RESUMEN
INTRODUCTION: International medical graduates (IMGs) make up a small but important percentage of the U.S. surgical workforce. Detailed and contemporary studies on IMGs matching into U.S. general surgery residency positions are lacking. Our objective was to study these trends over a 30-y period. METHODS: We utilized the National Resident Matching Program reports from 1994 to 2023 to analyze the trends of U.S. M.D. seniors, D.O. seniors, and U.S. citizen and non-U.S. citizen IMGs matching into first-year categorical and preliminary general surgery residency positions. The percent of positions filled were calculated and trended over time using linear regression, where ß coefficient estimated the percentage of annual change in matched positions, and the R2 coefficient measured the amount of variance explained (perfect regression R2 = 1.0). RESULTS: Over the last 30 y, IMG match percentages have increased for both categorical (ß = 0.218%, R2 = 0.49, P < 0.001) and preliminary (ß = 0.705%, R2 = 0.76, P < 0.001) general surgery positions, with a greater increase in preliminary positions (ß = 0.705%). The percentage of positions filled by M.D. U.S. seniors in categorical positions has steadily decreased over the 30-y period (ß = -0.625%, R2 = 0.79, P < 0.001), and this decrease has largely occurred with a concurrent greater increase in U.S. D.O. seniors match percentage rates (ß = 0.430%, R2 = 0.64, P < 0.001), rather than IMGs (ß = 0.218%). Allopathic M.D. U.S. seniors preliminary match percentages have steadily decreased at the steepest rate (ß = -0.927%, R2 = 0.80, P < 0.001). In categorical positions, non-U.S. citizen IMGs' match percentages (ß = 0.069%, R2 = 0.204, P = 0.012) increased at a slightly slower rate than U.S. citizen IMGs (ß = 0.149%, R2 = 0.607, P < 0.001). In preliminary positions, non-U.S. citizen IMGs' match percentages (ß = 0.33%, R2 = 0.478, P < 0.001) increased at a similar rate as U.S. citizen IMGs (ß = 0.375%, R2 = 0.823, P < 0.0.001). In the 2023 National Resident Matching Program match, U.S. citizen and non-U.S. citizen IMGs together made up 10.3% of the categorical and 44.5% of the preliminary general surgery positions that were filled. For categorical positions in 2023, there was no major difference between positions matched by U.S. citizen IMGs (4.62%) and non-U.S. citizen IMGs (5.72%); on the other hand, for preliminary positions in 2023, non-U.S. citizen IMGs (31.96%) filled 2.5× times the number of positions as U.S. citizen IMGs (12.54%). CONCLUSIONS: Over the last 30 y, U.S. allopathic M.D. seniors matching into categorical general surgery positions have steadily decreased, while both U.S. osteopathic D.O. seniors and IMGs matching have increased. These data have important implications for the future U.S. surgical workforce.
RESUMEN
Neoadjuvant chemoimmunotherapy with pembrolizumab now defines the standard of care for early high-risk triple-negative breast cancer (TNBC). However, the role of pembrolizumab in neoadjuvant therapy (NAT) for estrogen receptor-positive (ER+) breast cancer remains uncertain. A 39-year-old G2P2 female discovered a palpable mass in the right breast while breastfeeding her 7-month-old child, leading to the diagnosis of a high-grade ER+ (80% moderate staining), human epidermal growth factor receptor 2-negative (ErbB2-) invasive ductal carcinoma with axillary nodal involvement. Gene expression profiling with the MammaPrint 70-gene signature and BluePrint 80-gene signature revealed a tumor with high-risk, basal-type biology. The multidisciplinary breast cancer team recommended NAT with pembrolizumab, carboplatin, paclitaxel, doxorubicin, and cyclophosphamide. Within six weeks, the patient exhibited a remarkable response, with no palpable mass or lymph node, and post-treatment examinations confirmed a complete clinical and radiologic response. The patient underwent lumpectomy and sentinel lymph node biopsy, revealing a pathological complete response with minimal ductal carcinoma in situ and negative axillary nodes. Adjuvant radiation therapy was administered, and the patient completed adjuvant pembrolizumab, currently showing no evidence of recurrence. This case underscores the potential benefits of neoadjuvant chemoimmunotherapy for patients with ER+ErbB2- high-risk, basal-type breast cancer. The use of immunotherapy in patients with pregnancy-associated breast cancer remains to be further investigated.
