RESUMO
BACKGROUND: Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS: Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS: Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS: Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Neoplasias Peritoneais/terapia , Gastrectomia , Adenocarcinoma/cirurgia , Neoplasias Gástricas/cirurgia , Junção Esofagogástrica/cirurgia , Neoplasias Esofágicas/cirurgia , Estadiamento de NeoplasiasRESUMO
Background: We present our experience and established management strategy for endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in diagnosing suspected pancreatic neoplasms at a tertiary referral cancer hospital. Method: Relevant data were extracted from our database for patients who underwent EUS-FNA for suspected pancreatic neoplasms at our institution between 2007 and 2016. Results: Among the 309 patients, the median age was 67 years and 56% were men. The most common presenting symptoms were abdominal pain (37%) and jaundice (29%). Concordance between radiographic diagnosis and final pathology was 89%. The mean lesion size was 34.9 mm on computed tomography and 31.5 mm on EUS. There were 197 patients (64%) with localized disease, of whom 115 (58%) had resectable lesions, 61 (31%) had borderline resectable, and 21 (11%) had unresectable lesions (mean CA 19-9 levels 1705 U/mL, 2490 U/mL, and 479 U/mL, respectively). A median of 3 FNA passes were performed to establish a pathologic diagnosis. Two patients (1%) had postprocedural adverse events. Median overall survival was 47 months in those who underwent surgery after EUS and 12 months in those who did not (P<0.001). Conclusions: A multidisciplinary approach is employed for management of suspected pancreatic neoplasm at our tertiary cancer center. A combination of cross-sectional imaging and EUS-FNA serves as a highly effective duo in establishing a tissue diagnosis and staging with a low adverse event rate. Counterintuitively, CA 19-9 is not necessarily higher with resectable lesions than with unresectable lesions, indicating the limitation of CA 19-9 as a pancreatic tumor marker.
RESUMO
BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care regimens. Differences between ODSA results and patient tumor responses were assessed by exact McNemar's test.RESULTSImmunofluorescence signals, organoid growth curves, and Ki-67 levels were measured and authenticated through the OBP for up to 14 days. ODSA drug responses were not different from patient tumor responses, as reflected by CA19-9 reductions following neoadjuvant chemotherapy (P = 0.99). PDOs demonstrated unique apoptotic and tumor-stroma modulation profiles (P < 0.0001). α-SMA/CK-19 ratio levels of more than 1.0 were associated with improved outcomes (P = 0.0179) and longer parental patient survival by Kaplan-Meier analysis (P = 0.0046).CONCLUSIONHeterogenous apoptotic drug responses and tumor-stroma modulation are present in PDOs after standard-of-care chemotherapy. Ratios of α-SMA and CK-19 levels in PDOs are associated with patient survival, and the OBP could aid in the selection of personalized therapies to improve the efficacy of systemic therapy in patients with PDAC.FUNDINGNIH/National Cancer Institute grants (K08CA218690, P01 CA117969, R50 CA243707-01A1, U54CA224065), the Skip Viragh Foundation, the Bettie Willerson Driver Cancer Research Fund, and a Cancer Center Support Grant for the Flow Cytometry and Cellular Imaging Core Facility (P30CA16672).
