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BACKGROUND AND AIMS: Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, and tumor microenvironment (TME) features that contribute to peritoneal organotropism in GC. METHODS: We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues, peritoneal metastases, and adjacent-normal peritoneal tissues. We employed whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM. RESULTS: Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3, CDH1, and PIGR, and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared to liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis. CONCLUSION: Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes.
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BACKGROUND: Transhiatal esophagectomy (THE) avoids thoracotomy but sacrifices mediastinal lymphadenectomy. Mediastinoscopy-assisted transhiatal esophagectomy (MATHE) allows for visualisation and en-bloc dissection of mediastinal lymph nodes while retaining the benefits of THE. However, given its novel inception, there is a paucity of literature. This study aimed to conduct the first meta-analysis to explore the efficacy of MATHE and clarify its role in the future of esophagectomy. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to May 1, 2023. Studies were included if they reported outcomes for patients with esophageal cancer who underwent MATHE. Meta-analyses of proportions and pooled means were performed for the outcomes of intraoperative blood loss, lymph node (LN) harvest, mean hospital length of stay (LOS), mean operative time, R0 resection, conversion rates, 30-day mortality rate, 5-year OS, and surgical complications (anastomotic leak, cardiovascular [CVS] and pulmonary complications, chyle leak and recurrent laryngeal nerve palsy [RLN]). Sensitivity analyses were performed for outcomes with substantial statistical heterogeneity. RESULTS: The search yielded 223 articles; 28 studies and 1128 patients were included in our analysis. Meta-analyses of proportions yielded proportion rates: 30-day mortality (0 %, 95 %CI 0-0), 5-year OS (60.5 %, 95 %CI 47.6-72.7), R0 resection (100 %, 95 %CI 99.3-100), conversion rate (0.1 %, 95 %CI 0-1.2). Among surgical complications, RLN palsy (14.6 %, 95 %CI 9.5-20.4) were most observed, followed by pulmonary complications (11.3 %, 95 %CI 7-16.2), anastomotic leak (9.7 %, 95 %CI 6.8-12.8), CVS complications (2.3 %, 95 %CI 0.9-4.1) and chyle leak (0.02 %, 95 %CI 0-0.8). Meta-analysis of pooled means yielded means: LN harvest (18.6, 95 %CI 14.3-22.9), intraoperative blood loss (247.1 ml, 95 %CI 173.6-320.6), hospital LOS (18.1 days, 95 %CI 14.4-21.8), and operative time (301.5 min, 95 %CI 238.4-364.6). There was moderate-to-high statistical heterogeneity. Findings were robust to sensitivity analyses. CONCLUSION: MATHE is associated with encouraging post-operative mortality and complication rates, while allowing for radical mediastinal lymphadenectomy with reasonable lymph node harvest.
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Neoplasias Esofágicas , Esofagectomia , Mediastinoscopia , Humanos , Esofagectomia/métodos , Esofagectomia/mortalidade , Mediastinoscopia/métodos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Prognóstico , Excisão de Linfonodo/métodos , Complicações Pós-Operatórias/epidemiologiaRESUMO
BACKGROUND: Anastomotic leak (AL) in upper gastrointestinal (UGI) surgery continues to be a diagnostic challenge. We seek to identify clinical parameters that predict AL and examine the effectiveness of investigations in evaluating AL following UGI surgeries. METHODS: 592 patients underwent UGI surgeries with an anastomosis between January 2011 and January 2021. Data on patient characteristics, surgery, postoperative investigations and outcomes were prospectively collected and analysed. RESULTS: The overall occurrence of AL was 6.4 %. Tachycardia >120 BPM (OR 6.959, 95 % CI 1.856-26.100, p = 0.004) and leukocyte count >19 × 109/L (OR 3.327, 95 % CI 1.009-10.967, p = 0.048) were independent predictors of AL. On multivariate analysis, patients whose anastomosis was deemed high risk and had pre-emptive investigation done postoperatively to exclude a leak were less likely to require intervention and were more likely to be managed conservatively (66.7 % vs 14.3 %, p = 0.025). Methylene blue test, oral contrast study and Computed Tomography scan with intravenous and oral contrast had 50.0 %, 20.0 % and 9.1 % false negative results, while esophagogastroduodenoscopy had none. There was no misdiagnosed AL when more than 1 investigation (n = 15, 39.5 %) were performed. CONCLUSION: Our study demonstrates that the presence of a triad including desaturation, tachycardia and leucocytosis predicts for AL following UGI surgery and for confirmation of a leak, evaluation with 2 or more investigation is needed. A practice of evaluating high risk anastomosis prior to commencement of feeding decreased the need for surgical intervention and improves success of conservative treatment.
