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1.
Pol Przegl Chir ; 96(3): 69-82, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38940248

RESUMO

<b><br>Introduction:</b> Obesity's associated comorbidities and treatment costs have risen significantly, highlighting the importance of early weight loss strategies. Bariatric surgeries like Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) have been effective in promoting weight loss and improving type 2 diabetes mellitus (T2DM) management.</br> <b><br>Aim:</b> The aim was to determine whether Roux-en-Y gastric bypass is more effective than vertical sleeve gastrectomy in the remission of type 2 diabetes mellitus (T2DM).</br> <b><br>Methods:</b> A systematic review and meta-analysis was performed. A literature search was performed in the databases Web of Science, Medline/PubMed, Embase, Scopus, and Medline/Ovid. A total of 1323 results were identified; after screening, 14 articles were selected and included in the systematic review. Primary and secondary outcomes were measured by RR with a 95% CI.</br> <b><br>Results:</b> The primary outcome of T2DM remission was 15% in favor of VSG (RR: 1.15, [95% CI: 1.04-1.28]). For secondary outcomes, hypertension remission was 7% in favor of VSG (RR: 1.07, [95% CI: 1.00-1.16]). Remission of dyslipidemia was 16% in favor of VSG (RR: 1.16, [95% CI: 1.06-1.26]). BMI after surgery was in favor of RYGB (MD: -1.31, [95% CI: -1.98 to -0.64]). For weight loss, the results favored VSG (MD: 6.50, [95% CI: 4.99-8.01]). In relation to total cholesterol, they were 65% favorable for RYGB (MD: -0.35, [95% CI: -0.46 to -0.24]), with a value of p <0.05. For LDL values, our results were 69% favorable for RYGB (MD: -0.31, [95% CI: -0.45 to -0.16]), p <0.01 value.</br> <b><br>Conclusions:</b> Laparoscopic sleeve gastrectomy is more effective in T2DM remission, hypertension remission, dyslipidemia remission, and weight loss compared to Roux-en-Y gastric bypass. Roux-en-Y gastric bypass is more effective at lowering BMI, total cholesterol, LDL, and TG compared to laparoscopic sleeve gastrectomy.</br>.


Assuntos
Diabetes Mellitus Tipo 2 , Gastrectomia , Derivação Gástrica , Humanos , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica/métodos , Gastrectomia/métodos , Feminino , Masculino , Resultado do Tratamento , Redução de Peso , Adulto , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Indução de Remissão
2.
Ann Surg Oncol ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879670

RESUMO

BACKGROUND: In 2023 alone, it's estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC. METHODS: Retrospective analysis of single-institution data. RESULTS: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease. CONCLUSIONS: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.

4.
Clin Cancer Res ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695832

RESUMO

PURPOSE: Minimal residual disease (MRD) detection identifies patients with colorectal adenocarcinoma (CRC) likely to recur following definitive treatment. We evaluated a plasma only MRD assay to predict recurrence and survival in metastatic CRC patients undergoing curative intent procedures (surgery and/or radiotherapy), with or without (neo)adjuvant chemotherapy. The primary objective of this study was to assess the correlation of post-procedure tumor cfDNA detection status with radiographic disease recurrence (RFS). EXPERIMENTAL DESIGN: Pre- and post-procedure longitudinal samples were collected from 53 patients and analyzed with a multiomic MRD assay detecting circulating tumor DNA (ctDNA) from genomic and epigenomic signals. Pre- and post-procedure ctDNA detection correlated with recurrence-free and overall survival. RESULTS: 230/233 samples from 52 patients were successfully analyzed. At the time of data cutoff, 36 (69.2%) patients recurred with median follow-up of 31 months. 19/42 patients (45.2%) with ctDNA analyzed 3 weeks post-procedure had detectable ctDNA. ctDNA detection 3 weeks post-procedure was associated with shorter median RFS (HR 5.27; 95% CI, 2.31-12.0, p<0.0001) and overall survival (OS) (HR 12.83; 95% CI, 3.6-45.9, p<0.0001). Pre-procedure ctDNA detection status was not associated with RFS but was associated with improved OS (HR 4.65; 95% CI, 1.4-15.2, p=0.0111). Undetectable ctDNA pre-procedure had notable long-term overall survival, >90% 3 years post-procedure. CONCLUSION: In this cohort of oligometastatic CRC, detection of ctDNA pre- or post-procedure was associated with inferior outcomes even after accounting for prognostic clinicopathologic variables. This suggests ctDNA may enhance current risk stratification methods helping evaluate novel treatments and surveillance strategies toward improving patient outcomes.

