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Purpose@#Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines. @*Materials and Methods@#We constructed subcutaneous syngeneic tumors with murine gastric cancer cell lines, YTN3 and YTN16, in C57BL/6J mice. Mice were intraperitoneally treated with IgG isotype control or an anti–programmed death-ligand 1 (PD-L1) neutralizing antibody. We used immunohistochemistry to evaluate the tumor-infiltrating immune cells of formalin-fixed paraffin-embedded mouse tumor tissues. We compared the protein and RNA expression between YTN3 and YTN16 cell lines using a mouse cytokine array and RNA sequencing. @*Results@#The mouse tumors revealed distinct histological and molecular characteristics. YTN16 cells showed upregulation of genes and proteins related to immunosuppression, such as Ccl2 (CCL2) and Csf1 (M-CSF). Macrophages and exhausted T cells were more enriched in YTN16 tumors than in YTN3 tumors. Several YTN3 tumors were completely regressed by the PD-L1 inhibitor, whereas YTN16 tumors were unaffected. Although treatment with a PD-L1 inhibitor increased infiltration of T cells in both the tumors, the proportion of exhausted immune cells did not decrease in the non-responder group. @*Conclusion@#We confirmed the histological and molecular features of cancer cells with various responses to ICI. Our models can be used in preclinical research on ICI resistance mechanisms to enhance clinical efficacy.
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Purpose@#Bisphenol A (BPA) is a widely used environmental contaminant that is associated with type 2 diabetes mellitus and a shift of gut microbial community. However, little is known about the influence of BPA on gut microbial changes related to bariatric surgery. We investigated whether long-term exposure to dietary BPA causing alterations of gut microbiome occurred after bariatric surgery. @*Methods@#Six-week-old male Wistar rats were fed either a high- fat diet (HFD) or HFD + BPA for 40 weeks. Then sleeve gastrectomy (SG) or Roux-en Y gastric bypass (RYGB) was performed in each diet group and observed for 12 weeks postoperatively. Fecal samples were collected at the 40th weeks and 12th postoperative weeks. Using 16S ribosomal RNA gene sequencing analysis on fecal samples, a comparative metagenomic analysis on gut microbiome composition was performed. @*Results@#Long-term exposure to HFD with BPA showed higher body weight change and higher level of fasting blood sugar after 40 weeks-diet challenge than those of the HFD only group. After bariatric surgeries, mean body weight of the HFD with BPA group was significantly higher than the HFD only group, but there was no difference between the SG and RYGB groups. The metagenomic analyses demonstrated that long-term exposure to dietary BPA did not affect significant alterations of gut microbiome before and after bariatric surgery, compared with the HFD groups. @*Conclusion@#Our results highlighted that BPA was a risk factor for obesity and may contribute to glucose intolerance, but it did not affect alterations of gut microbiome after bariatric/metabolic surgery.
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Purpose@#Minimally invasive gastrectomy is a promising surgical method with well-known benefits, including reduced postoperative complications. However, for total gastrectomy of gastric cancers, this approach does not significantly reduce the risk of complications. Therefore, we aimed to evaluate the incidence and risk factors for the severity of complications associated with minimally invasive total gastrectomy for gastric cancer. @*Materials and Methods@#The study included 392 consecutive patients with gastric cancer who underwent either laparoscopic or robotic total gastrectomy between 2011 and 2019.Clinicopathological and operative characteristics were assessed to determine the features related to postoperative complications after minimally invasive total gastrectomy. Binomial and multinomial logistic regression models were used to identify the risk factors for overall complications and mild and severe complications, respectively. @*Results@#Of 103 (26.3%) patients experiencing complications, 66 (16.8%) and 37 (9.4%) developed mild and severe complications, respectively. On multivariate multinomial regression analysis, independent predictors of severe complications included obesity (OR, 2.56; 95% CI, 1.02−6.43; P=0.046), advanced stage (OR, 2.90; 95% CI, 1.13−7.43; P=0.026), and more intraoperative bleeding (OR, 1.04; 95% CI, 1.02−1.06; P=0.001). Operation time was the only independent risk factor for mild complications (OR, 1.06; 95% CI, 1.001−1.13; P=0.047). @*Conclusions@#The risk factors for mild and severe complications were associated with surgery, indicating surgical difficulty. Surgeons should be aware of these potential risks that are related to the severity of complications so as to reduce surgery-related complications after minimally invasive total gastrectomy for gastric cancer.
