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BACKGROUND: Organoids are approved by the US FDA as an alternative to animal experiments to guide drug development and for sensitivity screening. Stable organoids models of gastric cancer are desirable for personalized medicine and drug screening. METHODS: Tumor tissues from a primary cancer of the stomach and metastatic cancer of the lymph node were collected for 3D culture. By long-term culture for over 50 generations in vitro, we obtained stably growing organoid lines. We analyzed short tandem repeats (STRs) and karyotypes of cancer cells, and tumorigenesis of the organoids in nude mice, as well as multi-omics profiles of the organoids. A CCK8 method was used to determine the drugs sensitivity to fluorouracil (5-Fu), platinum and paclitaxel. RESULTS: Paired organoid lines from primary cancer (SPDO1P) and metastatic lymph node (SPDO1LM) were established with unique STRs and karyotypes. The organoid lines resulted in tumorigenesis in vivo and had clear genetic profiles. Compared to SPDO1P from primary cancer, upregulated genes of SPDO1LM from the metastatic lymph node were enriched in pathways of epithelial-mesenchymal transition and angiogenesis with stronger abilities of cell migration, invasion, and pro-angiogenesis. Based on drug sensitivity analysis, the SOX regimen (5-Fu plus oxaliplatin) was used for chemotherapy with an optimal clinical outcome. CONCLUSIONS: The organoid lines recapitulate the drug sensitivity of the parental tissues. The paired organoid lines present a step-change toward living biobanks for further translational usage.
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Metástase Linfática , Camundongos Nus , Organoides , Medicina de Precisão , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Organoides/efeitos dos fármacos , Organoides/patologia , Humanos , Animais , Metástase Linfática/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Carcinogênese/patologia , Carcinogênese/genética , Carcinogênese/efeitos dos fármacos , Camundongos , Repetições de Microssatélites/genéticaRESUMO
BACKGROUND: Data on the long-term oncological outcomes of patients who undergo conversion surgery (CS) in gastric cancer (GC) patients with peritoneal metastasis (PM) are limited. METHODS: GC patients with PM who received intraperitoneal (ip) and systemic chemotherapy between April 2015 and January 2021 were enrolled. Multivariate analysis was performed to identify risk factors associated with survival. Clinicopathological and survival outcomes were compared between those with CS and those without CS (NCS). The paclitaxel (PTX) plus tegafur-gimeracil-oteracil potassium capsules (S-1) (PS) + ip PTX and oxaliplatin plus S-1 (SOX) + ip PTX groups were matched in a 1:1 ratio using propensity score matching. Oncological and survival data were collected and analyzed. RESULTS: A total of 540 patients who received ip chemotherapy via subcutaneous port and systemic chemotherapy were analyzed and 268 patients were enrolled, including 113 who underwent CS and 155 who did not. Overall survival (OS) were 27.0 months and 11.8 months in the CS and NCS groups (P < 0.0001), respectively. R0 resection was an independent prognostic factor for patients who underwent CS. The OS of patients with or without ovariectomy was 21.3 or 12.0 months (P < 0.0001). No difference of clinicopathological and survival outcomes was found between the PS + ip PTX and SOX + ip PTX groups. CONCLUSION: Conversion therapy is safe and adverse events were manageable. CS improves the survival of GC patients with PM after ip and systemic chemotherapy. R0 is an important prognostic factor. Furthermore, outcomes are comparable between the PS + ip PTX and SOX + ip PTX groups.
