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OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.
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Cordoma , Sacro , Neoplasias de la Columna Vertebral , Humanos , Cordoma/cirugía , Cordoma/diagnóstico por imagen , Cordoma/patología , Sacro/cirugía , Sacro/diagnóstico por imagen , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/patología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Adulto , Procedimientos de Cirugía Plástica/métodosRESUMEN
BACKGROUND: Malignant melanoma in-situ, lentigo maligna (MMIS-LM) can be successfully treated with several different surgical techniques; however, the literature is inconsistent in defining them. OBJECTIVE: To comprehensively define and describe the national guideline recommended surgical techniques used to treat MMIS-LM to help clarify and standardize this terminology to ensure compliance with the guidelines. METHODS: A targeted literature review was performed from 1990 to 2022 focusing on articles that discussed the national guideline recommended surgical techniques of wide local excision, Mohs micrographic surgery (MMS), modified Mohs surgery, and staged excision/Slow-Mohs for MMIS-LM, as well as the related methods of tissue processing. National Comprehensive Cancer Network and American Academy of Dermatology guidelines were reviewed to identify how the techniques need to be employed to be compliant with guideline recommendations. RESULTS: We describe the various surgical and tissue processing techniques and discuss advantages and disadvantages of each. LIMITATIONS: This paper was styled as a narrative review defining and clarifying terminology and technique and does not investigate these topics more broadly. CONCLUSION: Understanding the methodology and terminology for these surgical procedures and tissue processing methods is critical so that both general dermatologists and surgeons can employ these techniques effectively for optimal patient care.
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Peca Melanótica de Hutchinson , Melanoma , Neoplasias Cutáneas , Humanos , Peca Melanótica de Hutchinson/patología , Adhesión a Directriz , Melanoma/patología , Neoplasias Cutáneas/patología , Cirugía de Mohs/métodos , Melanoma Cutáneo MalignoRESUMEN
Proper patient selection for palliative surgery requires a challenging and often complex decision-making process. Optimally, proposed palliative procedures must be undertaken with an intent to provide the greatest possible value to patients at the end of life. This review describes the process of patient selection and identifies psychosocial, biochemical, and functional markers that can complement sound surgical judgment.
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Costo de Enfermedad , Cuidados Paliativos/normas , Selección de Paciente , Análisis Costo-Beneficio , Toma de Decisiones , Humanos , Calidad de Vida , Valores SocialesRESUMEN
AIMS: The immune microenvironment is a prognostic factor for various malignancies. The significance of key players of this immune microenvironment, including tumour-infiltrating lymphocytes (TILs) and expression of programmed death-ligand 1 (PD-L1), indoleamine 2,3-dioxygenase (IDO) and tryptophanyl-tRNA synthetase (WARS) in gastrointestinal stromal tumours (GISTs) is largely unknown. METHODS AND RESULTS: Tissue microarrays were constructed from pathology files, 1996-2016. Immunohistochemistry for PD-L1, IDO and WARS was correlated with tumour size, mitoses and outcomes. TILs expressing CD3, CD4, CD8, FoxP3 and GBP5 were counted. A total of 129 GISTs were analysed. Mean patient age was 62.5 years; 52.0% were male. Tumour location included 89 stomach (69.0%), 33 small bowel (25.6%) and seven other (5.4%). Mean tumour size was 5.6 cm; mean mitoses were 7.2 per 50 high-power field. Nineteen patients (15.0%) developed disease progression, to abdominal wall (n = 8), liver (n = 6) and elsewhere (n = 5). Median progression-free survival was 56.6 months; five patients died of disease. PD-L1 was positive in 88 of 127 tumour samples (69.0%), 114 of 127 tumours were IDO-positive (89.8%) and 60 of 127 were positive for WARS (47.2%). PD-L1 was associated with increased size (P = 0.01), necrosis (P = 0.018) and mitoses (P = 0.006). Disease progression was not associated with PD-L1 (P = 0.44), IDO (P = 0.14) or WARS (P = 0.36) expression. PD-L1-positive GISTs with CD8+ or CD3+ TILs were significantly smaller than tumours with CD8+ or CD3+ TILs. CONCLUSIONS: PD-L1 expression was associated with increased size and mitoses. High CD8+ or CD3+ TIL counts were associated with decreased PD-L1/IDO+ GIST size. PD-L1 and IDO could be significant in GIST tumour biology, which invites consideration of immunotherapy as a potential treatment option.
