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BACKGROUND: Lymph node metastasis is a critical prognostic factor for patients with gastric carcinoma (GC). Sentinel lymph node (SLN) mapping has the potential to identify the initial site of draining lymph node metastasis and reduce the extent of surgical lymphadenectomy. This study aimed to evaluate the diagnostic accuracy of SLN mapping in GC. METHODS: The study enrolled 129 GC patients undergoing total or partial gastrectomy with D2 lymphadenectomy and indocyanine green fluorescence-guided SLN mapping. The primary outcomes were the negative predictive value (NPV) and sensitivity of SLN mapping. The secondary outcomes were clinicopathologic factors associated with SLN mapping accuracy and successful SLN mapping. RESULTS: The SLN detection rate in this study was 86.8 %. The study had an overall NPV of 83.1 % and an overall sensitivity of 65.8 %. The NPV was found to be significantly higher in the patients with no lymphovascular invasion (LVI) than in those with LVI (96.0 % vs 59.3 %; p < 0.001) and in the patients whose pathologic T (pT) stage lower than 3 than in those whose T stage was 3 or higher (92.0 % vs 66.7 %; p = 0.009). The sensitivity of SLN mapping was 50 % in the patients with no LVI and 33 % in the patients with a pT stage lower than 3. CONCLUSION: The study results showed that for patients with early-stage GC with no LVI, negative SLN findings may represent a potential additive predictor indicating the absence of regional LN metastasis. However, given the low sensitivity rates noted, further research is needed to identify specific patient populations that may benefit from SLN mapping in GC.
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OBJECTIVE: The aim of this study was to elucidate the impact of intraoperative blood loss on outcomes following pancreatoduodenectomy (PD). BACKGROUND: The negative impact of intraoperative blood loss on outcomes in PD has long been suspected but not well characterized, particularly those factors that may be within surgeons' control. METHODS: From 2001 to 2015, 5323 PDs were performed by 62 surgeons from 17 institutions. Estimated blood loss (EBL) was discretized (0 to 300, 301 to 750, 751 to 1300, and >1300âmL) using optimal scaling methodology. Multivariable regression, adjusted for patient, surgeon, and institutional variables, was used to identify associations between EBL and perioperative outcomes. Factors associated with both increased and decreased EBL were elucidated. The relative impact of surgeon-modifiable contributors was estimated through beta coefficient standardization. RESULTS: The median EBL of the series was 400âmL [interquartile range (IQR) 250 to 600]. Intra-, post-, and perioperative transfusion rates were 15.8%, 24.8%, and 37.2%, respectively. Progressive EBL zones correlated with intra- but not postoperative transfusion in a dose-dependent fashion (P < 0.001), with a key threshold of 750âmL EBL (8.14% vs 40.9%; P < 0.001). Increasing blood loss significantly correlated with poor perioperative outcomes. Factors associated with increased EBL were trans-anastomotic stent placement, neoadjuvant chemotherapy, pancreaticogastrostomy reconstruction, multiorgan or vascular resection, and elevated operative time, of which 38.7% of the relative impact was "potentially modifiable" by the surgeon. Conversely, female sex, small duct, soft gland, minimally invasive approach, pylorus-preservation, biological sealant use, and institutional volume (≥67/year) were associated with decreased EBL, of which 13.6% was potentially under the surgeon's influence. CONCLUSION: Minimizing blood loss contributes to fewer intraoperative transfusions and better perioperative outcomes for PD. Improvements might be achieved by targeting modifiable factors that influence EBL.