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Neoplasias Peritoneais , Neoplasias Gástricas , Feminino , Humanos , Neoplasias Gástricas/patologia , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paclitaxel/uso terapêuticoRESUMO
Intraperitoneal chemotherapy combined with systemic chemotherapy is one of the therapeutic modalities currently used for the treatment of gastric cancer patients with peritoneal metastasis. This study was designed to evaluate the efficacy and safety of sintilimab plus S-1 combined intraperitoneal and intravenous paclitaxel. This is an open-label, single-center, phase II study including 36 gastric adenocarcinoma patients with peritoneal metastases diagnosed by laparoscopy. All enrolled patients received sintilimab, intraperitoneal and intravenous paclitaxel plus oral S-1 every 3 weeks. Conversion operation should be considered when a patient responds to the regimen and the peritoneal metastasis disappears. After gastrectomy, the protocol treatment is repeated until disease progression, unacceptable toxicity, investigator decision or patient withdrawal. The primary end point is the 1-year survival rate. Clinical Trial Registration: NCT05204173 (ClinicalTrials.gov).
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Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Neoadjuvante , Paclitaxel , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologiaRESUMO
Although recent advances in systemic chemotherapy have improved the clinical outcomes of gastric cancer patients with peritoneal metastasis, the peritoneum still represents a common site of treatment failure and disease recurrence. Neoadjuvant intraperitoneal-systemic chemotherapy has been acknowledged as a more aggressive treatment for gastric cancer patients with peritoneal metastasis. In this multicenter phase III randomized controlled trial, 238 patients will be randomly separated into two groups in a 2:1 ratio after laparoscopic exploration. The experimental arm will receive the proposed neoadjuvant intraperitoneal-systemic chemotherapy regimen, whereas the control group will receive a Paclitaxel + S-1 (PS) chemotherapy regimen. The endpoints for the study are overall survival, response rate, gastrectomy radicality rate, progression-free survival and adverse events.
Recent advances in technology have improved the outcomes of stomach cancer patients. However, there are still many patients who die of cancer that has spread from another part of the body. Neoadjuvant intraperitonealsystemic chemotherapy has been acknowledged as a more aggressive treatment for stomach cancer patients with peritoneal metastasis (cancer that has spread to the very thin layer of tissue on the inside of the abdomen that covers the stomach and other organs). In this study, 238 patients will be randomly separated into two groups in a 2:1 ratio after evaluation. The experimental group will receive the proposed neoadjuvant intraperitonealsystemic chemotherapy regimen, whereas the control group will receive a Paclitaxel + S-1 (PS) chemotherapy regimen. The endpoints for the study are how long patients live, number of patients who respond to treatment, number of patients who undergo surgery, how long patients live without their disease getting worse and problems caused by treatment. Trial registration number: ChiCTR-IIR-16009802.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Humanos , Estadiamento de Neoplasias , Paclitaxel/uso terapêutico , Estudos ProspectivosRESUMO
Although gastric cancer with para-aortic lymph node (PAN) metastasis is commonly regarded as unresectable, surgeons have explored the optimal treatment for patients with PAN metastases limited to No.16a2/b1 in the past few decades. Preoperative systemic therapy combined with D2 gastrectomy plus PAN dissection may improve the prognosis of these patients. In this multicenter phase II trial, 29 gastric cancer patients with PAN metastasis limited to No.16a2/b1 will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 (nab-POS: nab-paclitaxel, oxaliplatin, S-1) and sintilimab followed by D2 gastrectomy plus PAN dissection; and postoperative treatment with oral S-1, intravenous sintilimab and intraperitoneal paclitaxel. The end points for the study are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events.
Stomach cancer with metastases in the para-aortic lymph nodes is usually considered inoperable. Chemotherapy combined with resection of the stomach and more extensive lymph node dissection may prolong the life of these patients. In this multicenter study, 29 stomach cancer patients with para-aortic lymph node metastases will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 and sintilimab, followed by resection of the stomach combined with para-aortic lymph node dissection and use of continued oral, intravenous and intraperitoneal chemotherapy. The study's end points are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events. Clinical Trial Registration: ChiCTR2200061125 (ChiCTR.org.cn).