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Purpose@#Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity. @*Results@#The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
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Purpose@#Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity. @*Results@#The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
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Laparoscopic surgery is rapidly evolving with technological advances, but there are several drawbacks. An articulating device, with freedom of a perfect 360°, is attractive as a solution to overcome the restriction of instrument movement caused by straight tools. Its usefulness or efficacy should be supported by relevant scientific evidence. However, it is sometimes difficult to prove it because the factors influencing the surgical outcomes are complex and closely related to each other.
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Purpose@#To compare long-term disease-free survival (DFS) between patients receiving tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (CAPOX) adjuvant chemotherapy (AC) for gastric cancer (GC). @*Materials and Methods@#This retrospective multicenter observational study enrolled 983 patients who underwent curative gastrectomy with consecutive AC with S-1 or CAPOX for stage II or III GC at 27 hospitals in Korea between February 2012 and December 2013. We conducted propensity score matching to reduce selection bias. Long-term oncologic outcomes, including DFS rate over 5 years (over-5yr DFS), were analyzed postoperatively. @*Results@#The median and longest follow-up period were 59.0 and 87.6 months, respectively. DFS rate did not differ between patients who received S-1 and CAPOX for pathologic stage II (P=0.677) and stage III (P=0.899) GC. Moreover, hazard ratio (HR) for recurrence did not differ significantly between S-1 and CAPOX (reference) in stage II (HR, 1.846; 95% confidence interval [CI], 0.693–4.919; P=0.220) and stage III (HR, 0.942; 95% CI, 0.664–1.337; P=0.738) GC. After adjustment for significance in multivariate analysis, pT (4 vs. 1) (HR, 11.667; 95% CI, 1.595–85.351; P=0.016), pN stage (0 vs. 3) (HR, 2.788; 95% CI, 1.502–5.174; P=0.001), and completion of planned chemotherapy (HR, 2.213; 95% CI, 1.618–3.028; P<0.001) were determined as independent prognostic factors for DFS. @*Conclusions@#S-1 and CAPOX AC regimens did not show significant difference in over-5yr DFS after curative gastrectomy in patients with stage II or III GC. The pT, pN stage, and completion of planned chemotherapy were prognostic factors for GC recurrence.
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PURPOSE: Although linear-shaped gastroduodenostomy (LSGD) was reported to be a feasible and reliable method of Billroth I anastomosis in patients undergoing totally laparoscopic distal gastrectomy (TLDG), the feasibility of LSGD for patients undergoing totally robotic distal gastrectomy (TRDG) has not been determined. This study compared the feasibility of LSGD in patients undergoing TRDG and TLDG.MATERIALS AND METHODS: ALL C: onsecutive patients who underwent LSGD after distal gastrectomy for gastric cancer between January 2009 and December 2017 were analyzed retrospectively. Propensity score matching (PSM) analysis was performed to reduce the selection bias between TRDG and TLDG. Short-term outcomes, functional outcomes, learning curve, and risk factors for postoperative complications were analyzed.RESULTS: This analysis included 414 patients, of whom 275 underwent laparoscopy and 139 underwent robotic surgery. PSM analysis showed that operation time was significantly longer (163.5 vs. 132.1 minutes, P<0.001) and postoperative hospital stay significantly shorter (6.2 vs. 7.5 days, P<0.003) in patients who underwent TRDG than in patients who underwent TLDG. Operation time was the independent risk factor for LSGD after intracorporeal gastroduodenostomy. Cumulative sum analysis showed no definitive turning point in the TRDG learning curve. Long-term endoscopic findings revealed similar results in the two groups, but bile reflux at 5 years showed significantly better improvement in the TLDG group than in the TRDG group (P=0.016).CONCLUSIONS: LSGD is feasible in TRDG, with short-term and long-term outcomes comparable to that in TLDG. LSGD may be a good option for intracorporeal Billroth I anastomosis in patients undergoing TRDG.
