RESUMO
BACKGROUND: Two distinct histological growth patterns (HGPs) were described in patients with peritoneal metastasis of colorectal cancer origin (PMCRC) with limited Peritoneal Cancer Index (PCI) ≤ 6 who did not receive neoadjuvant chemotherapy (NAC) and were treated with cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC): pushing HGP (P-HGP) and infiltrating HGP (I-HGP). Patients with dominant P-HGP (> 50%) had significantly better disease-free survival (DFS) and overall survival (OS). OBJECTIVE: We aimed to determine whether these previous observations regarding the prognostic value of HGP in patients with PMCRC with low PCI (≤ 6) are also valid in all operable patients, regardless of whether they received NAC or not and regardless of PCI score. METHODS: This was a retrospective study including 76 patients who underwent complete CRS ± HIPEC for PMCRC between July 2012 and March 2019. In each patient, up to five of the largest excised peritoneal nodules were analyzed for their tumor-to-peritoneum interface. Correlations between NAC, HGP, and prognosis were further explored. RESULTS: Thirty-seven patients (49%) had dominant P-HGP and 39 (51%) had dominant I-HGP. On univariate analysis, patients with P-HGP ≤ 50% had significantly lower OS than those with dominant P-HGP > 50% (39 versus 60 months; p = 0.014) confirmed on multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.3-4.5; p = 0.006). There were no significant associations between NAC and type of HGP. CONCLUSIONS: This study confirms the prognostic value and reproducibility of the two previously reported HGPs in PMCRC. Dominant P-HGP is associated with better DFS and OS in patients undergoing curative-intent CRS ± HIPEC compared with I-HGP, independently of the extent of peritoneal disease burden.
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Neoplasias Colorretais , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Feminino , Masculino , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Estudos Retrospectivos , Pessoa de Meia-Idade , Taxa de Sobrevida , Prognóstico , Idoso , Seguimentos , Terapia Neoadjuvante/mortalidade , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Different histological growth patterns (HGP) describing the tumor-to-liver interface have been described in colorectal liver metastases and have been associated with a strong prognostic value. However, HGP of peritoneal metastases (PM) of colorectal cancer (CRC) have not yet been described. Our objective was to determine whether distinct HGP can be identified in PMCRC and to evaluate their potential prognostic value in these patients. METHODS: This retrospective study included 38 patients who underwent curative-intent surgery for PMCRC between July 2012 and March 2019, with PCI≤6, and who had not received preoperative chemotherapy. In each patient, the tumor-to-peritoneum interface was evaluated in the excised peritoneal nodules. The association between HGP and postoperative survival was analyzed by using the Kaplan-Meier method. RESULTS: Two distinct HGP were identified: a pushing-type (P-HGP), characterized by a fibrous rim separating the PM and peritoneum, and an infiltrating-type (I-HGP), characterized by focal penetration of tumor cells into the surrounding peritoneal lining without a fibrous rim. Fifteen patients had dominant P-HGP, and 23 patients had dominant I-HGP. Patients with dominant P-HGP (>50% tumor-peritoneum interface) had a significantly better DFS (30 months) than those with P-HGP <50% (9 months; p = 0.029). Patients with a P-HGP dominance >60% had better OS (131 months) than those with P-HGP <60% (41 months; p = 0.044). CONCLUSIONS: This is the first description of two distinct, reproducible HGP in PMCRC. The dominant P-HGP is associated with a favorable prognosis in patients with PMCRC, compared with I-HGP, suggesting that this parameter could ultimately represent a new prognostic biomarker.