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Pérdida de Sangre Quirúrgica/prevención & control , Pancreaticoduodenectomía , Complicaciones Posoperatorias/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to identify the optimal fistula mitigation strategy following pancreaticoduodenectomy. BACKGROUND: The utility of technical strategies to prevent clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) may vary by the circumstances of the anastomosis. The Fistula Risk Score (FRS) identifies a distinct high-risk cohort (FRS 7 to 10) that demonstrates substantially worse clinical outcomes. The value of various fistula mitigation strategies in these particular high-stakes cases has not been previously explored. METHODS: This multinational study included 5323 PDs performed by 62 surgeons at 17 institutions. Mitigation strategies, including both technique related (ie, pancreatogastrostomy reconstruction; dunking; tissue patches) and the use of adjuvant strategies (ie, intraperitoneal drains; anastomotic stents; prophylactic octreotide; tissue sealants), were evaluated using multivariable regression analysis and propensity score matching. RESULTS: A total of 522 (9.8%) PDs met high-risk FRS criteria, with an observed CR-POPF rate of 29.1%. Pancreatogastrostomy, prophylactic octreotide, and omission of externalized stents were each associated with an increased rate of CR-POPF (all P < 0.001). In a multivariable model accounting for patient, surgeon, and institutional characteristics, the use of external stents [odds ratio (OR) 0.45, 95% confidence interval (95% CI) 0.25-0.81] and the omission of prophylactic octreotide (OR 0.49, 95% CI 0.30-0.78) were independently associated with decreased CR-POPF occurrence. In the propensity score matched cohort, an "optimal" mitigation strategy (ie, externalized stent and no prophylactic octreotide) was associated with a reduced rate of CR-POPF (13.2% vs 33.5%, P < 0.001). CONCLUSIONS: The scenarios identified by the high-risk FRS zone represent challenging anastomoses associated with markedly elevated rates of fistula. Externalized stents and omission of prophylactic octreotide, in the setting of intraperitoneal drainage and pancreaticojejunostomy reconstruction, provides optimal outcomes.
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Fístula Pancreática/prevención & control , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/métodos , Anastomosis Quirúrgica/efectos adversos , Drenaje , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Humanos , Octreótido/efectos adversos , Octreótido/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , StentsRESUMEN
BACKGROUND: Rates of superficial surgical site infection (SSI) following pancreaticoduodenectomy remain high. Following resection for cancer, complications such as SSI impact adjuvant therapy delivery and portend worse survival. An incisional negative pressure dressing (iVAC) has been demonstrated to reduce SSI in other high-risk cohorts. METHODS: Following a comprehensive effort to identify patients at high risk for SSI, the practice patterns at a single academic center shifted and iVAC use increased. SSI rates were tracked in a prospectively maintained database and are reported. RESULTS: 394 patients underwent pancreaticoduodenectomy over 21 months. 120 patients (30.5%) had an iVAC applied. The overall rate of SSI was 19.8%. On multivariate analysis, increased risk for SSI was associated with neoadjuvant therapy, preoperative biliary interventions and prior abdominal surgery. iVAC use decreased the rate of SSI (OR 0.45, p = 0.015). In the highest-risk patients, SSI rate declined from 50% in patients without an iVAC to 19.1% with iVAC use (p = 0.015). CONCLUSION: The use of an iVAC following pancreaticoduodenectomy is associated with decreased SSI rates. This is particularly true for patients at highest risk as defined by a previously established risk scoring system in patients undergoing open pancreaticoduodenectomy.
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Terapia de Presión Negativa para Heridas , Pancreaticoduodenectomía/efectos adversos , Infección de la Herida Quirúrgica/prevención & control , Centros Médicos Académicos , Anciano , Baltimore , Bases de Datos Factuales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Terapia de Presión Negativa para Heridas/efectos adversos , Oportunidad Relativa , Pautas de la Práctica en Medicina , Factores Protectores , Estudios Retrospectivos , Factores de Riesgo , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/microbiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effect of providing personal clinical effectiveness performance feedback to general surgery residents regarding prescription of appropriate venous thromboembolism (VTE) prophylaxis. BACKGROUND: Residents are frequently charged with prescribing medications for patients, including VTE prophylaxis, but rarely receive individual performance feedback regarding these practice habits. METHODS: This prospective cohort study at the Johns Hopkins Hospital compared outcomes across 3 study periods: (1) baseline, (2) scorecard alone, and (3) scorecard plus coaching. All general surgery residents (nâ=â49) and surgical patients (nâ=â2420) for whom residents wrote admission orders during the first 9 months of the 2013-2014 academic year were included. Outcomes included the proportions of patients prescribed appropriate VTE prophylaxis, patients with preventable VTE, and residents prescribing appropriate VTE prophylaxis for every patient, and results from the Accreditation Council for Graduate Medical Education resident survey. RESULTS: At baseline, 89.4% of patients were prescribed appropriate VTE prophylaxis and only 45% of residents prescribed appropriate prophylaxis for every patient. During the scorecard period, appropriate VTE prophylaxis prescription significantly increased to 95.4% (Pâ<â0.001). For the scorecard plus coaching period, significantly more residents prescribed appropriate prophylaxis for every patient (78% vs 45%, Pâ=â0.0017). Preventable VTE was eliminated in both intervention periods (0% vs 0.35%, Pâ=â0.046). After providing feedback, significantly more residents reported receiving data about practice habits on the Accreditation Council for Graduate Medical Education resident survey (87% vs 38%, Pâ<â0.001). CONCLUSIONS: Providing personal clinical effectiveness feedback including data and peer-to-peer coaching improves resident performance, and results in a significant reduction in harm for patients.