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Humanos , Refluxo Biliar , Gastrectomia , Gastroenterostomia , Laparoscopia , Curva de Aprendizado , Tempo de Internação , Métodos , Complicações Pós-Operatórias , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Robóticos , Viés de Seleção , Neoplasias GástricasRESUMO
PURPOSE: Although standard radical gastrectomy is recommended after noncurative resection of endoscopic submucosal dissection (ESD) for early gastric cancer in most cases, residual tumor and lymph node metastasis have not been identified after surgery. The aim of this study is to evaluate the feasibility of sentinel node navigation surgery after noncurative ESD. MATERIALS AND METHODS: This trial is an investigator-initiated, multicenter prospective phase II trial. Patients who underwent ESD for clinical stage T1N0M0 gastric cancer with noncurative resections were eligible. Qualified investigators who completed the prior phase III trial (SENORITA 1) are exclusively allowed to participate. In this study, 2 detection methods will be used: 1) intraoperative endoscopic submucosal injection of dual tracer, including radioisotope and indocyanine green (ICG) with sentinel basins detected using gamma-probe; 2) endoscopic injection of ICG, with sentinel basins detected using a fluorescence imaging system. Standard laparoscopic gastrectomy with lymphadenectomy will be performed. Sample size is calculated based on the inferior confidence interval of the detection rate of 95%, and the calculated accrual is 237 patients. The primary endpoint is detection rate, and the secondary endpoints are sensitivity and postoperative complications. CONCLUSIONS: This study is expected to clarify the feasibility of laparoscopic sentinel basin dissection after noncurative ESD. If the feasibility is demonstrated, a multicenter phase III trial will be initiated to compare laparoscopic sentinel node navigation surgery versus laparoscopic standard gastrectomy in early gastric cancer after endoscopic resection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03123042
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Humanos , Estudos de Viabilidade , Gastrectomia , Verde de Indocianina , Excisão de Linfonodo , Linfonodos , Metástase Neoplásica , Neoplasia Residual , Imagem Óptica , Complicações Pós-Operatórias , Estudos Prospectivos , Pesquisadores , Tamanho da Amostra , Neoplasias GástricasRESUMO
PURPOSE: This study aims to investigate the actual compliance with chemotherapy and analyze several factors affecting the compliance in patients with gastric cancer. METHODS: From February 2012 to December 2014, we collected data of patients with gastric cancer who received adjuvant chemotherapy (TS-1 monotherapy or XELOX: capecitabine/oxaliplatin) in Korea. RESULTS: We collected data of 1,089 patients from 31 institutions. The completion rate and dose reduction rate by age (≥60 years vs. <60 years) were 57.5% vs. 76.8% (P < 0.001) and 17.9% vs. 21.3% (P = 0.354); by body mass index (BMI) (≥23 kg/m2 vs. <23 kg/m2) were 70.2% vs. 63.2% (P = 0.019) and 19.2% vs. 19.9% (P = 0.987), respectively. The compliance by American Society of Anesthesiologists physical status (ASA PS) classification was as follows: completion rate was 74.4%, 62.8%, and 60% (P = 0.001) and the dose reduction rate was 18.4%, 20.7%, and 17.8% (P = 0.946) in ASA PS classification I, II, and III, respectively. The completion rate of TS-1 and XELOX was 65.9% vs. 70.3% (P = 0.206) and the dose reduction rate was 15.7% vs. 33.6% (P < 0.001). Furthermore, the completion rate of chemotherapy by surgical oncologists and medical oncologists was 69.5% vs. 63.2% (P = 0.028) and the dose reduction rate was 17.4% vs. 22.3% (P = 0.035), respectively. CONCLUSION: The compliance was lower in patients who were older than 60 years, had BMI <23 kg/m2, and had higher ASA PS classification. Furthermore, the patients showed higher compliance when they received chemotherapy from surgical oncologists rather than from medical oncologists.
