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1.
Langenbecks Arch Surg ; 408(1): 442, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37987850

RESUMEN

BACKGROUND: Locally advanced gastric cancer (GC) extending to the surrounding tissues may require a multivisceral resection (MVR) to provide the best chance of cure. However, little is known about how the extent of organ resection affects the risks and benefits of surgery. METHODS: An electronic database of patients treated between 1996 and 2020 in an academic surgical centre was reviewed. MVRs were defined as partial or total gastrectomy combined with splenectomy, distal pancreatectomy, or partial colectomy. RESULTS: Suspected intraoperative tumour invasion of perigastric organs (cT4b) was found in 298 of 1476 patients with non-metastatic GC, and 218 were subject to MVRs, including the spleen (n = 126), pancreas (n = 51), and colon (n = 41). MVRs were associated with higher proportions of surgical and general complications, but not mortality. A nomogram was developed to predict the risk of major postoperative morbidity (Clavien-Dindo's grade ≥ 3a), and the highest odds ratio for major morbidity identified by logistic regression modelling was found for distal pancreatectomy (2.53, 95% CI 1.23-5.19, P = 0.012) and colectomy (2.29, 95% CI 1.04-5.09, P = 0.035). Margin-positive resections were identified by the Cox proportional hazards model as the most important risk factor for patients' survival (hazard ratio 1.47, 95% CI 1.10-1.97). The extent of organ resection did not affect prognosis, but a MVR was the only factor reducing the risk of margin positivity (OR 0.44, 95% CI 0.21-0.87). CONCLUSIONS: The risk of multivisceral resections is associated with the organ being removed, but only MVRs increase the odds of complete tumour clearance for locally advanced gastric cancer.


Asunto(s)
Gastrectomía , Neoplasias Primarias Secundarias , Neoplasias Gástricas , Humanos , Gastrectomía/efectos adversos , Pronóstico , Neoplasias Gástricas/cirugía , Colectomía , Esplenectomía , Pancreatectomía
2.
J Gastrointest Surg ; 27(1): 7-16, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36138310

RESUMEN

BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system has limited accuracy in predicting survival of gastric cancer patients with inadequate counts of evaluated lymph nodes (LNs). We therefore aimed to develop a prognostic nomogram suitable for clinical applications in such cases. METHODS: A total of 1511 noncardia gastric cancer patients treated between 1990 and 2010 in the academic surgical center were reviewed to compare the 7th and 8th editions of the AJCC staging system. A nomogram was developed for the prediction of 5-year survival in patients with less than 16 LNs evaluated (n = 546). External validation was performed using datasets derived from the Polish Gastric Cancer Study Group (n = 668) and the SEER database (n = 11,225). RESULTS: The 8th edition of AJCC staging showed better overall discriminatory power compared to the previous version, but no improvement was found for patients with < 16 evaluated LNs. The developed nomogram had better concordance index (0.695) than the former (0.682) or latest (0.680) staging editions, including patients subject to neoadjuvant treatment, and calibration curves showed excellent agreement between the nomogram-predicted and actual survival. High discriminatory power was also demonstrated for both validation cohorts. Subsequently, the nomogram showed the best accuracy for the prediction of 5-year survival through the time-dependent ROC curve analysis in the training and validation cohorts. CONCLUSIONS: A clinically relevant nomogram was built for the prediction of 5-year survival in patients with inadequate numbers of LNs evaluated in surgical specimens. The predictive accuracy of the nomogram was validated in two Western populations.


Asunto(s)
Nomogramas , Neoplasias Gástricas , Humanos , Pronóstico , Estadificación de Neoplasias , Neoplasias Gástricas/patología , Ganglios Linfáticos/patología
3.
Pol Przegl Chir ; 94(4): 53-60, 2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-36047361

RESUMEN

This document - "Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022" - represents an expert consensus following a year's worth of dedicated effort by a team of specialists throughout 2021, put forward in a conference in December 2021 in Krakow, and finalized below for publication in 2022. The effective date of this document is June 14th 2022. The work that went into updating this consensus was made under auspices of the Polish Society of Surgical Oncology and the Association of Polish Surgeons.