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Medicina de Precisão , Estudos Retrospectivos , Imageamento Tridimensional , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Organoides/patologia , Neoplasias PancreáticasRESUMO
BACKGROUND: In retrospective studies the definition of salvage esophagectomy has been inconsistent and is a source of bias. We sought to describe how variability in the definition of salvage affects comparative outcomes of trimodality therapy (TMT) and bimodality therapy (BMT). METHODS: Patients with locally advanced esophageal squamous cell carcinoma who completed chemoradiation therapy (CRT) from 2002 to 2017 were identified. TMT included patients who had a planned esophagectomy after CRT. BMT included patients treated with CRT only plus salvage esophagectomy, variably defined as an esophagectomy occurring (A) 3 months after CRT; (B) 3 months after CRT, excluding delayed recovery; (C) 3 months after CRT, excluding delayed workup; or (D) 6 months after CRT. Long-term survival outcomes between the TMT and BMT groups were compared for each definition of salvage esophagectomy. Time to surgery was included a priori in a multivariable model for overall survival. RESULTS: Of 143 patients, 90 (63%) underwent esophagectomy and 53 (37%) received CRT only. Although the total patients remained the same, the composition of the TMT and BMT groups varied by salvage definitions A through D. Various definitions resulted in different 5-year survival rates for TMT vs BMT groups: (A) 56% vs 39%, (B) 61% vs 34%, (C) 50% vs 42%, and (D) 51% vs 39%. In a Cox multivariable analysis age and proximal/middle esophageal tumors were associated with worse postoperative survival, but time to surgery was not. CONCLUSIONS: Slight variations in the definition of salvage esophagectomy can influence the interpretation of TMT and BMT outcomes. Future studies should consistently define treatment groups.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Esofagectomia/métodos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/etiologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Estudos Retrospectivos , Terapia de Salvação/métodos , Quimiorradioterapia , Células Epiteliais/patologia , Resultado do TratamentoRESUMO
PURPOSE: Precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC) are imperative for improving disease outcomes. With molecular subtypes of PDAC gaining relevance in the context of therapeutic stratification, the ability to characterize heterogeneity of cancer-specific gene expression patterns is of great interest. In addition, understanding patterns of immune evasion within PDAC is of importance as novel immunotherapeutic strategies are developed. EXPERIMENTAL DESIGN: Single-cell RNA sequencing (scRNA-seq) is readily applicable to limited biopsies from human primary and metastatic PDAC and identifies most cancers as being an admixture of previously described epithelial transcriptomic subtypes. RESULTS: Integrative analyses of our data provide an in-depth characterization of the heterogeneity within the tumor microenvironment, including cancer-associated fibroblast subclasses, and predicts for a multitude of ligand-receptor interactions, revealing potential targets for immunotherapy approaches. CONCLUSIONS: Our analysis demonstrates that the use of de novo biopsies from patients with PDAC paired with scRNA-seq may facilitate therapeutic prediction from limited biopsy samples.
Assuntos
Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Transcriptoma , Biópsia , Humanos , Microambiente Tumoral , Sequenciamento do ExomaRESUMO
BACKGROUND: Previous studies evaluating self-expandable metal stents (SEMS) for management of malignant extrinsic colon obstruction have yielded conflicting results. We evaluated the efficacy of uncovered SEMS for extrinsic colon malignancy (ECM) versus intrinsic colon malignancy (ICM). METHODS: Retrospective review of all patients referred for colonic SEMS at a tertiary cancer center between 2007 and 2018 was performed. Primary outcome measures were technical success, clinical success, intervention rate, and overall survival. RESULTS: 138 patients with ECM and 119 patients with ICM underwent attempted stent placement. The rectum and/or sigmoid colon was the most common stricture site. Technical success was lower in the ECM group [86% vs 96% (p = .009)]. Clinical success was lower in the ECM group both at 7 days [82% vs 95% (p = .004)] and at 90 days [60% vs 86% (p < .001)]. Subsequent intervention was required more frequently [44% vs 35%; p = .23] and earlier [median 9 vs 132 days; p < .001] in the ECM group. Median overall survival in the ECM group was 92 vs 167 days. Among predictive variables analyzed, the ECM group had a higher frequency of peritoneal metastasis (87% vs 32%; p < .001), multifocal strictures with requirement for multiple stents (20% vs 6%; p = .002), sharp angulated strictures (39% vs 25%; p = .04) , and radiation therapy (21% vs 10%; p = .02). CONCLUSIONS: Colonic SEMS for ECM is associated with lower technical and clinical success with earlier intervention rates compared with ICM. Our findings can be used to better inform patients and referring providers as well as guide new stent design to enhance efficacy in this population.
Assuntos
Neoplasias do Colo , Obstrução Intestinal , Neoplasias do Colo/complicações , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Cuidados Paliativos , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
PURPOSE: Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials. EXPERIMENTAL DESIGN: Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC. RESULTS: Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort. CONCLUSIONS: Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis.