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Neoplasias Colorretais , Neoplasias Hepáticas , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Humanos , Prognóstico , Peritônio/patologia , Projetos Piloto , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
BACKGROUND: Cytoreductive surgery (CRS) for peritoneal metastases of colorectal cancer (PMCRC) is associated with a high risk of postoperative morbidity, thus making patient selection of upmost importance. Further to data showing an association between preoperative serological biomarkers and patient outcome in various solid tumors, in this study we aim to evaluate their prognostic value in patients with PMCRC treated with curative intent. PATIENTS AND METHODS: This is a retrospective study including patients with PMCRC treated by complete CRS ± HIPEC at our institution between 2011 and 2020. Preoperative serological biomarkers, along with other standard clinicopathological variables, were studied to determine their prognostic value. RESULTS: A total of 94 out of 108 patients met the inclusion criteria. Forty-three patients (46%) presented with synchronous PM. The median peritoneal cancer index (PCI) was 6. On univariate analysis, a higher neutrophil-to-lymphocyte ratio (NLR) was associated with poor prognosis in terms of overall survival (OS) [cutoff 3.567, hazard ratio (HR) 2.8 (1.4-5.3), p = 0.002], whereas a higher platelet-to-lymphocyte ratio (PLR) predicted favorable prognosis in terms of disease-free survival (DFS) [cutoff 185.4, HR 1.9 (1.07-3.53), p = 0.030]. On multivariate analysis, NLR > 3.567, positive lymph nodes (LNs), and PCI > 7 were independent predictive factors for worse OS, whereas NLR > 3.567 and positive LNs were significantly associated with worse DFS. PLR > 185.4 was associated with better DFS. CONCLUSION: High preoperative NLR (> 3.567) and PLR (> 185.4) can predict outcome of patients with PMCRC treated by complete CRS ± HIPEC.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Peritoneais , Neoplasias Retais , Humanos , Prognóstico , Neoplasias Peritoneais/patologia , Estudos Retrospectivos , Procedimentos Cirúrgicos de Citorredução , Neoplasias do Colo/patologia , Neoplasias Retais/patologia , Neutrófilos/patologia , Biomarcadores , Neoplasias Colorretais/patologiaRESUMO
The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.
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Neoplasias Colorretais , Neoplasias Hepáticas , Animais , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/patologiaRESUMO
BACKGROUND: The American College of Surgeons (ACS) has developed a Surgical Risk Calculator (SRC) to predict postoperative surgical complications. No studies have reported the performance of the ACS-SRC in oncogeriatric patients. Our objective was to evaluate the predictive performance of the ACS-SRC in these patients, treated with curative surgery for an abdominal malignancy. METHODS: This is a retrospective study including 136 patients who underwent elective abdominal oncological surgery, between 2017 and 2019, at our institution. Postoperative complications were classified according to the ACS-SRC, and its predictive performance was analyzed by assessing discrimination and calibration and using receiver operating characteristics and area under the curve (AUC). RESULTS: Discrimination was adequate with AUC of 0.7113 (95% confidence interval [CI]: 1.062-1.202, p = 0.0001; Brier 0.198) for serious complications and 0.7230 (95% CI: 1.101-1.756, p = 0.0057; Brier 0.099) for pneumonia; and poor for sepsis, surgical site infection (SSI), and urinary tract infection (UTI) with AUCs of 0.6636 (95% CI: 1.016-1.353, p = 0.0299; Brier 0.142), 0.6167 (95% CI: 1.003-1.266, p = 0.0450; Brier 0.175), and 0.6598 (95% CI: 1.069-2.145, p = 0.0195; Brier 0.082), respectively. CONCLUSION: The ACS-SRC is an adequate predictor for serious complications and pneumonia in oncogeriatric patients treated surgically for abdominal cancer. However, the predictive power of the calculator appears to be low for sepsis, UTI, and SSI.
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Neoplasias Abdominais , Sepse , Cirurgiões , Humanos , Estados Unidos , Estudos Retrospectivos , Medição de Risco , Infecção da Ferida Cirúrgica , Neoplasias Abdominais/cirurgia , Complicações Pós-Operatórias/etiologia , Melhoria de Qualidade , Fatores de RiscoRESUMO
INTRODUCTION: The aim of this retrospective study was to assess the efficacy of Salivary Bypass Tube (SBT) for preventing pharyngo-cutaneous fistula (PCF) in a recent cohort of patients who underwent primary and salvage total laryngectomy (TL). METHODS: A consecutive series of 133 patients who underwent total laryngectomy between 1997 and 2019 was reviewed. The incidence of PCF was compared between patients who did not receive SBT (nSBT group; n = 55) and those preventively receiving SBT (SBT group; n = 78) in both primary and salvage TL. Risk factors for PCF were evaluated in a univariate and multivariate analyses. RESULTS: The overall PCF rate was 30%. Preoperative characteristics were similar between the nSBT and SBT groups, except for older age (p = 0.016), lower preoperative hemoglobin (p = 0.043), and lesser neoadjuvant chemotherapy (p = 0.015) in the SBT group. The rate of PCF the nSBT group, was 41.5%, compared to 21.8% in the SBT group (p = 0.020). In multivariate analysis, only the use of SBT was associated with lower risk of PCF (OR = 0.41 (95% CI 0.19-0.89), p = 0.026). This effect was verified only in the subgroup of patient operated for salvage TL (OR = 0.225; 95% CI 0.09-0.7; p = 0.008). CONCLUSION: The use of SBT in our series in salvage TL, appears to be associated with a decreased risk of PCF.