Asunto(s)
Neoplasias Gástricas , Consenso , Humanos , Polonia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia
4.
Langenbecks Arch Surg ; 407(7): 2969-2980, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35788774

RESUMEN

PURPOSE: The value of the lymph node ratio (LNR) in patients with rectal cancer has not yet been unequivocally established. This study aims to assess the effect of the lymph node ratio on the prognosis of rectal cancer in patients operated after short-course preoperative 25 Gy radiotherapy, at 10-year follow-up. METHODS: This is a substudy based on data from a prospective randomized clinical trial. A total of 141 patients with resectable rectal cancer were included. Lymph node yield was compared in patients with short and long time intervals between radiotherapy and surgery. Survival curves were compared between patients with different ypN and LNR categories. Univariate and multivariate analyses were performed to identify independent prognostic factors for overall survival and disease-free survival. RESULTS: Survival and recurrence data were available for a median follow-up of 11.6 years. The lymph node yield did not differ significantly between the patients in the short- and long-interval groups. A greater difference in 10-year survival was observed in patients with LNR ≤ 0.41 and > 0.41 when compared to the ypN categories. Separate prognostic factor analyses were performed for the entire population and for subgroups that had < 12 and 12 lymph nodes resected. LNR was identified as an independent prognostic factor for overall survival, in multivariate analyses, for all patients and those with less than 12 retrieved lymph nodes. CONCLUSION: The lymph node yield is comparable in patients with different time intervals between radiation therapy and surgery. LNR better discriminates patients in terms of overall survival than ypN categories. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01444495, date of registration: September 30, 2011.


Asunto(s)
Índice Ganglionar , Neoplasias del Recto , Humanos , Pronóstico , Escisión del Ganglio Linfático/métodos , Metástasis Linfática/patología , Estudios Prospectivos , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Ganglios Linfáticos/patología
5.
PLoS One ; 17(4): e0266111, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35390022

RESUMEN

The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.


Asunto(s)
Neoplasias de la Mama , Carcinoma , Neoplasias Colorrectales , Bancos de Muestras Biológicas , Neoplasias de la Mama/genética , Variación Genética , Humanos , Masculino , Mastectomía , Neoplasias Pancreáticas , Neoplasias Pancreáticas
6.
Radiother Oncol ; 164: 268-274, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34653526

RESUMEN

BACKGROUND: Studies on short-course preoperative radiotherapy in combination with total mesorectal excision for rectal cancer reported improved local control without clear survival benefits. The optimal fractionation and interval between radiotherapy and surgery are still under debate. We, therefore, aimed to report 10-year results of a randomized clinical trial (RCT, NCT01444495) comparing different time intervals between irradiation and surgery for rectal cancer. MATERIAL AND METHODS: Data from the RCT conducted at a single academic centre were reviewed based on regular control visits with the median follow-up of 12 years. Patients with rectal cancer were randomly assigned to short-course preoperative radiotherapy (5 × 5 Gy) followed by surgery 7-10 days (short interval) or 4-5 weeks (long interval) after the end of irradiation. The primary endpoint was the local recurrence rate at 5 years. The secondary endpoints included overall survival, disease-free survival, systemic recurrence rate, and downstaging. RESULTS: A total of 154 patients were randomly assigned to short (n = 77) or long interval (n = 77) surgery. The cumulative incidence of local recurrence at 10 years was 1.3% and 11.7% in the short and long-interval groups, respectively (p = 0.031). Accordingly, the incidence of systemic relapse was 14.3% versus 9.1% (p = 0.0319). There were no differences in the overall 10-year survival between patients subject to short and long-interval surgery (58% vs 61%, p = 0.754). However, patients with downstaging after radiotherapy had significantly better 10-year survival rates than non-responders. CONCLUSIONS: Short-course preoperative radiotherapy with delayed surgery demonstrated an increased risk of local relapse over a 10-year follow-up.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias del Recto , Fraccionamiento de la Dosis de Radiación , Estudios de Seguimiento , Humanos , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Tasa de Supervivencia
7.
Biomedicines ; 9(7)2021 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-34202691

