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1.
Artículo en Inglés | MEDLINE | ID: mdl-38748352

RESUMEN

BACKGROUND: Stage IV gastric cancer patients with Krukenberg tumors typically exhibit poor survival outcomes, often less than 2 years. The management of this tumor subgroup remains non-standardized, and the impact of oophorectomy on survival remains uncertain. In this study, we systematically analyzed survival outcomes among gastric cancer patients with ovarian metastases who underwent standard chemotherapy, surgical resection of ovarian metastases, or combined chemotherapy and surgery. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies retrieved from MEDLINE (PubMed), Embase, and the Cochrane Library until January 25, 2024, applying the Boolean logic. Participants included individuals with pathologically and radiologically confirmed ovarian metastasis or clinically symptomatic cases with imaging evidence. Statistical analyses were performed using R (v.4.3.2., Vienna). The study was registered with PROSPERO (ID-CRD42023488373). RESULTS: A total of 1502 patients from 17 retrospective studies were pooled for analysis of overall survival (OS) outcomes. The OS in the standard chemotherapy cohort, as determined by the random effects model, was 6.708 months (95% CI 3.867 to 9.548; P<0.0001), with non-significant heterogeneity (I2 = 5.5%). In the surgical resection cohort, OS was 12.786 months (95% CI 6.9 to 18.671; P<0.0001), with low heterogeneity (I2 = 0%). In the combined chemotherapy and surgical resection cohort, OS was 16.228 months (95% CI 12.254 to 20.202), with insignificant heterogeneity (I2 = 0%). CONCLUSION: This meta-analysis offers key insights into survival outcomes associated with different therapeutic modalities in gastric cancer with Krukenberg metastases. It provides valuable evidence for clinical decision-making and future research directions. While the combined approach of chemotherapy and surgery demonstrates the highest effect size for OS, careful consideration of patient-centric approaches is essential in the oncological care landscape.

2.
JCO Precis Oncol ; 8: e2300543, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38781542

RESUMEN

PURPOSE: Claudin 18 isoform 2 (CLDN18.2) is an emerging biomarker and therapeutic target in gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. This study aimed to obtain deeper understanding of CLDN18.2 positivity patterns, prognostic implications, and associations with various demographic, clinical, and molecular characteristics in G/GEJ adenocarcinoma. METHODS: Archived tumor tissue samples from 304 patients with G/GEJ adenocarcinoma in the United States were assessed for CLDN18.2 positivity by immunohistochemistry. CLDN18.2 positivity was defined as ≥50% or ≥75% of tumor cells with CLDN18 staining intensity ≥2+. CLDN18.2 positivity patterns were analyzed for association with prognosis and clinicopathologic/demographic characteristics. Where possible, CLDN18.2 positivity was analyzed for matched tissue samples to assess concordance between primary and metastatic tumors and concordance before and after chemotherapy. RESULTS: The overall prevalence of CLDN18.2-positive tumors (with ≥75% cutoff) was 44.4% (n = 135 of 304). CLDN18.2-positive tumors had a prevalence of 51.4% (n = 91 of 177) in gastric and 34.6% (n = 44 of 127) in GEJ adenocarcinoma. With a ≥50% cutoff, the prevalence of CLDN18.2-positive tumors was 64.4% (n = 114 of 177) in gastric adenocarcinoma and 44.9% (n = 57 of 127) in GEJ adenocarcinoma. There was no association between overall survival and CLDN18.2 positivity using either threshold. Statistically significant associations were noted between CLDN18.2 positivity and sex, histologic type of G/GEJ adenocarcinoma, and adenocarcinoma subtype (≥75% cutoff), and metastasis site and tumor grade (≥50% cutoff). The overall concordance of CLDN18.2 positivity (≥75% cutoff) was 73% (27 of 37) for matched primary versus metastatic tumor samples and 74% (29 of 39) for matched samples before and after chemotherapy. CONCLUSION: This study demonstrated that CLDN18.2 positivity did not correlate with survival in G/GEJ adenocarcinoma, consistent with published data. On the basis of matched sample analysis, CLDN18.2 appears to demonstrate >70% concordance as a biomarker. Observed correlations with certain patient/tumor characteristics warrant further study.


