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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.
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BACKGROUND AND OBJECTIVES: Selecting frail elderly patients with pancreatic cancer (PC) for pancreas resection using biologic age has not been elucidated. This study determined the feasibility of the deficit accumulation frailty index (DAFI) in identifying such patients and its association with surgical outcomes. METHODS: The DAFI, which assesses frailty based on biologic age, was used to identify frail patients using clinical and health-related quality-of-life data. The characteristics of frail and nonfrail patients were compared. RESULTS: Of 242 patients (median age, 75.5 years), 61.2% were frail and 32.6% had undergone pancreas resection (surgery group). Median overall survival (mOS) decreased in frail patients (7.13 months, 95% confidence interval [CI]: 5.65-10.1) compared with nonfrail patients (16.1 months, 95% CI: 11.47-34.40, p = 0.001). In the surgery group, mOS improved in the nonfrail patients (49.4%; 49.2 months, 95% CI: 29.3-79.9) compared with frail patients (50.6%, 22.1 months, 95% CI: 18.3-52.4, p = 0.10). In the no-surgery group, mOS was better in nonfrail patients (54%; 10.81 months, CI 7.85-16.03) compared with frail patients (66%; 5.45 months, 95% CI: 4.34-7.03, p = 0.02). CONCLUSIONS: The DAFI identified elderly patients with PC at risk of poor outcomes and can identify patients who can tolerate more aggressive treatments.
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Productos Biológicos , Fragilidad , Neoplasias Pancreáticas , Humanos , Anciano , Fragilidad/complicaciones , Anciano Frágil , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/complicaciones , Evaluación Geriátrica , Neoplasias PancreáticasRESUMEN
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.
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Adenocarcinoma , Neoplasias de la Tiroides , Humanos , Estadificación de Neoplasias , Neoplasias de la Tiroides/cirugíaRESUMEN
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.
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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: Given the survival advantage of neoadjuvant treatment for locally advanced esophageal cancer, accurate clinical staging is necessary. The aim of this study was to assess the clinical (c) and pathologic (p) staging concordance rates for presumably early stage esophageal adenocarcinoma patients that had upfront esophagectomy (UFE) and evaluate if survival (OS) was negatively affected by inaccurate preoperative staging and subsequent treatment selection. METHODS: An NCDB retrospective review of nonmetastatic esophageal adenocarcinoma patients that had UFE. The rates of concordance between c and p staging system and OS were calculated. RESULTS: Of 2775 patients, most patients presented with cN0 (82.8%) and cT1 tumors (53.6%). The overall concordance between c and p staging was 78.8% for T-classification (moderate agreement; weighted κ = 0.729; P < .001) and 78.8% for N-classification (weak agreement; weighted κ = 0.448; P < .001). Patients that were upstaged due to a lack of concordance between T-classification had decreased 5- and 10-year OS (30% and 16%, P < .001) and those upstaged due to discordant N-classification had decreased 5- and 10-year OS (28% and 23%, P < .001)." CONCLUSIONS: Preoperative staging of esophageal adenocarcinoma has moderate reliability and accuracy for predicting pT and pN classification. Up to 25% of patients have discordant clinical and pathological staging, which impacts OS.
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Adenocarcinoma/patología , Adenocarcinoma/cirugía , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Adenocarcinoma/mortalidad , Anciano , Neoplasias Esofágicas/mortalidad , Esofagectomía/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Preoperatorios , Estudios Retrospectivos , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
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.
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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
In today's medical community, when people say the name Herman Boerhaave, most assimilate it to Boerhaave syndrome. His influence on medicine is seen every day in hospitals around the world. His methodologies revolutionized medical education and the way physicians approach the examination of patients. It has been said that during the Age of Reason, he was the "Bearer of the Enlightenment of Medicine." He is a forgotten father of medicine. To preserve medical history, educators should give students a brief summary of the contributors to medicine to remind us how much of their lives they gave to further medical knowledge.
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Educación Médica/historia , Historia del Siglo XVII , Historia del Siglo XVIII , Humanos , Países Bajos , Examen Físico/historiaRESUMEN
BACKGROUND: Cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival and decrease recurrence of peritoneal metastasis in a select population of patients. Abdominal wall resection is often needed to achieve complete CRS and the extent of abdominal wall resection may necessitate abdominal wall reconstruction (AWR). We sought to investigate if postoperative morbidity and mortality was increased in patients who underwent AWR with CRS-HIPEC (AWR group) compared to CRS-HIPEC without AWR (non-AWR group) and to identify if patient, tumor, and operative risk factors were associated with poor outcomes following AWR. We postulate that AWR is a safe and viable treatment option in appropriately selected patients with peritoneal disease. METHODS: A retrospective chart review was conducted from 2012 to 2015. Demographics, comorbidities, intraoperative variables, and postoperative outcomes were analyzed and compared between the non-AWR group and the AWR group. RESULTS: A total of 30 patients underwent CRS-HIPEC at our institution; 19 recruited in non-AWR group and 11 in the AWR arm. Median follow-up was 19.1 mo for the non-AWR group and 15.6 mo for AWR. Overall survival and complications were not significantly different between groups. Six patients in the non-AWR group and three patients in AWR group died during the follow-up period (32% versus 27%, P = 0.75). Grade III/IV Clavien-Dindo complications were similar in AWR compared to non-AWR group (64% versus 50%, P = 0.46) however estimated blood loss (1000 mL versus 450 mL, P = 0.01) and operative time (663 min versus 510 min, P = 0.02) were significantly increased in the AWR group. CONCLUSIONS: The results of this study demonstrate that AWR is a safe and viable option and can improve wound closure and strength in select patient populations undergoing CRS-HIPEC. AWR is not associated with an increase in mortality or complication rate. Future studies will need larger sample sizes and randomization to identify patient and operative factors that increase morbidity with AWR and identify the ideal timing of AWR.