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Competencia Clínica , Cirugía General/educación , Tromboembolia Venosa/prevención & control , Adulto , Baltimore , Educación de Postgrado en Medicina , Retroalimentación , Femenino , Humanos , Internado y Residencia , Masculino , Grupo Paritario , Estudios ProspectivosRESUMEN
OBJECTIVE: We assessed circulating tumor cells (CTCs) with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for patients with pancreatic adenocarcinoma (PDAC). BACKGROUND: PDAC is the fourth leading cause of cancer death in the United States. There is an urgent need to develop biomarkers that predict patient prognosis and allow for better treatment stratification. METHODS: Peripheral and portal blood samples were obtained from 50 patients with PDAC before surgical resection and filtered using the Isolation by Size of Epithelial Tumor cells method. CTCs were identified by immunofluorescence using commercially available antibodies to cytokeratin, vimentin, and CD45. RESULTS: Thirty-nine patients (78%) had epithelial CTCs that expressed cytokeratin but not CD45. Twenty-six (67%) of the 39 patients had CTCs which also expressed vimentin, a mesenchymal marker. No patients had cytokeratin-negative and vimentin-positive CTCs. The presence of cytokeratin-positive CTCs (P < 0.01), but not mesenchymal-like CTCs (P = 0.39), was associated with poorer survival. The presence of cytokeratin-positive CTCs remained a significant independent predictor of survival by multivariable analysis after accounting for other prognostic factors (P < 0.01). The detection of CTCs expressing both vimentin and cytokeratin was predictive of recurrence (P = 0.01). Among patients with cancer recurrence, those with vimentin-positive and cytokeratin-expressing CTCs had decreased median time to recurrence compared with patients without CTCs (P = 0.02). CONCLUSIONS: CTCs are an exciting potential strategy for understanding the biology of metastases, and provide prognostic utility for PDAC patients. CTCs exist as heterogeneous populations, and assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers.
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Adenocarcinoma/patología , Adenocarcinoma/cirugía , Células Neoplásicas Circulantes/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Queratinas/sangre , Antígenos Comunes de Leucocito/sangre , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Fenotipo , Pronóstico , Tasa de Supervivencia , Vimentina/sangreRESUMEN
BACKGROUND: Sandwich ventral hernia repair (SVHR) may reduce ventral hernia recurrence rates, although with an increased risk of surgical site occurrences (SSOs) and surgical site infections (SSIs). Previously, we found that a modified negative pressure wound therapy (hybrid vacuum-assisted closure [HVAC]) system reduced SSOs and SSIs after ventral hernia repair. We aimed to describe our outcomes after SVHR paired with HVAC closure. METHODS: We conducted a 4-y retrospective review of all complex SVHRs (biologic mesh underlay and synthetic mesh overlay) with HVAC closure performed at our institution by a single surgeon. All patients had fascial defects that could not be reapproximated primarily using anterior component separation. Descriptive statistics were used to report the incidence of postoperative complications and hernia recurrence. RESULTS: A total of 60 patients (59.3 ± 11.4 y, 58.3% male, 75% American Society of Anesthesiologists class ≥3) with complex ventral hernias being underwent sandwich repair with HVAC closure. Major postoperative morbidity (Dindo-Clavien class ≥3) occurred in 14 (23.3%) patients, but incidence of SSO (n = 13, 21.7%) and SSI (n = 4, 6.7%) was low compared with historical reports. Median follow-up time for all patients was 12 mo (interquartile range 5.8-26.5 mo). Hernia recurrence occurred in eight patients (13.3%) after a median time of 20.6 months (interquartile range 16.4- 25.4 months). CONCLUSIONS: Use of a dual layer sandwich repair for complex abdominal wall reconstruction is associated with low rates of hernia recurrence at 1 year postoperatively. The addition of the HVAC closure system may reduce the risk of SSOs and SSIs previously reported with this technique and deserves consideration in future prospective studies assessing optimization of ventral hernia repair approaches.