RESUMEN
Taxonomy of hepatobiliary cancer (HBC) categorizes tumors by location or histopathology (tissue of origin, TO). Tumors originating from different TOs can also be grouped by overlapping genomic alterations (GA) into molecular subtypes (MS). The aim of this study was to create novel HBC MSs. Next-generation sequencing (NGS) data from the AACR-GENIE database were used to examine the genomic landscape of HBCs. Machine learning and gene enrichment analysis identified MSs and their oncogenomic pathways. Descriptive statistics were used to compare subtypes and their associations with clinical and molecular variables. Integrative analyses generated three MSs with different oncogenomic pathways independent of TO (n = 324; p < 0.05). HC-1 "hyper-mutated-proliferative state" MS had rapidly dividing cells susceptible to chemotherapy; HC-2 "adaptive stem cell-cellular senescence" MS had epigenomic alterations to evade immune system and treatment-resistant mechanisms; HC-3 "metabolic-stress pathway" MS had metabolic alterations. The discovery of HBC MSs is the initial step in cancer taxonomy evolution and the incorporation of genomic profiling into the TNM system. The goal is the development of a precision oncology machine learning algorithm to guide treatment planning and improve HBC outcomes. Future studies should validate findings of this study, incorporate clinical outcomes, and compare the MS classification to the AJCC 8th staging system.
RESUMEN
Brain metastasis (BrM) is a major threat to the survival of melanoma, breast, and lung cancer patients. Circulating tumor cells (CTCs) cross the blood-brain barrier (BBB) and sustain in the brain microenvironment. Genetic mutations and epigenetic modifications have been found to be critical in controlling key aspects of cancer metastasis. Metastasizing cells confront inflammation and gradually adapt in the unique brain microenvironment. Currently, it is one of the major areas that has gained momentum. Researchers are interested in the factors that modulate neuroinflammation during BrM. We review here various epigenetic factors and mechanisms modulating neuroinflammation and how this helps CTCs to adapt and survive in the brain microenvironment. Since epigenetic changes could be modulated by targeting enzymes such as histone/DNA methyltransferase, deacetylases, acetyltransferases, and demethylases, we also summarize our current understanding of potential drugs targeting various aspects of epigenetic regulation in BrM.
Asunto(s)
Neoplasias Encefálicas , Neoplasias Pulmonares , Humanos , Epigénesis Genética , Enfermedades Neuroinflamatorias , Neoplasias Encefálicas/genética , Inflamación/genética , Microambiente Tumoral/genéticaRESUMEN
OBJECTIVE: To characterize industry nonresearch payments made to general and fellowship-trained surgeons between 2016 and 2020. BACKGROUND: The Centers for Medicare & Medicaid Services Open Payments Data (OPD) reports industry payments made to physicians related to drugs and medical devices. General payments are those not associated with research. METHODS: OPD data were queried for general and fellowship-trained surgeons who received general payments from 2016 to 2020. Payments' nature, amount, company, covered product, and location were collected. Surgeons' demographics, subspecialty, and leadership roles in hospitals, societies, and editorial boards were evaluated. RESULTS: From 2016 to 2020, 44,700 general and fellowship-trained surgeons were paid $535,425,543 in 1,440,850 general payments. The median payment was $29.18. The most frequent payments were for food and beverage (76.6%) and travel and lodging (15.6%); however, the highest dollar payments were for consulting fees ($93,128,401; 17.4%), education ($88,404,531; 16.5%), royalty or license ($87,471,238; 16.3%), and travel and lodging ($66,333,149; 12.4%). Five companies made half of all payments ($265,654,522; 49.6%): Intuitive Surgical ($128,517,411; 24%), Boston Scientific ($48,094,570; 9%), Edwards Lifesciences ($41,835,544, 