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Excisão de Linfonodo , Metástase Linfática/patologia , Oxaliplatina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfonodos/patologia , Gastrectomia/efeitos adversos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
BACKGROUND: In this study, we tried to access the efficacy and safety of oxaliplatin plus S-1 with intraperitoneal paclitaxel (PTX) for the treatment of Chinese advanced gastric cancer with peritoneal metastases. PATIENTS AND METHODS: Thirty patients diagnosed with advanced gastric cancer underwent laparoscopic exploration and were enrolled when macroscopic disseminated metastases (P1) were confirmed. PTX was diluted in 1 l of normal saline and IP administered through peritoneal port at an initial dose of 40 mg/m2 over 1 h on day1,8, respectively. Oxaliplatin was administered intravenously at an initial dose of 100 mg/m2 on day1, and S-1 was administered orally at an initial dose of 80 mg/m2 for 14 days followed by 7 days rest, repeated by every 3 weeks. RESULTS: Of all these 30 patients, the median number of cycles was 6 (range 2-16) due to the limitation of hematotoxicity and peripheral neuropathy by oxaliplatin. There were 11 (36.7%) patients received conversion surgery. The median progression free survival (PFS) was 6.6 months (95% CI = 4.7-8.5 months) and the median overall survival (OS) was 15.1 months (95% CI = 12.4-17.8 months). The grade 3-4 hematological toxicities were leucopenia (23.3%), neutropenia (23.3%), anemia (16.7%), and thrombocytopenia (20%), respectively. The grade 3-4 non-hematological toxicities were tolerated, most of which were peripheral sensory neuropathy (40%) due to oxaliplatin, diarrhea (20%), nausea and vomiting (26.7%). CONCLUSIONS: SOX+ip PTX regimen was effective in advanced gastric cancer with peritoneal metastasis. Survival time was significantly prolonged by conversion surgery. Grade 3-4 toxicities were uncommon. Large scale clinical trial is necessary to get more evidence to identify its efficacy. TRAIL REGISTRATION: ChiCTR, ChiCTR-IIR-16009802 . Registered 9 November 2016.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Peritônio/patologia , Intervalo Livre de Progressão , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Adulto JovemRESUMO
Although complete omentectomy is traditionally performed in patients with gastric cancer as part of radical gastrectomy to ensure the elimination of micrometastases, the prognostic value of omentectomy during gastrectomy remains unclear. Retrospective studies have shown that the incidence of metastases in the greater omentum is very low in T1-T3 gastric cancer. Thus radical gastrectomy with D2 lymphadenectomy and preservation of the greater omentum may be a proper curative treatment for gastric cancer patients with T1-T3 tumors. The aim of this article is to describe the design and rationale for this prospective, randomized controlled DRAGON-05 trial, conducted to evaluate the prognostic value of omentum-preserving gastrectomy for patients with T1-T3 gastric cancer. Clinical trial registration: ChiCTR2000040045 (ClinicalTrials.gov).
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Gastrectomia/métodos , Recidiva Local de Neoplasia/epidemiologia , Omento/cirurgia , Tratamentos com Preservação do Órgão/métodos , Neoplasias Gástricas/cirurgia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Gastrectomia/estatística & dados numéricos , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Prognóstico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP). METHODS: 3011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis. RESULTS: The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH < 7.3, PaO2/FiO2 < 200 mmHg, sodium < 130 mmol/L, healthcare-associated pneumonia, white blood cells > 10,000/mm3, pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors. CONCLUSIONS: Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP. TRIAL REGISTRATION: A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb.
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Antibacterianos/uso terapêutico , Pneumonia Associada a Assistência à Saúde/diagnóstico , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Feminino , Hospitais de Ensino/estatística & dados numéricos , Humanos , Incidência , Masculino , Mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Falha de TratamentoRESUMO
Following publication of the original article [1], the authors reported the following errors/updates.