5.
Am J Surg ; : 115779, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38811243

RESUMO

INTRODUCTION: Pancreatic neuroendocrine tumors (PNETs) are typically diagnosed using endoscopic ultrasound-guided (EUS) biopsy, which can be associated with complications. Since 2016, DOTATATE PET/CT has emerged as an effective tool to localize and stage PNETs. METHODS: Patients with PNETs who underwent R0 resections were identified from the 2004-2019 National Cancer Database PUF. Joinpoint regression and multivariable logistic regression were used to analyze trends in the use of biopsy. RESULTS: Of 16,746 R0 resected PNET patients, 44 â€‹% underwent diagnostic biopsy. Joinpoint regression showed a significant increase in the use of biopsy from 2004 to 2019 (APC 1.80, p â€‹< â€‹0.001). A higher percentage of patients diagnosed after DOTATATE approval underwent biopsy compared to those diagnosed before (48 â€‹% vs. 42 â€‹%, p â€‹< â€‹0.001). Adjusted analysis showed diagnosis after 2016 was associated with increased odds of biopsy (OR â€‹= â€‹1.67, p â€‹< â€‹0.001). CONCLUSIONS: Despite technologic advancement with DOTATATE PET/CT, there has been a significant increase in the proportion of resectable PNETs undergoing preoperative biopsy.

6.
Ann Surg Oncol ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797790

RESUMO

BACKGROUND: Ileal neuroendocrine tumors (i-NETs) are characterized by their multifocality and bulky mesenteric mass. Having shown that minimally invasive surgery (MIS) utilizing a hand-access port device has favorable short-term outcomes and achieves the goals of surgery for i-NETs, we sought to analyze long-term survival outcomes of MIS. METHODS: One hundred and sixty-eight patients who underwent resection of primary i-NETs at a single institution between January 2007 and February 2023 were retrospectively studied. Patients were categorized into the MIS or open surgery cohorts on an intention-to-treat basis. Open surgery was selected mainly based on the need for hepatectomy or bulky mesenteric mass resection. Overall survival was analyzed using log-rank tests with propensity score matching (PSM) and Cox proportional hazards regression. PSM was performed to reduce standardized mean differences of the variables to <0.2. RESULTS: Overall, 129 (77%) patients underwent MIS and 39 (23%) underwent open surgery. Twenty-seven MIS patients were converted to an open procedure. The median follow-up time was 49 months (interquartile range 23-87 months). In the PSM cohorts, overall survival did not differ significantly between the MIS and open surgery cohorts {median 99 months (95% confidence interval [CI] 91-not applicable [NA]) vs. 103 months (95% CI 86-NA), p = 0.77; hazard ratio 0.87 (95% CI 0.33-2.2), p = 0.77}. CONCLUSIONS: MIS is an alternative to open surgery for i-NETs, achieving similar short- and long-term oncological outcomes. Bulky mesenteric mass and a plan for concurrent liver resection are potential criteria for open surgery.