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Hernia Ventral/cirugía , Herniorrafia/métodos , Terapia de Presión Negativa para Heridas , Anciano , Baltimore/epidemiología , Femenino , Estudios de Seguimiento , Herniorrafia/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios RetrospectivosRESUMEN
Intraductal papillary mucinous neoplasms (IPMN) are cystic precursors to pancreatic cancer believed to arise within a widespread neoplastic field defect. The tendency for some patients to present with multifocal disease and/or develop additional lesions over time argues in favor of a field defect and complicates surgical management decisions. Surgery usually consists of partial pancreatic resection, which leaves behind a pancreatic remnant at risk for recurrent disease and progression to cancer. As an alternative, total pancreatectomy (TP) provides the most complete oncologic resection, but postoperative morbidity and quality of life (QoL) issues have generally limited its use to only the highest risk patients. Significant progress has been made in the management of the post-TP apancreatic state and studies now show less morbidity with acceptable QoL comparable to type 1 diabetic and post-pancreaticoduodenectomy patients. These improvements do not yet justify the routine use of TP, but they have opened the door for expansion to additional subsets of non-invasive IPMN. Here, we have identified several groups of patients that we believe would benefit from TP over partial resection based on the most current literature.
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Recurrencia Local de Neoplasia , Neoplasias Quísticas, Mucinosas y Serosas/patología , Neoplasias Quísticas, Mucinosas y Serosas/cirugía , Neoplasias Primarias Múltiples/cirugía , Pancreatectomía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Humanos , Márgenes de Escisión , Neoplasia Residual , Neoplasias Primarias Múltiples/patología , Pancreatectomía/efectos adversos , Pancreatectomía/métodos , Conductos Pancreáticos/patología , Selección de Paciente , Guías de Práctica Clínica como Asunto , Calidad de VidaRESUMEN
BACKGROUND: Although pancreaticoduodenectomy (PD) outcomes have improved, complications including surgical site infection (SSI) remain common. We present a stratification tool to predict risk for SSI after PD. METHODS: Data was retrospectively reviewed on all patients undergoing PD at a tertiary hospital (9/2011-8/2014). Potential SSI risk factors identified by univariate analysis were incorporated into a multivariate logistic regression model. The resulting odds ratios were converted into a point system to create an SSI risk score with internal validation. RESULTS: Six hundred seventy nine patients underwent PD and were chronologically split into derivation (443 patients) and validation (236 patients) groups. There was no difference in demographics or perioperative outcomes between groups. Overall thirty-day SSI was observed in 17.2% (n = 117). Neoadjuvant chemotherapy and/or radiation, intraoperative red blood cell transfusion, operative time greater than 7 h, preoperative bile stent/drain, and vascular resection were associated with SSI in univariate analysis (all p < 0.05). On multivariate analysis, preoperative bile stent/drain and neoadjuvant chemotherapy were independent predictors of SSI, each assigned 1 point (both p < 0.001). Patients with 0, 1, and 2 points, respectively, had 0%, 32%, and 64% predicted risk of SSI (AUC = 0.73, R2 = 0.93). The model performed equivalently in the validation group (AUC = 0.77, R2 = 0.99). CONCLUSION: This novel, validated risk score accurately predicts SSI risk after pancreaticoduodenectomy. Identifying the highest risk patients can help target interventions to reduce SSI.
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Carcinoma Ductal Pancreático/cirugía , Técnicas de Apoyo para la Decisión , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/efectos adversos , Infección de la Herida Quirúrgica/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/patología , Quimioterapia Adyuvante/efectos adversos , Drenaje/efectos adversos , Drenaje/instrumentación , Femenino , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Terapia de Presión Negativa para Heridas , Terapia Neoadyuvante/efectos adversos , Oportunidad Relativa , Neoplasias Pancreáticas/patología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Stents , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/prevención & control , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19(th) century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20(th) century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.
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The incidence of pancreatic adenocarcinoma (PDAC) has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy (PM) has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.