Asunto(s)
Adenocarcinoma , Claudinas , Neoplasias Esofágicas , Unión Esofagogástrica , Neoplasias Gástricas , Humanos , Masculino , Neoplasias Gástricas/patología , Neoplasias Gástricas/epidemiología , Adenocarcinoma/patología , Femenino , Unión Esofagogástrica/patología , Persona de Mediana Edad , Anciano , Pronóstico , Estudios Retrospectivos , Neoplasias Esofágicas/patología , Isoformas de Proteínas , Adulto , Anciano de 80 o más Años , Prevalencia
3.
BMJ Case Rep ; 17(4)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38631812

RESUMEN

We present the case of an elderly man with a history of diastolic congestive heart failure, severe aortic stenosis and atrial fibrillation, who presented with fatigue, weakness, coffee ground emesis and black tarry stool. Haemoglobin was 68 g/L. Lactate dehydrogenase was elevated at 1038. Evaluation by cardiology and gastroenterology specialists revealed reflux oesophagitis and a mild hiatal hernia on oesophagogastroduodenoscopy, normal colonoscopy and small bowel series without obstruction. Capsule endoscopy identified angiodysplasia in the small intestine.The patient was diagnosed with Heyde's syndrome based on the triad of severe aortic stenosis, gastrointestinal bleeding from angiodysplasia and acquired von Willebrand syndrome. The patient underwent transcatheter aortic valve replacement, resulting in the resolution of symptoms.Heyde's syndrome represents a challenging clinical entity requiring a multidisciplinary approach for accurate diagnosis and management. Early recognition, prompt intervention and interdisciplinary collaboration are crucial in optimising patient outcomes.


Asunto(s)
Angiodisplasia , Estenosis de la Válvula Aórtica , Enfermedades de von Willebrand , Masculino , Humanos , Anciano , Estenosis de la Válvula Aórtica/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Colonoscopía , Angiodisplasia/diagnóstico
5.
Cancer Epidemiol Biomarkers Prev ; 32(10): 1338-1347, 2023 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-37540502

RESUMEN

BACKGROUND: It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States. METHODS: We conducted a case-control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor. RESULTS: Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P < 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively. CONCLUSIONS: In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals. IMPACT: The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Colangitis Esclerosante , Humanos , Adulto , Lactante , Estudios de Casos y Controles , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/epidemiología , Colangitis Esclerosante/patología , Colangiocarcinoma/epidemiología , Colangiocarcinoma/etiología , Cirrosis Hepática/patología , Factores de Riesgo , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/patología , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/etiología
6.
Cancer Cell ; 41(8): 1407-1426.e9, 2023 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-37419119

RESUMEN

Understanding tumor microenvironment (TME) reprogramming in gastric adenocarcinoma (GAC) progression may uncover novel therapeutic targets. Here, we performed single-cell profiling of precancerous lesions, localized and metastatic GACs, identifying alterations in TME cell states and compositions as GAC progresses. Abundant IgA+ plasma cells exist in the premalignant microenvironment, whereas immunosuppressive myeloid and stromal subsets dominate late-stage GACs. We identified six TME ecotypes (EC1-6). EC1 is exclusive to blood, while EC4, EC5, and EC2 are highly enriched in uninvolved tissues, premalignant lesions, and metastases, respectively. EC3 and EC6, two distinct ecotypes in primary GACs, associate with histopathological and genomic characteristics, and survival outcomes. Extensive stromal remodeling occurs in GAC progression. High SDC2 expression in cancer-associated fibroblasts (CAFs) is linked to aggressive phenotypes and poor survival, and SDC2 overexpression in CAFs contributes to tumor growth. Our study provides a high-resolution GAC TME atlas and underscores potential targets for further investigation.