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Fístula Anastomótica , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Estudos Retrospectivos , Anastomose Cirúrgica/efeitos adversos , Taquicardia/diagnóstico , Taquicardia/epidemiologia , Taquicardia/etiologiaRESUMO
Surgical resection is the mainstay treatment for resectable gastrointestinal stromal tumors (GISTs). However, resection in anatomically challenging locations, such as near the gastroesophageal junction, lesser curve and fundus, remain technically challenging. We herein report the outcomes of the largest series of patients who underwent single-incision transgastric resection of an intraluminal gastric GIST. Our reduced-port resection technique for intraluminal GISTs in these anatomically challenging locations involves a single incision in the left hypochondrium, deepened to access the gastric lumen, with the surgery completed in a transgastric manner. A total of 22 patients received surgery with this technique at the National University Hospital in Singapore from November 2012 to September 2020. The median operative time was 101 (range 50-253) min, with no conversions to open surgery, median lesion size 3.6 (range 1.8-8.2) cm and median postoperative length of stay 5 (range 1-13) days. There was no 30-day mortality and no recurrence during the follow-up period. Our laparoscopic approach for reduced-port transgastric excision of intraluminal GISTs allows for adequate surgical clearance, convenient extraction and secure gastrostomy closure with low morbidity.
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Tumores do Estroma Gastrointestinal , Laparoscopia , Neoplasias Gástricas , Ferida Cirúrgica , Humanos , Resultado do Tratamento , Laparoscopia/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Computer-aided diagnosis (CADx) of polyp histology could support endoscopists in clinical decision-making. However, this has not been validated in a real-world setting. METHODS: We performed a prospective, multicenter study comparing CADx and endoscopist predictions of polyp histology in real-time colonoscopy. Optical diagnosis based on visual inspection of polyps was made by experienced endoscopists. After this, the automated output from the CADx support tool was recorded. All imaged polyps were resected for histological assessment. Primary outcome was difference in diagnostic performance between CADx and endoscopist prediction of polyp histology. Subgroup analysis was performed for polyp size, bowel preparation, difficulty of location of the polyps, and endoscopist experience. RESULTS: A total of 661 eligible polyps were resected in 320 patients aged ≥40 years between March 2021 and July 2022. CADx had an overall accuracy of 71.6% (95% confidence interval [CI] 68.0-75.0), compared with 75.2% (95% CI 71.7-78.4) for endoscopists ( P = 0.023). The sensitivity of CADx for neoplastic polyps was 61.8% (95% CI 56.9-66.5), compared with 70.3% (95% CI 65.7-74.7) for endoscopists ( P < 0.001). The interobserver agreement between CADx and endoscopist predictions of polyp histology was moderate (83.1% agreement, κ 0.661). When there was concordance between CADx and endoscopist predictions, the accuracy increased to 78.1%. DISCUSSION: The overall diagnostic accuracy and sensitivity for neoplastic polyps was higher in experienced endoscopists compared with CADx predictions, with moderate interobserver agreement. Concordance in predictions increased this diagnostic accuracy. Further research is required to improve the performance of CADx and to establish its role in clinical practice.