8.
World J Surg Oncol ; 22(1): 77, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468341

RESUMO

BACKGROUND: Metastatic melanoma to the small bowel is an aggressive disease often accompanied by obstruction, abdominal pain, and gastrointestinal bleeding. With advancements in melanoma treatment, the role for metastasectomy continues to evolve. Inclusion of novel immunotherapeutic agents, such as checkpoint inhibitors, into standard treatment regimens presents potential survival benefits for patients receiving metastasectomy. CASE PRESENTATION: We report an institutional experience of 15 patients (12 male, 3 female) between 2014-2022 that underwent small bowel metastasectomy for metastatic melanoma and received perioperative systemic treatment. Median age of patients was 64 years (range: 35-83 years). No patients died within 30 days of their surgery, and the median hospital length of stay was 5 days. Median overall survival in these patients was 30.1 months (range: 2-115 months). Five patients died from disease (67 days, 252 days, 426 days, 572 days, 692 days postoperatively), one patient died of non-disease related causes (1312 days postoperatively), six patients are alive with disease, and three remain disease free. CONCLUSIONS: This case series presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment. Small bowel metastasectomy for advanced melanoma performed in conjunction with perioperative systemic therapy is safe and appears to promote long-term survival and enhanced quality of life.


Assuntos
Melanoma , Metastasectomia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Melanoma/terapia , Melanoma/patologia , Qualidade de Vida , Imunoterapia , Intestino Delgado/patologia , Estudos Retrospectivos
9.
J Gastrointest Surg ; 28(3): 246-251, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38445916

RESUMO

BACKGROUND: Despite significant advancements in the treatment of patients with colorectal liver metastases (CRLMs), only a minority will experience long-term survival. This study aimed to determine the effect of chemotherapy (CT) and immunotherapy (IT) compared with that of CT alone on patient survival after surgical resection. METHODS: Patients undergoing curative-intent liver resection followed by adjuvant systemic therapy for stage IV colon cancer were identified using the National Cancer Database. Patients were stratified into type of therapy (CT alone vs CT + IT) and microsatellite status. Propensity score-weighted analysis was performed through 1:1 matching based on the nearest neighbor method. RESULTS: Of 9943 patients who underwent resection of CRLMs, 7971 (80%) received systemic adjuvant therapy. Of 7971 patients, 1432 (18%) received a combination of CT and IT. Microsatellite status was not associated with overall survival (OS). Adjuvant CT + IT was associated with increased 3-year OS compared with that of CT alone in both the unmatched cohort (55% vs 48%, respectively; P < .001) and matched cohort (52% vs 48%, respectively; P = .050). On multivariate analysis, older age, positive resection margins, and KRAS mutation were independent predictors of poor survival, whereas the administration of adjuvant CT + IT was an independent predictor of improved survival. CONCLUSION: IT combined with CT was associated with improved survival compared with that of CT alone after curative-intent resection of CRLMs, regardless of microsatellite instability status. Clinical trials to determine optimal patient selection, IT regimen, and long-term efficacy to improve outcomes of patients with CRLMs are warranted.


Assuntos
Neoplasias do Colo , Neoplasias Hepáticas , Humanos , Imunoterapia , Neoplasias Hepáticas/terapia , Quimioterapia Adjuvante , Hepatectomia , Neoplasias do Colo/terapia
10.
JAMA Surg ; 159(3): 345-347, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38150246

RESUMO

This cross-sectional study assesses the association between venous thrombosis and embolization in patients with hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Trombose Venosa , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Veia Porta/patologia , Resultado do Tratamento
11.
Arq Bras Cir Dig ; 36: e1782, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38088727

