postoperative complications between approaches. Postoperative anti-TNF-α antibody agents were used in 17 (81%) cases, and there were no cases of recurrent EVF. In conclusion, definitive resection of the intestinal tract and minimal treatment on the bladder side were sufficient to achieve satisfactory outcomes for EVF in CD.
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Doença de Crohn , Fístula Intestinal , Fístula da Bexiga Urinária , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/complicações , Masculino , Feminino , Adulto , Fístula Intestinal/cirurgia , Fístula Intestinal/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fístula da Bexiga Urinária/cirurgia , Fístula da Bexiga Urinária/etiologia , Resultado do Tratamento , Complicações Pós-Operatórias , Adulto Jovem , Laparoscopia/métodos , Adolescente , Laparotomia/métodos , Laparotomia/efeitos adversos , IdosoRESUMO
Temperature control is the only neuroprotective intervention suggested in current international guidelines for patients with return of spontaneous circulation after cardiac arrest, but the prevalence of temperature control therapy, temperature settings, and outcomes have not been clearly reported. We aimed to investigate changes over 7 years in provision of temperature control treatment among out-of-hospital cardiac arrest (OHCA) patients in Kanto region, Japan. Data of all adult OHCA patients who survived for more than 24 hours in the prospective cohort studies, SOS-KANTO 2012 (conducted from 2012 to 2013) and SOS-KANTO 2017 (conducted from 2019 to 2021), in Japan were included. We compared the prevalence of temperature control and the proportion of mild (≥35°C) and moderate (from 32°C to 34.9°C) hypothermia between the two study groups. We also performed a Cox regression analysis to evaluate 30-day mortality adjusted by temperature control therapy (none, moderate hypothermia, or mild hypothermia), age, sex, past medical history, witnessed status, bystander cardiopulmonary resuscitation, initial rhythm, location of arrest, and dataset (SOS-KANTO 2012 or 2017). We analyzed data from 2936 patients (n = 1710, SOS-KANTO 2012; n = 1226, SOS-KANTO 2017). Use of temperature control was lower (45.3% vs. 41.4%, p = 0.04), moderate hypothermia was lower (p < 0.01), and mild hypothermia was higher (p < 0.01) in SOS-KANTO 2017 compared with SOS-KANTO 2012. The survival rate was significantly higher for patients with mild (p < 0.01) and moderate (p < 0.01) hypothermia compared with those who did not receive temperature control therapy. Overall, the incidence of moderate hypothermia decreased and that of mild hypothermia increased and the use of temperature control decreased between the two studies conducted 7 years apart in the Kanto area, Japan. Temperature control management might improve survival of patients with OHCA.
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BACKGROUND/AIM: Proximal gastrectomy (PG) is a therapy for early-stage proximal gastric cancer and offers advantages such as the preservation of food storage capacity and less body weight loss (BWL). Nevertheless, significant BWL following PG may occur, affecting the patient's well-being and survival. In this study, we aimed to identify the relevant factors for BWL following PG by analyzing an institutional database of patients. PATIENTS AND METHODS: We enrolled 58 consecutive patients who underwent PG for gastric or esophagogastric junction cancer at our institution between April 2004 and March 2021. Based on BWL at 12 months postoperatively, we retrospectively compared and examined patient characteristics, surgical details, and nutritional markers. RESULTS: The mean BWL of the 58 patients included in this analysis was 14.0±7.2%. When the patients were divided into BWL-moderate (n=29) and BWL-severe (n=29) groups using a cutoff value of 15.7%, the latter experienced early BWL within 1 month postoperatively, primarily due to body fat mass reduction, with no recovery during the 60 months of follow up. In contrast, gradual recovery was observed among patients in the BWL-moderate group after experiencing the lowest body weight 24 months postoperatively. A greater decrease in body fat mass than in muscle mass was observed in both groups. Blood hemoglobin levels did not recover in the BWL-severe group. CONCLUSION: The BWL-severe group after proximal gastrectomy demonstrated significantly greater early postoperative BWL, primarily attributed to a reduction in body fat mass, with hardly any recovery. Early postoperative nutritional intervention might be proposed to prevent long-term BWL.