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Fístula Cutânea , Neoplasias Laríngeas , Doenças Faríngeas , Idoso , Fístula Cutânea/epidemiologia , Fístula Cutânea/etiologia , Fístula Cutânea/prevenção & controle , Humanos , Neoplasias Laríngeas/cirurgia , Laringectomia , Doenças Faríngeas/epidemiologia , Doenças Faríngeas/etiologia , Doenças Faríngeas/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos RetrospectivosRESUMO
The liver ischemia-reperfusion (IR) injury that occurs consequently to hepatic resection performed in patients with metastases can lead to tumor relapse for not fully understood reasons. We assessed the effects of liver IR on tumor growth and the innate immune response in a mouse model of colorectal (CR) liver metastasis. Mice subjected to liver ischemia 2 days after intrasplenic injection of CR carcinoma cells displayed a higher metastatic load in the liver, correlating with Kupffer cells (KC) death through the activation of receptor-interating protein 3 kinase (RIPK3) and caspase-1 and a recruitment of monocytes. Interestingly, the immunoregulatory mediators, tumor necrosis factor-α (TNF-α) and heme oxygenase-1 (HO-1) were strongly upregulated in recruited monocytes and were also expressed in the surviving KC following IR. Using TNFflox/flox LysMcre/wt mice, we showed that TNF deficiency in macrophages and monocytes favors tumor progression after IR. The antitumor effect of myeloid cell-derived TNF involved direct tumor cell apoptosis and a reduced expression of immunosuppressive molecules such as transforming growth factor-ß, interleukin (IL)-10, inducible nitric oxyde synthase (iNOS), IL-33 and HO-1. Conversely, a monocyte/macrophage-specific deficiency in HO-1 (HO-1flox/flox LysMcre/wt ) or the blockade of HO-1 function led to the control of tumor progression post-liver IR. Importantly, host cell RIPK3 deficiency maintains the KC number upon IR, inhibits the IR-induced innate cell recruitment, increases the TNF level, decreases the HO-1 level and suppresses the tumor outgrowth. In conclusion, tumor recurrence in host undergoing liver IR is associated with the death of antitumoral KC and the recruitment of monocytes endowed with immunosuppressive properties. In both of which HO-1 inhibition would reinforce their antitumoral activity.
Assuntos
Neoplasias Colorretais/patologia , Heme Oxigenase-1/fisiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/secundário , Fígado/irrigação sanguínea , Recidiva Local de Neoplasia/etiologia , Traumatismo por Reperfusão/complicações , Fator de Necrose Tumoral alfa/fisiologia , Animais , Progressão da Doença , Células de Kupffer/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/fisiologia , Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: We report, for the first time in the literature, a metastatic lymphatic pathway along the inferior epigastric vessels, through the inferior epigastric lymph nodes (IELNs), in patients with peritoneal carcinomatosis (PC). Interestingly, these lymph nodes (LNs) in the anterior retroperitoneum were not detectable on preoperative imaging. They may, however, represent a pertinent systemic dissemination pathway for PC. PATIENTS AND METHODS: In patients undergoing indocyanine green-fluorescence imaging during cytoreductive surgery for PC, an incidental finding of a hyperfluorescent LN, harboring metastatic tumorous cells, around the inferior epigastric artery was made. RESULTS: In three out of five patients with clear fluorescent hotspot, the harvested LN was harboring metastatic cancerous cells. None of these nodes, whether negative or positive, was visible on any preoperative imaging modalities. A protocol to sample, in a systematic manner, the IELN in patients with PC, is currently being devised at our institution. CONCLUSION: These lymphatic nodes basin and channels might reveal to be a potential passage from peritoneal metastasis to the extraperitoneal lymphatic compartment, representing an independent pathway for cancerous cell dissemination. This will bring us to further investigate the prevalence and the prognostic significance of these LNs.
