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Background: Superficial leiomyosarcoma is a rare malignant soft tissue tumor arising from smooth muscle cells, accounting for 2-3% of superficial sarcomas, with limited literature available on the subject. It is typically observed in patients aged 50-60 years and affects both men and women equally in the subcutaneous subtype, whereas the cutaneous subtype predominantly affects men., Objective: This study aims to examine the clinicopathological features and therapeutic outcomes of patients with leiomyosarcoma., Method: This is a descriptive retrospective study of 26 cases of cutaneous and subcutaneous leiomyosarcomas, with histological confirmation., Results: We identified 10 (38.5%) subcutaneous leiomyosarcomas and 16 (61.5%) cutaneous leiomyosarcomas. The majority of tumors were located in the lower limbs, accounting for 13 (50%) cases. During follow-up, 6 patients experienced recurrence, and 7 developed metastases, including 2 of the 7 patients who had R0 resection margins. Among these, 3 out of the 6 recurrent cases and 3 out of the 7 metastatic cases were subcutaneous leiomyosarcomas. The average time to recurrence was 6.2 years., Conclusion: The observed risk of metastases and recurrences, despite clear surgical margins, in both cutaneous and subcutaneous leiomyosarcomas, along with the delayed onset of these events, justifies prolonged patient follow-up. The lungs, bones and liver have been identified as the most common site of metastasis., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

We report a patient with isolated ptosis secondary to orbital metastasis but no evidence of a neoplastic process on magnetic resonance imaging (MRI). A 69-year-old male was referred to our hospital with ptosis of the right upper eyelid and secondary frontalis muscle overaction on the left side for six months. The palpebral fissure was 3mm on the right and 16mm on the left, and levator function was 6mm and 19mm respectively. Three years previously, he had undergone surgical resection of the left lower lobe of the lung due to a T1 N0 M0 adenocarcinoma, and no recurrence had since been observed. An MRI was performed to rule out ptosis secondary to metastasis. Thyroid dysfunction and myasthenia were also ruled out. The ptosis was attributed to an isolated microvascular third nerve palsy. A standard external levator advancement was performed. Six months after the surgery, the patient presented with intense pain, minimal ptosis, edema and diplopia. A new MRI revealed an orbital metastasis measuring 2.4×1.0×1.6cm in the superior orbit, exerting mass effect on the superior rectus and the levator palpebrae superioris muscle. A positron emission tomography scan revealed a recurrence of the lung cancer with multiple bony metastases. The patient underwent chemotherapy consisting of the taxol-carboplatin protocol. Our report highlights the importance of a high index of suspicion of a neoplastic etiology in patients with mild symptoms and a history of cancer even if imaging does not initially reveal a mass or infiltration., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Introduction: This case series describes the clinical course of ocular and non-ocular squamous cell carinoma (SCC) in the Haflinger horse and is intended to raise awareness of the high recurrence rate and tendency to metastasize. Eight Haflingers with histologically confirmed SCC were included, five ocular and three non-ocular, who were presented at the Institut Suisse de Médecine Équine (ISME) Bern between July 2015 and January 2022. The ocular SCC cases were all presented because of an apparent mass, which in most cases was post-treatment recurrence. The occurrence of recurrences was observed between 3 weeks and 16 years after initial therapy. Four of five Haflingers with ocular SCC had an enucleation, three of which were clinically normal at the time of the completion of this study, one case was euthanized due to confirmed metastases and one due to lameness. The result of enucleations for therapy of ocular SCC was good if no metastases occurred. Of the three non-ocular SCC cases, only one case, a penile SCC, had an apparent mass. Therapy was initiated in this case, while the other two cases were euthanized shortly after diagnosis due to the poor prognosis of SCC in the appropriate locations (maxillary sinus, mandible). Metastases occurred three and two years after removal of the primary tumor in ocular SCC in the scapula, liver and lungs and in non-ocular SCC from the penis to the nostrils. Since a postmortem pathological examination was not carried out on all Haflingers, further metastases cannot be ruled out. Haflingers with SCC should be monitored by a veterinarian over the long term, as recurrences and/or metastases can still occur years later.