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Biomarcadores de Tumor/inmunología , Neoplasias Gastrointestinales/inmunología , Tumores del Estroma Gastrointestinal/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Microambiente Tumoral/inmunología , Adulto , Anciano , Antígeno B7-H1/análisis , Antígeno B7-H1/biosíntesis , Femenino , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/patología , Humanos , Interpretación de Imagen Asistida por Computador , Indolamina-Pirrol 2,3,-Dioxigenasa/análisis , Indolamina-Pirrol 2,3,-Dioxigenasa/biosíntesis , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Triptófano-ARNt Ligasa/análisis , Triptófano-ARNt Ligasa/biosíntesisRESUMEN
AIMS: The tumour microenvironment is increasingly important in several tumours. We studied the relationship of key players of immune microenvironment with clinicopathological parameters in gastric adenocarcinomas. METHODS AND RESULTS: Tissue microarrays were constructed from gastrectomy specimens, 2004-13. Immunohistochemistry was performed for programmed cell death ligand 1 (PD-L1), indoleamine 2,3-dioxygenase (IDO), tryptophanyl-tRNA synthetase (WARS), guanylate-binding protein 5 (GBP5), tumour-infiltrating lymphocytes (TIL) expressing CD3/CD8/FoxP3/PD1 and mismatch repair proteins (MMRs) MLH1, PMS2, MSH2 and MSH6. Clinicopathological parameters and clinical follow-up were recorded. The study included 86 patients; median follow-up was 34 months (0-148). Tumour types were 45% tubular, 38% diffuse, 17% mixed. PD-L1 was positive in 70%, epithelial IDO in 58%, stromal IDO in 91%, epithelial WARS in 67%, stromal WARS in 100%, epithelial GBP5 in 53% and stromal GBP5 in 71%. MMR-deficiency was found in 22%. There was no difference in biomarker expression by histological subtype, with the exception of fewer diffuse-type being MMR-deficient. Low stromal IDO was associated with decreased progression-free, overall and disease-specific survival. PD-L1-positive tumours were larger with MMR-deficiency and with increasing TILs, and had significantly higher FoxP3TILs. CONCLUSIONS: PD-L1 is expressed in a large proportion of gastric carcinomas, suggesting that therapy targeting this pathway could be relevant to many patients. PD-L1 expression and MMR-deficiency are associated with increased TILs and larger tumour size, emphasising their role in tumour biology. Higher stromal IDO expression is associated with better prognosis. Finally, we observed that immune modulators WARS and GBP5 are expressed highly in gastric adenocarcinomas, suggesting an important role in tumour pathobiology.
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Adenocarcinoma/inmunología , Antígeno B7-H1/biosíntesis , Indolamina-Pirrol 2,3,-Dioxigenasa/biosíntesis , Neoplasias Gástricas/inmunología , Microambiente Tumoral/inmunología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/inmunología , Biomarcadores de Tumor , Supervivencia sin Enfermedad , Femenino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/inmunología , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVE: Defining processes of care, which are appropriate and necessary for management of gastric cancer (GC), is an important step toward improving outcomes. METHODS: Using a RAND/UCLA Appropriateness Method, an international multidisciplinary expert panel created 22 statements reflecting optimal management. All statements were scored for appropriateness and necessity. RESULTS: The following tenets were scored appropriate and necessary: (1) preoperative staging by computed tomography of abdomen/pelvis; (2) positron-emission tomographic scans not routinely indicated; (3) consideration for adjuvant therapy; (4) further clinical trials; (5) multidisciplinary decision making; (6) sufficient support at hospitals; (7) assessment of 16 or more lymph nodes (LNs); (8) in metastatic disease, surgery only for palliation of major symptoms; (9) surgeons experienced in GC management; (10) and surgeons experienced in both GC management and advanced laparoscopic surgery for laparoscopic resection. The following were scored appropriate, but of indeterminate necessity: (1) diagnostic laparoscopy before treatment; (2) a multidisciplinary approach to linitis plastica; (3) genetic assessment for diffuse GC and family history, or age less than 45 years; (4) endoscopic removal of select T1aN0 lesions; (5) D2 LN dissection in curative intent cases; (6) D1 LN dissection for early GC or patients with comorbidities; (7) frozen section analysis of margins; (8) nonemergent cases performed in a hospital with a volume of more than 15 resections per year; and (9) by a surgeon with more than 6 resection per year. CONCLUSIONS: The expert panel has created 22 statements for the perioperative management of GC patients, to provide guidance to clinicians and improve the care received by patients.