7.8%), Medtronic Vascular ($33,607,136; 6.3%), and W. L. Gore & Associates ($16,626,371; 3.1%). Medical devices comprised 74.7% of payments ($399,897,217), followed by drugs and biologicals ($33,945,300; 6.3%). Texas, California, Florida, New York, and Pennsylvania received the most payments; however, the top dollar payments were in California ($65,702,579; 12.3%), Michigan ($52,990,904, 9.9%), Texas ($39,362,131; 7.4%), Maryland ($37,611,959; 7%), and Florida ($33,417,093, 6.2%). General surgery received the highest total payments ($245,031,174; 45.8%), followed by thoracic surgery ($167,806,514; 31.3%) and vascular surgery ($60,781,266; 11.4%). A total of 10,361 surgeons were paid >$5000, of which 1614 were women (15.6%); in this group, men received higher payments than women (means, $53,446 vs $22,571; P <0.001) and thoracic surgeons received highest payments (mean, $76,381; NS, P =0.14). A total of 120 surgeons were paid >$500,000 ($203,011,672; 38%)-5 non-Hispanic White (NHW) women (4.2%) and 82 NHW (68.3%), 24 Asian (20%), 7 Hispanic (5.8%), and 2 Black (1.7%) men; in this group, men received higher payments than women (means, $1,735,570 vs $684,224), and NHW men received payments double those of other men (means, $2,049,554 vs $955,368; NS, P =0.087). Among these 120 highly paid surgeons (>$500,000), 55 held hospital and departmental leadership roles, 30 were leaders in surgical societies, 27 authored clinical guidelines, and 16 served on journal editorial boards. During COVID-19, 2020 experienced half the number of payments than the preceding 3 years. CONCLUSIONS: General and fellowship-trained surgeons received substantial industry nonresearch payments. The highest-paid recipients were men. Further work is warranted in assessing how race, gender, and leadership roles influence the nature of industry payments and surgical practice. A significant decline in payments was observed early during the COVID-19 pandemic.
Asunto(s)
COVID-19 , Cirujanos , Anciano , Masculino , Humanos , Femenino , Estados Unidos , Becas , Pandemias , COVID-19/epidemiología , Medicare , Conflicto de Intereses , Bases de Datos FactualesRESUMEN
A 46-year-old man presented with a left shoulder mass. He reported limited shoulder movements and denied other symptoms. What is your diagnosis?
Asunto(s)
Hombro , Masculino , Humanos , Persona de Mediana EdadRESUMEN
A 76-year-old woman presents with a palpable left axillary mass, yet no breast lesions are found. What is your diagnosis?
Asunto(s)
Adenocarcinoma , Neoplasias de la Mama , Humanos , Femenino , Axila/patología , Mama/patología , Ganglios Linfáticos/patología , Adenocarcinoma/patología , Neoplasias de la Mama/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Melanoma mutational burden is high and approximately 50% have oncogenic mutations in BRAF. We sought to evaluate age-related mutational differences in melanoma. METHODS: We analyzed melanoma samples in the Genomics Evidence Neoplasia Information Exchange database. Targetable mutations were identified using the Precision Oncology Knowledge Base (OncoKB). RESULTS: We found 1194 patients with a common set of 30 genes. The top mutated genes in patients <40 years old (y/o) (n = 98) were BRAF (59%), TP53 (31%), NRAS (17%), and PTEN (14%); in 40-59 y/o (n = 354) were BRAF (51%), NRAS (30%), TP53 (26%), and APC (13%); and in ≥60 y/o (n = 742) were BRAF (38%), NRAS (33%), TP53 (26%), and KDR (19%). BRAF mutations were almost mutually exclusive from NRAS mutations in <40 y/o (58/59). Mutational burden increased with age, with means of 2.39, 2.92, and 3.67 mutations per sample in patients <40, 40-59, and ≥60 y/o, respectively (p < 0.0001). There were 10 targetable mutations meeting OncoKB criteria for melanoma: BRAF (level 1), RET (level 1), KIT (level 2), NRAS (level 3A), TP53 (level 3A), and FGFR2, MET, PTEN, PIK3CA, and KRAS (level 4). CONCLUSIONS: Mutations in melanoma have age-related differences and demonstrates potential targetable mutations for personalized therapies.
Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Adulto , Proteínas Proto-Oncogénicas B-raf/genética , Medicina de Precisión , Melanoma/genética , Mutación , Secuenciación de Nucleótidos de Alto Rendimiento , Análisis Mutacional de ADN , Neoplasias Cutáneas/genéticaRESUMEN
BACKGROUND: The impact of AJCC8 among self-reported racial/ethnic groups on differentiated thyroid cancer (DTC) outcomes is unknown. METHODS: Multivariate-regression evaluated the association between AJCC7 to AJCC8 stage change and race/ethnicity in patients with DTC in the NCDB. Cox-proportional-regression evaluated whether AJCC7 to AJCC8 stage change affects overall survival (OS) differently based on reported race/ethnicity. RESULTS: After adjusting for confounders, Hispanics and Asian-Pacific-Islanders (APIs) were 27% and 12% less likely to be down-staged compared to white-non-Hispanics (WNHs) (p < 0.001); black-non-Hispanics (BNHs) had no significant down-staging difference. Down-staged patients had an increased risk of death compared to patients with unchanged staging, regardless of race/ethnicity. However, based on two-way interaction, the magnitude of this negative change on survival from down-staging was only different between WNHs (HR = 2.64) and BNHs (HR = 1.77), (p = 0.04). CONCLUSIONS: Outcome disparities persist among self-reported racial/ethnic groups with AJCC8. Down-staged patients across all racial/ethnic groups had decreased survival compared to those with unchanged stage, with the least impact in BNHs.
Asunto(s)
Adenocarcinoma , Neoplasias de la Tiroides , Humanos , Estadificación de Neoplasias , Neoplasias de la Tiroides/cirugíaRESUMEN
PURPOSE OF REVIEW: To review and update surgeons about the evolving complexities in the surgical management of melanoma including lymph node staging and treatment. RECENT FINDINGS: Primary resection with adequate margins continues to be the standard of care for localized cutaneous melanoma. Sentinel lymph node biopsy is confirmed to be a powerful tool due to its prognostic value and informative guidance for adjuvant treatments and surveillance. Due to the lack of benefit in melanoma-specific survival and distant metastasis-free survival, completion lymph node dissection is not performed routinely after a positive sentinel lymph node biopsy. Neoadjuvant systemic treatment approaches for advanced loco-regional disease show promise in phase I and II clinical trial data, and phase III studies. The surgical management of cutaneous melanoma continues to evolve with further de-escalation of the extent of excision of primary melanomas and the management of lymph node disease.
Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/patología , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Metástasis Linfática , Biopsia del Ganglio Linfático Centinela , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Estadificación de Neoplasias , Melanoma Cutáneo MalignoRESUMEN
Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the uniquely distinct brain microenvironment. Keeping abreast with the recent breakthroughs in the context of various biomolecules detections and identifications, the circulating tumor cells (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, and metabolites can be pursued in human body fluids such as blood, serum, cerebrospinal fluid (CSF), and urine to obtain potential candidates for biomarker development. The liquid biopsy-based biomarkers can overlay with current imaging techniques to amplify the signal viable for improving the early detection and treatments of occult BrM.
Asunto(s)
Neoplasias Encefálicas , Neoplasias de la Mama , Células Neoplásicas Circulantes , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Femenino , Humanos , Biopsia Líquida/métodos , Células Neoplásicas Circulantes/patología , Microambiente TumoralRESUMEN
Brain metastasis (BrM) is one of the major causes of death in cancer patients and is associated with an estimated 10-40 % of total cancer cases. The survival rate of brain metastatic patients has not improved due to intratumor heterogeneity, the survival adaptations of brain homing metastatic cells, and the lack of understanding of underlying molecular mechanisms that limit the availability of effective therapies. The heterogeneous population of immune cells and tumor-initiating cells or cancer stem cells in the tumor microenvironment (TME) release various factors, such as chemokines that upon binding to their cognate receptors enhance tumor growth at primary sites and help tumor cells metastasize to the brain. Furthermore, brain metastatic sites have unique heterogeneous microenvironment that fuels cancer cells in establishing BrM. This review explores the crosstalk of chemokines with the heterogeneous TME during the progression of BrM and recognizes potential therapeutic approaches. We also discuss and summarize different targeted, immunotherapeutic, chemotherapeutic, and combinatorial strategies (with chemo-/immune- or targeted-therapies) to attenuate chemokines mediated BrM.