RESUMO

BACKGROUND: Bariatric surgery is the most effective option to reduce weight in morbid obesity patients. The techniques most employed are the restrictive surgery laparoscopic sleeve gastrectomy (LSG), surgical procedures of intestinal malabsorption, and both types (restrictive and intestinal malabsorption) such as the Roux-en-Y laparoscopic gastric bypass (RYLGB). AIMS: To determine if LSG is more effective than RYLGB for weight loss. METHODS: A systematic review and meta-analysis was carried out, including five clinical trials and sixteen cohorts comparing LSG versus RYLGB in weight loss and secondary outcomes: resolution of comorbidities, postoperative complications, operative time, hospital stay, and improvement in quality of life. RESULTS: Excess weight loss was 10.2% (mean difference [MD] 10.2; 95%CI -10.14; -9.90) higher in patients undergoing LSG than in patients submitted to RYLGB. Diabetes mellitus type 2 was resolved in 17% (relative risk [RR] 0.83; 95%CI 0.77-0.90) of cases, more significantly after LSG, arterial hypertension in 23% (RR 0.77; 95%CI 0.69-0.84), and dyslipidemia in 17% (RR 0.83; 95%CI 0.77-0.90). Postoperative complications were 73% higher in patients undergoing RYLGB (MD 0.73; 95%CI 0.63-0.83). The operative time was 35.76 minutes shorter in the LSG (MD -35.76; 95%CI -37.28; -34.24). Finally, the quality of life improved more in patients operated by LSG (MD 0.37; 95%CI -0.48; -0.26). CONCLUSIONS: The study demonstrated that LSG could be more effective than RYLGB in reducing the percentage of excess weight, comorbidities, postoperative complications, operative time, hospital stay, and in improving quality of life.


Assuntos
Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Humanos , Derivação Gástrica/métodos , Qualidade de Vida , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Laparoscopia/métodos , Gastrectomia/métodos , Redução de Peso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
12.
Rev. cir. (Impr.) ; 75(5)oct. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1530073

RESUMO

Introducción: Existe una controversia acerca del mejor enfoque para el tratamiento de la apendicitis aguda no complicada. Este metaanálisis buscó evaluar la eficacia, recurrencia de la patología, presencia de complicaciones mayores, y duración de la estancia hospitalaria en adultos con apendicitis aguda no complicada. Materiales y Método: Se realizó una búsqueda sistemática de ensayos clínicos aleatorizados en las bases de datos PubMed, Scopus, Web of Science, Embase y Cochrane Library hasta finales de octubre del 2022. El riesgo de sesgo y calidad de los estudios incluidos en el estudio fueron evaluados mediante la herramienta RoB 2.0. de la Colaboración Cochrane. La síntesis de datos fue realizada a través del software Cochrane Review Manager (RevMan; version 5.3). Resultados: 6 estudios fueron incluidos, con un total de 1.862 pacientes. La probabilidad de presentar una mejoría clínica definitiva en el grupo que recibió antibioticoterapia fue menor (RR 0,5; IC95% 0,92-0,98; p = 0,004; IC2 = 44%). La probabilidad de presentar una recurrencia de la apendicitis en el grupo que recibió antibioticoterapia fue notablemente superior (RR 94,86; IC95% 30,73-292,81; p < 0,00001; IC2 = 0%). El grupo conservador presentó un menor riesgo de presentar una complicación mayor (RR 0,55; IC95% 0,36-0,85; p = 0,007; IC2 = 0%). El tratamiento conservador presentó una duración de la estancia hospitalaria superior que la apendicectomía (MD 0,34; IC95% 0,25-0,42; p < 0,00001; IC2 = 64%). Conclusiones: Esta revisión sistemática demuestra que, en términos de eficacia, recurrencia del cuadro y duración de la estancia hospitalaria, la antibioticoterapia es inferior a la apendicectomía en adultos con apendicitis aguda no complicada y superior en evitar la presencia de complicaciones mayores.


Introduction: There is controversy about the best approach for the treatment of uncomplicated acute appendicitis. This meta-analysis sought to assess efficacy, disease recurrence, presence of major complications, and length of hospital stay in adults with uncomplicated acute appendicitis. Materials and Method: A systematic search for randomized clinical trials was performed in the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases up to the end of October 2022. The risk of bias and quality of the studies included in the study were assessed. using the RoB 2.0 tool. of the Cochrane Collaboration. Data synthesis was performed using the Cochrane Review Manager software (RevMan; version 5.3). Results: 6 studies were included, with a total of 1.862 patients. The probability of presenting a definitive clinical improvement in the group that received antibiotic therapy was lower (RR 0.5; CI95% 0.92-0.98; p = 0.004; CI2 = 44%). The probability of presenting a recurrence of appendicitis in the group that received antibiotic therapy was notably higher (RR 94.86; 95%CI 30.73-292.81; p < 0.00001; CI2 = 0%). The conservative group presented a lower risk of presenting a major complication (RR 0.55; CI95% 0.36-0.85; p = 0.007; CI2 = 0%). Conservative treatment had a longer hospital stay than appendectomy (MD 0.34; 95%CI 0.250.42; p < 0.00001; CI2 = 64%). Conclusions: This systematic review shows that, in terms of efficacy, recurrence of the condition, and length of hospital stay, antibiotic therapy is inferior to appendectomy in adults with uncomplicated acute appendicitis, and superior in avoiding the presence of major complications.