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Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Humanos , Internacionalidad , Metástasis Linfática , Tomografía de Emisión de Positrones , Guías de Práctica Clínica como Asunto , Neoplasias Gástricas/cirugía , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Positron emission tomography/computed tomography (PET/CT) scanning is commonly used for the preoperative staging of patients with at least intermediate thickness (>1 mm) melanomas. Its role in staging at initial diagnosis for clinically asymptomatic patients is not yet established. METHODS: We examined records of all patients receiving an operation for at least an intermediate thickness melanoma from June 2005 to June 2011. Results of preoperative PET/CT scans were evaluated in asymptomatic patients with a negative physical exam. Outcome measures included changes in clinical management, as well as incidence of true- and false-positives. RESULTS: PET/CT scans were performed for 149 patients with at least an intermediate thickness melanoma. Positive scans were identified in 28% (41/149) of patients. An invasive procedure to further aid in diagnosis was performed in 44% (18), yet only 6 (15%) patients were diagnosed with metastatic cancer (85% false positive rate). Each of these patients had regional disease subsequently diagnosed by a sentinel lymph node biopsy. No distant metastatic disease was identified. CONCLUSIONS: Preoperative PET/CT in asymptomatic patients is of limited benefit in staging asymptomatic melanoma patients with at least an intermediate thickness melanoma and may lead to unnecessary invasive procedures.
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Melanoma/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Femenino , Humanos , Escisión del Ganglio Linfático , Masculino , Melanoma/patología , Estudios Retrospectivos , Biopsia del Ganglio Linfático CentinelaRESUMEN
BACKGROUND AND OBJECTIVES: Optimal surgical decision-making and informed consent for palliative procedures is limited by a lack of appropriate outcomes data. Elevated C-reactive protein (CRP) may help guide patient selection for palliative surgery. METHODS: Procedures to palliate symptoms of advanced cancer were identified from a prospective palliative surgery database. Patients with a recorded preoperative serum CRP were identified and observed for at least 180 days or until death. RESULTS: Fifty patients were identified who underwent an elective palliative procedure from July 2006 to June 2012. Presenting symptoms included gastrointestinal obstruction (40%), tumor-related pain (38%) or bleeding (12%), and other (10%). Symptom improvement was documented for 37 patients (74%). Palliative procedures were associated with 30-day postoperative morbidity (42%) and mortality (10%). CRP (range 1-144 mg/L, median 9.7 mg/L) was elevated in 27 patients (54%) and was independently associated with developing a major complication (P = 0.005) and decreased overall survival (166 vs. 659 days, P < 0.0001). CONCLUSIONS: Patients with advanced cancer can be afforded symptom improvement and the opportunity for improved quality of life following palliative procedures. Elevated preoperative CRP may help identify patients who are less likely to realize the benefits of palliative operations.