Assuntos
Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Variações do Número de Cópias de DNA , Análise Mutacional de DNA/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Estudos de Viabilidade , Feminino , Heterogeneidade Genética , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Projetos Piloto , Prognóstico , Intervalo Livre de Progressão , Sequenciamento do ExomaRESUMO
BACKGROUND AND OBJECTIVE: The widespread use of colonoscopy has led to an increasing number of subepithelial lesions (SELs) being detected in the lower gastrointestinal (GI) tract. This study aimed to analyze the utility of EUS and its role in the management of lower GI SELs. PATIENTS AND METHODS: Records of all patients who were referred for lower EUS evaluation of a SEL at a tertiary center between 2007 and 2018 were retrospectively reviewed after IRB approval. Data collection included patient/lesion characteristics, technical details of procedure, and pathology results. RESULTS: A total of 47 patients underwent EUS examinations for the evaluation of 49 suspected SEL in the lower GI tract (2 patients had 2 SELs each). Out of the 49 suspected lesions, the most frequent location was in the rectum (30/49, 61.2%). EUS showed extraluminal compression in 2 cases (2/49, 4.1%) and intraluminal lesions were identified in 40 cases (40/49, 81.6%). In 7 patients (7/49, 14.3%), no lesion could be identified by EUS. Twenty (20/49, 40.8%) SELs were malignant or had malignant potential. Twenty-six EUS-guided fine-needle aspirations (FNAs) and 14 EUS-core biopsies were performed. EUS-FNA alone was able to correctly diagnose 15/26 (57.7%) of the lower SELs. When EUS-guided fine needle biopsies (FNB) were performed during the same procedure, the final diagnosis was confirmed in 21/26 (80.8%) cases. There was only one procedure-related complication caused by use of narcotics. CONCLUSION: EUS-guided FNA/FNB are feasible and safe techniques for assessing lower GI SELs and provide valuable information regarding lesion characteristics and their malignant potential with high diagnostic accuracy.
RESUMO
BACKGROUND: Adenocarcinoma of the gastroesophageal junction (AEG) poses a management challenge, as preoperative prediction of occult mediastinal nodal metastasis is difficult. We sought to identify factors predictive of mediastinal involvement among patients undergoing trimodality therapy. METHODS: Patients undergoing trimodality therapy for Siewert II and III AEG at a single institution between 2000 and 2015 were identified. Mediastinal involvement was defined as pathologic nodal involvement after neoadjuvant chemoradiation (ypN+) in mediastinal stations or mediastinal recurrence 2 years or less after resection. Maximal χ2 analysis and Youden's J index were used to identify the pretreatment proximal tumor extent that best discriminated mediastinal involvement. RESULTS: In all, 204 patients (151 [74%] AEG II, 53 [26%] AEG III) were included, of whom 47 (23%) had clinical evidence of thoracic nodal disease. Thirty-one of the 204 patients (15%) met criteria for mediastinal involvement (24 of 31 ypN+, 10 of 31 mediastinal recurrence). Patients with mediastinal involvement had greater proximal tumor extent (median 2 cm [interquartile range, 1.0 to 3.0 cm] vs 1.4 cm [interquartile range, 0.7 to 3.0 cm], P = .030), were more frequently Siewert II lesions (27 of 31 [87.1%] vs 124 of 173 [71.7%], P = .071), and were more often observed to have clinical thoracic nodal metastasis (cN) evidence (13 of 31 [42%] vs 34 of 173 [20%], P = .007) than patients who did not. On multivariable analysis of patients with intrathoracic cN0, esophageal extent of 1.5 cm or greater was independently predictive of mediastinal involvement (odds ratio 5.46, P = .011), whereas Siewert classification was not (Siewert II odds ratio 3.48, P = .116). CONCLUSIONS: Pretreatment proximal tumor extent, rather than Siewert classification, is an independent predictor of mediastinal involvement among AEG II/III patients without clinical evidence of mediastinal metastasis and should be considered during treatment planning.
Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Linfonodos/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/mortalidade , Idoso , Quimiorradioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Neoplasias Esofágicas/classificação , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Esofagectomia/métodos , Junção Esofagogástrica/cirurgia , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Mediastino/patologia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/classificação , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Análise de SobrevidaRESUMO
Endoscopic mucosal resection (EMR) can be an effective therapy for superficial esophageal cancer. Many patients with cT2 invasion by endoscopic ultrasound (EUS) receive surgery but are subsequently found to have superficial disease. The purpose of this study was to investigate the safety profile and the added value of attempting EMR for EUS-staged cT2N0 esophageal cancer. A retrospective review was performed at a single institution from 2008 to 2017. Patients who were staged cT2N0 by EUS were identified from a prospectively maintained surgical database. Among 75 patients identified for analysis, 30 underwent an attempt at EMR. No perforations or other immediate complications occurred. EMR was more likely to be attempted among older patients (P = 0.001) with smaller tumor size (P < 0.001) and diminished SUVmax (P = 0.001). At the time of treatment, EMR was successful in clearing all known disease among 17/30 patients, with 12 representing pT1a or less and 5 representing pT1b with negative margins. Among the 17 patients for whom EMR was able to clear all known disease, there were no recurrences or cancer-related deaths. Although all the patients were staged as cT2N0 by EUS, many patients were identified by EMR to have superficial disease. There were no perforations or other adverse events related to EMR. Furthermore, EMR cleared all known disease among 17 patients with no known recurrences or cancer-related deaths. The results indicate that EMR for cT2N0 esophageal cancer is a safe diagnostic option that is therapeutic for some.
Assuntos
Ressecção Endoscópica de Mucosa/estatística & dados numéricos , Neoplasias Esofágicas/cirurgia , Esofagectomia/estatística & dados numéricos , Seleção de Pacientes , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , UltrassonografiaRESUMO
INTRODUCTION: Barrett's esophagus (BE) may be present in patients with esophageal adenocarcinoma (EAC) after bimodality therapy (BMT). There is no specific guidance for follow-up of these patients with regard to the presence of BE or dysplasia. In this study, we assessed the outcomes of patients who, after BMT, had BE and those who did not. METHOD: Patients with EAC who had BMT were identified and analyzed retrospectively in two groups, with and without BE. We compared patient characteristics and outcome variables (local, distant, and no recurrence). RESULTS: Of 228 patients with EAC, 68 (29.8%) had BE before BMT. Ninety-eight (42.9%) had BE after BMT, and endoscopic intervention was done in 11 (11.2%). With a median follow-up of 37 months, the presence of post-BMT BE was not significantly associated with overall survival (OS) and local recurrence-free survival (LRFS). Similarly, endoscopic intervention was not significantly associated with OS and LRFS. Fifty (73.5%) patients with BE before BMT had BE after BMT (p < 0.0001). CONCLUSION: The presence of BE after BMT was not associated with increased risk of local recurrence. The local recurrence rate was not influenced by endoscopic intervention. Prospective studies are warranted to generate guidance for intervention, if necessary, for this group of EAC patients.
Assuntos
Adenocarcinoma/terapia , Esôfago de Barrett/patologia , Quimiorradioterapia/métodos , Endoscopia/métodos , Neoplasias Esofágicas/terapia , Esôfago/patologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/terapia , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
OBJECTIVE: The goal of surveillance after therapy of localized esophageal cancer (LEC) is to identify actionable relapses amenable to salvage; however, the current surveillance algorithms are not optimized. We report on a large cohort of LEC patients with actionable locoregional relapses (LRRs). METHODS: Between 2000 and 2013, 127 (denominator = 752) patients with actionable LRR were identified. Histologic/cytologic confirmation was the gold standard. All surveillance tools (imaging, endoscopy, fine needle aspiration) were assessed. RESULTS: Most patients were men (89%), had adenocarcinoma (79%), and had no new symptoms (72%) when diagnosed with LRR. In trimodality patients, endoscopic confirmation of positron emission tomography-computed tomography-suspected LRR occurred in only 44%, and 56% required additional tools (e.g., fine needle aspiration). Alternatively, in bimodality patients, endoscopy confirmed LRRs in 81%. Trimodality patients had a higher risk of subsequent LRR/distant metastases after the first LRR than the bimodality patients (p = 0.03). In all patients, 78% of the subsequent relapses were distant. For patients who were salvaged, survival was significantly prolonged (50.6 vs. 25.1 months, p < 0.01). CONCLUSIONS: Patients live longer after successful salvage of the LRR than if salvage is not possible. After LRR, patients have a high risk of subsequent distant metastasis and whether the second relapse is local or distant, survival is uniformly poor.