14.
Ann Surg Oncol ; 30(12): 7738-7747, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37550449

RESUMO

BACKGROUND: Clinically-relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) is a major postoperative complication and the primary determinant of surgical outcomes. However, the majority of current risk calculators utilize intraoperative and postoperative variables, limiting their utility in the preoperative setting. Therefore, we aimed to develop a user-friendly risk calculator to predict CR-POPF following PD using state-of-the-art machine learning (ML) algorithms and only preoperatively known variables. METHODS: Adult patients undergoing elective PD for non-metastatic pancreatic cancer were identified from the ACS-NSQIP targeted pancreatectomy dataset (2014-2019). The primary endpoint was development of CR-POPF (grade B or C). Secondary endpoints included discharge to facility, 30-day mortality, and a composite of overall and significant complications. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated and a user-friendly risk calculator was then developed. RESULTS: Of the 8666 patients who underwent elective PD, 13% (n = 1160) developed CR-POPF. XGBoost was the best performing model (AUC = 0.72), and the top five preoperative variables associated with CR-POPF were non-adenocarcinoma histology, lack of neoadjuvant chemotherapy, pancreatic duct size less than 3 mm, higher BMI, and higher preoperative serum creatinine. Model performance for 30-day mortality, discharge to a facility, and overall and significant complications ranged from AUC 0.62-0.78. CONCLUSIONS: In this study, we developed and validated an ML model using only preoperatively known variables to predict CR-POPF following PD. The risk calculator can be used in the preoperative setting to inform clinical decision-making and patient counseling.

16.
Ann Surg Oncol ; 30(8): 5119-5129, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37140748

RESUMO

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignancy with a historically poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an effective therapy for patients with peritoneal malignancies. A contemporary analysis of trends in management of and survival from MPM is warranted. METHODS: Patients with MPM were identified from the National Cancer Database (2004-2018). Patients were categorized by treatment (CRS-HIPEC, CRS-chemotherapy, CRS only, chemotherapy only, no treatment), and joinpoint regression was employed to compute the annual percent change (APC) in treatment over time. Multivariable Cox proportional hazards models were used to analyze factors associated with survival. RESULTS: Of 2683 patients with MPM, 19.1% underwent CRS-HIPEC, and 21.1% received no treatment. Joinpoint regression revealed a statistically significant increase in the proportion of patients undergoing CRS-HIPEC over time (APC 3.21, p = 0.01), and a concurrent decrease in the proportion of patients who underwent no treatment (APC - 2.21, p = 0.02). Median overall survival was 19.5 months. Factors independently associated with survival included CRS-HIPEC, CRS, histology, sex, age, race, Charlson Comorbidity Index, insurance, and hospital type. Although there was a strong association between year of diagnosis and survival on univariate analysis (2016-2018 HR 0.67, p < 0.001), this association was attenuated after adjustment for treatment. CONCLUSIONS: CRS-HIPEC is increasingly employed as a treatment for MPM. In parallel, there has been a decrease in patients receiving no treatment with an increase in overall survival. These findings suggest that patients with MPM may be receiving more appropriate therapy; however, a substantial proportion of patients may remain undertreated.