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BACKGROUND: To investigate the implications of prophylactic intraoperative Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with D2 radical gastrectomy for locally advanced Gastric Cancer (AGC) in a randomized case control study. METHOD: Eighty consecutive patients with locally AGC were randomly separated into 2 groups: HIPEC group (Curative Resection + intraoperative HIPEC with cisplatin 50 mg/m2 at 42.0 ± 1.0 °C for 60 min) and Control group (Curative Resection only). Intraoperative and post-operative events, clinical recovery, morbidity and the disease-free survival (DFS) rates were closely monitored. RESULTS: Among the 40 HIPEC group patients, the highest intracranial temperature recorded during the procedure was 38.2 °C but the patient made an eventless recovery. Mild renal dysfunction, hyperbilirubinemia and mild liver dysfunction were recorded in the HIPEC group but their incidences were found to be statistically insignificant when compared with the control group (P > 0.05). The initial post-operative analysis revealed shorter post-operative stay for in the HIPEC group but further analysis revealed that it was related to the incidence of postoperative complication. During a median follow-up time of 41 months, there were 9/39 and 15/38 cases of disease progression in HIPEC and Control groups respectively, with a more favorable 3-year DFS (76.9% vs 60.5%) and a lower peritoneal recurrence rate (5% vs 30%) in the HIPEC group. CONCLUSION: Prophylactic HIPEC with radical D2 Gastrectomy is safe and shows favorable survival and peritoneal recurrence rates for AGC with acceptable morbidity. Nevertheless, more structured multi-centered RCT should be carried out for more substantial evidence.
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Hipertermia Induzida , Neoplasias Peritoneais/prevenção & controle , Neoplasias Gástricas/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Estudos de Casos e Controles , Cisplatino/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Distribuição Aleatória , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: Limited information exists on the clinical characteristics predictive of mortality in patients aged ≥65 years in many countries. The impact of adherence to current antimicrobial guidelines on the mortality of hospitalized elderly patients with community-acquired pneumonia (CAP) has never been assessed. METHODS: A total of 3131 patients aged ≥65 years were enrolled from a multi-center, retrospective, observational study initiated by the CAP-China network. Risk factors for death were screened with multivariable logistic regression analysis, with emphasis on the evaluation of age, comorbidities and antimicrobial treatment regimen with regard to the current Chinese CAP guidelines. RESULTS: The mean age of the study population was 77.4 ± 7.4 years. Overall in-hospital and 60-day mortality were 5.7% and 7.6%, respectively; these rates were three-fold higher in those aged ≥85 years than in the 65-74 group (11.9% versus 3.2% for in-hospital mortality and 14.1% versus 4.7% for 60-day mortality, respectively). The mortality was significantly higher among patients with comorbidities compared with those who were otherwise healthy. According to the 2016 Chinese CAP guidelines, 62.1% of patients (1907/3073) received non-adherent treatment. For general-ward patients without risk factors for Pseudomonas aeruginosa (PA) infection (n = 2258), 52.3% (1094/2090) were over-treated, characterized by monotherapy with an anti-pseudomonal ß-lactam or combination with fluoroquinolone + ß-lactam; while 71.4% of intensive care unit (ICU) patients (120/168) were undertreated, without coverage of atypical bacteria. Among patients with risk factors for PA infection (n = 815), 22.9% (165/722) of those in the general ward and 74.2% of those in the ICU (69/93) were undertreated, using regimens without anti-pseudomonal activity. The independent predictors of 60-day mortality were age, long-term bedridden status, congestive heart failure, CURB-65, glucose, heart rate, arterial oxygen saturation (SaO2) and albumin levels. CONCLUSIONS: Overtreatment in general-ward patients and undertreatment in ICU patients were critical problems. Compliance with Chinese guidelines will require fundamental changes in standard-of-care treatment patterns. The data included herein may facilitate early identification of patients at increased risk of mortality. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov ( NCT02489578 ).
