Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain. The investigations revealed a caecal volvulus. A lesion in the middle third of the ileum was incidentally discovered and removed during surgery. Pathology examination revealed a Meckel's diverticulum adenocarcinoma, with metastasis of extraskeletal myxoid chondrosarcoma. Resection was complete; however, the patient had diffuse metastatic pulmonary disease and died eight months later due to disease progression. This mechanism of tumour-to-tumour metastasis is described in other locations, but, regarding the Meckel's diverticulum, this is a unique situation, previously unreported in the literature. (AU)
El condrosarcoma mixoide extraesquelético es un tumor de tejidos blandos poco frecuente, con una elevada tasa de recurrencia y metástasis a distancia y una respuesta limitada a la quimioterapia. El divertículo de Meckel es la anomalía congénita más frecuente y se asocia a un riesgo considerable de transformación maligna. En este caso clínico describimos a una paciente de 50 años con antecedentes de condrosarcoma mixoide extraesquelético de miembro inferior y metástasis en el antebrazo que acudió al servicio de urgencias por dolor abdominal. La exploración reveló un vólvulo cecal. Se descubrió incidentalmente una lesión en el tercio medio del íleon, que se extirpó durante la intervención quirúrgica. El examen patológico reveló un adenocarcinoma de divertículo de Meckel, afectado por metástasis de condrosarcoma mixoide extraesquelético. La resección fue completa; sin embargo, la paciente presentaba enfermedad pulmonar metastásica difusa y falleció ocho meses después debido a la progresión de la enfermedad. Este mecanismo de metástasis entre tumores está descrito en otras localizaciones, pero en lo que respecta al divertículo de Meckel, se trata de una situación única en la literatura. (AU)
Humans , Female , Adult , Sarcoma , Meckel Diverticulum , Colonic Neoplasms , Neoplasm Metastasis , Chondrosarcoma
Introduction: Embryonal sarcoma of the liver (ESL) is a rare neoplasm of the liver occurring mainly in paediatric ages. Making the correct diagnosis can be challenging as the laboratory and radiological findings that are often nonspecific, and the tumour immunophenotype is poorly defined and even somewhat variable. Case Presentation: A large epigastric mass was detected in a computerized tomography scan of a 43-year-old woman presenting with abdominal pain and bloating. The mass was biopsied and submitted to histopathological study. Microscopically the tumour had sarcomatoid features and showed multinucleated cells with periodic acid-Schiff (PAS)-positive globules. Immunostaining revealed positivity for vimentin, CD10, glypican-3, and α1-antitrypsin and negativity for keratins, muscle, adipocytic, and melanocytic differentiation markers. The patient was then submitted to a left hepatectomy with similar histological findings. Discussion: ESL in adults is a rarity and its diagnosis requires the exclusion of other entities. While some microscopic features are very common, they remain nonspecific. The main feature is the presence of multinucleated cells with PAS-positive hyaline globules. While ancillary testing is key, the immunophenotype also lacks specificity and ESL may have variable staining for glypican-3 and epithelial or muscle differentiation markers. Although it has been described for more than 3 decades, the prognosis and optimal treatment are still not well defined, but surgery has yielded favourable results.