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Biomarcadores de Tumor/sangre , Proteína C-Reactiva/análisis , Neoplasias/mortalidad , Neoplasias/cirugía , Cuidados Paliativos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hemorragia/etiología , Hemorragia/cirugía , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/sangre , Neoplasias/complicaciones , Dolor/etiología , Dolor/cirugía , Complicaciones Posoperatorias , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: Determine whether use of reflective questions asked on a twice monthly basis is a useful addition to our intern wellness curriculum, with a goal of longitudinal development. Prior studies have demonstrated the use of reflection in processing educational experiences toward professional growth at both the medical student and resident level. DESIGN: During the first year, every 2 weeks, the 13 interns were asked and answered 2 reflective prompts by email. Their responses went to a single faculty member and were then blinded for analysis. The second year of the program, prompts were discussed by participants in a closed group setting. Participation was voluntary. The questions fell into 6 major categories: role expectations, role assessment, role affirmation, role reflection, emotional self-assessment, work-life integration, and boundaries. Thematic analysis of the responses was performed using an inductive approach by 2 independent expert reviewers. SETTING: Brown General Surgery Residency Program, academic years 2021 to 2022 and 2022 to 2023. CONCLUSIONS: Use of reflective questions is a valuable tool as part of an intern wellness curriculum and can be easily implemented. It is inexpensive, does not require a huge time commitment, and is easily adaptable to a program's specific needs. It encourages developing surgeons to recognize and share in their emotions as they encounter the new and stressful experiences inherent in residency and may help to prevent burnout. Sustained participation through the year and robust responses suggest good resident engagement and acceptance of the program.
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Agotamiento Profesional , Internado y Residencia , Humanos , Competencia Clínica , Educación de Postgrado en Medicina , Curriculum , Agotamiento Profesional/prevención & controlRESUMEN
Introduction Educators continue to evaluate ways to assess resident performance in conjunction with the Accreditation Council for Graduate Medical Education (ACGME) general surgery milestones. We investigated whether the rate of medication errors could reflect general surgery resident competency. We hypothesized that the identification of increased medication errors made by general surgery residents could be a potential screening tool to identify residents who are academically at risk prior to their formal biannual milestone evaluation by the clinical competency committee. Methods This is a retrospective cohort study comparing rates of medication ordering errors against ACGME core competency scores over four years in a general surgery residency program at an academic, university-affiliated, level 1 trauma center in the Northeastern United States. Results We identified 95 general surgery residents who inputted 1,164,663 medication orders during the four years studied. There were 1,214 (0.1%) errors identified. Of those, 1,146 (94.4%) were level 3 errors, and 68 (5.6%) were level 4 errors. This represents an error rate of 1.04 errors per 1,000 medication orders. There was a statistically significant decrease in the error rate as the post-graduate year (PGY) level increased (p=0.005). However, there was no correlation between the error rate and individual ACGME milestone competency scores by PGY level. Conclusions We explored whether medication errors may be an early measurement of worsening resident performance as demonstrated by a decrease in ACGME core competency scores. However, the rate of errors did not correlate consistently with these measures. This may underscore that medication errors measure an aspect of resident performance that we do not capture with our current assessments.
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Palliative surgery is defined as an operation or procedure performed with the primary intention of relieving symptoms or improving quality of life. Gastrostomy tubes are often employed with palliative intent but, like many palliative interventions, there is insufficient data to facilitate surgical decision-making. This can be challenging for healthcare professionals as caring for palliative patients often encompasses end of life care, severe life-altering symptoms, and poor prognosis. Thus, we have gathered available data for the appropriate use of gastrostomy tube in palliative surgery and propose our mini-review as a primer to aid in medical and surgical decision-making. We first provide the background for palliative surgery and the definition, brief history and techniques pertinent to palliative gastrostomy tube (PGT). Then we review the data relevant to two common indications-head/ neck cancer and malignant bowel obstruction-for PGT. As our deliverable, we present an effective paradigm for delivering the data to patients and families utilizing known palliative communication and decision-making frameworks such as the Palliative Triangle, Best Case/Worst Case and Defining Value. Moreover, we highlight the necessity of conducting more palliative care research that involves palliative outcome measures in addition to traditional metrics such as overall survival. We end our discussion by emphasizing the importance of multidisciplinary team, individualized decision-making, and relationship-based care for palliative patients.