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Pólipos do Colo , Neoplasias Colorretais , Humanos , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Estudos Prospectivos , Valor Preditivo dos Testes , Colonoscopia/métodos , Computadores , Neoplasias Colorretais/patologia , Imagem de Banda Estreita/métodosRESUMO
BACKGROUND: Colorectal cancer (CRC) screening using the faecal immunochemical test (FIT) kits based on the detection of occult blood in stool is widely advocated in numerous screening programs worldwide. However, CRC is not commonly diagnosed in positive cases. We undertook this review to determine if there is evidence to suggest the use of opportunistic oesophago-gastro-duodenoscopy (OGD) in patients without CRC. METHODS: A systematic review encompassing three electronic databases was performed. All peer-reviewed studies of FIT-positive patients who underwent either OGD and colonoscopy concurrently or OGD post-colonoscopy were included. Only studies from 2008 to 2022 using FIT kits were included to ensure studies not previously included in an earlier review were being analysed. A forward citation search of the included articles was also conducted to ensure no relevant articles were missed. RESULTS: A total of 2409 records were extracted. Only four studies fulfilled the selection criteria and were included. Although the rates of abnormal OGD results were relatively high in the four studies, only 3 of 605 (0.50%) patients had gastric cancer in the entire review sample. No other malignancies were identified in all four studies. Other notable pathologies such as gastric polyps and gastritis were also reported. CONCLUSIONS: There is little overall evidence to recommend UGI screening for all FIT-positive patients following a colonoscopy. However, there may be a role for clinicians to consider opportunistic OGD in this group of patients. Future research should examine patient populations from other sociocultural contexts including cost-effective analysis when considering changes in health guidelines on UGI screening.
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Neoplasias Colorretais , Gastroscopia , Humanos , Sangue Oculto , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Programas de Rastreamento/métodos , Detecção Precoce de Câncer/métodos , FezesRESUMO
Smartphone weight loss apps are constantly being developed but the essential elements needed by a multi-ethnic population with overweight and obesity remains unclear. Purpose: To explore the perceptions of an Asian multi-ethnic population with overweight and obesity on the essential elements of weight loss apps. Twenty two participants were purposively sampled from a specialist weight management clinic in Singapore from 13 April to 30 April 2021. Recorded interviews were conducted using face-to-face and videoconferencing modalities. Data saturation was reached at the 18th participant. Data analysis was performed using inductive content analysis with constant comparison between and within transcripts. Findings: Three themes and eight subthemes on the essential app components emerged-(a) comprehensive and flexible calorie counters; (b) holistic, gradual and individualized behavior change recommendations tailored for people with overweight and obesity, and (c) just-in-time reminders of future consequences. There was a need to incorporate flexible options for food logging; break down general recommendations into small steps towards sustainable changes; tailor app contents for people with overweight and obesity; and evoke one's considerations of future consequences. Future weight loss apps should be designed to meet the needs of those with overweight and obesity, the very population that needs assistance with weight loss. Future apps could consider leveraging the capacity of artificial intelligence to provide personalized weight management in terms of sustaining self-regulation behaviors, optimizing goal-setting and providing personalized and timely recommendations for weight loss.
Weight loss smartphone apps are ubiquitous but the essential elements needed and preferred by people with overweight and obesity remains unclear. Therefore, we conducted a qualitative study to explore the perceptions and needs of this population in a weight loss app to prolong app engagement and enhance weight loss success. 22 participants were interviewed through face-to-face or videoconferencing sessions during the peak of the COVID-19 pandemic. Interview transcripts were analyzed within and between participants to develop codes, subthemes and themes that represent the participants' perceptions and needs in weight loss apps. Participants expressed the need for (a) comprehensive and flexible calorie counters; (b) holistic, gradual, and individualized behavior change recommendations tailored for people with overweight and obesity; and (c) just-in-time reminders of future consequences. Our findings showed a need to incorporate flexible options for food logging; break down general recommendations into small steps towards sustainable changes; tailor app contents for people with overweight and obesity; and evoke one's considerations of future consequences. Future apps could consider leveraging the capacity of artificial intelligence to provide personalized weight management in terms of sustaining self-regulation behaviors, optimizing goal-setting and providing personalized and timely recommendations for weight loss.