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Even with improved cancer care generally, the incidence and death rate is increasing for pancreatic cancer. Concern exists that a further increase in deaths caused by pancreatic cancer will be seen as other causes of death, such as heart disease and other cancers, decline. Critical exploration of screening high-risk patients as a tool to reduce deaths from pancreatic cancer should be considered. Technological advances and improved understanding of pancreatic cancer biology provides an opportunity to identify and test a panel of early detection biomarkers easily, accurately, and inexpensively measured in blood, urine, stool, or saliva samples. These biomarkers may have additional usefulness in staging, stratification for treatment, establishing prognosis, and assessing response to therapy in this disease. Screening may prove to be one of several strategies to improve outcomes in a disease that has otherwise been difficult to defeat.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/prevención & control , Tamizaje Masivo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/prevención & control , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Biomarcadores de Tumor/sangre , Diagnóstico por Imagen , Diagnóstico Precoz , Humanos , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/cirugía , Lesiones Precancerosas/diagnóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Despite numerous potential benefits of outpatient surgery, there is currently a lack of national benchmarking data available for hospitals and surgeons to compare their own outcomes as they transition toward outpatient surgery. MATERIALS AND METHODS: Patients who underwent 14 common general surgery operations from 2016-2020 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Operations were selected based on frequency and the ability to be performed both in- and outpatient. Postoperative complications and readmissions were compared between patients who underwent inpatient vs outpatient surgery. After adjusting for patient comorbidities, multivariable models assessed the effect of patient characteristics on the odds of experiencing postoperative complications. A separate multiinstitutional study of 21 affiliated hospitals assessed practice variation. RESULTS: In 13 of the 14 studied procedures, complications were lower for patients who were selected for outpatient surgery (all P<0.01); minimally invasive (MIS) adrenalectomy showed no difference (P=0.61). Multivariable analysis confirmed these findings; the odds of experiencing any adverse events were lower following outpatient surgery in all operations but MIS adrenalectomy (OR 0.97; 95% CI 0.47-2.02). Analysis of institutional practices demonstrated variation in the rate of outpatient surgery in certain breast, endocrine, and hernia repair operations. CONCLUSIONS: Institutional practice patterns may explain the national variation in the rate of outpatient surgery. While the present data does not support the adoption of outpatient surgery to less optimal candidates, addressing unexplained practice variations could result in improved utilization of outpatient surgery.
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Pancreatic cancer is the fourth most common cause of cancer mortality in the United States, with 5-year survival rates for patients with resectable tumors ranging from 15% to 20%. However, most patients presenting with distant metastases, are not resectable, and have a 5-year survival rate of close to 0%. This demonstrates a need for improved screening to identify pancreatic cancer while the tumor is still localized and amenable to surgical resection. Studies of patients with pancreatic tumors incidentally diagnosed demonstrate longer median survival than tumors discovered only when the patient is symptomatic, suggesting that early detection may improve outcome. Recent evidence from genomic sequencing indicates a 15-year interval for genetic progression of pancreatic cancer from initiation to the metastatic stage, suggesting a sufficient window for early detection. Still, many challenges remain in implementing effective screening. Early diagnosis of pancreatic cancer relies on developing screening methodologies with highly sensitive and specific biomarkers and imaging modalities. It also depends on a better understanding of the risk factors and natural history of the disease to accurately identify high-risk groups that would be best served by screening. This review summarizes our current understanding of the biology of pancreatic cancer relevant to methods available for screening. At this time, given the lack of proven benefit in this disease, screening efforts should probably be undertaken in the context of prospective trials.