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BACKGROUND: Hereditary diffuse gastric cancer (HDGC) represents a minority of gastric cancer (GC) cases. The goal of this study is to use a RAND/University of California Los Angeles (UCLA) appropriateness methodology to examine indications for genetic referral, CDH1 testing, and consideration of prophylactic total gastrectomy (PTG). METHODS: A multidisciplinary expert panel of 16 physicians from six countries scored 47 scenarios. Appropriateness of scenarios was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) of 1-3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 of 16 panelists scored the statement similarly. Appropriate scenarios agreed upon were subsequently scored for necessity. RESULTS: The panel felt that patients with family history of diffuse gastric cancer (DGC), lobular breast cancer, or multiple family members with GC should be referred for genetic assessment and multidisciplinary decision-making. The panel felt that it is appropriate for patients with DGC to have CDH1 mutation testing in a family with (1) ≥2 cases of GC, with at least one case of DGC diagnosed before age of 50 years; (2) ≥3 cases of GC diagnosed at any age, one or more of which is DGC; (3) a patient diagnosed with DGC and lobular breast carcinoma; or (4) patients diagnosed with DGC under age of 35 years. The panel felt that PTG should be offered to CDH1 mutation carriers 20 years or older. CONCLUSIONS: Identification of genetic mutations in patients at risk for hereditary GC is important, and criteria for testing are suggested.
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Neoplasias de la Mama/genética , Cadherinas/genética , Carcinoma Lobular/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Mutación/genética , Neoplasias Gástricas/genética , Adulto , Antígenos CD , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Lobular/patología , Carcinoma Lobular/cirugía , Manejo de la Enfermedad , Familia , Femenino , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND: Patient selection for palliative surgery is complex, and appropriate outcomes measures are incompletely defined. We explored the usefulness of a specific outcomes measure "was it worth it" in patients after palliative-intent operations for advanced malignancy. STUDY DESIGN: A retrospective review of a comprehensive longitudinal palliative surgery database was performed at an academic tertiary care center. All patients who underwent palliative-intent operation for advanced cancer from 2003 to 2022 were included. Patient satisfaction ("was it worth it") was reported within 30 days of operation after palliative-intent surgery. RESULTS: A total of 180 patients were identified, and 81.7% self-reported that their palliative surgery was "worth it." Patients who reported that their surgery was "not worth it" were significantly older and were more likely to have recurrent symptoms and to need reoperation. There was no significant difference in overall, recurrence-free, and reoperation-free survival for patients when comparing "worth it" with "not worth it." Initial symptom improvement was not significantly different between groups. Age older than 65 years (hazard ratio 0.25, 95% CI 0.07 to 0.80, p = 0.03), family engagement (hazard ratio 6.71, 95% CI 1.49 to 31.8, p = 0.01), and need for reoperation (hazard ratio 0.042, 95% CI 0.01 to 0.16, p < 0.0001) were all independently associated with patients reporting that their operation was "worth it." CONCLUSIONS: Here we demonstrate that simply asking a patient "was it worth it" after a palliative-intent operation identifies a distinct cohort of patients that traditional outcomes measures fail to distinguish. Family engagement and durability of an intervention are critical factors in determining patient satisfaction after palliative intervention. These data highlight the need for highly individualized care with special attention paid to patients self-reporting that their operation was "not worth it."
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Neoplasias , Cuidados Paliativos , Humanos , Anciano , Neoplasias/cirugía , Reoperación , Satisfacción del Paciente , Oncología MédicaRESUMEN
Gastric adenocarcinoma typically presents with advanced stage when inoperable. Chemotherapy options include non-targeted and toxic agents, leading to poor 5-year patient survival outcomes. Small molecule ONC201/TIC10 (TRAIL-Inducing Compound #10) induces cancer cell death via ClpP-dependent activation of the integrated stress response (ISR) and up-regulation of the TRAIL pathway. We previously found in breast cancer, pancreatic cancer and endometrial cancer that ONC201 primes tumor cells for TRAIL-mediated cell death through ISR-dependent upregulation of ATF4, CHOP and TRAIL death receptor DR5. We investigated the ability of ONC201 to induce apoptosis in gastric adenocarcinoma cells in combination with recombinant human TRAIL (rhTRAIL) or PEGylated trimeric TRAIL (TLY012). AGS (caspase 8-, KRAS-, PIK3CA-mutant, HER2-amplified), SNU-1 (KRAS-, MLH1-mutant, microsatellite unstable), SNU-5 (p53-mutant) and SNU-16 (p53-mutant) gastric adenocarcinoma cells were treated with ONC201 and TRAIL both in cell culture and in vivo. Gastric cancer cells showed synergy following dual therapy with ONC201 and rhTRAIL/TLY012 (combination indices < 0.6 at doses that were non-toxic towards normal fibroblasts). Synergy was observed with increased cells in the sub-G1 phase of the cell cycle with dual ONC201 plus TRAIL therapy. Increased PARP, caspase 8 and caspase 3 cleavage after ONC201 plus TRAIL further documented apoptosis. Increased cell surface expression of DR5 with ONC201 therapy was observed by flow cytometry, and immunoblotting revealed ONC201 upregulation of the ISR, ATF4, and CHOP. We observed downregulation of anti-apoptotic cIAP-1 and XIAP in all cells except AGS, and cFLIP in all cells except SNU-16. We tested the regimen in an organoid model of human gastric cancer, and in murine sub-cutaneous xenografts using AGS and SNU-1 cells. Our results suggest that ONC201 in combination with TRAIL may be an effective and non-toxic option for the treatment of gastric adenocarcinoma by inducing apoptosis via activation of the ISR, increased cell surface expression of DR5 and down-regulation of inhibitors of apoptosis. Our results demonstrate in vivo anti-tumor effects of ONC201 plus TLY012 against gastric cancer that could be further investigated in clinical trials.