Assuntos
Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico , Terapia de Salvação/métodos , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Neoplasias Esofágicas/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
BACKGROUND AND AIMS: Pancreatic cancer (PC) is a deadly disease that is most commonly diagnosed at an incurable stage. Different high-risk genetic variants and cancer syndromes increase the lifetime risk of developing PC. This study aims to assess the yield of initial PC screening in patients with high-risk germline mutations. METHODS: Asymptomatic adults underwent PC screening by EUS, magnetic resonance imaging, or CT during a 10-year period and were retrospectively identified. High-risk individuals were defined as carrying germline mutations in BRCA1, BRCA2, p53 (Li-Fraumeni), STK11 (Peutz-Jeghers), MSH2 (Lynch), ATM (ataxia-telangiectasia), or APC (familial adenomatous polyposis). Patients without germline mutations were excluded. RESULTS: In total, 86 patients met the study criteria. The median age was 48.5 years (interquartile range, 40-58), 79.1% (68) were women, and 43.0% (37) had a family history of PC. The genetic mutations were BRCA2 (50, 58.1%), BRCA1 (14, 16.3%), p53 (12, 14.0%), STK11 (5, 5.8%), MSH2 (3, 3.5%), ATM (1, 1.2%), and APC (1, 1.2%). Screening detected a pancreatic abnormality (PA) in 26.7% (23/86), including cysts (11, 47.8%), hyperechoic strands and foci (10, 43.5%), and mild pancreatic duct dilation (2, 8.7%). Patients older than 60 years were more likely to have a PA detected (P = .043). EUS detected more PAs than magnetic resonance imaging or CT. No cases of PC were diagnosed by screening or during follow-up (median, 29.8 months; interquartile range, 21.7-43.5). CONCLUSIONS: Unless indicated otherwise by family or personal history, PC screening under the age of 50 is low yield. Linear EUS may be the preferred modality for initial PC screening.
Assuntos
Pâncreas/diagnóstico por imagem , Cisto Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Quinases Proteína-Quinases Ativadas por AMP , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Ataxia Telangiectasia/complicações , Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Detecção Precoce de Câncer , Endossonografia , Feminino , Seguimentos , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Síndrome de Li-Fraumeni/complicações , Síndrome de Li-Fraumeni/genética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteína 2 Homóloga a MutS/genética , Síndromes Neoplásicas Hereditárias/complicações , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/genética , Síndrome de Peutz-Jeghers/complicações , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND AND STUDY AIMS: The optimal technique for sampling pancreatic lesions with a 22âG Procore needle (pc) is unknown. The aims of this study were to evaluate the 22âGpc using standard suction technique (SST) and capillary suction technique (CST) and compare diagnostic adequacy of 22âGpc with the standard 25âG needle. PATIENTS AND METHODS: Sixty consecutive patients referred for EUS-FNA of a solid pancreatic mass were prospectively evaluated. All patients underwent 2 passes with a standard 25âG needle for cytologic analysis. The first group of 30 patients underwent a single pass with the 22âGpc needle using SST for cytology and histology. The second group underwent a single pass with the 22âGpc needle using CST. The sequence of passes was randomized. The diagnostic adequacy of each pass was graded by 2 cytopathologists blinded to technique and needle type for comparison. RESULTS: For a cytologic diagnosis with 22âGpc, an adequate sample was obtained in 82.8â% SST vs. 80.0â% CST ( P â=â0.79). For a histologic diagnosis with 22âGpc, an adequate sample was obtained in 70.4â% SST vs. 69.0â% CST ( P â=â0.91). A single pass with 22âGpc provided comparable results to a single pass with the 25âG needle for a cytologic diagnosis; both were superior to a single 22âGpc pass for a histologic diagnosis. Two passes with the 25âG needle provided a diagnostic specimen in 95.0â% vs 81.4â% with one pass using 22âGpc ( P â=â0.01). CONCLUSIONS: No significant difference in diagnostic adequacy was observed between techniques for the 22âGpc. Two passes with a 25âG needle performed better than 1 pass with 22âGpc. (NCT01598194).