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Adenocarcinoma/diagnóstico , Detección Precoz del Cáncer/métodos , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/sangre , Adenocarcinoma/etiología , Adenocarcinoma/mortalidad , Biomarcadores de Tumor/sangre , Endosonografía , Humanos , Imagen por Resonancia Magnética , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/mortalidad , Lesiones Precancerosas/diagnóstico , Factores de Riesgo , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Estados UnidosRESUMEN
PURPOSE: We determined whether a large, multianalyte panel of circulating biomarkers can improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: We defined a biologically relevant subspace of blood analytes on the basis of previous identification in premalignant lesions or early-stage PDAC and evaluated each in pilot studies. The 31 analytes that met minimum diagnostic accuracy were measured in serum of 837 subjects (461 healthy, 194 benign pancreatic disease, and 182 early-stage PDAC). We used machine learning to develop classification algorithms using the relationship between subjects on the basis of their changes across the predictors. Model performance was subsequently evaluated in an independent validation data set from 186 additional subjects. RESULTS: A classification model was trained on 669 subjects (358 healthy, 159 benign, and 152 early-stage PDAC). Model evaluation on a hold-out test set of 168 subjects (103 healthy, 35 benign, and 30 early-stage PDAC) yielded an area under the receiver operating characteristic curve (AUC) of 0.920 for classification of PDAC from non-PDAC (benign and healthy controls) and an AUC of 0.944 for PDAC versus healthy controls. The algorithm was then validated in 146 subsequent cases presenting with pancreatic disease (73 benign pancreatic disease and 73 early- and late-stage PDAC cases) and 40 healthy control subjects. The validation set yielded an AUC of 0.919 for classification of PDAC from non-PDAC and an AUC of 0.925 for PDAC versus healthy controls. CONCLUSION: Individually weak serum biomarkers can be combined into a strong classification algorithm to develop a blood test to identify patients who may benefit from further testing.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Adenocarcinoma/diagnóstico , Biomarcadores de Tumor , Estudios de Casos y Controles , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Neoplasias PancreáticasRESUMEN
BACKGROUND: Surgery for intraductal papillary mucinous neoplasm (IPMN) in older adults requires a careful balance of risk and benefit. We sought to analyze patient outcomes in the older individuals after pancreatic resection for IPMN. METHODS: Retrospective analysis of a prospectively maintained database was performed for patients 65 years or older undergoing IPMN resection between January 1, 2012 and December 31, 2017. Statistical analysis was performed based on age and Memorial Sloan Kettering Frailty Index (MSKFI) score. RESULTS: 148 patients underwent resection of an IPMN, including five patients who required two operations for recurrent disease. Median age at surgery was 74 (range, 65-90 years), and 52% were male. Most patients underwent pancreaticoduodenectomy (53%) or distal pancreatectomy/splenectomy (35%). An associated adenocarcinoma was seen on pathology for 56 patients (37%). Median hospital length of stay was 7 days (range, 4-46 days). Grade 3 or higher post-operative complications on the Clavien-Dindo classification scale were seen in 20%. No patient died within 30-days. Patient outcomes were evaluated by age, split at age ≥75 (considered "elderly"), and separately by MSKFI score. No differences in post-operative morbidity or mortality was seen when stratified by age (65 - 74 vs > 75 years) or by MSKFI frailty score. CONCLUSION: Pancreatic resection can be safely performed in selected patients 65 years and older with low morbidity and mortality. More analysis is needed to determine if MSKFI score is a useful predictor of complications in older individuals.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Fragilidad , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/patología , Anciano , Carcinoma Ductal Pancreático/patología , Femenino , Humanos , Masculino , Pancreatectomía , Neoplasias Intraductales Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to the development of pancreatic adenocarcinoma. We determined if non-O blood groups are more common in patients with IPMN and if blood group is a risk factor for progression to invasive pancreatic cancer among patients with IPMN. METHODS: The medical records were reviewed of all patients undergoing resection of an IPMN at Johns Hopkins Hospital from June 1997 to August 2016. Potential risk factors of high-grade dysplasia and associated adenocarcinoma were identified through a multivariate logistic regression model. RESULTS: Seven hundred and seventy-seven patients underwent surgical resection of an IPMN in which preoperative blood type was known. Sixty-two percent of IPMN patients had non-O blood groups (vs. 57% in two large US reference cohorts, P = 0.002). The association between non-O blood group was significant for patients with IPMN with low- or intermediate-grade dysplasia (P < 0.001), not for those with high-grade dysplasia (P = 0.68). Low- and intermediate-grade IPMNs were more likely to have non-type O blood compared to those with high-grade IPMN and/or associated invasive adenocarcinoma (P = 0.045). Blood type O was an independent predictor of having high-grade dysplasia without associated adenocarcinoma (P = 0.02), but not having associated invasive cancer (P = 0.72). The main risk factor for progression to invasive cancer after surgical resection was IPMN with high-grade dysplasia (P = 0.002). CONCLUSION: IPMN patients are more likely to have non-O blood groups than controls, but type O blood group carriers had higher odds of having high-grade dysplasia in their IPMN. These results indicate blood group status may have different effects on the risk and progression of IPMNs.