A 75 years old patient presented with a papular easily bleeding lesion of the lower lip that had been growing for two months. He was known for alcoholic cirrhosis complicated with hepatocellular carcinoma treated since one year. A working diagnostic hypothesis of benign vascular lesion was proposed. Microscopic examination showed a neoplastic dermal proliferation that had been fully excised, made of lobules segregated by thin fibrous septae. The neoplastic architecture was trabecular and delineating spaces forming pseudo-rosettes. Tumour cells were monomorphic, cuboidal or cylindric with abundant eosinophilic and granulous cytoplasm and centered by a lone nucleus that often contained a prominent nucleolus. Some spaces were filled with a brownish-greenish pigmented material. Immunohistochemical study showed that tumour cells were positive with the hepatocyte paraffin 1 antibody as well as cytokeratin 8 antibody. Chromogranin A and synaptophysin stainings were negative. Thus we concluded to a lip metastasis from the previously known hepatocellular carcinoma. Skin metastasis arise in around 3% of cases of hepatocellular carcinoma. They account for less than 1% of all cutaneous metastasis. Overall appearance of cutaneous metastasis of hepatocellular carcinoma is associated with a poor prognosis and an aggravated risk of metastasis to other locations and organs and a median overall survival of less than 5 months. Since incidence of hepatocellular carcinoma is rising pathologists might face more frequently in years to come to cutaneous metastasis whose varied clinical presentations make a diagnostic challenge., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Testis tumors are uncommon in oncology, and testicular metastasis from distant solid tumors are even rarer. We present two cases encountered in our department of pathology in CHU de Rennes, France. Moreover, we collected all reported cases in the Medline/PubMed databases of non-hematopoietic secondary testis tumors in adults, excluding autopsy studies, to propose an integrative study on this topic. In total, we report 98 cases of secondary testis lesions to prostate (n=38, 38.77 %), colorectal (n=19, 19.39%), gastric (n=12, 12.24%), kidney (n=7, 7.14%), lung (n=6, 6.12%) and other primary cancers. The median age at diagnosis was 66.5 years. We identified significantly more prostate adenocarcinoma (P<0.0001) when the primary tumor was known and significantly more colorectal adenocarcinoma (P=0.035) and pancreatic adenocarcinoma (P=0.002) when the primary tumor was unknown. The age at diagnosis was older when the primary tumor was known (P=0.007). We present the challenges for the diagnosis and propose some elements for diagnosis orientation. Finally, we discuss the possible ways of metastatic dissemination from primary site to testis, as illustrated by the two cases we present., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: Gastrointestinal (GI) metastases in lung cancer rarely occur., Case Report: We report here the case of a 43-year-old male active smoker who was admitted to our hospital for cough, abdominal pain and melena. Initial investigations revealed poorly differentiated adenocarcinoma of the superior-right lobe of the lung: positive for thyroid transcription factor-1 and negative for protein p40 and for antigen CD56, with peritoneal, adrenal and cerebral metastasis, as well as anemia requiring major transfusion support. Over 50% of cells were positive for PDL-1, and ALK gene rearrangement was detected. GI endoscopy showed a large ulcerated nodular lesion of the genu superius with active intermittent bleeding, as well as an undifferentiated carcinoma with positivity for CK AE1/AE3 and TTF-1, and negativity for CD117, corresponding to metastatic invasion originating from lung carcinoma. Palliative immunotherapy with pembrolizumab was proposed, followed by targeted therapy with brigatinib. Gastrointestinal bleeding was controlled with a single 8Gy dose of haemostatic radiotherapy., Conclusion: GI metastases are rare in lung cancer and present nonspecific symptoms and signs but no characteristic endoscopic features. GI bleeding is a common revelatory complication. Pathological and immunohistological findings are critical to diagnosis. Local treatment is usually guided by the occurrence of complications. In addition to surgery and systemic therapies, palliative radiotherapy may contribute to bleeding control. However, it must be used cautiously, given a present-day lack of evidence and the pronounced radiosensitivity of certain gastrointestinal tract segments., (Copyright © 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