Introdução: O sarcoma embrionario do figado (SEF) e uma neoplasia rara do figado que ocorre principalmente em idades pediatricas. Fazer o diagnostico correto pode ser um desafio, uma vez que os achados laboratoriais e radiologicos sao muitas vezes inespecificos e o imunofenotipo desta entidade e mal definido e algo variavel. Apresentação do caso: Foi detetada em tomografia computorizada (CT) abdominal uma massa epigastrica volu-mosa numa mulher de 43 anos apresentando dor abdominal e distensao abdominal. A massa foi biopsada e submetida a estudo histopatologico. Microscopicamente, o tumor tinha caracteristicas sarcomatoides e apresentava celulas multinucleadas com globulos hialinos com positividade para acido periodico Schiff (APS). O estudo imunohistoquimico revelou positividade para vimentina, CD10, glipicano-3 e α1-antitripsina e negatividade para queratinas e marcadores de diferenciacao muscular, adipocitica e melanocitica. Discussão/Conclusão: O SEF no adulto e uma raridade e o seu diagnostico requer a exclusao de outras entidades. Embora algumas caracteristicas microscopicas sejam muito comuns, estas permanecem inespecificas. A principal caracteristica e a presenca de celulas multinucleadas com globulos hialinos positivos para APS. Ainda que o estudo imunohistoquimico seja fundamental, o imunofenotipo tambem carece de especificidade e o SEF pode ter marcacao variavel para glipicano− 3 e marcadores de diferenciacao epitelial ou muscular. Apesar de ter sido descrito ha mais de tres decadas, o prognostico e o tratamento ideal ainda nao estao bem definidos, mas a cirurgia tem apresentado resultados favoraveis.
Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD.
Breast cancer is a major health burden, and up to one-third of patients with breast cancer develop brain metastases, which are linked to a very poor prognosis. Few biomarkers are available to predict the prognosis of patients with metastases. Assessment by immunohistochemistry may be used as a tool to predict the behavior of these tumors. A retrospective transversal study including 114 patients (diagnosed between 2000 and 2016) with breast cancer brain metastases was carried out using archival biological material from 114 patients with breast cancer brain metastases. Expression of CD44, HER2, ER, PR, CA9, PDL-1, CD133, ALDH1, PTEN, AKT, PI3K, and AR markers was assessed by immunohistochemistry. The overexpression of CD44 and AKT was associated with worse overall survival ( P =0.047 and P =0,034, respectively), on univariate analysis, in the cohort of parenchymal and bone metastases; the impact of AKT expression was also evident in the parenchymal cohort on uni ( P =0.021) and multivariate analysis ( P =0.027). The remaining markers did not exhibit a statistical correlation. Immunohistochemistry markers such as CD44 and AKT may have a prognostic impact on survival in patients with breast cancer brain metastases. The conjugation with other markers may help with the stratification of patients and therapy.
Brain Neoplasms , Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Proto-Oncogene Proteins c-akt , Retrospective Studies , Biomarkers, Tumor/metabolism , Hyaluronan Receptors
AIMS: Cholangiocarcinoma (CC) is a rare tumour arising from the biliary tract epithelium. The aim of this study was to perform a genomic characterisation of CC tumours and to implement a model to differentiate extrahepatic (ECC) and intrahepatic (ICC) cholangiocarcinoma. METHODS: DNA extracted from tumour samples of 23 patients with CC, namely 10 patients with ECC and 13 patients with ICC, was analysed by array comparative genomic hybridisation. A support vector machine algorithm for classification was applied to the genomic data to distinguish between ICC and ECC. A survival analysis comparing both groups of patients was also performed. RESULTS: With these whole genome results, we observed several common alterations between tumour samples of the same CC anatomical type, namely gain of Xp and loss of 3p, 11q11, 14q, 16q, Yp and Yq in ICC tumours, and gain of 16p25.3 and loss of 3q26.1, 6p25.3-22.3, 12p13.31, 17p, 18q and Yp in ECC tumours. Gain of 2q37.3 was observed in the samples of both tumour subtypes, ICC and ECC. The developed genomic model comprised four chromosomal regions that seem to enable the distinction between ICC and ECC, with an accuracy of 71.43% (95% CI 43% to 100%). Survival analysis revealed that in our cohort, patients with ECC survived on average 8 months less than patients with ICC. CONCLUSIONS: This genomic characterisation and the introduction of genomic models to clinical practice could be important for patient management and for the development of targeted therapies. The power of this genomic model should be evaluated in other CC populations.