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Aplicativos Móveis , Sobrepeso , Humanos , Sobrepeso/terapia , Índice de Massa Corporal , Inteligência Artificial , Obesidade/terapia , Redução de PesoAssuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Capecitabina , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Oxaliplatina/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêuticoRESUMO
This Delphi exercise aimed to gather consensus surrounding risk factors, diagnosis, and management of chyle leaks after esophagectomy and to develop recommendations for clinical practice. Background: Chyle leaks following esophagectomy for malignancy are uncommon. Although they are associated with increased morbidity and mortality, diagnosis and management of these patients remain controversial and a challenge globally. Methods: This was a modified Delphi exercise was delivered to clinicians across the oesophagogastric anastomosis collaborative. A 5-staged iterative process was used to gather consensus on clinical practice, including a scoping systematic review (stage 1), 2 rounds of anonymous electronic voting (stages 2 and 3), data-based analysis (stage 4), and guideline and consensus development (stage 5). Stratified analyses were performed by surgeon specialty and surgeon volume. Results: In stage 1, the steering committee proposed areas of uncertainty across 5 domains: risk factors, intraoperative techniques, and postoperative management (ie, diagnosis, severity, and treatment). In stages 2 and 3, 275 and 250 respondents respectively participated in online voting. Consensus was achieved on intraoperative thoracic duct ligation, postoperative diagnosis by milky chest drain output and biochemical testing with triglycerides and chylomicrons, assessing severity with volume of chest drain over 24 hours and a step-up approach in the management of chyle leaks. Stratified analyses demonstrated consistent results. In stage 4, data from the Oesophagogastric Anastomosis Audit demonstrated that chyle leaks occurred in 5.4% (122/2247). Increasing chyle leak grades were associated with higher rates of pulmonary complications, return to theater, prolonged length of stay, and 90-day mortality. In stage 5, 41 surgeons developed a set of recommendations in the intraoperative techniques, diagnosis, and management of chyle leaks. Conclusions: Several areas of consensus were reached surrounding diagnosis and management of chyle leaks following esophagectomy for malignancy. Guidance in clinical practice through adaptation of recommendations from this consensus may help in the prevention of, timely diagnosis, and management of chyle leaks.
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BACKGROUND: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM. METHODS: Forty-four patients with GCPM received IP PTX (40 mg/m2, Days 1, 8), oral capecitabine (1000 mg/m2 twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m2, Day 1) in 21-day cycles. Patients with synchronous GCPM underwent conversion surgery if they had good response after chemotherapy, conversion to negative cytology, no extraperitoneal metastasis, and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were compared against a matched cohort of 39 GCPM patients who received systemic chemotherapy (SC) comprising platinum/fluoropyrimidine. RESULTS: The median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p < 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%. CONCLUSIONS: IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.
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Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Capecitabina , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/patologia , Paclitaxel , Neoplasias Peritoneais/secundário , Platina/uso terapêutico , Fluoruracila , Desoxicitidina , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
OBJECTIVE: To explore motivations, self-regulation barriers and strategies in a multi-ethnic Southeast Asian population with overweight and obesity. DESIGN: Qualitative design using semi-structured face-to-face and videoconferencing interviews. Data were analysed using thematic framework analysis and constant comparison method. SETTING: Specialist weight management clinic. PARTICIPANTS: Twenty-two participants were purposively sampled from 13 April to 30 April 2021. Median age and BMI of the participants were 37·5 (interquartile range (IQR) = 13·3) and 39·2 kg/m2 (IQR = 6·1), respectively. And 31·8 % were men, majority had a high intention to adopt healthy eating behaviours (median = 6·5; IQR = 4·8-6·3) and 59 % of the participants had a medium level of self-regulation. RESULTS: Six themes and fifteen subthemes were derived. Participants were motivated to lose weight by the sense of responsibility as the family's pillar of support and to feel 'normal' again. We coupled self-regulation barriers with corresponding strategies to come up with four broad themes: habitual overconsumption - mindful self-discipline; proximity and convenience of food available - mental tenacity; momentary lack of motivation and sense of control - motivational boosters; and overeating triggers - removing triggers. We highlighted six unique overeating triggers namely: trigger activities (e.g. using social media); eating with family, friends and colleagues; provision of food by someone; emotions (e.g. feeling bored at home, sad and stressed); physiological condition (e.g. premenstrual syndrome); and the time of the day. CONCLUSIONS: Future weight management interventions should consider encompassing participant-led weight loss planning, motivation boosters and self-regulation skills to cope with momentary overeating triggers.