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Pared Abdominal/cirugía , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Hipertermia Inducida , Neoplasias/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , New Jersey/epidemiología , Estudios RetrospectivosRESUMEN
INTRODUCTION: Due to its increasing incidence and its major contribution to healthcare costs, cancer is a major public health problem in the United States. The impact across different services is not well documented and utilization of emergency departments (ED) by cancer patients is not well characterized. The aim of our study was to identify factors that can be addressed to improve the appropriate delivery of quality cancer care thereby reducing ED utilization, decreasing hospitalizations and reducing the related healthcare costs. METHODS: The New Jersey State Inpatient and Emergency Department Databases were used to identify the primary outcome variables; patient disposition and readmission rates. The independent variables were demographics, payer and clinical characteristics. Multivariable unconditional logistic regression models using clinical and demographic data were used to predict hospital admission or emergency department return. RESULTS: A total of 37,080 emergency department visits were cancer related with the most common diagnosis attributed to lung cancer (30.0%) and the most common presentation was pain. The disposition of patients who visit the ED due to cancer related issues is significantly affected by the factors of race (African American OR=0.6, p value=0.02 and Hispanic OR=0.5, p value=0.02, respectively), age aged 65 to 75years (SNF/ICF OR 2.35, p value=0.00 and Home Healthcare Service OR 5.15, p value=0.01, respectively), number of diagnoses (OR 1.26, p value=0.00), insurance payer (SNF/ICF OR 2.2, p value=0.02 and Home Healthcare Services OR 2.85, p value=0.07, respectively) and type of cancer (breast OR 0.54, p value=0.01, prostate OR 0.56, p value=0.01, uterine OR 0.37, p value=0.02, and other OR 0.62, p value=0.05, respectively). In addition, comorbidities increased the likelihood of death, being transferred to SNF/ICF, or utilization of home healthcare services (OR 1.6, p value=0.00, OR 1.18, p value=0.00, and OR 1.16, p value=0.04, respectively). Readmission is significantly affected by race (American Americans OR 0.41, standard error 0.08, p value=0.001 and Hispanics OR 0.29, standard error 0.11, p value=0.01, respectively), income (Quartile 2 OR 0.98, standard error 0.14, p value 0.01, Quartile 3 OR 1.07, standard error 0.13, p value 0.01, and Quartile 4 OR 0.88, standard error 0.12, p value 0.01, respectively), and type of cancer (prostate OR 0.25, standard error 0.09, p value=0.001). CONCLUSION: Web based symptom questionnaires, patient navigators, end of life nursing and clinical cancer pathways can identify, guide and prompt early initiation of treat before progression of symptoms in cancer patients most likely to visit the ED. Thus, improving cancer patient satisfaction, outcomes and reduce health care costs.
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Servicio de Urgencia en Hospital/tendencias , Hospitalización/tendencias , Neoplasias/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , New Jersey , Estados UnidosRESUMEN
BACKGROUND: Medical malpractice is a growing concern for physicians in all fields. Surgical fields have some of the highest malpractice premiums and litigation rates. Pancreaticoduodenectomy (PD) has become a popular procedure; however, it is still associated with significant morbidity and mortality. This study is the first to analyze factors involved in litigation regarding PD cases. METHODS: The Westlaw database was searched for jury verdicts and settlements using the terms "medical malpractice" and "pancreaticoduodenectomy". Twenty-nine cases from 1991 to 2012 were initially collected. Seven entries not involving PD and three duplicate cases were excluded. Nineteen cases were included for analysis. RESULTS: Of the 19 cases included in the analysis, three (15.8%) reached a settlement, three (15.8%) were ruled in favor of the plaintiff, and 13 (68.4%) were ruled in favor of the physician. The average settlement award was $398,333 (range, $195,000-500,000), and the average plaintiff award was $4,288,869 (range, $1,066,608-10,300,000). The most common factors raised in litigation included PD being allegedly unnecessary (47.4%), followed by postoperative negligence and misdiagnosis (36.8% each). CONCLUSIONS: The most common factors present in litigation included the allegation that PD was unnecessarily performed. The cases that are awarded large monetary sums are those that involve continued medical care. Ways to improve patient safety and limit litigation include increasing transparency and communication with a thorough discussion between surgeon and patient of the most common topics of litigation discussed.