RESUMEN

A significant problem for long-term rectal cancer survivors may be the late toxicity of radiotherapy. It creates the possible risk of developing second primary malignancy and a theoretical decrease in overall survival. This study aimed to assess the influence of short-course preoperative radiotherapy in patients with locally advanced rectal cancer on overall survival, local recurrence rate, and second malignancy at 18-year follow-up. The rectal cancer trial was conducted in a single tertiary center between February 1992 and June 2006. A total of 389 patients with locally advanced rectal cancer (cT2-cT4, cN0/+, cM0) were included in the study. Preoperative radiotherapy was conducted in 148 patients and 241 patients underwent surgery alone. The propensity-matched group consisted of 105 patients operated on after radiotherapy and 105 controls. The number of local recurrences was 7 (6.7%) in the preoperative radiotherapy group and 22 (21%) in the surgery alone group (p = 0.016). The 18-year survival analysis showed no survival benefit in the preoperative radiotherapy group (38% versus 48%, p = 0.107) but improved recurrence-free survival (81% versus 58%, p = 0.001). The preoperative short-course radiotherapy significantly decreases the risk of local recurrence in locally advanced rectal cancer and may improve recurrence-free survival without an increased risk of second primary malignancy.

8.
Anticancer Res ; 41(7): 3523-3534, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34230148

RESUMEN

BACKGROUND: The aim of this study was the analysis of the influence of prognostic factors on short- and long-term outcomes of gastric cancer resection. PATIENTS AND METHODS: A database of 709 patients who had gastric cancer resection between 2007 and 2015 was compiled. RESULTS: Total gastrectomy (TG) and subtotal proximal gastrectomy (SPG) significantly increased the risk of overall complications (p=0.0015 and 0.0173, respectively) and surgical complications (p=0.0141 and 0.0035, respectively). Moreover the resection of an additional organ was an independent prognostic factor of overall complications (p<0.0001), systemic complications (p=0.0503), surgical complications (p<0.0001) and relaparotomy (p=0.0259). T stage (p<0.0001), N stage (p<0.0001), M stage (p<0.0001) and radical resection (p<0.0001) significantly affected 5-year survival rates. CONCLUSION: Early diagnosis and radical resection was crucial in 5-year survival rates. However, the type of gastrectomy and the resection of an additional organ were the most important factors in short-term outcomes of treatment for such patients.


Asunto(s)
Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Anciano , Femenino , Gastrectomía/métodos , Humanos , Masculino , Estadificación de Neoplasias/métodos , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/patología , Pronóstico , Estudios Retrospectivos , Estómago/patología , Tasa de Supervivencia , Resultado del Tratamiento
9.
HPB (Oxford) ; 22(7): 961-968, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32360186

RESUMEN

BACKGROUND: The number of pancreatic resections due to cancers is increasing. While concomitant venous resections are routinely performed in specialized centers, arterial resections are still controversial. Nevertheless they are performed in patients presenting with locally advanced tumors. Our aim was to summarize currently available literature comparing peri-operative and long-term outcomes of arterial and non-arterial pancreatic resections. METHODS: We included studies comparing pancreatic operations with and without concomitant arterial resection. Inclusion criteria were morbidity or mortality. Studies additionally reporting venous resections with no possibility of excluding this data during the extraction were discarded. RESULTS: The initial search yielded 1651 records. Finally, 19 studies were included in the analysis involving 2710 patients. Arterial resection was associated with a greater risk of death(RR: 4.09; p < 0.001) and complications (RR: 1.4; p = 0.01). There were no differences in the rate of pancreatic fistula, biliary fistula rate, cardiopulmonary complications, length of hospital stay and non-R0 rate. Oncologically, patients after arterial resection were at higher risk of worse 3-year survival. CONCLUSION: Arterial resection in pancreatic cancer is associated with an increased risk of mortality and complications in comparison to standard non-arterial resections. Nevertheless, arterial resection may become a viable treatment for selected patients in high volume centers.