We report the case of a 79 year-old woman, who was admitted in the department of digestive surgery for an occlusive syndrome. The abdominopelvic computed tomography revealed a voluminous mass infiltrating the uterus, the bladder and the colon. A monobloc surgery is performed. The histopathological examination evidences an invasion of these organs by a well-differentiated glandular proliferation composed of epithelial cells without atypia stained with keratin 7 and carcinoembryonar antigen, without expression of p16, hormonal receptors and keratin 20. Ki-67 labeling index was low. The diagnosis of minimal deviation gastric mucinous adenocarcinoma was proposed. This is an uncommon neoplasm comprising approximately 1% of all endocervical adenocarcinomas. This is a difficult histopathological which should be known by pathologist. It is correlated to a poor clinical outcome with a high tendency to lymph node and extra-uterine metastases, as illustrated in our observation., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

We report a rare entity in adults with an exceptional secondary complication. This is a case of a splenic localization of a yolk sac tumor responsible for a splenic rupture in a 52-year-old man., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Metastatic prostate cancer (mPCa) is an heterogeneous disease. Metachronous mPCa (MM) seems to have a better prognosis than synchronous mPCa (SM). However, it is difficult to analyze their specificities from national registries. Data from the so-called "sentinel multidisciplinary meeting" (SMDM) would represent a "real life" data collection. The objective of this national pilot study was to evaluate the concept of SMDM through the description and comparison of the diagnosis, management and follow-up of patients with synchronous or metachronous mPCa in 2018., Methods: A survey covering clinical, biological, radiological data as well as treatment initiated and follow-up at 3 and 6 months was sent to the SMDM. All patients diagnosed with metastatic disease (SM or MM) between 01/01/2018 and 11/30/2018 were included., Results: In total, 780 patients from 39 centers were included, 408 SM and 372 MM. SM were more symptomatic and had a higher metastatic burden than MM. PET were mostly performed in MM without a prior standard staging. SM patients received more chemotherapy than MM patients whereas new generation androgen deprivation therapy was mostly given to MM patients. At 6 months, there were no more significant difference in clinical presentation between the two groups., Conclusion: Specificities of SM and MM patients in terms of clinical presentation, metastatic burden and management were described, validating the concept of SMDM as a source of reliable informations., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction: Cutaneous and vascular manifestations of cancer are numerous. Among paraneoplastic acral vascular syndrome, we report a case of blue toe syndrome as the first manifestation of a prostate cancer following with analysis of this syndrome according literature., Observation: A 56-year-old man, with Raynaud's phenomenon of the upper limbs for 2 to 3 years, had 4 blue toes of the left foot evolving for 18 months, without ulceration, the pulses being present. Vascular and cardiac explorations (ultrasound, angio-MRI) were normal. There was no biological or immunological abnormality except an elevated PSA level. Prostate biopsies confirmed diagnosis and abdomino-pelvic CT scan proved the bone and lymph node metastasis., Conclusion: The revelation of a prostate cancer with bone metastases by a blue toe syndrome is a rare situation. In a patient with a blue toe syndrome with no obvious clinical or biological abnormality, especially atheromatous, investigations should include a search for cancer, which can be revealed by blue toes., (Copyright © 2022 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Exosomes or other extracellular vesicles released from cells play an important role in cell-to-cell communication by transferring bio-information (DNA, coding/non-coding RNA, and proteins), which indicates parental cell status to recipient cells in the extracellular environment. Increasingly, evidence shows that tumor-derived exosomes mediate tumor pre-metastatic niche (PMN) remodeling to establish a supportive and receptive niche to promote tumor cell colonization and metastasis. Uptake of genetic information by target cells in the extracellular environment triggers epigenetic changes that contribute to PMN formation. Here, we provide a comprehensive overview of the current understanding of exosomes-mediated reprogramming of cells in PMN formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Zhang, Zhang, Zhang, Qiu, Zhuang, Wei, Deng, Wang and Han.)