RESUMO
Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-ß pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-ß signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-ß signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-ß in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression.
Assuntos
Adenoma/genética , Antígeno Carcinoembrionário/genética , Colo/metabolismo , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Mutação/genética , Fator de Crescimento Transformador beta/genética , Adenoma/metabolismo , Adenoma/patologia , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Antígeno Carcinoembrionário/metabolismo , Movimento Celular , Proliferação de Células , Células Cultivadas , Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Progressão da Doença , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND AND AIMS: Patients with complex colon polyps were traditionally referred for surgery to avoid adverse events associated with endoscopic resection. Recent advances in endoscopic imaging as well as endoscopic hemostasis and clip closure allow for the use of EMR as an alternative to surgery for such lesions. To determine the outcome of treatment of complex colon polyps with EMR as an alternative to surgery, we conducted a retrospective observational study. METHODS: Two hundred three patients with complex colon polyps were referred to an EMR center as an alternative to surgery. Patients underwent a protocol-driven EMR. The primary endpoint was the complete resection rate. Secondary endpoints were safety, residual adenoma rate, and incidence of missed synchronous polyps. RESULTS: EMR was performed in 155 patients and was deferred in 48 patients who were referred to surgery. EMR specimens revealed benign polyps in 149 and cancer in 6 patients. EMR adverse events occurred in 7 patients, requiring hospitalization in 5 of them. None of the patients died as a result of their adverse events. Surveillance colonoscopy at 4 to 6 months after resection of a benign lesion in 137 patients revealed residual adenoma at the scar site in 6 patients and additional synchronous precancerous lesions in 117 patients that were not removed by the referring endoscopist. None underwent surgery for failure of EMR. The overall precancerous lesion burden was 2.83 per patient, the adenoma burden was 2.13 per patient, and the serrated polyp burden was .69 per patient. CONCLUSIONS: EMR can be used instead of surgery for complex colon polyps in 75% of patients with few adverse events and few residual adenomas at resection sites. In addition, careful repeat examination of the entire colon for synchronous lesions overlooked by the referring endoscopist is required for most patients. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01827241.).
Assuntos
Adenoma/cirurgia , Pólipos do Colo/cirurgia , Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colectomia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
INTRODUCTION: The purpose of this study was to evaluate if a baseline, an interim or a post-chemoradiation (CTRT) 18-fluorodeoxy-glucose positron emission computed tomography (18F-FDG PET/CT) studies could provide information on pathologic response to CTRT and overall survival (OS). MATERIALS AND METHODS: Thirty-one patients with histologically proven adenocarcinoma or squamous cell carcinoma of the oesophagus, fit for trimodality therapy were prospectively enrolled. Most were men (93.5%), and had a stage III cancer (74.2%). Chemotherapy consisted of oxaliplatin/5-fluorouracil (45.2%) and taxane/5-fluorouracil (54.8%). All patients underwent a baseline, an interim (performed 12 ± 2 days after the onset of CTRT) and a post-CTRT 18F-FDG PET/CT study. The 18F-FDG PET/CT variables evaluated were at baseline, interim and post-CTRT studies maximum standardised uptake value (SUV max) and total lesion glycolysis (TLG). Clinical and 18F-FDG PET/CT parameters were correlated with pathologic complete response (pathCR) and OS. RESULTS: Among the 31 patients studied, 61.3% achieved a clinical complete response (cCR) and 87.1% had surgery. The median OS was 35.1 months (95% confidence interval (CI): 19.9-NA). PathCR rate was 22.2%. There was only a marginal association between cCR and pathCR (p = 0.06). None of the other variables was predictive of pathCR. There was association between OS and baseline TLG (p = 0.03) at the optimal cutoff TLG value of 75.15. Additionally, TLG and ΔTLG post-CTRT were also associated with OS (p = 0.01 and 0.03, respectively). CONCLUSION: None of the PET parameters is predictive of pathCR but TLG at baseline and post-CTRT are prognostic of OS.