Asunto(s)
Pancreatectomía , Neoplasias Pancreáticas , Arterias/diagnóstico por imagen , Arterias/cirugía , Humanos , Pancreatectomía/efectos adversos , Fístula Pancreática , Neoplasias Pancreáticas/cirugía , Venas
10.
J Surg Oncol ; 121(4): 698, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31965570
11.
Acta Chir Belg ; 120(5): 315-320, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31060443

RESUMEN

Background: Little data are available for abscess and non-abscess abdominal fluid collections (AFCs) after gastric cancer surgery and their clinical implications. We sought to analyse the natural history of such collections in a population of patients subject to routine postoperative imaging.Methods: From 1996 to 2012, 1381 patients underwent gastric resections and routine postoperative monitoring with abdominal ultrasound. As a unit protocol, examinations were carried out in all patients prior to drain removal, immediately before discharge, and at follow-up visits.Results: AFCs were diagnosed in 134 (9.7%) patients after a median time from surgery of seven days (interquartile range (IQR) 5-11 days). Sixty-four of the 134 AFCs (48%) were asymptomatic and resolved spontaneously after a median follow-up of 26.5 days (IQR 14-91 days). Seventy (52%) AFCs required interventional drainage. A stepwise logistic regression model demonstrated that interventional treatment was much more likely among patients with enteric fistula (odds ratio (OR) 9.542, 95% CI 1.418-46.224, p=.003) and pancreatic fistula (OR 7.157, 95% CI 1.340-39.992, p=.012).Conclusions: About one half of AFCs after gastric surgery were asymptomatic and eventually resolved spontaneously without any intervention. However, the need for interventional drainage was significantly increased by coexisting pancreatic or enteric fistula.


Asunto(s)
Absceso Abdominal/diagnóstico , Absceso Abdominal/epidemiología , Gastrectomía/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Neoplasias Gástricas/cirugía , Absceso Abdominal/terapia , Anciano , Drenaje , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Oportunidad Relativa , Polonia , Complicaciones Posoperatorias/terapia , Factores de Riesgo , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/patología , Resultado del Tratamiento
13.
Medicina (Kaunas) ; 55(6)2019 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-31242584

RESUMEN

Background and objectives: T regulatory lymphocytes (Treg) are one of the subsets of T-lymphocytes involved in the interaction of neoplastic tumors and the host immune system, and they may impair the immune reaction against cancer. It has been shown that Treg are increased in the peripheral blood of patients with various cancers. In colorectal cancer, the prognostic role of Treg remains controversial. Colorectal cancer is a heterogenous disease, with many variations stemming from its primary tumor location. The aim of this study is to analyse the relationship between the amount of Treg in the peripheral blood of patients with left-sided colorectal cancer in various stages of disease and long-term survival. Materials and Methods: A prospective analysis of 94 patients with left-sided colorectal cancer and a group of 21 healthy volunteers was carried out. Treg levels in peripheral blood were analysed using flow cytometry. Results: There was a statistically significant difference between the amount of Treg in the Ist and IInd TNM stages (p = 0.047). The number of Treg in the entire study group was significantly lower than in the control group (p = 0.008) and between patients in stages II and III and the control group (p = 0.003 and p = 0.018). The group of pT3+pT4 patients also had significantly lower Treg counts in their peripheral blood than the control group (p = 0.005). In the entire study group, the level of Treg cells in the peripheral blood had no influence on survival. The analysis of the TNM stage subgroups also showed no difference in survival between patients with "low" and "high" Treg counts. Conclusion: The absolute number of Treg in the peripheral blood of patients with left-sided colorectal cancer was significantly decreased in comparison to healthy controls, especially for patients with stage II+III disease. Treg presence in the peripheral blood had no impact on survival.