Asunto(s)
Adenocarcinoma , Fibroblastos Asociados al Cáncer , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Ecotipo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Adenocarcinoma/patología , Fibroblastos Asociados al Cáncer/patología , Lesiones Precancerosas/patología , Células del Estroma/patología , Microambiente Tumoral
7.
Thorac Surg Clin ; 32(4): 457-465, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36266033

RESUMEN

Esophageal cancer is the sixth most common cause of cancer mortality worldwide and is considered a major worldwide health challenge. Most patients diagnosed with esophageal cancer require extensive workup and management strategies. Multiple clinical trials have been conducted to evaluate the role of chemotherapy, chemoradiotherapy, and recently immunotherapy before or after surgery in the setting of localized esophageal cancer. Trimodality approaches, including preoperative chemoradiation followed by surgery or perioperative chemotherapy, have been widely accepted for treating localized esophageal cancer. However, the addition of immunotherapy to the current trimodality approach produced an advantage in disease-free survival. Our review will focus on the existing data on adjuvant therapies for locally advanced esophageal and gastroesophageal adenocarcinomas and squamous cell carcinomas.


Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/patología , Terapia Combinada , Adenocarcinoma/terapia , Adenocarcinoma/patología , Quimioradioterapia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Quimioradioterapia Adyuvante , Terapia Neoadyuvante , Quimioterapia Adyuvante
8.
World J Gastrointest Oncol ; 14(1): 181-202, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35116110

RESUMEN

Gastric and gastroesophageal junction (GEJ) cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage, with an increasing incidence both in Asia and in Western countries. These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses. Accordingly, the understanding of phenotypic and genotypic correlations/classifications has been improved. Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone, with the incorporation of other treatment modalities, such as radiation and chemotherapy (including biologics). Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival. Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate, which is associated with improved long-term outcomes. Several studies have defined various chemotherapy regimens to accompany radiation (before and after surgery). Recently, addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval. Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results. The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers, highlight the remaining questions and present the current research effort addressing them.

9.
Cancer Med ; 10(20): 7308-7319, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34535983

RESUMEN

BACKGROUND AND AIMS: The role of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) remains unclear. We investigated the associations of total fat and fatty acids with risk of HCC among US adults in a hospital-based case-control study. METHODS: We analyzed data from 641 cases and 1034 controls recruited at MD Anderson Cancer Center during 2001-2018. Cases were new patients with a pathologically or radiologically confirmed diagnosis of HCC; controls were cancer-free spouses of patients with cancers other than gastrointestinal, lung, liver, or head and neck. Cases and controls were frequency-matched by age and sex. Dietary intake was assessed using a validated food frequency questionnaire. Odds ratios (ORs) and corresponding confidence intervals (CIs) were computed using unconditional logistic regression with adjustment for major HCC risk factors, including hepatitis B virus and hepatitis C virus infection. RESULTS: Monounsaturated fatty acid (MUFA) intake was inversely associated with HCC risk (highest vs. lowest tertile: OR, 0.49; 95% CI, 0.33-0.72). Total polyunsaturated fatty acid (PUFA) intake was directly associated with HCC risk (highest vs. lowest tertile: OR, 1.82; 95% CI, 1.23-2.70). Omega-6 PUFA was directly associated with HCC risk (highest vs. lowest tertile: OR 2.29; 95% CI, 1.52-3.44). Long-chain omega-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) intake was also inversely associated with HCC risk (highest vs. lowest tertile: OR, 0.50; 95% CI, 0.33-0.70). No association was observed for saturated fat and HCC risk. CONCLUSION: Our findings support a direct association of omega-6 PUFA intake with HCC and an inverse association of MUFA and long-chain omega-3 PUFA intake with HCC.