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Anti-Infecciosos/uso terapêutico , Infecções Comunitárias Adquiridas/epidemiologia , Fidelidade a Diretrizes/estatística & dados numéricos , Pneumonia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/mortalidade , Comorbidade , Feminino , Fluoroquinolonas/uso terapêutico , Mortalidade Hospitalar , Humanos , Masculino , Pneumonia/tratamento farmacológico , Pneumonia/mortalidade , Estudos Retrospectivos , Fatores de Risco , beta-Lactamas/uso terapêuticoRESUMO
Tumors are genetic changes that develop in an organism as a result of many internal and external causes. They affect the biological behavior of cells, cause them to grow independently, and give rise to new, perpetually proliferating organisms. Recent research has supported the critical function of tumor-associated macrophages in the development, progression, and metastasis of tumors through efferocytosis. Yet, there is still much to learn about the mechanisms behind their contribution to tumor pathological processes. As a result, it's critical to actively investigate how cytosolic processes contribute to the growth of tumors and to create novel therapeutic approaches.
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BACKGROUND: In the JCOG0501 study, neoadjuvant chemotherapy (NAC) failed to demonstrate survival benefits for type 4 and large type 3 gastric cancer (GC). The prognosis of these patients is still poor. We conducted this study to explore the value of NAC with non-SP regimens for type 4 and large type 3 âGC in the Chinese population. METHODS: We retrospectively collected data from our electronic medical record system. Patients with large type 3 or type 4 âGC who underwent D2 gastrectomy and AC were included. Patients were divided into two groups based on whether they received NAC: the CSC (NAC â+ âsurgery â+ âAC) and SC (surgery â+ âAC) groups. The survival and perioperative outcomes for large type 3 or type 4 âGC were analyzed between the CSC and SC groups, separately. RESULTS: Between May 2009 and December 2018, 189 patients were reviewed. Among large type 3 âGC, the 5-year overall survival (OS) rates for patients in the CSC and SC groups were 54.4 â% and 28.0 â%, respectively (P â= â0.0008). Among type 4 âGC, the 5-year OS rates for patients in the CSC and SC groups were 15.8 â% and 24.8 â%, respectively (P â> â0.05). CONCLUSIONS: This study showed NAC can improve the prognosis of large type 3 âGC. However, NAC did not demonstrate significant survival advantages for type 4 âGC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Terapia Neoadjuvante , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Quimioterapia Adjuvante , Estadiamento de NeoplasiasRESUMO
Background: Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) has shown promising results in gastric cancer (GC) with peritoneal metastasis. However, clinical practice experience of NIPS is still lacking in China. In this study, we investigate the efficacy and safety of NIPS in Chinese patients. Methods: Eligible patients received NIPS every 3 weeks. Gastrectomy was performed for patients who met the criteria of conversion surgery. The primary end point was 1-year overall survival (OS) rate. Secondary end points were the response rate, toxic effects, conversion surgery outcomes and median survival time (MST). Results: Sixty-seven patients were enrolled. The primary endpoint was achieved with 1-year OS rate reached 67.2% (95% CI, 56.8%-79.4%). Conversion surgery was performed in 42 patients (62.9%), and R0 resection was achieved in 23 patients (54.8%) with the MST of 31.3 months (95% CI, 24.3-38.3). And the MST was 19.3 months (95% CI, 16.4-22.2) for all patients. Toxicity and surgical complications were well-tolerated. Moreover, sex, R0 resection, pathological nodal stage and tumor regression grade (TRG) were independent prognostic factors for patients who underwent conversion surgery. Conclusion: The NIPS is effective and safe in treating GC patients with peritoneal metastasis. Male patients, patients who underwent R0 resection, patients with ypN0-1 or TRG 1 after conversion surgery are more likely to benefit from the NIPS. Clinical Trial Registration: http://www.chictr.org.cn/, identifier https://clinicaltrials.gov/ (