Asunto(s)
Biomarcadores/análisis , Neoplasias Colorrectales/sangre , Linfocitos T Reguladores/fisiología , Adulto , Biomarcadores/sangre , Neoplasias Colorrectales/fisiopatología , Femenino , Citometría de Flujo/métodos , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Linfocitos T Reguladores/patología
14.
J Surg Oncol ; 120(3): 473-482, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31124178

RESUMEN

INTRODUCTION: Sarcopenia is highly prevalent in patients with gastrointestinal malignancies, including gastric cancer, but there is a lack of adequate data from Western populations. METHODS: Computed tomography scans of 138 Caucasian patients subject to stomach resections due to gastric adenocarcinoma between 2012 and 2015 were reviewed to evaluate the impact of sarcopenia. The definition of sarcopenia was based on the lumbar skeletal muscle index (SMI) using cut-off values formulated by the international consensus definitions of sarcopenia (SMI <52.4 cm2 /m2 for men and <38.5 cm2 /m2 for women). RESULTS: Sixty (43%) of 138 patients were sarcopenic. Sarcopenia was associated with postoperative morbidity (43% vs 23%; P = .011), major postoperative complications (Clavien-Dindo ≥3a; 36% vs 21%; P = .035), and reoperations (23% vs 9%; P = .020). Patients with sarcopenia also had prolonged postoperative hospital stay (8.0 vs 6.5 days; P = .010). The overall median survival of patients with sarcopenia was significantly lower than those with normal skeletal muscles (11.0 vs 36.7 months; P = .005) and sarcopenia remained an independent prognostic factor with an odds ratio of 1.94 (95% confidence interval, 1.08 to 3.48; P = .026). CONCLUSION: Sarcopenia, defined by SMI, is associated with an increased risk of postoperative morbidity and impaired long-term survival.


Asunto(s)
Sarcopenia/fisiopatología , Neoplasias Gástricas/cirugía , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Sarcopenia/diagnóstico por imagen , Sarcopenia/mortalidad , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/mortalidad , Tomografía Computarizada por Rayos X
15.
Gastric Cancer ; 22(2): 264-272, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30056567

RESUMEN

BACKGROUND: The phenotypic heterogeneity of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells (DTC) in bone marrow is an important constraint for clinical decision making. Here, we investigated the implications of two different subpopulations of these cells in gastric cancer (GC). METHODS: GC patients (n = 228) who underwent elective gastric resections were prospectively examined for CTC/DTC. The cells obtained from peripheral blood and bone marrow aspirates were sorted by flow cytometry and CD45- cells expressing cytokeratins (8, 18, and 19) and CD44 were identified by immunofluorescent double staining. RESULTS: Ninety-three (41%) patients had cytokeratin-positive tumor cells in either blood or bone marrow, while cells expressing CD44 were found in 22 (10%) cases. CK+CD44+ cells were significantly more common among patients with distant metastases (50 vs 19%, P = 0.001), while no such correlations were demonstrated for CK+CD44- cells. Detection of CK+CD44+ cells, but not CK+CD44-, was associated with significantly shortened survival. Moreover, the Cox proportional hazards model identified CK+CD44+ cells as a negative prognostic factor with an odds ratio of 2.38 (95% CI 1.28-4.41, P = 0.006). CONCLUSION: CD44+ phenotype of cytokeratin-positive cells in blood and bone marrow is an independent prognostic factor in patients with gastric cancer.


Asunto(s)
Médula Ósea/patología , Receptores de Hialuranos/biosíntesis , Queratinas/biosíntesis , Células Neoplásicas Circulantes/patología , Neoplasias Gástricas/patología , Adulto , Anciano , Biomarcadores de Tumor/análisis , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
16.
Pancreatology ; 18(8): 977-982, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30268674

RESUMEN

BACKGROUND: Aberrantly expressed mucin glycoproteins (MUC) play important roles in pancreatic ductal adenocarcinoma (PDAC), yet their use as a diagnostic aid in fine-needle aspiration biopsy (FNAB) is poorly documented. The aim of this study was to investigate the rationale and feasibility of mucin (MUC1, MUC2, MUC3, MUC4, MUC5AC, and MUC6) expression profiling by RT-PCR for diagnostic applications in cytology. METHODS: Mucin expression was examined by RT-PCR and immunohistochemistry in specimens resected from patients with pancreatic (n = 101), ampullary (n = 23), and common bile duct (n = 10) cancers and 33 with chronic pancreatitis. Furthermore, mucin profiling by RT-PCR was prospectively compared in surgical and biopsy specimens of 40 patients with pancreatic solid tumours qualified for FNAB prior to surgery. RESULTS: A logistic regression model to distinguish PDAC from chronic pancreatitis using RT-PCR profiling included MUC3, MUC5AC, and MUC6. The same set of mucins differentiated ampullary and bile duct cancers from chronic pancreatitis. AUCs for the ROC curves derived from the two models were 0.95 (95%CI 0.87-0.99) and 0.92 (95%CI 0.81-0.98), respectively. The corresponding positive likelihood ratios were 6.02 and 5.97, while the negative likelihood ratios were 0.10 and 0.12. AUCs of ROC curves obtained by RT-PCR and immunohistochemistry demonstrated that both analytical methods were comparable. Surgical and cytological samples showed significantly correlated values of ΔCt for individual mucins with the overall Pearson's correlation coefficient r = 0.841 (P = 0.001). CONCLUSIONS: Mucin expression profiling of pancreatic cancer with RT-PCR is feasible and may be a valuable help in discriminating malignant lesions from chronic pancreatitis in FNAB cytology.