Asunto(s)
Carcinoma Hepatocelular/etiología , Grasas de la Dieta/efectos adversos , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Grasos Omega-6/efectos adversos , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Neoplasias Hepáticas/etiología , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Ácidos Grasos Omega-3/farmacología , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos
10.
Oncology ; 99(10): 659-664, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34352788

RESUMEN

BACKGROUND: The value of baseline fluorodeoxyglucose-positron emission tomography-computed tomography (PET-CT) remains uncertain once gastroesophageal cancer is metastatic. We hypothesized that assessment of detailed PET-CT parameters (maximum standardized uptake value [SUVmax] and/or total lesion glycolysis [TLG]), and the extent of metastatic burden could aid prediction of probability of response or prognosticate. METHODS: We retrospectively analyzed treatment-naive patients with stage 4 gastroesophageal cancer (December 2002-August 2017) who had initial PET-CT for cancer staging at MD Anderson Cancer Center. SUVmax and TLG were compared with treatment outcomes for the full cohort and subgroups based on metastatic burden (≤2 or >2 metastatic sites). RESULTS: We identified 129 patients with metastatic gastroesophageal cancer who underwent PET-CT before first-line therapy. The median follow-up time was 61 months. The median overall survival (OS) was 18.5 months; the first progression-free survival (PFS) was 5.5 months. SUVmax or TLG of the primary tumor or of all metastases combined had no influence on OS or PFS, whether the number of metastases was ≤2 or >2. Overall response rates (ORRs) to first-line therapy were 48% and 45% for patients with ≤2 and >2 metastases, respectively (nonsignificant). ORR did not differ based on low or high values of SUVmax or TLG. CONCLUSIONS: This is the first assessment of a unique set of PET-CT data and its association with outcomes in metastatic gastroesophageal cancer. In our large cohort of patients, detailed analyses of PET-CT (by SUVmax and/or TLG) did not discriminate any parameters examined. Thus, baseline PET-CT in untreated metastatic gastroesophageal cancer patients has limited or no utility.


Asunto(s)
Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/mortalidad , Unión Esofagogástrica/diagnóstico por imagen , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Esofágicas/patología , Unión Esofagogástrica/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Gástricas/patología , Tasa de Supervivencia , Texas/epidemiología
11.
Nutrients ; 13(6)2021 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-34208122

RESUMEN

The objective of this study was to assess the association between dietary patterns and risk of hepatocellular carcinoma (HCC) among US adults in a hospital-based case-control study. We analyzed data from 641 cases and 1002 controls recruited at The University of Texas MD Anderson Cancer Center during 2001-2018. Cases were patients with a pathologically or radiologically confirmed new diagnosis of HCC; controls were cancer-free spouses of patients with cancers other than gastrointestinal, lung, liver, or head and neck cancer. Cases and controls were frequency-matched by age and sex. Dietary patterns were identified by principal component analysis. Odds ratios (ORs) and corresponding confidence intervals (CIs) were computed using unconditional logistic regression with adjustment for major HCC risk factors, including hepatitis B virus and hepatitis C virus infection. A vegetable-based dietary pattern was inversely associated with HCC risk (highest compared with lowest tertile: OR 0.66, 95% CI 0.46-0.94). A Western diet pattern was directly associated with HCC risk (highest compared with lowest tertile: OR 1.79, 95% CI 1.19-2.69). These findings emphasize the potential role of dietary intake in HCC prevention and clinical management.


Asunto(s)
Carcinoma Hepatocelular/epidemiología , Dieta Occidental , Dieta , Neoplasias Hepáticas/epidemiología , Verduras , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo
12.
Hepatology ; 74(6): 3161-3173, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34233041