Bile Duct Neoplasms , Cholangiocarcinoma , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/pathology , DNA Copy Number Variations , Genomics , Humans
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Current clinical/pathological criteria contribute to risk stratification, but are far from the desired on individualized medicine. Recently, HCC classifications have been published based on immunohistochemical and morphological features. METHODS: A retrospective review of patients submitted to surgical treatment-partial hepatectomy (PH) or liver transplantation (LT), with pathological diagnosis of HCC, in a 9-year period (2007-2015) was performed. RESULTS: Applying the classification of Srivastava et al. (#1), based on the expression of CD31, p53, AFP and CD44, tumour size and presence of vascular invasion, HCC were categorized as low- and high-risk HCC. With the classification of Tsujikawa et al. (#2), HCC were classified into biliary/stem cell marker positive, Wnt signalling positive and the "all negative" HCC, according to the expression of CK19, SALL4, ß-catenin glutamine synthetase, EpCAM and p53. There were sixty-six patients (53 males; 13 females), with median age of 64.5 ± 9.46 years (range 38-86), with solitary HCC, comprehending 37 PH (56.1%) and 29 LT (43.9%). The mean overall survival (OS) was 75.4 ± 6.9 months. Biliary/stem cell type of HCC was a predictive factor of worse OS on the overall population (24.4 versus 78.3 months, p = 0.032) and in PH cohort (11.5 versus 64.01 months, p = 0.016), on uni- and multivariate analyses. CONCLUSION: These results support the relevance of a risk stratification classification of HCC. Classification #2 seems adequate to our reality demonstrating OS impact, allowing its application in future biopsies, prompting individualized medicine.
Carcinoma, Hepatocellular , Liver Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Patient Selection , Retrospective Studies , Stem Cells
PURPOSE: Hepatectomy (Hp) is an alternative approach for the treatment of gastric carcinoma liver metastases (GCLM). However, prognostic factors that may assist patient selection are still controversial. Several pathologic features, such as the growth pattern (GP), associated with prognosis in colorectal cancer liver metastases, were never investigated in GCLM. Our principal aim was to assess if the GP has prognostic impact on GCLM. PATIENTS AND METHODS: Review of the clinical and pathological characteristics of 19 consecutive patients submitted to surgical resection of GCLM with curative intent at our department. Major potential prognostic factors considered were patients' gender, age, timing and extent of Hp, postoperative course, as well as histopathological characteristics of primary and secondary tumors. RESULTS: Major morbidity occurred in four patients, mortality in one. Median and 5-year overall survival were 17 months and 26.7%, respectively. Ten patients developed recurrent disease and two patients survived more than 10 years. Factors independently associated with overall survival were the absence of major morbidity, distal location of the primary tumor, and desmoplastic GP (p<0.05). CONCLUSION: The selection of patients is crucial for the improvement of survival rates of GCLM. Consequently, we demonstrate for the first time that the desmoplastic GP of GCLM is associated with improved outcomes, prompting further research on tumor-host interactions.
INTRODUCTION: Mesenchymal tumors of the liver are rare, and in this group, myxoid leiomyomas are even rarer. So far, only 2 cases have been reported in the literature. CASE PRESENTATION: We aim to report the case of a 16-year-old female with a large lesion on the right hepatic lobe, grossly composed of gelatinous and heterogeneous tissue. DISCUSSION: Histological evaluation revealed a benign mesenchymal neoplasm with expansive growth, paucicellular, with monotonous and dispersed spindle and ovoid cells, positive for α-smooth actin and h-caldesmon, without atypia or mitoses, consistent with the diagnosis of primary myxoid leiomyoma.
INTRODUÇÃO: Tumores mesenquimatosos do fígado são raros, e deste grupo os leiomiomas mixoides são ainda mais incomuns. Até ao momento foram apenas descritos dois casos na literatura. CASO CLÍNICO: Pretendemos efetuar a descrição de uma caso de uma menina de 16 anos com uma volumosa lesão no lobo hepático direito, que macroscopicamente era composta por um tecido gelatinoso e heterogéneo. CONCLUSÃO: Estudo histológico revelou uma lesão mesenquimatosa benigna de crescimento expansive, pouco celular, com células fusiformes e ovaladas, monótonas, com expressão de actina do músculo liso e h-caldesmon, sem atipia nem mitoses, consistente com o diagnóstico de leiomioma mixoide.