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Humanos , Índice de Massa Corporal , Quimioterapia Adjuvante , Classificação , Complacência (Medida de Distensibilidade) , Tratamento Farmacológico , Coreia (Geográfico) , Neoplasias GástricasRESUMO
PURPOSE: We investigated complications after laparoscopic sentinel basin dissection (SBD) for patients with gastric cancer who were enrolled in a quality control study, prior to the phase III trial of sentinel lymph node navigation surgery (SNNS). MATERIALS AND METHODS: We analyzed prospective data from a Korean multicenter prerequisite quality control trial of laparoscopic SBD for gastric cancer and assessed procedure-related and surgical complications. All complications were classified according to the Clavien-Dindo Classification (CDC) system and were compared with the results of the previously published SNNS trial. RESULTS: Among the 108 eligible patients who were enrolled in the quality control trial, 8 (7.4%) experienced complications during the early postoperative period. One patient with gastric resection-related duodenal stump leakage recovered after percutaneous drainage (grade IIIa in CDC). The other postoperative complications were mild and patients recovered with supportive care. No complications were directly related to the laparoscopic SBD procedure or tracer usage, and there were no mortalities. The laparoscopic SBD complication rates and patterns that were observed in this study were comparable to those of a previously reported trial. CONCLUSIONS: The results of our prospective, multicenter quality control trial demonstrate that laparoscopic SBD is a safe procedure during SNNS for gastric cancer.
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Humanos , Classificação , Drenagem , Linfonodos , Mortalidade , Complicações Pós-Operatórias , Período Pós-Operatório , Estudos Prospectivos , Controle de Qualidade , Biópsia de Linfonodo Sentinela , Neoplasias GástricasRESUMO
No abstract available.
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No abstract available.
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Since its introduction as an alternative intestinal lengthening technique, the serial transverse enteroplasty (STEP) procedure has been used increasingly as the surgical treatment of choice for children with short bowel syndrome (SBS). On the other hand, there are few report of its efficacy in adults with SBS, particularly those who have previously undergone a gastrectomy. This case report describes a 34-year-old woman with a short bowel after an esophagectomy and total gastrectomy due to lye ingestion followed by an extensive intestinal resection due to small bowel strangulation. The STEP procedure was performed successfully and the small intestine was lengthened from 55 to 75 cm. The patient tolerated the procedure well and was weaned off total parenteral nutrition. The frequency and characteristics of diarrhea improved, and her weight remained acceptable via management with intermittent parenteral nutritional support for 6 months postoperatively. This case suggests that the STEP procedure should be considered for gastrectomized patients with SBS.
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Adulto , Criança , Feminino , Humanos , Diarreia , Ingestão de Alimentos , Esofagectomia , Gastrectomia , Mãos , Intestino Delgado , Lixívia , Apoio Nutricional , Nutrição Parenteral Total , Síndrome do Intestino CurtoRESUMO
PURPOSE: Although Roux-en-Y (R-Y) reconstruction after distal gastrectomy has several advantages, such as prevention of bile reflux into the remnant stomach, it is rarely used because of the technical difficulty. This prospective randomized clinical trial aimed to show the efficacy of a novel method of R-Y reconstruction involving the use of 2 circular staplers by comparing this novel method to Billroth-I (B-I) reconstruction. MATERIALS AND METHODS: A total of 118 patients were randomly allocated into the R-Y (59 patients) and B-I reconstruction (59 patients) groups. R-Y anastomosis was performed using two circular staplers and no hand sewing. The primary end-point of this clinical trial was the reflux of bile into the remnant stomach evaluated using endoscopic and histological findings at 6 months after surgery. RESULTS: No significant differences in clinicopathological findings were observed between the 2 groups. Although anastomosis time was significantly longer for the patients of the R-Y group (P<0.001), no difference was detected between the 2 groups in terms of the total surgery duration (P=0.112). Endoscopic findings showed a significant reduction of bile reflux in the remnant stomach in the R-Y group (P<0.001), and the histological findings showed that reflux gastritis was more significant in the B-I group than in the R-Y group (P=0.026). CONCLUSIONS: The results of this randomized controlled clinical trial showed that compared with B-I reconstruction, R-Y reconstruction using circular staplers is a safe and feasible procedure. This clinical trial study was registered at www.ClinicalTrials.gov (registration No. NCT01142271).
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Humanos , Bile , Refluxo Biliar , Gastrectomia , Coto Gástrico , Gastrite , Mãos , Métodos , Estudos Prospectivos , Neoplasias GástricasRESUMO
No abstract available.