RESUMEN

BACKGROUND AND AIMS: N-nitroso compounds (NOCs) are among the most potent dietary carcinogens. N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), and N-nitrosopiperidine (NPIP) are abundant in foods and carcinogenic to the liver. We investigated the relationship between dietary NOCs and HCC risk. APPROACH AND RESULTS: In this large, hospital-based, case-control study of 827 pathologically or radiologically confirmed HCC cases and 1,013 controls, NOC intake was calculated by linking food frequency questionnaire-derived dietary data with a comprehensive NOC concentration database. Multivariable-adjusted ORs and 95% CIs of HCC by quartiles of NOC consumption were estimated using logistic regression models, with the lowest quartile as the referent. We further investigated joint effects of consuming the highest quartile of NOCs that were associated with increased HCC risk and hepatitis, diabetes, or alcohol drinking on HCC risk. After adjustment for confounding factors, higher intake of NDEA from plant sources (ORQ4 vs. Q1  = 1.58; 95% CI = 1.03-2.41), NDMA from plant sources (ORQ4 vs. Q1  = 1.54; 95% CI = 1.01-2.34), and NPIP (ORQ4 vs. Q1  = 2.52; 95% CI = 1.62-3.94) was associated with increased HCC risk. No association was observed for nitrate or total NOC intake and HCC risk. Higher consumption of HCC-inducing NOCs and positive hepatitis virus status jointly increased the risk of developing HCC. CONCLUSIONS: In conclusion, though some of our findings may indicate the presence of reverse causation owing to lower meat intake among cases with chronic liver diseases before HCC diagnosis, the potent dietary HCC carcinogens, NDEA, NDMA, and NPIP, and their enhanced carcinogenic effects among chronic carriers of hepatitis virus warrant further prospective investigation.


Asunto(s)
Carcinoma Hepatocelular/epidemiología , Encuestas sobre Dietas/estadística & datos numéricos , Exposición Dietética/efectos adversos , Neoplasias Hepáticas/epidemiología , Compuestos Nitrosos/efectos adversos , Anciano , Carcinoma Hepatocelular/inducido químicamente , Estudios de Casos y Controles , Femenino , Humanos , Incidencia , Neoplasias Hepáticas/inducido químicamente , Masculino , Persona de Mediana Edad , Factores de Riesgo
13.
Cancers (Basel) ; 13(3)2021 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-33498613

RESUMEN

Diffuse type of gastric adenocarcinoma (dGAC) generally confers a poor prognosis compared to intestinal type. Some dGACs are not avid on fluorine-18 fluoro-2-deoxy-D-glucose PET (FDG-PET) while others seem to consume glucose avidly. We analyzed the outcomes based on the avidity (high with standardized uptake value (SUV) > 3.5 or low with SUV ≤ 3.5) of the primary on baseline FDG-PET. We retrospectively selected 111 localized dGAC patients who had baseline FDG-PET (all were treated with preoperative chemotherapy and chemoradiation). FDG-PET avidity was compared with overall survival (OS) and response to therapy. The mean age was 59.4 years and with many females (47.7%). The high-SUV group (58 (52.3%) patients) and the low-SUV group (53 (47.7%) patients) were equally divided. While the median OS for all patients was 49.5 months (95% CI: 38.5-98.8 months), it was 98.0 months (95% CI: 49.5-NE months) for the low-SUV group and 36.0 months for the high-SUV (p = 0.003). While the median DFS for all patients was 38.2 months (95%CI: 27.7-97.6 months), it was 98.0 (95% CI: 36.9-NE months) months for the low-SUV group was and only 27.0 months (95% CI: 15.2-63.2 months) for the high-SUV group (p = 0.005). Clinical responses before surgery were more common in the low-SUV group but overall we observed only 4 pathologic complete responses in 111 patients. Our unique data suggest that if dGACs used glucose as an energy source then the prognosis was very poor while non-glucose sources improved prognosis. Multi-platform (including metabolomics) profiling of dGACs would yield useful biologic understanding.