Introduction: Lymph node metastasis is a well-known prognostic factor for laryngeal carcinoma. However, current nodal staging systems provide limited information regarding prognosis. Additional parameters should be considered to improve prognostic capacity., Objectives: To assess the prognostic values of metastatic lymph node number, ipsilateral/contralateral harvested lymph nodes, and lymph node ratio in patients undergoing surgical treatment of laryngeal squamous cell carcinoma., Methods: Seventy-four patients diagnosed with laryngeal squamous cell carcinoma primarily managed surgically were included in this study. The patients' pathological and survival data were obtained from their medical records. The effects of harvested lymph nodes and lymph node ratio on disease-free survival, disease-specific survival, and overall survival were analyzed., Results: Ipsilateral, contralateral, and bilateral evaluations of harvested lymph nodes showed no significant associations with prognosis. Lymph node ratio was significantly associated with overall survival when evaluated bilaterally. Metastatic lymph node number showed more suitable stratification than TNM classification., Conclusions: Metastatic lymph node number and bilateral lymph node ratio parameters should be taken into consideration to improve the prognostic capacity of TNM., (Copyright © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Purpose: To present the technique of combined temperature monitoring and hydrodissection of the anterior epidural space during thermal ablation in the thoracic spine., Materials and Methods: Data from 8 patients were retrieved retrospectively with thoracic spinal metastases located near the posterior wall of the vertebral body. Thermal ablation was performed with temperature monitoring and hydrodissection of the anterior epidural space., Results: Technical success, defined as a fulfilled ablation protocol without changes of the temperature of the epidural space below 10°/above 45° that could not be controlled by active hydrodissection, was 100%. The mean time to deploy the thermosensor was 19.5 ± 4.8 min (range 13-35). There was one post-operative transient intercostal neuralgia. No spinal cord or nerve root injuries arose. Two local recurrences occurred at a mean follow-up of 20 ± 9 months., Conclusion: Transosseous temperature monitoring of the anterior epidural space in the thoracic spine is a feasible technique and seems safe.

We report a case of malignant melanoma revealed by a metastasis to the pituitary gland. The tumor was misdiagnosed as a pituitary adenoma and aggressive transsphenoidal surgery was complicated by a cerebrospinal fluid fistula. Nine weeks later, the patient presented multiple leptomeningeal and brain metastases spreading from the sellar region. Regarding these observations, we conducted a systematic review of the literature in order to investigate clinicoradiological features that should lead clinicians to suspect pituitary metastasis and how it should impact the surgical management., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Colorectal cancer is a common malignancy. NTS receptor 3 (NTSR3) is known to play an important role in several cancers. This study examined the effects of NTSR3 on cell growth and metastasis in colorectal cancer. Western blot analysis, real-time PCR, immunofluorescence staining, MTT, cell cycle assay, cell apoptosis assay, Hoechst staining, caspase-3 and caspase-9 activity assays, cell adhesion assay, wound healing assay, and a Transwell assay were used in this study. We found that NTSR3 was expressed at relatively high levels in the colorectal cancer cell lines SW620 and SW480. NTSR3 knockdown suppressed cell growth and promoted cell apoptosis. Meanwhile, the protein expression levels of cyclinD1, cyclinE1, CDK4, and p-RB were reduced, and the levels of p-P27, P15, P21, cleaved caspase-3, and cleaved caspase-9 protein were increased. Cell invasiveness and cell migration were reduced with knockdown of NTSR3. In addition, our rescue experiments demonstrated that overexpression of the siRNA-resistant alleles of NTSR3 abrogated the NTSR3-siRNA-mediated effects on cell function. Further, down-regulation of NTSR3 inactivated the PI3K-AKT and MAPK signaling pathways. Collectively, these data demonstrate that knockdown of NTSR3 inhibits cell growth and metastasis, as well as the PI3K-AKT and MAPK signaling pathways in colorectal cancer. Thus, our results indicate that NTSR3 is a potential therapeutic target for treating colorectal cancer.