Assuntos
Neoplasias do Colo/patologia , Artérias Epigástricas/patologia , Linfonodos/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Neoplasias do Colo/cirurgia , Artérias Epigástricas/cirurgia , Feminino , Seguimentos , Humanos , Verde de Indocianina , Excisão de Linfonodo , Linfonodos/cirurgia , Imagem Óptica , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: The histological growth pattern (HGP) represents a strong prognostic factor in patients undergoing surgery for colorectal liver metastases (CRLM). We evaluated whether the combination of HGP with clinico-metabolic parameters could improve its prognostic value. METHODS: In a series of 108 patients undergoing resection of CRLM, the HGP of CRLM was scored according to international guidelines. Baseline clinico-metabolic clinical status was evaluated using a metabolic-Clinical Risk Score (mCRS), combining traditional Memorial Sloan Kettering-CRS parameters with the tumor-to-liver glucose uptake ratio as measured with 18 Fluorodeoxyglucose/positron emission tomography. RESULTS: In patients with desmoplastic HGP (DHGP) CRLM (20% of all patients), 5- and 10-years overall survival (OS) and disease free survival (DFS) were 66% and 43% and 37% and 24.5%, as compared with 35% and 21% and 11% and 11% in the non-DHGP group (p = 0.07 and 0.054). Among DHGP patients, those with a low-risk mCRS had improved postoperative outcomes, 5- and 10-years OS and DFS reaching 83.3% and 62.5% and 50% and 33%, as compared with 18% and 0% and 0% and 0% in high-risk mCRS patients (p = 0.007 and 0.003). In contrast, mCRS did not influence postoperative survivals in non-DHGP patients. CONCLUSIONS: Combining the clinico-metabolic characteristics with the HGP may improve prognostication in patients undergoing surgery for CRLM.
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Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Idoso , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Immunotherapy represents a promising option for treatment of hepatocellular carcinoma (HCC) in cirrhotic patients but its efficacy is currently inconsistent and unpredictable. Locoregional therapies inducing immunogenic cell death, such as transarterial chemoembolization (TACE) or selective internal radiation therapy (SIRT), have the potential to act synergistically with immunotherapy. For the development of new approaches combining locoregional treatments with immunotherapy, a better understanding of the respective effects of TACE and SIRT on recruitment and activation of immune cells in HCC is needed. To address this question, we compared intra-tumor immune infiltrates in resected HCC after preoperative treatment with TACE or SIRT. METHODS: Data fromr patients undergoing partial hepatectomy for HCC, without preoperative treatment (SURG, n = 32), after preoperative TACE (TACE, n = 16), or preoperative SIRT (n = 12) were analyzed. Clinicopathological factors, tumor-infiltrating lymphocytes (TILs), CD4+ and CD8+ T cells, and granzyme B (GZB) expression in resected HCC, and postoperative overall and progression-free survival were compared between the three groups. RESULTS: Clinicopathological and surgical characteristics were similar in the three groups. A significant increase in TILs, CD4+ and CD8+ T cells, and GZB expression was observed in resected HCC in SIRT as compared to TACE and SURG groups. No difference in immune infiltrates was observed between TACE and SURG patients. Within the SIRT group, the dose of irradiation affected the type of immune infiltrate. A significantly higher ratio of CD3+ cells was observed in the peri-tumoral area in patients receiving < 100 Gy, whereas a higher ratio of intra-tumoral CD4+ cells was observed in patients receiving > 100 Gy. Postoperative outcomes were similar in all groups. Irrespective of the preoperative treatment, the type and extent of immune infiltrates did not influence postoperative survival. CONCLUSIONS: SIRT significantly promotes recruitment/activation of intra-tumor effector-type immune cells compared to TACE or no preoperative treatment. These results suggest that SIRT is a better candidate than TACE to be combined with immunotherapy for treatment of HCC. Evaluation of the optimal doses for SIRT for producing an immunogenic effect and the type of immunotherapy to be used require further evaluation in prospective studies.