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Sistema del Grupo Sanguíneo ABO , Adenocarcinoma/sangre , Adenocarcinoma/patología , Neoplasias Gastrointestinales/sangre , Neoplasias Gastrointestinales/patología , Conductos Pancreáticos/patología , Adenocarcinoma/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Gastrointestinales/etiología , Humanos , Hiperplasia/patología , Masculino , Persona de Mediana Edad , Pancreatectomía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Purpose: Circulating tumor cells (CTCs) have been identified in the blood of patients with pancreatic adenocarcinoma (PDAC), but little is known about the exact phenotype of these cells. We assessed expression of aldehyde dehydrogenase (ALDH), CD133, and CD44 as markers of CTCs with a tumor-initiating cell (TIC) phenotype in patients with PDAC and the relationship of this expression to patient outcomes.Experimental Design: Peripheral blood from 60 consecutive patients with PDAC undergoing surgical resection was obtained and processed using the Isolation by Size of Epithelial Tumor (ISET) method. Immunofluorescence was used to identify CTCs expressing cytokeratin, CD133, CD44, and ALDH.Results: Forty-seven patients (78%) had epithelial CTCs staining positive for pan-cytokeratin and at least one TIC marker. Forty-six patients (77%) had epithelial CTCs that labeled with antibodies to cytokeratin and ALDH. By separate analysis, 34 (57%) had cytokeratin-positive, CD133-positive, and CD44-positive (triple-positive) CTCs, whereas 40 (67%) had cytokeratin-positive, CD133-positive, CD44-negative CTCs. The remaining 13 patients did not have CTCs, as defined by cytokeratin expression. ALDH-positive CTCs and triple-positive CTCs were significantly associated with worse survival by univariate analysis, even when accounting for other significant prognostic factors (all, P ≤ 0.01). ALDH-positive CTCs, triple-positive CTCs, and dual cytokeratin- and CD133-positive CTCs were independent predictors of tumor recurrence by logistic regression analysis and associated with decreased disease-free survival (all, P ≤ 0.03).Conclusions: CTCs labeling with one or more markers of TICs are found in a majority of patients with PDAC and are independently predictive of decreased disease-free and overall survival. Clin Cancer Res; 23(11); 2681-90. ©2016 AACR.
Asunto(s)
Antígeno AC133/sangre , Adenocarcinoma/sangre , Aldehído Deshidrogenasa/sangre , Carcinoma Ductal Pancreático/sangre , Receptores de Hialuranos/sangre , Queratinas/sangre , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , PronósticoRESUMEN
OBJECTIVES: Circulating epithelial cells (CECs) are identified in the blood of patients with intraductal papillary mucinous neoplasms (IPMNs) despite the absence of malignancy. We assessed the blood of patients undergoing resection for IPMN or other benign pancreatic lesions for CECs. METHODS: Peripheral blood was collected from 26 patients prior to pancreatic resection and filtered by the ISET (Isolation by Size of Epithelial Tumor Cells) method. Circulating epithelial cells were identified with antibodies to cytokeratin and Pdx1 (pancreas and duodenal homeobox protein 1), a pancreas marker. RESULTS: Nineteen patients underwent resection of an IPMN without associated malignancy. Eleven patients (58%) had cytokeratin-positive CECs. Circulating epithelial cells were significantly more likely to be found in patients with IPMNs with high-grade dysplasia (P = 0.04). In addition, 10 of the 11 patients with cytokeratin-positive CECs also had separate populations of cytokeratin-positive, Pdx1-positive CECs, suggesting a pancreatic source. Dual-staining CECs were more frequently found in patients with high-grade dysplasia (P = 0.04). Patients with IPMNs were significantly more likely to have pan-cytokeratin CECs in the blood compared with those without IPMNs (P = 0.01). CONCLUSIONS: Circulating epithelial cells staining with potential pancreas-specific markers have been found in patients with IPMNs, even without malignancy. Circulating epithelial cells may help to differentiate patients with high-grade IPMN from lower grades of dysplasia and other pancreatic cysts.