14.
Nat Med ; 27(1): 141-151, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33398161

RESUMEN

Intratumoral heterogeneity (ITH) is a fundamental property of cancer; however, the origins of ITH remain poorly understood. We performed single-cell transcriptome profiling of peritoneal carcinomatosis (PC) from 15 patients with gastric adenocarcinoma (GAC), constructed a map of 45,048 PC cells, profiled the transcriptome states of tumor cell populations, incisively explored ITH of malignant PC cells and identified significant correlates with patient survival. The links between tumor cell lineage/state compositions and ITH were illustrated at transcriptomic, genotypic, molecular and phenotypic levels. We uncovered the diversity in tumor cell lineage/state compositions in PC specimens and defined it as a key contributor to ITH. Single-cell analysis of ITH classified PC specimens into two subtypes that were prognostically independent of clinical variables, and a 12-gene prognostic signature was derived and validated in multiple large-scale GAC cohorts. The prognostic signature appears fundamental to GAC carcinogenesis and progression and could be practical for patient stratification.


Asunto(s)
Adenocarcinoma/secundario , Neoplasias Gástricas/patología , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Linaje de la Célula/genética , Cromosomas Humanos Par 17/genética , Estudios de Cohortes , Variaciones en el Número de Copia de ADN , Femenino , Perfilación de la Expresión Génica , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/secundario , Pronóstico , RNA-Seq , Análisis de la Célula Individual , Neoplasias Gástricas/genética
15.
Gut ; 70(11): 2055-2065, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33334899

RESUMEN

OBJECTIVE: Prognosis of patients with advanced oesophagogastric adenocarcinoma (mEGAC) is poor and molecular determinants of shorter or longer overall survivors are lacking. Our objective was to identify molecular features and develop a prognostic model by profiling the genomic features of patients with mEGAC with widely varying outcomes. DESIGN: We profiled 40 untreated mEGACs (20 shorter survivors <13 months and 20 longer survivors >36 months) with whole-exome sequencing (WES) and RNA sequencing and performed an integrated analysis of exome, transcriptome, immune profile and pathological phenotypes to identify the molecular determinants, developing an integrated model for prognosis and comparison with The Cancer Genome Atlas (TCGA) cohorts. RESULTS: KMT2C alterations were exclusively observed in shorter survivors together with high level of intratumour heterogeneity and complex clonal architectures, whereas the APOBEC mutational signatures were significantly enriched in longer survivors. Notably, the loss of heterozygosity in chromosome 4 (Chr4) was associated with shorter survival and 'cold' immune phenotype characterised by decreased B, CD8, natural killer cells and interferon-gamma responses. Unsupervised transcriptomic clustering revealed a shorter survivor subtype with distinct expression features (eg, upregulated druggable targets JAK2, MAP3K13 and MECOM). An integrated model was then built based on clinical variables and the identified molecular determinants, which significantly segregated shorter and longer survivors. All the above features and the integrated model have been validated independently in multiple TCGA cohorts. CONCLUSION: This study discovered novel molecular features prognosticating overall survival in patients with mEGAC and identified potential novel targets in shorter survivors.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Perfil Genético , Neoplasias Gástricas/genética , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Masculino , Pronóstico , Medición de Riesgo , Análisis de Secuencia de ARN , Secuenciación del Exoma
16.
Ann Surg ; 273(4): 751-757, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31188215