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PURPOSE: The cost-effectiveness of different guideline-concordant antimicrobial regimens for elderly patients with community-acquired pneumonia (CAP) was rarely discussed. This study attempts to explore the most appropriate cost-effectiveness of guideline-concordant antimicrobial regimen for elderly patients with CAP in general wards. PATIENTS AND METHODS: This was a multicenter, retrospective, 4:2:1 matched study enrolling 511 elderly patients with CAP hospitalized in general wards. Two hundred ninety-two patients prescribed with ß-lactam monotherapy (group A), 146 patients prescribed with fluoroquinolone monotherapy (group B) and 73 patients prescribed with ß-lactam/macrolide combination therapy (group C). Clinical outcomes and medical costs were analyzed by χ 2 test for categorical variables or Kruskal-Wallis H-test for continuous variables. RESULTS: There were no statistical differences in imaging features, etiology and complications during hospitalization among these three groups. The rates of clinical failure occurrence, in-hospital mortality, 30-day mortality and 60-day mortality also had no significant differences among group A, B and C patients; however, the median length of stay (LOS) in group A patients was 12.0 days, which was significantly higher than that in group B and C patients (both 10.0 days, p<0.02). The median total, drug, and antibiotic costs for one elderly CAP episode in group B patients were RMB 10368.4, RMB 3874.8, and RMB 1796.3, respectively, which were significantly lower than those in group A and C patients (p<0.01). CONCLUSION: Non-inferiority of clinical failure occurrence and short-term mortality was observed in different guideline-concordant antimicrobial regimens for elderly patients with CAP in general wards; however, the median LOS and hospitalization-associated costs for one elderly CAP episode with fluoroquinolone monotherapy were significantly lowest, and this strategy was considered to be the most cost-effective strategy in general wards.
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BACKGROUND: Neoadjuvant chemotherapy (NAC) plays an important role in the therapeutic strategy of locally advanced gastric cancer (LAGC). However, the response of LAGC after NAC varies among different patients. The objective response after NAC has proven to be an excellent indicator for benefiting from NAC, yet effective predictors of objective response are still lacking. The present study aimed to identify potential predictors of objective response in LAGC patients treated with NAC. METHODS: Clinicopathological data from 267 patients with LAGC who received NAC and met the inclusion criteria between July 2009 and December 2018 were retrospectively reviewed. Patients were randomly divided into the training and test sets at a 2:1 ratio. Univariate analysis was used to investigate whether any factors were correlated with objective response in the training set. Multivariate logistic regression analysis was applied to find independent predictors. A risk score model was then constructed based on the independent predictors, and its performance in predicting objective response was validated in the test set. RESULTS: Univariate analysis found that gender, age, short axis diameter of the largest regional lymph node (LNmax), serum total protein content, CEA detection value, tumor location, tumor differentiation, signet ring cell carcinoma component and Borrmann type were potential predictors for objective response. In multivariate logistic regression analysis, gender, LNmax and signet ring cell carcinoma component were independent predictors for objective response. Based on independent predictors, we developed a prediction model for objective response. CONCLUSIONS: We found gender, LNmax and signet ring cell carcinoma component were independent predictors for objective response. The prediction model is a good tool to predict the objective response for LAGC patients treated with NAC, which can be applied to guide clinical practice.
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BACKGROUND: Preoperative chemotherapy (PCT) has been considered an important treatment for advanced gastric cancer (AGC). The tumor regression grade (TRG) system is an effective tool for the assessment of patient responses to PCT. Pathological complete response (TRG = 0) of the primary tumor is an excellent predictor of better prognosis. However, which patients could achieve pathological complete response (TRG = 0) after chemotherapy is still unknown. The study aimed to find predictors of TRG = 0 in AGC. METHODS: A total of 304 patients with advanced gastric cancer from July 2009 to November 2018 were enrolled retrospectively. All patients were randomly assigned (2:1) to training and internal validation groups. In addition, 124 AGC patients receiving PCT from December 2018 to June 2020 were included prospectively in the external validation cohort. A prediction model for TRG = 0 was established based on four predictors in the training group and was validated in the internal and external validation groups. RESULTS: Through univariate and multivariate analyses, we found that CA199, CA724, tumor differentiation and short axis of the largest regional lymph node (LNmax) were independent predictors of TRG = 0. Based on the four predictors, we established a prediction model for TRG = 0. The AUC values of the prediction model in the training, internal and external validation groups were 0.84, 0.73 and 0.82, respectively. CONCLUSIONS: We found that CA199, CA724, tumor differentiation and LNmax were associated with pathological response in advanced gastric cancer. The prediction model could provide guidance for clinical work.