Asunto(s)
Biomarcadores de Tumor/análisis , Perfilación de la Expresión Génica , Mucinas/biosíntesis , Mucinas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Anciano , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Biopsia con Aguja Fina , Diagnóstico Diferencial , Estudios de Factibilidad , Femenino , Humanos , Inmunohistoquímica , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Pancreatitis Crónica/genética , Pancreatitis Crónica/patología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa
17.
Br J Cancer ; 117(2): 266-273, 2017 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-28641313

RESUMEN

BACKGROUND: High stability and disease-specific disarrangements suggest that microRNA molecules (miRNAs) present in body fluids are ideally suited for diagnostic applications, including gastric cancer (GC). However, the actual source of circulating miRNA biomarkers in GC has not been adequately evaluated, particularly in the Western populations that have some distinct characteristics compared with Asian patients. METHODS: Twenty treatment-naive patients with GC along with 20 cancer-free controls were recruited. miRCURY LNA miRNA microarrays were used for miRNA expression profiling in primary tumours and adjacent healthy mucosa. Differentially expressed serum miRNAs were identified with a high throughput TaqMan OpenArray technology in tumour-draining veins of the portal system, as well as peripheral blood of the patients and controls. RESULTS: Tissue profiling identified 108 sequences differentially expressed between primary tumours and adjacent mucosa (87 upregulated and 21 downregulated). Twenty miRNAs found in serum of GC patients showed expression levels higher than in controls. However, only seven of these molecules were overexpressed in primary tumours (miR-130a, miR-331, miR-19a, miR-223, miR-106a, miR-21, and miR-374). Moreover, expression of miR-331 and miR-21 was significantly higher in the peripheral circulation compared to tumour-draining veins of the portal system. CONCLUSIONS: The results indicate that the majority of potential serum miRNA biomarkers may originate from tissues other than the primary tumour.


Asunto(s)
Biomarcadores de Tumor/sangre , MicroARNs/sangre , Neoplasias Gástricas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patología
18.
J Proteome Res ; 16(4): 1436-1444, 2017 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-28244758

RESUMEN

After more than a decade of biomarker discovery using advanced proteomic and genomic approaches, very few biomarkers have been involved in clinical diagnostics. Most candidate biomarkers are focused on the protein component. Targeting post-translational modifications (PTMs) in combination with protein sequences will provide superior diagnostic information with regards to sensitivity and specificity. Glycosylation is one of the most common and functionally important PTMs. It plays a central role in many biological processes, including protein folding, host-pathogen interactions, immune response, and inflammation. Cancer-associated aberrant glycosylation has been identified in various types of cancer. Expression of cancer-specific glycan epitopes represents an excellent opportunity for diagnostics and potentially specific detection of tumors. Here, we report four proteins (LIFR, CE350, VP13A, HPT) found in sera from pancreatic cancer patients carrying aberrant glycan structures as compared to those of controls.