RESUMEN

OBJECTIVE: We aimed to evaluate the frequency of paratracheal lymph nodes (LN) metastases and their prognostic influence. SUMMARY BACKGROUND DATA: Paratracheal LNs are considered regional nodes in the esophageal cancer classification, but their metastatic rate and influence on survival remain unclear. METHODS: One thousand one hundred ninety-nine patients with resectable esophageal or gastroesophageal junction adenocarcinoma (EAC) (January 2002 and December 2016) in our Gastrointestinal Medical Oncology Database were analyzed. Paratracheal LNs were defined as1R, 1L, 2R, 2L, 4R, and 4L, according to the 8th American Joint Committee on Cancer classification. RESULTS: Of 1199 patients, 73 (6.1%) had positive paratracheal LNs at diagnosis. The median overall survival (OS) of 73 patients with initial paratracheal LN involvement was 2.10 years (range 0.01-10.1, 5-yrs OS 24.2%). Of 1071 patients who were eligible for recurrence evaluation, 70 patients (6.5%) developed paratracheal LN metastases as the first recurrence. The median time to recurrence was 1.28 years (range 0.28-5.96 yrs) and the median OS following recurrence was only 0.95 year (range 0.03-7.88). OS in 35 patients who had only paratracheal LN recurrence was significantly longer than in patients who had other recurrences (median OS 2.26 vs 0.51 yrs, 5-yrs OS; 26.8% vs 0%, P < 0.0001). Higher T stage (T3/T4) was an independently risk factor for paratracheal LN recurrence (odds ratio 5.10, 95% confidence interval 1.46-17.89). We segregated patients in 3 groups based on the distance of tumor's proximal edge to esophagogastric junction (low; ≤2 cm, medium; 2.0-7.0 cm, and high; >7.0 cm). Paratracheal LN metastases were more frequent with the proximal tumors (low, 4.2%; medium, 12.0%; high, 30.3%; Cochran-Armitage Trend test, P < 0.001). CONCLUSION: Paratracheal LN metastases were associated with a shorter survival in resectable EAC patients. Alternate approaches to prolong survival of this group of patients are warranted.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Unión Esofagogástrica , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Estadificación de Neoplasias , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/secundario , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiología , Adulto Joven
17.
Oncology ; 98(12): 884-888, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32998149

RESUMEN

BACKGROUND: Prior studies have shown that patients whose tumor overexpresses Her2 at 3+ level by immunohistochemistry (IHC) fare better than those whose tumor overexpresses Her2 at 2+ level (with ERBB2 amplified). Therefore, it would be important to compare the outcome of patients whose tumor expresses Her2 at 2+ level but further classify by gene amplification studies as positive or negative. METHODS: We retrospectively identified patients with advanced gastroesophageal adenocarcinoma with low Her2 protein expression (2+ by IHC) whose tumors were evaluated for gene amplification of ERBB2 by fluorescence in situ hybridization (FISH). All patients received first-line therapy, and trastuzu-mab was added according to Her2 status. We compared overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) of the entire cohort and compared Her2-positive tumor patients' outcomes with Her2-negative tumor patients' outcomes. All patients had treatment response assessments and follow-ups at our institution. RESULTS: We identified 87 patients whose tumors expressed Her2 at 2+ level. 51 (58.6%) were Her2-negative and 36 (41.4%) were Her2-positive by FISH. For the entire cohort, the median OS was 26 months (95% confidence interval 16.6-37.6), and the median PFS was 12.2 months (95% confidence interval 9.7-19.3). Median OS, median PFS, and ORR did not differ between Her2-positive and Her2-negative patients (p = 0.70, p = 0.60, p = 0.91, respectively). CONCLUSIONS: Our data suggest that patients with Her2 positivity or negativity when tumors have lower Her2 protein expression (2 + by IHC) have similar clinical outcomes. Further research is warranted in this cohort.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Esofágicas/genética , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Esofágicas/patología , Femenino , Amplificación de Genes/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Oncogenes/genética , Supervivencia sin Progresión , Neoplasias Gástricas/patología
18.
Gastric Cancer ; 23(5): 904-912, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32347396