Hepatic adenomatosis is defined as the presence of 10 or more adenomas in an otherwise normal liver. Half of the cases are clinically silent and detected incidentally in imaging exams. A 42-year-old woman with previous history of arterial hypertension and mixed dyslipidemia had multiple liver nodules incidentally identified in an abdominal computed tomography scan. She was asymptomatic and her physical examination was unremarkable but laboratory analysis revealed increased alkaline phosphatase and mildly persistent elevated systemic inflammatory markers. A subsequent hepatic magnetic resonance imaging (MRI) suggested the diagnosis of hepatic adenomatosis and the liver biopsy confirmed the presence of inflammatory adenomas. The patient stopped oral contraception and, at 6 months of follow-up, laboratory inflammatory markers had normalized. She is now under biannual follow-up with MRI and alpha-fetoprotein dosing. This case provides an example of the complex management of this disease in terms of diagnosis, treatment, and follow-up.
A adenomatose hepática define-se pela presença de 10 ou mais adenomas num fígado normal. Cerca de metade dos casos são silenciosos e de identificação incidental em exames de imagem. Uma mulher de 42 anos, com antecedentes pessoais de hipertensão arterial e dislipidémia mista, realizou uma tomografia computorizada abdominal, com identificação incidental de múltiplos nódulos hepáticos. Apresentava-se assintomática e sem alterações ao exame objetivo mas as análises laboratoriais revelaram fosfatase alcalina elevada e aumento ligeiro mas persistente dos parâmetros inflamatórios sistémicos. A ressonância magnética hepática (RMH) subsequente sugeriu o diagnóstico de adenomatose hepática e a biópsia de nódulo confirmou a presença de adenoma do tipo inflamatório. Foi suspensa a toma de contraceptivo oral e, aos 6 meses de follow-up, observou-se normalização dos parâmetros inflamatorios. Actualmente encontra-se sob vigilância semestral com RMH e doseamento de alfa-feto-proteína. Este caso representa a complexidade inerente à abordagem do diagnòstico, tratamento e follow-up da adenomatose hepática.
Cholangiocarcinoma (CCA) mortality rates are increasing as a result of rising incidence and limited curative treatment(s) for patients with advanced disease. NOTCH pathway reactivation has been reported in biliary malignancies to conflicting degrees, hindering prioritization of key therapeutic targets within the network and identification of candidate responder patients for NOTCH-directed therapies. We analyzed genomic data from 341 patients with CCA and identified NOTCH1 significantly increased in a subgroup characterized by distinct stromal infiltration. Network-wide imbalance of the NOTCH pathway was seen in CCA, including correlation of NOTCH1 with NOTCH3 and NOTCH ligands. Given the diversity of observed NOTCH receptor engagement, γ-secretase modulation was rationalized as a therapeutic option. Indeed, subcutaneous transplantation of sensitive and resistant CCA cell lines pretreated with a γ-secretase inhibitor (GSi) cocktail demonstrated the antineoplastic effects of GSi in a subset of CCA and led to the development of a 225-gene responder signature. This signature was validated in an independent cohort of 119 patients. Further, this signature was enriched in liver tumors initiated by hydrodynamic injections of activated-NOTCH as compared with the AKT-RAS-driven tumors. Candidate GSi-responder patients were characterized by distinct transcriptomes overlapping with previous hepatobiliary metastasis and stemness, unique stromal properties, and dysfunctional intratumoral immune infiltration. Pan-cancer analysis identified 41.9% of cancer types to harbor prospective GSi-responder patients, which was adapted into a 20-gene GSi-sensitivity score metric capable of discriminating nanomolar versus micromolar sensitivity to a cell-permeable GSi (Z-LLNle-CHO) across 60 diverse tumor lines (area under the curve = 1). Conclusion: We have established a GSi-responder signature with evidence across several patient cohorts, as well as in vitro and in vivo models, to enable precision medicine application of NOTCH-directed therapy in CCA as well as prospectively across diverse malignancies.