Asunto(s)
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/prevención & control , Quimiocinas , Células Madre Neoplásicas , Encéfalo , Microambiente Tumoral , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: Recent studies have shown an association in non-metastatic colorectal cancer between patient survival and immunoprofiling (expression of CD3, CD4, CD8, CD45, and FOXP3 T cells at the invasive margin (IM) and the tumor center (TC)) regardless of stage. Patients with peritoneal carcinomatosis have a dismal prognosis, but survival can be significantly improved in selected patients who undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, current patient selection for CRS/HIPEC is suboptimal. The purpose of this study is to evaluate immune profiles of patients with peritoneal carcinomatosis and their correlation with overall survival (OS). METHODS: The study cohort included patients from a prospectively maintained database of adults with colorectal peritoneal carcinomatosis who underwent CRS/HIPEC. Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 T cells was performed. IHC image density was calculated using ImageJ software, and an immunoscore was determined. RESULTS: Eighty tumors were evaluated from 66 patients. These included 14 primary sites and 66 metastatic sites. R0/R1 resection was achieved in 44 (66.7%) patients. Known prognostic factors including resection status (HR 1.99, p = 0.004) and lymph node status (HR 3.49, p = 0.002) were associated with overall survival. On multivariate analysis, increased CD3/CD4 IM (HR 0.54, p = 0.03) ratio positively was associated with improved OS. DISCUSSION: This is the first study to assess the utility of subtypes of T cells as prognostic markers in patients with colorectal peritoneal carcinomatosis, which may play a role in patients with low-volume disease. Further studies into immune mechanisms may improve patient selection for cytoreductive surgery and HIPEC as well as provide novel pathways for effective immunotherapy.
Asunto(s)
Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Colorrectales/terapia , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Selección de Paciente , Neoplasias Peritoneales/terapia , PronósticoRESUMEN
BACKGROUND: With reductions in public funding, alternate research funding is essential to surgical oncologists (SOs). We aimed to examine current trends in industry funding of SOs. METHODS: Society of Surgical Oncology surgeons were identified and matched with board certification and years in practice. Departmental and hospital data were evaluated, and industry payments from 2013 to 2017 were matched with the Open Payment Data. RESULTS: Of the 1670 SOs identified, 922 (55%) had academic positions: 588 (64%) males and 334 (36%) females. Between 2013 and 2017, research payments totaling $46,596,706 were made to 162 SOs (17.5%): $40,774,716 (87%) for research related to drugs and clinical trials, compared with $5,194,199 (11%) for surgical devices (p = 0.018). Funding correlated with academic leadership and years in practice (p = 0.0001 and p = 0.0037). Massachusetts ($9,060,976), Texas ($7,656,228), and New York ($4,210,864) received the most funding, whereas Utah ($1,533,166/SO), Massachusetts ($1,294,425/SO), and Oregon ($1,241,702/SO) received the highest average payments per SO. The majority of funding was from Novartis ($16,045,608), Amgen ($6,810,832), and Merck ($3,758,299), for an oncolytic vaccine (talimogene laherparepvec, $5,939,007), a BRAF inhibitor (dabrafenib, $5,727,309), and a KIT inhibitor (imatinib, $4,323,586). Male SOs received funding more frequently than females (120/588 [20%] vs. 42/334 [12.6%]; p = 0.0027). Males also received more general payments (travel/lodging, food/beverage, consulting/speaker fees): $48,830 vs. $11,867 per male and female, respectively (p = 0.0001). CONCLUSIONS: The majority of industry research payments to SOs are related to novel pharmaceuticals, which highlights the expanding influence SOs play in systemic therapies. Industry payments are influenced by location, gender, and academic leadership.
Asunto(s)
Investigación Biomédica/economía , Conflicto de Intereses/economía , Industrias/economía , Oncólogos/estadística & datos numéricos , Apoyo a la Investigación como Asunto/tendencias , Cirujanos/estadística & datos numéricos , Femenino , Humanos , Masculino , Apoyo a la Investigación como Asunto/economíaRESUMEN
INTRODUCTION: Murine Kupffer cells (KCs) comprise CD11bhi and F4/80hi subsets. Tissue-resident macrophages are known to express the tyrosine kinase receptors colony-stimulating factor 1 receptor (Csf1r) and Mer. However, the expression of Csf1r and Mer on KC subsets and the importance of these tyrosine kinases during liver regeneration (LR) are unknown. METHODS: KCs from wild-type and Csf1r-GFP mice were characterized by flow cytometry. Partial hepatectomy (PH) was performed in mice treated with clodronate liposomes, a Csf1r small molecule inhibitor or depleting antibody, or a small molecule Mer inhibitor. Sera and livers were analyzed. The function of sorted KC subsets was tested in vitro. RESULTS: Mer was specifically expressed on tissue-resident F4/80hi KCs, 55% of which also expressed Csf1r. Mer+Csf1r+ and Mer+Csf1r- KCs had distinct expression of macrophage markers. Csf1r inhibition in mice reduced F4/80hi KCs by approximately 50%, but did not affect CD11bhi KCs. Clodronate liposomes depleted F4/80hi KCs, but also altered levels of other intrahepatic leukocytes. Csf1r inhibition delayed LR, as demonstrated by a 20% reduction in liver-to-body weight ratios 7 days after PH. At 36h after PH, Csf1r inhibition increased serum ALT and histological liver injury, and decreased liver cell proliferation. A small molecule inhibitor of Mer did not alter the percentage of KCs or their proliferation and just modestly delayed LR. In vitro, Csf1r or Mer inhibition did not decrease KC viability, but did attenuate their cytokine response to stimulation. CONCLUSIONS: F4/80hi KCs are Mer+ and can be subdivided based on Csf1r expression. Csf1r or Mer inhibition each reduces KC cytokine production and delays LR.