Assuntos
Hipertermia Induzida , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Mesotelioma/patologia , Neoplasias Peritoneais/patologia , Neoplasias Pulmonares/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Taxa de Sobrevida , Estudos Retrospectivos
17.
J Natl Compr Canc Netw ; 21(4): 393-422, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37015332

RESUMO

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Segunda Neoplasia Primária , Humanos , Qualidade de Vida , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/terapia , Junção Esofagogástrica/patologia , Carcinoma de Células Escamosas/patologia , Segunda Neoplasia Primária/patologia
19.
PLoS One ; 18(4): e0271354, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37022995

RESUMO

Tumors rich in stroma are associated with advanced stage and poor prognosis in colorectal adenocarcinoma (CRC). Abundance of stromal cells also has implications for genomic analysis of patient tumors as it may prevent detection of somatic mutations. As part of our efforts to interrogate stroma-cancer cell interactions and to identify actionable therapeutic targets in metastatic CRC, we aimed to determine the proportion of stroma embedded in hepatic CRC metastases by performing computational tumor purity analysis based on whole exome sequencing data (WES). Unlike previous studies focusing on histopathologically prescreened samples, we used an unbiased in-house collection of tumor specimens. WES from CRC liver metastasis samples were utilized to evaluate stromal content and to assess the performance of three in silico tumor purity tools, ABSOLUTE, Sequenza and PureCN. Matching tumor derived organoids were analyzed as a high purity control as they are enriched in cancer cells. Computational purity estimates were compared to those from a histopathological assessment conducted by a board-certified pathologist. According to all computational methods, metastatic specimens had a median tumor purity of 30% whereas the organoids were enriched for cancer cells with a median purity estimate of 94%. In line with this, variant allele frequencies (VAFs) of oncogenes and tumor suppressor genes were undetectable or low in most patient tumors, but higher in matching organoid cultures. Positive correlation was observed between VAFs and in silico tumor purity estimates. Sequenza and PureCN produced concordant results whereas ABSOLUTE yielded lower purity estimates for all samples. Our data shows that unbiased sample selection combined with molecular, computational, and histopathological tumor purity assessment is critical to determine the level of stroma embedded in metastatic colorectal adenocarcinoma.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Sequenciamento do Exoma , Mutação , Exoma/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Adenocarcinoma/genética , Neoplasias Hepáticas/genética
20.
Ann Surg Oncol ; 30(6): 3413-3422, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36859704

RESUMO

INTRODUCTION: Complete resection of colorectal liver metastasis (CLM) improves long-term survival in colorectal cancer. However, there is limited recent data on conditional survival (CS) as postoperative survival milestones are achieved post-hepatectomy. METHODS: A retrospective analysis was performed on the penta-institutional Colorectal Liver Operative Metastasis International Collaborative (COLOMIC), with 906 consecutive CLM hepatectomy cases. CS was calculated using Bayes' theorem and Kaplan-Meier analysis. Additional CS analyses were performed on additional clinicopathologic risk factors, including colon cancer laterality, KRAS mutation status, and extrahepatic disease. RESULTS: The 5-year CS was 40.6%, 45.3%, 52.8%, and 65.3% at 0, 1, 2, and 3 years postoperatively, with significant improvements each year (p < 0.005). CS was not significantly different between right-sided and left-sided colorectal cancers by 3 years postoperatively. Patients with KRAS mutations had worse CS at all timepoints (p < 0.001). Extrahepatic disease was a poor prognostic factor for OS and CS (p < 0.001). However, CS for patients with KRAS mutations or extrahepatic disease improved significantly as 2-year, postoperative survival was achieved (p < 0.05). CONCLUSIONS: Five-year CS after hepatectomy for CLM improved with each passing year of survival postoperatively. Although extrahepatic disease and KRAS mutations are poor prognostic factors for OS, these populations still had improved CS after 2 years postoperatively.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Hepatectomia , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Teorema de Bayes , Proteínas Proto-Oncogênicas p21(ras)/genética , Prognóstico , Neoplasias Hepáticas/secundário , Taxa de Sobrevida
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