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PURPOSE: Identification of the infrapyloric artery (IPA) type is a key component of pylorus-preserving gastrectomy. As the indocyanine green (ICG) fluorescence technique is known to help visualize blood vessels and flow during reconstruction, we speculated that this emerging technique would be helpful in identifying the IPA type. MATERIALS AND METHODS: From August 2015 to February 2016, 20 patients who underwent robotic or laparoscopic gastrectomy were prospectively enrolled. After intravenous injection of approximately 3 mL of ICG (2.5 mg/mL), a near-infrared fluorescence apparatus was applied. The identified shape of the IPA was confirmed by examining the actual anatomy following infrapyloric dissection. RESULTS: The mean interval time between ICG injection and visualization of the artery was 22.2 seconds (range, 14–30 seconds), and the mean duration of the arterial phase was 16.1 seconds (range, 9–30 seconds). The overall positive predictive value (PPV) of ICG fluorescence in identifying the IPA type was 80% (16/20). The IPA type was incorrectly predicted in four patients, all of whom were obese with a body mass index (BMI) of more than 25 kg/m². CONCLUSIONS: Our preliminary results indicate that intraoperative vascular imaging using the ICG fluorescence technique may be helpful for robotic or laparoscopic pylorus-preserving gastrectomy.
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Humanos , Artérias , Vasos Sanguíneos , Índice de Massa Corporal , Fluorescência , Gastrectomia , Verde de Indocianina , Injeções Intravenosas , Laparoscopia , Estudos Prospectivos , Neoplasias GástricasRESUMO
PURPOSE: It is hypothesized that robotic gastrectomy may surpass laparoscopic gastrectomy after the operators acquire long-term experience and skills in the manipulation of robotic arms. This study aimed to evaluate the long-term learning curve of robotic distal gastrectomy (RDG) for gastric cancer compared with laparoscopic distal gastrectomy (LDG). MATERIALS AND METHODS: From October 2008 to December 2015, patients who underwent LDG (n=809) were matched to patients who underwent RDG (n=232) at a 1:1 ratio, by using a propensity score matching method after stratification for the operative year. The surgical outcomes, such as trends of operative time, blood loss, and complication rate, were compared between the two groups. RESULTS: The RDG group showed a longer operative time (171.3 minutes vs. 147.6 minutes, P<0.001) but less estimated blood loss (77.6 ml vs. 116.6 ml, P<0.001). The complication rate and postoperative recovery did not differ between the two groups. The RDG group showed a longer operative time and similar estimated blood loss compared with the LDG group after 5 years of experience (operative time: 159.2 minutes vs. 136.0 minutes in 2015, P=0.003; estimated blood loss: 72.9 ml vs. 78.1 ml in 2015, P=0.793). CONCLUSIONS: In terms of short-term surgical outcomes, RDG may not surpass LDG after a long-term experience with the technique.
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Humanos , Braço , Gastrectomia , Laparoscopia , Curva de Aprendizado , Métodos , Duração da Cirurgia , Pontuação de Propensão , Robótica , Neoplasias GástricasRESUMO
No abstract available.
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Accurate measurement of body composition between lean and adipose tissue mass and distribution of lipid burden may be important in the care of nutritional problems in patients observed in clinical practice and the measurement of outcomes in clinical research. In this review, we discuss the most accurate imaging methods for use as clinical tools in measurement of body composition and distribution. Dual-energy x-ray absorptiometry (DXA) is a non-invasive technique for assessment of body composition, and the radiation exposure is relatively minimal. However, measurements are influenced by thickness of tissue and lean tissue hydration. Computed tomography (CT) is a gold-standard imaging method for body composition analysis at the tissue-organ level, however the radiation generated by the CT scan is relatively high, thus it should not be considered for a measurement, which can be repeated frequently. Magnetic resonance imaging (MRI) has been a useful modality in the assessment of body composition changes in various clinical studies. However, limitations of MRI for assessment of body composition are related to its high cost and technical expertise necessary for analysis. Proper methods for measurement of body composition in specific medical situations like sarcopenia should be evaluated for determination of comparative validity and accuracy, within the context of cost-effectiveness in patient care. In conclusion, an ideal body imaging method would have a significant utility for earlier detection of nutritional risks, while overcoming the limitations of current imaging studies such as DXA, CT, and MRI.