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Benzazepines/pharmacology , Benzazepines/therapeutic use , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/etiology , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/etiology , Dibenzazepines/pharmacology , Dibenzazepines/therapeutic use , Fluorenes/pharmacology , Fluorenes/therapeutic use , Ketones/pharmacology , Ketones/therapeutic use , Receptors, Notch/drug effects , Receptors, Notch/physiology , Cell Line, Tumor , Humans , Treatment Outcome
Neuroendocrine carcinoma of the gallbladder is a very rare neoplasia comprising only 0.2% of all the gastrointestinal neuroendocrine tumors. We present the case of an 85-year-old male with nonspecific gastrointestinal symptoms, progressive weight loss, and deterioration in the preceding 15 days. Imaging study showed a 5-cm polypoid mass localized at the gallbladder fundus, leading to a radical cholecystectomy. Pathology revealed the known lobulated polypoid lesion, on cut section, constituted by friable tissue without evident infiltration of the gallbladder wall and a contiguous friable, brown, flat lesion. Histological evaluation displayed a small cell neuroendocrine carcinoma, consisting of intermediate and small cells, rounded or spindle, with extensive areas of necrosis, with positivity for neuroendocrine immunomarkers, associated with intracystic papillary neoplasm with high and low dysplasia. This is an uncommon association with few cases presented in the literature.
Carcinoma neuroendócrino da vesícula biliar é uma neoplasia muito rara, compreendendo cerca de 0.2% de todas as neoplasias neuroendócrinas do trato gastrointestinal. Apresentamos um caso de um homem de 85 anos, com sintomas gastrointestinais inespecíficos, perda de peso progressiva e deterioração do estado geral com 15 dias de evolução. Estudos de imagem demonstraram lesão polipóide com 5 cm localizada no fundo da vesícula biliar, motivando colecistectomia. Macroscopicamente observou-se lesão polipoide composta por tecido acastanhado e friável. Estudo histológico demonstrou lesão constituída por pequenas células, com extensas áreas de necrose e positivas para marcadores neuroendócrinos, associada a neoplasia papilar intraquística com displasia de baixo e alto grau. Esta associação é incomum, com apenas raros casos descritos na literatura.
A 78-year-old woman was admitted to our hospital with a pancreatic tumor, incidentally discovered in an abdominal ultrasound exam. She was asymptomatic and without any previous personal pathological condition. The computed tomography (CT) and the magnetic resonance imaging (MRI) scan showed a mass lesion of 4 cm in diameter, located in the pancreatic body, conditioning the invasion of the splenic vein. The patient was admitted to surgery. During the laparotomy, we found a tumoral lesion highly suspicious of pancreatic neoplasia located in the transition of the head/body of the pancreas, with an invasion of the portal vein and several peri-regional lymph nodes. We performed biopsies of the pancreatic mass and lymphadenectomy of the peri-regional pancreatic lymph nodes. Histological analysis found an inflammatory pseudotumor of the head/body of the pancreas, without signals of malign epithelial neoplasm and also without criteria for immunoglobulin G4-related disease. During the follow-up, a PET/CT and MRI confirmed that the pancreatic lesion had disappeared without any treatment. Inflammatory pseudotumor of the pancreas is a rare entity not fully understood. Despite this, the administration of corticosteroids and immunosuppressive therapy could be taken into consideration as the disease carries a risk.