Background: The current evidence suggests that oncological surgery, which is a therapy used in the treatment of solid tumors, increases the risk of metastasis. In this regard, a wide range of tumor cells express Voltage-Gated Sodium Channels (VGSC), whose biological roles are not related to the generation of action potentials. In epithelial tumor cells, VGSC are part of cellular structures named invadopodia, involved in cell proliferation, migration, and metastasis. Recent studies showed that lidocaine could decrease cancer recurrence through its direct effects on tumor cells and immunomodulatory properties on the stress response., Objective: The aim of this narrative review is to highlight the role of VGSC in tumor cells, and to describe the potential antiproliferative effect of lidocaine during the pathogenesis of metastasis., Contents: A critical review of literature from April 2017 to April 2019 was performed. Articles found on PubMed (2000-2019) were considered. A free text and MeSH-lidocaine; voltage-gated sodium channels; tumor cells; invadopodia; surgical stress; cell proliferation; metastasis; cancer recurrence-for articles in English, Spanish and Portuguese language-was used. A total of 62 were selected., Conclusion: In animal studies, lidocaine acts by blocking VGSC and other receptors, decreasing migration, invasion, and metastasis. These studies need to be replicated in humans in the context of oncological surgery., (Copyright © 2020 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Introduction: Nasopharyngeal carcinoma, an epithelial-derived malignant tumor which because of its anatomical location and atypical early symptoms, when diagnosed invasion and metastasis often have occurred. This requires a better understanding of the development mechanism, identifying diagnostic markers, and developing new treatment strategies., Objective: To study the relationship of LMP1 and Cripto-1 in nasopharyngeal carcinoma., Methods: The expression of LMP1 and Cripto-1 in specimens obtained from nasopharyngeal carcinoma patients (n=42) and nasopharyngitis patients (n=22) were examined. The expression of LMP1 and Cripto-1 in LMP1-negative and LMP1-positive (CNE1-LMP1) cells were also examined., Results: The expression of LMP1 and Cripto-1 was significantly higher in nasopharyngeal carcinoma than in nasopharyngitis (p<0.05). Their expression in nasopharyngeal carcinoma with metastasis were significantly higher than that without metastasis (p<0.05), which was correlated with TNM staging (p<0.05). High Cripto-1 expression and high proliferation rate were seen in CNE1-LMP1 cells., Conclusions: The expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma is positively related. Their co-expression might contribute to the proliferation and metastasis of nasopharyngeal carcinoma., (Copyright © 2019 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Patients treated with bladder augmentation have a higher risk of developing bladder cancer than the general population. In these patients, tumours are most frequently primary bladder cancers. Metastasis in an augmentation cystoplasty is extremely rare and here we describe the first case of metastasis from lobular breast carcinoma in an ileal patch. A 52-year-old woman, with a medical history of invasive lobular breast cancer, presented with gross hematuria seven years after an ileal augmentation cystoplasty. A large bladder mass was found exclusively on the enteric patch, with lymphadenopathies from iliac vessels to right kidney hilum. Asurgical resection of the ileal segment with trigonal preservation was performed, associated with a complete cytoreduction. The bladder was reconstructed with a new ileal segment. Pathology confirmed the diagnosis of metastatic lobular breast carcinoma. Patients treated with augmentation cystoplasty need a close and long follow-up to detect the warning signs of tumor development. We herein report our experience of a metastatic lesion on the enteric part of a cystoplasty. Unusual characteristics of the bladder tumor and personal oncologic history of the patient may be suggestive of a secondary lesion.

Introduction: Thymomas are epithelial neoplasms of thymic origin, preferentially localized in the anterior mediastinum. Recurrences after surgery are uncommon and usually occur in the intrathoracic area. The occurrence of extra-thoracic metastases is an unusual phenomenon., Case Report: Here we report the case of a 61-year-old man with no special medical history. He smoked about 40 pack years but stopped in 1999. Initially he presented with a mediastinal thymoma and underwent surgical resection. One year later the development of abdominal pain and bowel disorders lead to the discovery of an ileal ulcero-necrotic tumour. After surgical resection, histological examination revealed secondary thymoma. A few months later he underwent cerebral MRI because of neurological symptoms. This revealed a second metastasis located in the brain. Stereotactic radiotherapy led to an improvement. After more than one year of follow-up the patient developed a papillary thyroid carcinoma but there were no signs of recurrence of the thymoma., Conclusions: Extra-thoracic metastases of thymoma are exceptional but their existence should not be overlooked. Their management is not standardised because of lack of data in the literature. Though surgical excision in oligo-metastatic subjects is a frequently reported therapeutic option, a radiotherapeutic approach, particularly in cerebral situations, could be a credible alternative., (Copyright © 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Objective: The present study applied iTRAQ and LC-MS/MS techniques for proteome analysis and compared data between specimens of papillary thyroid microcarcinoma (PTMC) vs appropriate controls, in order to investigate the mechanisms underlying the invasion and metastasis process in PTMC development., Materials and Methods: Fresh-tissue specimens were collected from 40 patients with thyroid disease who underwent surgical treatment. Specimens were divided into four groups: normal histology (NH; n=8), benign thyroid tumor (BTT; n=10), classic PTMC with lymph node metastasis (PTC-LNM (+) ; n=11), and classic PTMC without lymph node metastasis (PTC-LNM (-) ; n=11). Proteomic studies were conducted on PTMC tissue samples without capsule invasion and with tumor diameter ranging from 0.5cm to 1cm, so as to focus the study on PTMC development excluding metastasis., Results: A total of 8036 proteins were identified in the four groups. Based on protein function analysis, proteins that might be associated with PTMC invasion and metastasis were screened: alpha-actinin-1, alpha-1-antitrypsin, hepatoma-derived growth factor (HDGF), high-mobility group protein HMGI-C, and carbonic anhydrase 4. In addition, proteins involved in the focal adhesion pathway were examined. Immunohistochemistry confirmed the reliability of the iTRAQ results and the universality of differentially expressed proteins. The data showed that HDGF and high-mobility group protein HMGI-C are up-regulated in PTMC and that the focal adhesion pathway that promotes PTMC LNM is activated., Conclusions: These findings provide insight into the mechanisms underlying PTMC invasion and metastasis., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Liver cancer is a leading cause of cancer-related deaths globally. Tumor response rate of liver cancer patients towards systemic chemotherapy is low and chemoresistance can easily develop. Identifying novel molecules that can repress drug resistance and metastasis of liver cancer will facilitate the development of new therapeutic strategies. The aim of this study is to determine the roles of NUAK1 and miR-204 in the drug resistance and metastasis of liver cancer and to reveal their relationship. We found that NUAK1 was increased in the tumor of primary liver cancer. Knockdown of NUAK1 significantly inhibited cell growth and migration. Moreover, NUAK1 was the direct downstream target of miR-204, and there was clinical relevance between miR-204 down-regulation and NUAK1 up-regulation in liver cancer. Furthermore, we found that miR-204 increased drug sensitivity by down-regulating NUAK1 expression. Based on these results, we identified miR-204 as a tumor suppressor by inhibiting NUAK1 expression in liver cancer, indicating both miR-204 and NUAK1 may act as promising targets for liver cancer therapy.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents, and metastatic OS is the major cause of OS-related death. Carboxypeptidase E (CPE) is known to be highly expressed in some cancer types, and its N-terminal truncated form, CPE-ΔN, is implicated in tumor metastasis and poor prognosis. In this study, we investigated the effect of CPE-ΔN on cell migration, invasiveness, and the epithelial-mesenchymal transition (EMT) of OS cells, and illustrated the molecular mechanisms. We first constructed CPE-ΔN overexpressing human OS cell lines (143B and U2OS cells), and found that ectopic CPE-ΔN expression in OS cells enhanced cell migration and invasiveness, and promoted the EMT process. Further, overexpression of CPE-ΔN increased the levels of c-myc and nuclear β-catenin in OS cells, which suggested the CPE-ΔN promotes activation of the Wnt-β-catenin pathway in OS cells. Treatment with β-catenin small interfering RNA (siRNA) inhibited the migration and invasiveness of CPE-ΔN-overexpressing cells, and reduced the expression of E-cadherin. Together, these results suggest that CPE-ΔN promotes migration, invasiveness, and the EMT of OS cells via the Wnt-β-catenin signaling pathway.

Objective: To review biology and management of oligometastatic prostate cancer., Material and Methods: Relevant publications were identified through Medline (www. ncbi.nlm.nih.gov), Embase (www.embase.com) and the US National Library of Medicine (www.clinicaltrials.org) databases using the following keywords, alone or in association, «prostate cancer; metastasis; oligo-metastasis». Articles were selected according to methods, language of publication and relevance. After careful selection 99 publications were eligible for our review., Results: Oligometastatic prostate cancer is a new entity including prostate cancer with a limited number of metastasis. This particular state becomes more frequent with the imaging progresses especially with the common use of new PET imaging with Choline or PSMA. There is no consensus about a strict definition of oligometastatic prostate cancer, number and sites of metastasis vary widely in the literature. Moreover, oligometastatic state can be observed de novo at the time of prostate cancer diagnosis as well as in case of recurrence after a primary treatment. There is actually an important lack of evidence-based medicine and no guidelines regarding treatment can be found. In de novo oligo-metatastatic prostate cancer, treatment of the primary tumor in association with androgen deprivation therapy seems to increase survival in selected patients but this needs to be confirmed by ongoing prospective clinical trials. In recurrent prostate cancer, metastasis directed therapy with or without androgen deprivation therapy is now routinely performed but its impact needs also to be analyzed., Conclusion: In absence of consensus or guidelines, management of prostate cancer should be an individualized, patient-based management taking into account primary tumor stage and grade, number and types of metastasis and patient characteristics., (© 2019 Elsevier Masson SAS. Tous droits réservés.)