Asunto(s)
Biomarcadores de Tumor/sangre , Haptoglobinas/análisis , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/sangre , Proteínas de Microtúbulos/sangre , Proteínas Nucleares/sangre , Neoplasias Pancreáticas/sangre , Proteínas de Transporte Vesicular/sangre , Anciano , Epítopos/biosíntesis , Epítopos/química , Epítopos/genética , Femenino , Glicosilación , Interacciones Huésped-Patógeno/genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Polisacáridos/biosíntesis , Polisacáridos/química , Polisacáridos/genética , Pliegue de Proteína , Procesamiento Proteico-Postraduccional/genética , Proteómica
19.
Pancreas ; 46(5): 684-689, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28196013

RESUMEN

OBJECTIVES: The aim of this study was to examine the relevance of expression profiling of 4 genes involved in the action of gemcitabine among patients with pancreatic ductal-cell adenocarcinoma (PDAC). METHODS: A group of 100 patients who underwent pancreatic resections for PDAC and received adjuvant chemotherapy with gemcitabine between 2007 and 2010 was identified. Expression of mRNAs for human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunits (RRM1, RRM2), and deoxycytidine kinase (dCK) was examined by quantitative real-time polymerase chain reaction, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and dichotomized into groups of low and moderate/high expression levels grouped by tertiles. RESULTS: Significantly better median survival times were found for high/moderate expression levels of hENT1 (27.9 vs 12.4 months, P = 0.001) and dCK (19.7 vs 10.5 months, P = 0.003), as well as low expression of RRM1 (23.4 vs 11.4 months, P = 0.027). A Cox proportional hazards model identified low expression of hENT1 (hazard ratio [HR], 3.38; 95% confidence intervals [CI], 2.28-10.50) and dCK (HR, 2.24; 95% CI, 1.63-3.39), and high/moderate levels of RRM1 (HR, 1.65; 95% CI, 1.23-2.45) as negative prognostic factors. CONCLUSIONS: Expression of hENT, RRM1, and dCK genes provides important prognostic information for PDAC patients treated with adjuvant gemcitabine.


Asunto(s)
Carcinoma Ductal Pancreático/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/cirugía , Quimioterapia Adyuvante , Desoxicitidina/uso terapéutico , Desoxicitidina Quinasa/genética , Tranportador Equilibrativo 1 de Nucleósido/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirugía , Pronóstico , Ribonucleósido Difosfato Reductasa/genética , Proteínas Supresoras de Tumor/genética , Gemcitabina
20.
Ann Surg Oncol ; 24(3): 808-815, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27770341

RESUMEN

BACKGROUND: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) may serve as a simple index of the immune function. The aim of this study was to investigate the prognostic significance of NLR, PLR, and LMR in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and to verify whether such biomarkers are associated with changes in populations of lymphoid cells. METHODS: The prognostic implications of blood count parameters were evaluated in a retrospective cohort of 442 subjects undergoing pancreatic resections for PDAC. Subpopulations of lymphocytes and monocytes in peripheral blood were identified by FACS in a prospective cohort of 54 patients. RESULTS: In the univariate analysis, NLR < 5 and LMR ≥ 3 were associated with significantly longer median survival of 25.7 vs 12.6 months and 29.2 vs 13.1 months, respectively. PLR did not influence survival. The Cox proportional hazards model showed that high NLR (HR 1.66, 95 % CI 1.12 to 2.46, P = 0.012) and low LMR (HR 1.65, 95 % CI 1.06 to 2.58, P = 0.026) were independent predictors of poor prognosis. NLR ≥ 5 and LMR < 3 correlated with an approximately twofold decrease in counts of helper and cytotoxic T cells, B cells, and NK cells. High NLR was also accompanied with increased neutrophil counts, while low LMR showed increased numbers of monocytes, mostly classical. CONCLUSIONS: NLR and LMR may carry important prognostic information for patients with resected PDAC. The unfavorable prognosis likely correlates with reduced numbers of immune cells effective against the tumor and increased populations of cells involved in immune suppression.


Asunto(s)
Carcinoma Ductal Pancreático/sangre , Linfocitos , Monocitos , Neutrófilos , Neoplasias Pancreáticas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos B , Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/cirugía , Femenino , Humanos , Células Asesinas Naturales , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/cirugía , Recuento de Plaquetas , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia , Linfocitos T Citotóxicos , Linfocitos T Colaboradores-Inductores , Adulto Joven
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