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Sobrepeso , Autocontrole , Feminino , Humanos , Hiperfagia , Masculino , Motivação , Obesidade , Sobrepeso/terapia , Pesquisa Qualitativa , Redução de PesoRESUMO
Gastric cancer heterogeneity represents a barrier to disease management. We generated a comprehensive single-cell atlas of gastric cancer (>200,000 cells) comprising 48 samples from 31 patients across clinical stages and histologic subtypes. We identified 34 distinct cell-lineage states including novel rare cell populations. Many lineage states exhibited distinct cancer-associated expression profiles, individually contributing to a combined tumor-wide molecular collage. We observed increased plasma cell proportions in diffuse-type tumors associated with epithelial-resident KLF2 and stage-wise accrual of cancer-associated fibroblast subpopulations marked by high INHBA and FAP coexpression. Single-cell comparisons between patient-derived organoids (PDO) and primary tumors highlighted inter- and intralineage similarities and differences, demarcating molecular boundaries of PDOs as experimental models. We complemented these findings by spatial transcriptomics, orthogonal validation in independent bulk RNA-sequencing cohorts, and functional demonstration using in vitro and in vivo models. Our results provide a high-resolution molecular resource of intra- and interpatient lineage states across distinct gastric cancer subtypes. SIGNIFICANCE: We profiled gastric malignancies at single-cell resolution and identified increased plasma cell proportions as a novel feature of diffuse-type tumors. We also uncovered distinct cancer-associated fibroblast subtypes with INHBA-FAP-high cell populations as predictors of poor clinical prognosis. Our findings highlight potential origins of deregulated cell states in the gastric tumor ecosystem. This article is highlighted in the In This Issue feature, p. 587.
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Fibroblastos Associados a Câncer , Neoplasias Gástricas , Fibroblastos Associados a Câncer/patologia , Ecossistema , Humanos , Análise de Célula Única , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Transcriptoma , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Peroral endoscopic myotomy (POEM) is gaining traction as a minimally invasive treatment of achalasia. Increased reflux is reported after POEM but the incidence, type and severity of reflux are not fully understood. We aimed to study the prevalence and nature of reflux after POEM and correlate reflux with endoscopy and pH-impedance findings. METHODS: This is a prospective cohort study of achalasia patients undergoing POEM since 2014. Data from Eckardt and GERD symptom scores, high-resolution oesophageal manometry (HRM) and gastroscopy were performed pre-procedure and repeated at 1-year follow-up. Data from 24-h pH-impedance, if performed, were also recorded. A standardized questionnaire was used to determine the severity and frequency of heartburn symptoms and the composite score for each patient was calculated. RESULTS: 58 patients underwent POEM between January 2014 and October 2018. The efficacy of POEM at 1 year was 93.0%. We observed reduction of median Integrated Relaxation Pressure (IRP) from 23.5 ± 33.1 mmHg to 13.4 ± 7.71 mmHg (p = 0.005) and mean Eckardt score improved from 6.09 ± 2.43 points to 1.16 ± 1.70 points (p < 0.001). At 1 year, 43.1% (n = 25) had symptomatic reflux. Of the 40 patients who underwent repeated gastroscopy, 60.0% (n = 24) had endoscopic evidence of oesophagitis with seven patients (18%) diagnosed with Grade C or D oesophagitis. 43.1% (n = 25) of patients had pH-impedance done post-POEM off PPIs. 14 patients (56%) had increased acid exposure. Sixteen percent of reflux episodes were acidic and 77.3% were weakly acidic. CONCLUSION: POEM was an effective treatment for achalasia. However, GERD was common after POEM with incidence of 43% on symptom score, 60% on endoscopy and 56% on pH-impedance test. Post-POEM reflux appeared to be predominantly acidic in nature. Routine surveillance for GERD after POEM is recommended.