Assuntos
Braquiterapia/mortalidade , Carcinoma Hepatocelular/imunologia , Quimioembolização Terapêutica/mortalidade , Hepatectomia/mortalidade , Imunoterapia/mortalidade , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Terapia Combinada , Feminino , Humanos , Morte Celular Imunogênica , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND OBJECTIVES: Selection for surgery in patients with colorectal liver metastases (CRLM) remains inaccurate. We evaluated if CRLM baseline metabolic characteristics, assessed by [18]F-fluorodeoxyglucose-positron emission tomography/computed tomography (18 FDG-PET/CT), could predict postoperative outcomes. METHODS: In a retrospective series of patients undergoing surgery for CRLM, we defined two groups: the long-term survival (LTS) and early relapse (ER) groups, where the postoperative recurrence-free survivals were ≥5 years or <1 year, respectively. We analyzed the patients in whom baseline 18 FDG-PET/CT was available. Clinicopathologic parameters, clinical risk score (CRS), and baseline 18 FDG-PET/CT characteristics were compared between LTS and ER groups. A metabolic CRS (mCRS) was implemented, adding one point to the standard five-point CRS when the highest tumor standardized uptake values (SUVmax )/normal liver mean SUV (SUVmean(liver) ) ratios were >4.3, defining low- and high-risk mCRS by scores of 0 to 2 and 3 to 6, respectively. RESULTS: From a series of 450 patients operated for CRLM (mean follow-up of 58 months), we included for analysis 23 and 30 patients in the LTS and ER groups, respectively. Clinicopathologic parameters and CRS were similar in the LTS and ER groups. Median SUVmax /SUVmean(liver) ratios were higher in ER vs LTS patients (4.2 and 2.8, P = .008, respectively). mCRS was increased in ER patients (P = .024); 61% of LTS patients had low-risk mCRS and 73% of the ER patients had high-risk mCRS (P = .023). CONCLUSIONS: 18 FDG-PET/CT characteristics combined with traditional CRS may represent a new tool to improve selection for surgery in patients with CRLM.
RESUMO
BACKGROUND: Low anterior resection (LAR) with total mesorectal excision (TME) for mid and low rectal cancer is standard of care, reducing local recurrence and enhancing long-term survival. However, this surgery is associated with a constellation of major defecatory problems that are collectively referred to as low anterior resection syndrome (LARS). The aims of this study were to evaluate the frequency of LARS in patients who have undergone LAR and to assess the impact of LARS on long-term quality of life (QoL). METHODS: This was a single-center prospective survey study on patients who underwent LAR and TME for low or mid rectal cancer between 2007 and 2015. LARS score and QLQ-C30 questionnaires were used to evaluate patient's bowel functions and quality of life, respectively. Associations between LARS and QoL were evaluated. RESULTS: Fifty-seven patients out of 65 eligible agreed to participate in the study. Forty-three (66%) patients returned complete questionnaires. Five patients (11.6%) had no LARS, 7 had minor LARS (16.3%), and 31 had major LARS (72.1%). In univariate analysis, BMI > 30 kg/m2 was predictive of major LARS (p = 0.047). Major LARS did not impair global QoL (p = 0.75), function scores, or social scales, and was not associated with any of the symptom scores except for diarrhea (p = 0.02). CONCLUSION: LARS is a frequent occurrence after LAR and TME for rectal cancer (72.1%) and is more prevalent in morbidly obese patients. However, the occurrence of LARS does not appear to have a direct impact on QoL except for the occurrence of diarrhea.
Assuntos
Complicações Pós-Operatórias/etiologia , Qualidade de Vida/psicologia , Neoplasias Retais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SíndromeRESUMO
BACKGROUND: Relatively high morbidity rates are reported after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, early predictors of complications after CRS plus HIPEC have not been identified. The aim of this study was to evaluate the predictive role of early postoperative serum C-reactive protein (CRP) level (Day 2-4) for the detection of post-operative complications. PATIENTS AND METHODS: We performed a retrospective study including 94 patients treated with complete CRS (R1) and HIPEC for PC from various primary origins (2011-2016). Post-operative complications were recorded. The values for postoperative inflammatory markers (white blood cells [WBC] and platelet counts, CRP) were compared between the different groups. RESULTS: CRP on post-operative days 2-4 was significantly higher in patients with than without complications (124 mg/L vs 46 mg/L; p < 0.0001) and higher in those with more major complications (162 mg/L vs 80 mg/L; p < 0.0012). WBC and platelet counts showed no difference within 5 days postoperatively. CONCLUSION: CRP levels, and kinetics mainly, between post-operative day 2 and 4, are decisive predictive markers of early and late post-operative complications after CRS plus HIPEC. The presence of post-operative complications should be suspected in patients with a high CRP mean, and a plateau level (days 2-4).
Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Proteína C-Reativa , Quimioterapia do Câncer por Perfusão Regional , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Quimioterapia Intraperitoneal Hipertérmica , Cinética , Neoplasias Peritoneais/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: The benefit of surgery in patients with non-colorectal non-neuroendocrine liver metastases (NCRNNELM) remains controversial. At the population level, several statistical prognostic factors and scores have been proposed but inconsistently verified. At the patient level, no selection criteria have been demonstrated to guide individual therapeutic decision making. We aimed to evaluate potential individual selection criteria to predict the benefit of surgery in patients undergoing treatment for NCRNNELM. METHODS: Data for 114 patients undergoing surgery for NCRNNELM were reviewed. In this population, we identified an early relapse group (ER), defined as patients with unresectable recurrence < 1 year postoperatively who did not benefit from surgery (N = 28), and a long-term survival group (LTS), defined as patients who were recurrence-free ≥ 5 years postoperatively and benefited from surgery (N = 20). Clinicopathologic parameters, the Association Française de Chirurgie (AFC) score, and a modified 4-point Clinical Risk Score (mCRS) (excluding CEA level) were analyzed and compared between LTS and ER groups. RESULTS: The majority of patients were female and a majority had an ASA score ≤ 2 at the time of liver surgery. The median age was 55 years. Almost half of the patients (46%) presented with a single-liver metastasis. Intermediate- and low-risk AFC scores represented 40% and 60% of the population, respectively. Five- and 10-year overall survival (OS) and disease-free survival (DFS) rates were 56% and 27%, and 30% and 12%, respectively. Negative prognostic factors were the size of liver metastases > 50 mm and delay between primary and NCRNNELM <24 months for OS and DFS, respectively. AFC score was not prognostic while high-risk mCRS (scores 3-4) was predictive for the poorer OS. The clinicopathologic parameters were similar in the ER and LTS groups, except the presence of N+ primary tumor, and the size of liver metastases was significantly higher in the ER group. CONCLUSION: In patients with resectable NCRNNELM, no predictive factors or scores were found to accurately preoperatively differentiate individual cases in whom surgery would be futile from those in whom surgery could be associated with a significant oncological benefit.
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Tomada de Decisão Clínica , Hepatectomia/normas , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Seleção de Pacientes , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Taxa de SobrevidaRESUMO
PURPOSE OF REVIEW: The concept of oligometastases, defining cancers with limited metastatic capacity and attaining a limited number of secondary sites, is now widely accepted, particularly in colorectal cancer. Currently, however, accurate predictive markers for oligometastatic tumors are still lacking. For this reason, it remains challenging to translate this concept into clinical recommendations. In the present work, we review recent publications on oligometastases in colorectal cancer, showing the evidences for such presentation and underlying the need for the identification of biomarkers, necessary to further develop new therapeutic strategies. RECENT FINDINGS: This review of recently published series confirms that long-term survival and cure could be obtained in patients undergoing surgical resection for colorectal metastases, particularly in the cases of liver metastases. Similar results are observed in other secondary sites such as in pulmonary metastases. Furthermore, in patients with unresectable metastases, significant survival benefit could be still obtained using nonresectional targeted approaches, as thermal ablation or stereotactic radiotherapy. Although these clinical evidences could now serve as proof-of-concept for the existence of an oligometastatic phenotype in colorectal cancer, neither clinical characteristics nor biological biomarkers have been established to be able to prospectively define the patients that will benefit from such therapeutic approaches targeting the metastatic sites. This emphasizes the need for further studies aiming at better defining early clinical and biological characteristics of these patients. As, currently, the reliable identification of the oligometastatic patients could only rely on the demonstration of favorable long-term outcomes after metastases-directed therapies, we propose that retrospective studies will be pivotal to analyze this question. SUMMARY: Extensive research is undergoing to define biologically the oligometastatic phenotype in colorectal cancer. Currently, the selection of the patients for potentially curative metastasectomy remains mostly empirical.