Asunto(s)
Antígenos de Diferenciación de Linfocitos B/metabolismo , Macrófagos del Hígado/metabolismo , Regeneración Hepática/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Receptores Inmunológicos/metabolismo , Animales , Antígenos de Diferenciación/análisis , Hepatectomía , Macrófagos del Hígado/citología , Macrófagos del Hígado/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Receptores Inmunológicos/antagonistas & inhibidoresRESUMEN
INTRODUCTION: Quality/core measures have been collected for over 10 years. Studies have demonstrated hospital performance is related to postoperative outcomes. We hypothesize that hospital quality measures are associated with long-term survival following surgical resection for hepatocellular carcinoma (HCC). METHODS: The National Cancer Data Base was queried for all HCC cases. Individual hospitals were deidentified. Quality markers were defined as hospital-specific median length of stay (LOS), 30-day mortality rate and readmit rate. A Cox regression stratified by stage estimated survival. To minimize confounding, a landmark analysis was estimated for patients that survived greater than 30 days. RESULTS: A total of 16 202 HCC patients underwent surgical resection and 996 (6.1%) died within 30 days following surgery. Calculated by unique hospital, median 30-day death rate was 4.6% (interquartile range [IQR]: 1.2% to 7.6%). Thirty-day readmit rate was 2.6% (IQR: 0% to 5.9%) and median LOS was 8.0 days (IQR: 6.5 to 9.2). In the multivariate Cox regression, 30-day death rate (hazard ratio [HR], 1.89; 95% confidence interval [CI]: 1.32 to 2.71) and longer LOS (HR, 1.02; 95% CI: 1.01 to 1.02) were associated with worse survival. Higher 30-day readmission rate was associated with improved survival (HR, 0.61; 95% CI, 0.38 to 0.97). CONCLUSIONS: Hospital-level surrogate markers of surgical quality appear to be significantly associated with HCC survival following resection. Patients treated in higher 30-day mortality centers, experienced worse outcomes. Individual hospitals should critically review disease-specific outcomes following resection to identify areas for improvement.
Asunto(s)
Biomarcadores , Carcinoma Hepatocelular/mortalidad , Hepatectomía/mortalidad , Neoplasias Hepáticas/mortalidad , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias , Calidad de la Atención de Salud , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Mejoramiento de la Calidad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. Although the Wnt/ß-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed ß-catenin and contained active, dephosphorylated nuclear ß-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4. Accordingly, in human GIST T1 cells, Wnt stimulation increased ß-catenin-mediated transcriptional activity in a reporter assay as well as transcription of the downstream target genes Axin2 and CCND1 In contrast, DKK4 overexpression in GIST T1 cells reduced Wnt/ß-catenin signaling. In addition, we showed that nuclear ß-catenin stability was partially regulated by the E3 ligase COP1, as demonstrated with coimmunoprecipitation and COP1 knockdown. Three molecular inhibitors of the Wnt/ß-catenin pathway demonstrated antitumor efficacy in various GIST models, both in vitro and in vivo Notably, the tankyrase inhibitor G007-LK alone had substantial activity against tumors of genetically engineered KitV558Δ/+ mice, and the effect was increased by the addition of the Kit inhibitor imatinib mesylate. Collectively, our findings demonstrate that Wnt/ß-catenin signaling is a novel therapeutic target for selected untreated or imatinib-resistant GISTs. Mol Cancer Ther; 16(9); 1954-66. ©2017 AACR.