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Acalasia Esofágica , Esofagite Péptica , Refluxo Gastroesofágico , Miotomia , Cirurgia Endoscópica por Orifício Natural , Acalasia Esofágica/diagnóstico , Esfíncter Esofágico Inferior/cirurgia , Esofagite Péptica/etiologia , Esofagoscopia/efeitos adversos , Esofagoscopia/métodos , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/cirurgia , Humanos , Miotomia/efeitos adversos , Miotomia/métodos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/métodos , Estudos Prospectivos , Resultado do TratamentoAssuntos
Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Eletrocirurgia/métodos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Laparoscopia/métodos , Vírus da Hepatite Murina/fisiologia , Fumaça , Animais , Eletrocirurgia/efeitos adversos , Eletrocirurgia/instrumentação , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/instrumentação , Camundongos , Viabilidade Microbiana , Vírus da Hepatite Murina/isolamento & purificação , Fumaça/efeitos adversos , Fumaça/análise , Fumaça/prevenção & controleRESUMO
BACKGROUND & AIMS: Metaplasia and dysplasia in the corpus are reportedly derived from de-differentiation of chief cells. However, the cellular origin of metaplasia and cancer remained uncertain. Therefore, we investigated whether pepsinogen C (PGC) transcript-expressing cells represent the cellular origin of metaplasia and cancer using a novel Pgc-specific CreERT2 recombinase mouse model. METHODS: We generated a Pgc-mCherry-IRES-CreERT2 (Pgc-CreERT2) knock-in mouse model. Pgc-CreERT2/+ and Rosa-EYFP mice were crossed to generate Pgc-CreERT2/Rosa-EYFP (Pgc-CreERT2/YFP) mice. Gastric tissues were collected, followed by lineage-tracing experiments and histologic and immunofluorescence staining. We further established Pgc-CreERT2;KrasG12D/+ mice and investigated whether PGC transcript-expressing cells are responsible for the precancerous state in gastric glands. To investigate cancer development from PGC transcript-expressing cells with activated Kras, inactivated Apc, and Trp53 signaling pathways, we crossed Pgc-CreERT2/+ mice with conditional KrasG12D, Apcflox, Trp53flox mice. RESULTS: Expectedly, mCherry mainly labeled chief cells in the Pgc-CreERT2 mice. However, mCherry was also detected throughout the neck cell and isthmal stem/progenitor regions, albeit at lower levels. In the Pgc-CreERT2;KrasG12D/+ mice, PGC transcript-expressing cells with KrasG12D/+ mutation presented pseudopyloric metaplasia. The early induction of proliferation at the isthmus may reflect the ability of isthmal progenitors to react rapidly to Pgc-driven KrasG12D/+ oncogenic mutation. Furthermore, Pgc-CreERT2;KrasG12D/+;Apcflox/flox mice presented intramucosal dysplasia/carcinoma and Pgc-CreERT2;KrasG12D/+;Apcflox/flox;Trp53flox/flox mice presented invasive and metastatic gastric carcinoma. CONCLUSIONS: The Pgc-CreERT2 knock-in mouse is an invaluable tool to study the effects of successive oncogenic activation in the mouse corpus. Time-course observations can be made regarding the responses of isthmal and chief cells to oncogenic insults. We can observe stomach-specific tumorigenesis from the beginning to metastatic development.
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Proliferação de Células , Transformação Celular Neoplásica/genética , Celulas Principais Gástricas/enzimologia , Integrases/genética , Pepsinogênio C/genética , Lesões Pré-Cancerosas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Gástricas/genética , Ativação Transcricional , Animais , Desdiferenciação Celular , Linhagem da Célula , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Celulas Principais Gástricas/patologia , Regulação Neoplásica da Expressão Gênica , Genes APC , Predisposição Genética para Doença , Integrases/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Metaplasia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Pepsinogênio C/metabolismo , Fenótipo , Lesões Pré-Cancerosas/enzimologia , Lesões Pré-Cancerosas/patologia , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Vermelha FluorescenteRESUMO
OBJECTIVE: Laparoscopic appendectomy is a common operation that is frequently performed by junior surgical residents. We investigated the effect of a structured training program on the proficiency of junior residents in acquiring skills necessary in this operation. DESIGN AND PARTICIPANTS: This is a randomized pilot trial. Between December 2014 and July 2018, twenty junior residents were recruited for this study. 11 were randomized to receive a structured training program of supervised, task-specific training. Each resident subsequently performed ten cases of laparoscopic appendectomy with their performance assessed for the last 5. The GOALS scale was used as the primary endpoint. Secondary endpoints were perioperative outcomes. The effect of intervention on these outcomes were evaluated assuming a linear mixed effect multi-level model. The study was single-blinded as the assessors did not know which group each resident belonged to. RESULTS: There were no statistically significant differences in the total GOALS score or any of its individual domains. After adjusting for the number of operations done within the trial, the mean difference between the total GOALS score was 0.07 (95% CI -0.76 to 0.90, P=0.866). Blood loss, hospital stay and postoperative complication rates were similar. There was suggestion of a shorter operative time (effect estimate -9.03, 95% CI -19.56 to 1.50) in the intervention arm although statistical significance was not achieved. No avoidable adverse events due to this study were recorded. CONCLUSION: Structured training program did not significantly improve surgical performance and outcomes in laparoscopic appendectomy in this pilot trial. Despite these findings, residents can still potentially mount their learning curves in laparoscopy earlier in a safe environment with such a program which is especially important in the era of minimally invasive surgery.