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BACKGROUND: Poor personal financial health has been linked to key components of health including burnout, substance abuse, and worsening personal relationships. Understanding the state of resident financial health is key to improving their overall well-being. STUDY DESIGN: A secondary analysis of a survey of New England general surgery residents was performed to understand their financial well-being. Questions from the National Financial Capability Study were used to compare to an age-matched and regionally matched cohort. RESULTS: Overall, 44% (250 of 570) of surveyed residents responded. Residents more frequently reported spending less than their income each year compared to the control cohort (54% vs 34%, p < 0.01). However, 17% (39 of 234) of residents reported spending more than their income each year. A total of 65% of residents (152 of 234), found it "not at all difficult" to pay monthly bills vs 17% (76 of 445) of the control cohort (p < 0.01). However, 32% (75 of 234) of residents reported it was "somewhat" or "very" difficult to pay monthly bills. Residents more frequently reported they "certainly" or "probably" could "come up with" $2,000 in a month compared to the control cohort (85% vs 62% p < 0.01), but 16% (37 of 234) of residents reported they could not. In this survey, 21% (50 of 234) of residents reported having a personal life insurance policy, 25% (59 of 234) had disability insurance, 6% (15 of 234) had a will, and 27% (63 of 234) had >$300,000 worth of student loans. CONCLUSIONS: Surgical residents have better financial well-being than an age-matched and regionally matched cohort, but there is still a large proportion who suffer from financial difficulties.
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Agotamiento Profesional , Internado y Residencia , Humanos , Renta , New England , Encuestas y Cuestionarios , Agotamiento Profesional/epidemiologíaRESUMEN
BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
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Obstrucción Intestinal , Neoplasias , Estados Unidos , Humanos , Masculino , Femenino , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Proyectos de Investigación , Selección de PacienteRESUMEN
PURPOSE: Continued assessment and redesign of the curriculum is essential for optimal surgical education. For the last 3 y, we have asked the residents to reflect on the previous week and describe "the best thing" they learned. We hypothesize that this statement could be used to assess the weaknesses or strengths of our curriculum. METHODS: Starting in 2007, residents filled out surveys approximately 4 times/y at the start of a mandatory conference. They were asked to describe the "best thing" they learned that week, where it was learned, and who taught it. Residents were not asked to classify the item learned by core competency (communication, knowledge, patient care, practice-based learning, professionalism, and systems-based practice). This categorization into core competencies was done as part of our study design. Attending, fellow, resident, or other were used as groups designating who taught each item. Where the item was learned was fit into either clinic, conference, operating room (OR), wards, or self. The impact of postgraduate year (PGY) level on learning was also assessed. χ(2) analysis was used to compare groups. RESULTS: During the study period, 304 surveys were completed and returned by 65 residents. The majority of responses came from PGY 1 residents (134, 43%). Patient care and knowledge were the most common core competencies learned. As PGY level increased, learning of professionalism (P = 0.035) increased. A majority of learning was experiential (wards and OR, P < 0.0125). Self-learning and learning in clinic was a minor component of learning (P < 0.0125). Learning on wards (P < 0.001) decreased as residents progressed and learning from the OR (P = 0.002) had the opposite trend. CONCLUSIONS: Patient care and knowledge are the most frequently cited competencies learned by the residents. Self-learning is not a significant source of learning, and the majority of the learning is experiential. It is not known if this was a sign that there was a lack of self-directed learning or that self-directed learning was not an efficient method of learning. In addition, each PGY level learns differently (teacher and location of learning), perhaps reflecting the different needs and/or structure of each PGY. We believe the reflective statement has been and will be a useful tool to assess our curriculum.