BACKGROUND: The presence of highly cellular stromal fragments in breast fine needle aspirates (FNA) suggests some classical differential diagnoses such as cellular fibroadenoma, phyllodes tumour (PT), metaplastic carcinomas, and some mesenchymal/myoepithelial proliferations. The other components of the smears can help in the differential diagnosis, but the presence of a low-grade epithelial proliferation does not always represent a fibro-epithelial lesion as we demonstrate in these two cases. CASES: We discuss two cases of breast FNA, previously presented in a slide seminar at the 29th European Congress of Pathology in Amsterdam, where the common cytological finding was the presence of stromal cellular fragments together with an epithelial component. One case is a typical PT and the other is a case of a mammary carcinoma with osteoclast-like giant cells. CONCLUSION: Mammary carcinoma with osteoclast-like giant cells is an unusual type of breast carcinoma that should be included in the differential diagnosis of breast lesions containing cellular stroma. Since the associated carcinoma is usually low grade, careful evaluation for malignant cells on cytological smears is necessary for an accurate differential diagnosis with PT where the epithelial component is benign.
Biopsy, Fine-Needle , Breast Neoplasms/pathology , Carcinoma/pathology , Giant Cells/pathology , Osteoclasts/pathology , Phyllodes Tumor/pathology , Stromal Cells/pathology , Breast Neoplasms/therapy , Carcinoma/therapy , Chemotherapy, Adjuvant , Diagnosis, Differential , Epithelial Cells/pathology , Female , Humans , Mastectomy, Segmental , Middle Aged , Phyllodes Tumor/therapy , Predictive Value of Tests , Treatment Outcome
No disponible
Humans , Male , Aged, 80 and over , Pleural Neoplasms/diagnostic imaging , Pleura/pathology , Pulmonary Atelectasis/diagnostic imaging , Lymphoma/diagnostic imaging , Pleural Neoplasms/pathology , Dyspnea/complications , Thorax/diagnostic imaging , Lymphadenopathy/diagnostic imaging , Pulmonary Atelectasis/pathology , Immunohistochemistry , Lymphoma/pathology
Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model. We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1â¯×â¯107 cells/animal) in RNU rats (nâ¯=â¯55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, ß-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (99mTc-MIBI). Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake. With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.
INTRODUCTION: Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). PATIENTS AND METHODS: Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). RESULTS: The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. CONCLUSION: The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients.
Colorectal Neoplasms/pathology , Hepatectomy/methods , Liver Neoplasms/diagnosis , Liver/pathology , Margins of Excision , Aged , Colorectal Neoplasms/mortality , Disease-Free Survival , Female , Follow-Up Studies , Humans , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Male , Portugal/epidemiology , Risk Factors , Survival Rate/trends , Time Factors , Treatment Outcome
Liver transplantation is a therapeutic regimen to treat patients with non-malignant end-stage liver diseases and malignant tumors of hepatic origin. The ischemia/reperfusion (I/R) injury in liver transplantation is associated with disruption of mitochondrial function in the hepatic parenchyma. Several studies have been conducted in animal models to identify pharmacological therapeutic strategies to minimize the injury induced by the cold/warm I/R in liver transplantation. Most of these studies were conducted in unrealistic conditions without the potential to be translated to clinical usage. Berberine (BBR) is a pharmacological compound with a potential protective effect of the mitochondrial function in the context of I/R. For the future clinical application of these pharmacological strategies, it is essential that a close resemblance exists between the methodology used in the animals models and real life. In this study, we have demonstrated that the addition of BBR to the preservation solution in an I/R setting preserves mitochondrial function and bioenergetics, protecting the liver from the deleterious effects caused by I/R. As such, BBR has the potential to be used as a pharmacological therapeutic strategy.
Berberine/administration & dosage , Liver Transplantation/adverse effects , Mitochondria/pathology , Reperfusion Injury/drug therapy , Animals , Apoptosis/drug effects , Cold Ischemia/adverse effects , Disease Models, Animal , Humans , Liver/drug effects , Liver/metabolism , Liver/pathology , Mitochondria/drug effects , Mitochondria/metabolism , Organ Preservation , Oxidative Stress/drug effects , Rats , Reperfusion Injury/physiopathology , Warm Ischemia/adverse effects