RESUMEN

BACKGROUND: As cancer patients are surviving longer, more patients manifest brain metastases (BRMs). However, the rate of BRMs from upper gastrointestinal cancer is unclear. We therefore evaluated the frequency and prognostic effect of BRMs in this setting. METHODS: We analyzed records of 2348 patients who were treated between January 2002 and December 2016 for upper gastrointestinal cancer, including esophageal and gastroesophageal junction adenocarcinoma (EAC; proximal EAC, Siewert types I and II), esophageal squamous cell carcinoma (ESCC), and gastric adenocarcinoma (GAC; Siewert type III and stomach cancer) in our Gastrointestinal Medical Oncology Database. Frequency, risk factors, and survival after BRMs were evaluated. RESULTS: Of 2348 patients, 68 (2.9%) had BRMs upon follow-up. The BRM rates were as follows: proximal EAC, 4.8%; Siewert type I, 5.9%; Siewert type II, 2.2%; Siewert type III, 0.7%; ESCC: 1.2%; and stomach cancer, 0%. Among EAC patients, Siewert type I and lymph node metastases were independent the risk factors for BRMs in the multivariable analysis. The median overall survival (OS) in the 68 patients with BRMs was only 1.16 years (95% CI 0.78-1.61). However, OS for patients who had a solitary BRM, who had BRM but no other distant metastasis, or who underwent surgery or stereotactic radiosurgery favorable. CONCLUSION: Patients with proximally located adenocarcinoma, or with lymph node metastases are at a higher risk for BRMs and patients fare better after treatment of isolated BRM.


Asunto(s)
Adenocarcinoma/patología , Neoplasias Encefálicas/secundario , Neoplasias Esofágicas/patología , Unión Esofagogástrica/patología , Neoplasias Gastrointestinales/patología , Neoplasias Gástricas/patología , Adenocarcinoma/cirugía , Neoplasias Encefálicas/cirugía , Neoplasias Esofágicas/cirugía , Unión Esofagogástrica/cirugía , Femenino , Estudios de Seguimiento , Neoplasias Gastrointestinales/cirugía , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Tasa de Supervivencia
19.
BMC Pregnancy Childbirth ; 19(1): 234, 2019 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-31286872

RESUMEN

BACKGROUND: The incidence of post cesarean intra-abdominal infection (IAI) and the independent risk factors associated with it were retrospectively studied at a tertiary referral hospital in Egypt. METHODS: The study targeted the period between January 2014 and December 2017 (4 years) at Minia University Hospital for Obstetrics and Gynecology (a tertiary referral hospital), Minia Governorate, Egypt. All cases that developed IAI following cesarean section (CS) during the study period were included (408 cases, which served as the case group); in addition, 1300 cases that underwent CS during the study period and were not complicated by IAI or surgical site Infection (SSI) were randomly chosen from the records (control group). The records of cases and controls were compared and bivariate analysis and multivariate logistic regression were used to identify risk factors for IAI. RESULTS: During the studied period, there were 35,500 deliveries in the hospital, and 14200 cases (40%) of these were by cesarean section, producing a rate of 40%. The incidence of IAI post CS was 2.87%, and the mortality rate was 1.2% (due to septicemia). The most identifiable risk factors for IAI were chorioamnionitis (AOR 9.54; 95% CI =6.15-16.2; p ≤ 0.001) and premature rupture of membranes (PROM) (AOR 7.54; 95% CI =5.69-10.24; p ≤ 0.001). Risk factors also included: prolonged duration of CS >  1 h (AOR 3.42; 95% CI =2.45-5.23; p = 0.005), no antenatal care (ANC) visits (AOR 3.14; 95% CI =2.14-4.26; p = 0.003), blood loss > 1000 ml (AOR 2.86; 95% CI =2.04-3.92; p = 0.011), emergency CS (AOR 2.24; 95% CI =1.78-3.29; p = 0.016), prolonged labor ≥24 h. (AOR 1.76; 95% CI =1.26-2.27; p = 0.034) and diabetes mellitus (AOR 1.68; 95% CI =1.11-2.39; p = 0.021). CONCLUSIONS: The incidence of IAI post CS in our hospital was 2.87%. Identification of predictors and risk factors for IAI is an important preventive measure.


Asunto(s)
Cesárea , Infecciones Intraabdominales/epidemiología , Infección de la Herida Quirúrgica/epidemiología , Adolescente , Adulto , Estudios de Casos y Controles , Egipto , Femenino , Humanos , Incidencia , Infecciones Intraabdominales/etiología , Modelos Logísticos , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Infección de la Herida Quirúrgica/etiología , Centros de Atención Terciaria , Adulto Joven
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