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BACKGROUND: For gastric cancer (GC) with extensive lymph node metastasis (bulky N2 and/or para-aortic lymph node metastases), there is no standard therapy worldwide. In Japan, preoperative chemotherapy (PCT) followed by D2 gastrectomy plus para-aortic lymph node dissection (PAND) is considered the standard treatment for these patients. However, in China, the standard operation for GC patients with only bulky N2 metastases was D2 gastrectomy. Besides, after PCT, whether doing PAND improves survival or not is debatable for GC patients with para-aortic lymph node (PAN) metastases. Therefore, we conducted this study to investigate whether D2 lymphadenectomy alone is suitable for these patients after PCT. METHODS: We retrospectively collected data on patients from our electronic medical record system. GC patients with bulky N2 and/or PAN metastases who underwent D2 lymphadenectomy alone after PCT were enrolled. The survival outcomes and chemotherapy responses were analyzed and compared with the results of the JCOG0405 study. RESULTS: From May 2009 to December 2017, a total of 83 patients met all eligibility criteria and were enrolled. The median survival duration for all patients was 40.0 months. The 3-year and 5-year OS rates for all patients were 50.3% and 45.6%, respectively. For patients with only bulky N2 metastasis, the 3-year and 5-year OS rates were 77.1% and 71.6%, respectively, which were similar to the results of the JCOG0405 study (82.7% and 73.4%). For patients with only PAN metastases, the 3-year and 5-year OS rates were 50.0% and 50.0%, respectively, which seemed to be lower than those of the JCOG0405 study (64.3% and 57.1%). For patients with bulky N2 and PAN metastases, the 3-year and 5-year OS rates were 7.4% and 0.0%, respectively, which were lower than those of the JCOG0405 study (20.0% and 20.0%). CONCLUSION: The results of our study suggest that D2 lymphadenectomy alone is suitable for GC patients with only bulky N2 metastasis after PCT. However, D2 lymphadenectomy alone perhaps is not suitable for patients with bulky N2 and PAN metastases after PCT.
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BACKGROUND: For locally advanced gastric cancer (LAGC) with serosal invasion (cT4NxM0), adjuvant chemotherapy (AC) after D2 gastrectomy is the standard therapy in Asia. However, perioperative chemotherapy (PCT) combined with D2 gastrectomy is mostly suggested in Europe and America. As a part of PCT, the value of neoadjuvant chemotherapy (NAC) is unclear. We investigated whether NAC could further improve survival and other outcomes for these patients. METHODS: Patients with cT4NxM0 gastric cancer who underwent D2 gastrectomy were analyzed. The patients were divided into two groups based on whether they received NAC: the neoadjuvant chemotherapy (NAC) and direct surgery (S) groups. After propensity score matching (1:1 ratio), survival and perioperative outcomes were analyzed between the two groups. RESULTS: A total of 902 patients met all the eligibility criteria and were enrolled. After propensity score matching, 221 matched pairs of patients were identified. The median overall survival (OS) and disease-free survival (DFS) of all patients were 75.10 and 43.67 months, respectively. The median OS of patients in the NAC and S groups were undefined and 29.80 months, respectively (P<0.0001). The median DFS of patients in the NAC and S groups were undefined and 22.60 months (P<0.0001). There were no significant differences in the radical degrees of operation between the two groups (P=0.07). However, there were significant differences in postoperative hospital stay (P<0.001) and complications (P=0.037) between the two groups. CONCLUSION: This study suggested NAC can further improve prognosis and prevent recurrence in LAGC (cT4NxM0) patients. NAC is feasible and safe for LAGC (cT4NxM0) patients, and does not increase the risk of perioperative surgery.