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Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Biomarcadores Tumorais/análise , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Metástase Neoplásica , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the ex vivo detection of metastatic lymph nodes (LNs) in advanced stage ovarian cancer (AOC). METHODS: Paraffin-embedded LNs from patients included in a previous ICG-FI study (Protocol NCT01834469) were further assessed for fluorescence. Intravenous injection of ICG was delivered intraoperatively. Tumor-to-background ratios (TBRs) were calculated. RESULTS: A total of 675 LNs from 19 patients were analyzed. The mean LN number per patient was 29.3 (median: 24; range 2-77). Seventy-three LNs were malignant (10.8%), 602 were benign (89.2%). The mean TBR of all LNs was 1.5 (SD 0.8). With a cut-off TBR of 1.3, the sensitivity, specificity, positive predictive, and negative predictive values of ICG-FI for retroperitoneal LNs were 80%, 41%, 2.8%, and 99%, respectively. On univariate analysis, only the fluorescence ratio (TBR ≥ 1.3) was correlated with malignancy at pathology (P = 0.03). No predictive factors of pathological LN status were found on multivariate analysis. CONCLUSIONS: Ex vivo ICG-FI of retroperitoneal LNs in AOC had good sensitivity but poor specificity. However, its high negative predictive value could make it an appropriate complementary tool to focus pathological analysis on fluorescent LNs.
Assuntos
Corantes Fluorescentes , Verde de Indocianina , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Imagem Óptica , Neoplasias Ovarianas/patologia , Adulto , Idoso , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND OBJECTIVES: No intraoperative imaging techniques exist for detecting tumor nodules or tumor scar tissues in patients treated with upfront or interval cytoreductive surgery (CS) after neoadjuvant chemotherapy (NAC). The aims of this study were to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of peritoneal metastases (PM) and evaluate whether it can be used to detect remnant tumor cells in scar tissue. METHODS: Patients with PM from ovarian cancer admitted for CS were included. ICG, at 0.25 mg per kg of patient weight, was injected intraoperatively after explorative laparotomy before CS. RESULTS: A total of 108 peritoneal lesions, including 25 scars, were imaged in 20 patients. Seventy-three were malignant (67.6%) and 35 benign (32.4%). The mean Tumor to Background Ratio (ex vivo) was 1.8 (SD 1.3) in malignant and 1.0 (SD 0.79) in benign nodules (P = 0.007). Of 25 post-NAC scars, the mean Tumor to Background Ratio (TBR) (in vivo) was 2.06 (SD 1.15) in malignant and 1.21 (SD 0.50) in benign nodules (P = 0.26). The positive predictive value of ICG-FI to detect tumor cells in scars was 57.1%. CONCLUSIONS: ICG-FI is accurate to demonstrate PM in ovarian cancer but unable to discriminate between benign and malignant post-NAC.
Assuntos
Fluorescência , Verde de Indocianina , Neoplasia Residual/patologia , Imagem Óptica/métodos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Adulto , Idoso , Procedimentos Cirúrgicos de Citorredução , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasia Residual/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Projetos Piloto , PrognósticoRESUMO
BACKGROUND: The development of a second primary tumor is a potential late side effect of radiotherapy. Particularly, an increased risk of secondary cancers, mostly of digestive or breast origin, has been observed in patients treated with high-dose radiotherapy for Wilms tumor (WT) in childhood. However, hepatocellular carcinoma (HCC) has been very rarely described as a potentially radiotherapy-induced tumor. We describe the case of a patient with an aggressive HCC 50 years after the treatment of a WT. CASE PRESENTATION: A 49-year old man, treated at the age of 6 weeks for a right WT by a right nephrectomy and adjuvant radiotherapy, presented with a right abdominal mass. Imaging demonstrated a 100-mm tumor invading the inferior segment of the right liver, the right colon and the right psoas muscle. The patient had no previous history of liver disease, nor of alcohol consumption, and hepatitis serologies were negatives. Biopsy demonstrated a poorly differentiated tumor of unknown origin. A panel of tumor markers was negative. Explorative surgery has been performed allowing en bloc R0 tumor resection, including resection of segments VI and VII of the liver, right hemicolectomy and resection of the anterior sheet of the right psoas muscle. Pathological examination revealed a poorly differentiated HCC. No signs of cirrhosis or chronic liver disease were observed in the non-tumor liver. Twenty weeks after surgery, the patient developed a multifocal tumor recurrence that was treated with intra-arterial 90Yttrium radioembolization. CONCLUSION: In this case, the absence of risk factors for HCC, such as cirrhosis, viral hepatitis and chronic liver disease, highly suggests the development of HCC to be related to previous high-dose radiation therapy given for a right WT to a field involving the inferior part of the liver. This observation shows radiotherapy to/near the liver, particularly in childhood, to be a potential risk factor for HCC, stressing the need for a long-term specific follow-up in patients irradiated in childhood.