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Internato e Residência , Laparoscopia , Apendicectomia/efeitos adversos , Competência Clínica , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/educação , Projetos PilotoRESUMO
BACKGROUND: Bleeding of the gastrointestinal tract (BGIT) is a common gastrointestinal emergency. There is no consensus whether this condition should be admitted to medical or surgical discipline. Timing of presentation may also impact patient outcomes due to differences in healthcare resource availability. This study thus aims to investigate the impact of admitting discipline and timing of admission on patient outcomes in BGIT. METHODS: A 2-year tertiary institution database was retrospectively reviewed. Outcome measures included 30-day mortality, 30-day readmissions and rebleeding requiring repeat endoscopic, angiographic or surgical interventions. Secondary outcome measures included time to endoscopy, percutaneous angiographic interventions and surgery. The effect of admission discipline (medical versus surgical) and time of admission (office-hours versus after office-hours) were analysed using a propensity-score-adjusted estimate. RESULTS: A total of 1384 patients were included for analysis, medical (n = 853), surgical (n = 530); during office-hours (n = 785) and after office-hours (n = 595). After propensity-score-adjusted analysis, no significant differences in mortality or readmissions were noted between medical or surgical admissions. Patients admitted under surgery were less likely to sustain rebleeding (P = 0.004) for lower BGIT and had an earlier time to endoscopy for upper BGIT (P = 0.04). Patients admitted after office-hours had similar outcomes with those admitted during office hours apart from a delay in time to endoscopy (P = 0.02). CONCLUSION: For BGIT patients, admission to a surgical discipline compared to a medical discipline appeared to have at least equivalent patient outcomes. Patients presenting with BGIT after office-hours were more likely to experience a delay to endoscopy, although it did not affect patient mortality.
Assuntos
Hemorragia Gastrointestinal , Hospitalização , Emergências , Endoscopia , Endoscopia Gastrointestinal , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Metabolic-bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy-especially stratified by pre-existing diabetes status-are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic-bariatric surgery versus usual care. METHODS: We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic-bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic-bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472. FINDINGS: Among 1470 articles identified, 16 matched cohort studies and one prospective controlled trial were included in the analysis. 7712 deaths occurred during 1·2 million patient-years. In the overall population consisting 174 772 participants, metabolic-bariatric surgery was associated with a reduction in hazard rate of death of 49·2% (95% CI 46·3-51·9, p<0·0001) and median life expectancy was 6·1 years (95% CI 5·2-6·9) longer than usual care. In subgroup analyses, both individuals with (hazard ratio 0·409, 95% CI 0·370-0·453, p<0·0001) or without (0·704, 0·588-0·843, p<0·0001) baseline diabetes who underwent metabolic-bariatric surgery had lower rates of all-cause mortality, but the treatment effect was considerably greater for those with diabetes (between-subgroup I2 95·7%, p<0·0001). Median life expectancy was 9·3 years (95% CI 7·1-11·8) longer for patients with diabetes in the surgery group than the non-surgical group, whereas the life expectancy gain was 5·1 years (2·0-9·3) for patients without diabetes. The numbers needed to treat to prevent one additional death over a 10-year time frame were 8·4 (95% CI 7·8-9·1) for adults with diabetes and 29·8 (21·2-56·8) for those without diabetes. Treatment effects did not appear to differ between gastric bypass, banding, and sleeve gastrectomy (I2 3·4%, p=0·36). By leveraging the results of this meta-analysis and other published data, we estimated that every 1·0% increase in metabolic-bariatric surgery utilisation rates among the global pool of metabolic-bariatric candidates with and without diabetes could yield 5·1 million and 6·6 million potential life-years, respectively. INTERPRETATION: Among adults with obesity, metabolic-bariatric surgery is associated with substantially lower all-cause mortality rates and longer life expectancy than usual obesity management. Survival benefits are much more pronounced for people with pre-existing diabetes than those without. FUNDING: None.