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Neoplasias Gástricas , Redução de Peso , Humanos , Estudos Retrospectivos , Gastrectomia/efeitos adversos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Organs of the digestive system are frequent sites of cancer development, and digestive tract cancers are the leading causes of death worldwide, including in Japan. Most of these cancers are associated with smoking or drinking habits. This study focused on the clinical and genomic characteristics of patients with these cancers using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which comprises a large volume of data on Japanese patients who have undergone tumor profiling gene panel tests. PATIENTS AND METHODS: The genomic and clinical data from patients with digestive tract cancers registered in C-CAT between 2019 and 2023 were retrospectively reviewed. The data were derived from 412 patients with esophageal squamous cell carcinoma, 558 with gastric adenocarcinoma, 3,368 with colorectal adenocarcinoma, 139 with hepatocellular carcinoma, 2,050 with cholangiocarcinoma, and 2,552 with pancreatic ductal adenocarcinoma. RESULTS: CDKN2A, CDKN2B, and MTAP mutations were associated with both smoking and drinking history, and patients with these mutations had a worse prognosis. Almost all gene alterations in CDKN2B and MTAP were deletions, often accompanied by CDKN2A deletion. CDKN2A mutation emerged as the most decisive prognostic factor among these mutations. Although CDKN2A mutations were frequently seen in esophageal squamous cell carcinoma, cholangiocarcinoma, and pancreatic ductal adenocarcinoma, statistically significant differences in survival outcomes were only identified in the latter two. CONCLUSION: CDKN2A mutations were associated with smoking and drinking in digestive cancers. This mutation was prevalent among patients with cholangiocarcinoma and pancreatic ductal adenocarcinoma, for whom they could serve as prognostic factors.
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Consumo de Bebidas Alcoólicas , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias do Sistema Digestório , Mutação , Fumar , Humanos , Masculino , Prognóstico , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Japão/epidemiologia , Fumar/efeitos adversos , Fumar/genética , Neoplasias do Sistema Digestório/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , População do Leste AsiáticoRESUMO
In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m2) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer.
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Demência Frontotemporal , Pirrolidinas , Neoplasias Gástricas , Timina , Humanos , Ramucirumab , Trifluridina/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Demência Frontotemporal/induzido quimicamente , Demência Frontotemporal/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Combinação de MedicamentosRESUMO
Whether empirical therapy with carbapenems positively affects the outcomes of critically ill patients with bacterial infections remains unclear. This study aimed to investigate whether the use of carbapenems as the initial antimicrobial administration reduces mortality and whether the duration of carbapenem use affects the detection of multidrug-resistant (MDR) pathogens. This was a post hoc analysis of data acquired from Japanese participating sites from a multicenter, prospective observational study [Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA study)]. A total of 268 adult patients with clinically suspected or confirmed bacterial infections from 31 Japanese intensive care units (ICUs) were analyzed. The patients were divided into two groups: patients who were administered carbapenems as initial antimicrobials (initial carbapenem group, n = 99) and those who were not administered carbapenems (initial non-carbapenem group, n = 169). The primary outcomes were mortality at day 28 and detection of MDR pathogens. Multivariate logistic regression analysis revealed that mortality at day 28 did not differ between the two groups [18 (18%) vs 27 (16%), respectively; odds ratio: 1.25 (95% confidence interval (CI): 0.59-2.65), P = 0.564]. The subdistribution hazard ratio for detecting MDR pathogens on day 28 per additional day of carbapenem use is 1.08 (95% CI: 1.05-1.13, P < 0.001 using the Fine-Gray model with death regarded as a competing event). In conclusion, in-hospital mortality was similar between the groups, and a longer duration of carbapenem use as the initial antimicrobial therapy resulted in a higher risk of detection of new MDR pathogens.IMPORTANCEWe found no statistical difference in mortality with the empirical use of carbapenems as initial antimicrobial therapy among critically ill patients with bacterial infections. Our study revealed a lower proportion of inappropriate initial antimicrobial administrations than those reported in previous studies. This result suggests the importance of appropriate risk assessment for the involvement of multidrug-resistant (MDR) pathogens and the selection of suitable antibiotics based on risk. To the best of our knowledge, this study is the first to demonstrate that a longer duration of carbapenem use as initial therapy is associated with a higher risk of subsequent detection of MDR pathogens. This finding underscores the importance of efforts to minimize the duration of carbapenem use as initial antimicrobial therapy when it is necessary.