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Evaluación Educacional/métodos , Cirugía General/educación , Internado y Residencia , Aprendizaje , Curriculum , HumanosRESUMEN
This review focuses on the role of palliative surgery in the care of the palliative care patient, and the appropriate role of the surgeon. The surgeon has much to bring to the palliative care team. The surgeon's role goes beyond the technical requirements of the palliative procedure, which itself must be strictly defined, and has recognized utility for improving quality of life in selected patients. These benefits may be substantial, but come at significant risk; requiring careful balancing of risks and benefits that is most completely understood by the surgeon. The surgeon's judgement can help determine which procedure best meets a patient's goals. The complex dialogue involved in the decision to undergo a palliative operation requires excellent communication between the palliative care team, the patient, and their family. Integrating the surgeon into the palliative care team could help with earlier initiation of those palliative discussions, and assist deliberation of palliative surgery. Surgeons also understand the importance of communication around palliative surgical interventions and have adapted several teaching models to the specifics of this crucial communication. A palliative team combining both surgeons and palliative care physicians may promote goal-concordant decision-making and remove barriers to communication and team engagement. The future of palliative surgery research will involve measures of success that go beyond physiology or mortality, to include more evaluations of communication and patient goals.
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Cuidados Paliativos , Cirujanos , Comunicación , Humanos , Calidad de VidaRESUMEN
BACKGROUND: Surgical culture has shifted to recognize the importance of resident well-being. This is the first study to longitudinally track regional surgical resident well-being over 5 years. STUDY DESIGN: An anonymous cross-sectional, multi-institutional survey of New England general surgery residents using novel and published instruments to create three domains: health maintenance, burnout, and work environment. RESULTS: Overall, 75% (15 of 20) of programs participated. The response rate was 44% (250 of 570), and 53% (133 of 250) were women, 94% (234 of 250) were 25 to 34 years old, and 71% (178 of 250) were in a relationship. For health maintenance, 57% (143 of 250) reported having a primary care provider, 26% (64 of 250) had not seen a primary care provider in 2 years, and 59% (147 of 250) endorsed being up to date with age-appropriate health screening, but only 44% (109 of 250) were found to actually be up to date. Only 14% (35 of 250) reported exercising more than 150 minutes/week. The burnout rate was 19% (47 of 250), with 32% (81 of 250) and 25% (63 of 250) reporting high levels of emotional exhaustion and depersonalization, respectively. For program directors and attendings, 90% of residents reported that they cared about resident well-being. Eighty-seven percent of residents believed that it was acceptable to take time off during the workday for a personal appointment, but only 49% reported that they would personally take the time. CONCLUSIONS: The personal health maintenance of general surgery residents has changed little over the past five years, despite an overwhelming majority of residents reporting that attendings and program directors care about their well-being. Further study is needed to understand the barriers to improvement of resident wellbeing.
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Agotamiento Profesional , Internado y Residencia , Adulto , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Estudios Transversales , Femenino , Humanos , Masculino , New England , Encuestas y CuestionariosRESUMEN
Surgical palliation in oncology can be defined as "procedures employed with non-curative intent with the primary goal of improving symptoms caused by an advanced malignancy," and is an important aspect of the end-of-life care of patients with incurable malignancies. Palliative interventions may provide great benefit, but they also carry high risk for morbidity and mortality, which may be minimized with careful patient selection. This can be done by consideration of the patient and his or her indication for the given intervention via open communication, as well as prediction of benefits and risks to define the therapeutic index of the operation or procedure.