Metastatic pheochromocytoma/paraganglioma (PPGL) represents a major clinical challenge due to limitations in accurate diagnostic tools and effective treatments. Currently, patients classified at high-risk by means of clinical, biochemical and genetic criteria, require a lifelong monitoring, while it remains difficult to determine the metastatic potential of PPGL only on the basis of histopathological features. Thus, tumor molecular markers that improve the risk stratification of these patients are needed. In the past few years, we have witnessed an unprecedented molecular characterization of PPGL, which led to the emergence of promising candidate biomarkers predictive of metastatic behavior. Here, we briefly discuss these breakthroughs and provide some insights for the prospective implementation of molecular markers of metastatic PPGL in the clinical setting in years to come., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Urothelial carcinoma of the bladder are rare but aggressive tumors with a high metastatic potential. The prognosis of these tumors has not drastically changed over the past 30 years, with an overall survival of less than two years in advanced or metastatic situations. Even though immune checkpoints inhibitors have changed this picture, it is beneficial for less than 30% of patients and there is no reliable biomarkers to identify this specific population of responders. Vinflunine is a vinca-alkaloid that was specifically developed as second line treatment post-platinum. As of today, it is the sole anticancer agent for which clinical trials have been pushed to phase III and that was approved for patients in good conditions. Unfortunately, it has been withdrawn from the list of reimbursed drugs, which impairs its prescription. Based on the results of phase III clinical trials with immunotherapies, this review provides the reader with argumentations in favor of patients' and clinicians' request to reimburse vinflunine for the treatment of advanced or metastatic urothelial carcinoma of the bladder., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Recognition of mammary metastases by pathologists is fundamental because their prognosis and treatment are different from those of primary mammary carcinomas. We report the case of a 54-year-old woman presenting on her mammography a left breast nodule known for 5 years, having discreetly increased in size. Breast ultrasound showed a regular 1.2cm hypoechogenic nodular formation. A microbiopsy was performed. On microscopic examination, we observed a tumor proliferation realizing nests within a small, richly vascularized stroma. The tumor cells had a moderately abundant, eosinophilic, granular cytoplasm and a rounded, slightly atypical nucleus. One mitosis was found for 10 fields at×400 magnification. Tumor cells did not express hormone receptors but chromogranin A, synaptophysin, TTF1 and thyrocalcitonin. The proliferation index established by the anti-Ki67 antibody was 5 %. The diagnosis was a secondary localization of a well-differentiated neuroendocrine tumor which immunohistochemical profile firstly suggests a thyroid origin. We later learned that the patient had a history of total thyroidectomy 13 years ago. It was a sporadic medullary carcinoma of the thyroid. Bone scintigraphy revealed a lacunar lesion of the posterior part of the right iliac wing suspicious of secondary location. This right iliac lesion was biopsied. It was also a localization of the medullary thyroid carcinoma. The final diagnosis is a metastatic medullary thyroid carcinoma, slowly progressive, the mammary metastasis having probably existed for 5 years., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Mycetoma is transmitted by thorns infected. The commonest site for mycetoma is the foot. The primary pulmonary are rare and usually secondary to other primary site. We report a case of pulmonary fungal mycetoma secondary to primary site in the knee. We do a review of the literature and we discuss the way of dissemination., Competing Interests: The authors have no conflicts of interest to declare

Uveal melanomas are the most frequent primary malignant eye tumor. Enucleation was historically the gold standard. Since then, several studies showed that conservative treatments did not increase the risk of metastasis or survival. Choroidal melanomas are both radioresistant and located close to visual structures (the optic nerve and macula) of the eye, which may be preserved in some settings without compromising tumor control, as this is the first priority. Different types of radiation therapy may be used for such tumors: brachytherapy and charged particles, including proton beam therapy. If visual prognosis is dependent to the local treatment, the vital prognosis is dependent on the metastatic risk, with a risk of liver involvement in 20 to 50% of patients, depending on tumor size and genomics. Median survival after the discovery of liver metastases is about 15 months. The management of these patients is often complex. Systemic therapies (chemotherapy, targeted therapies, immunotherapy, etc.) yield limited response rates and although local treatments of liver metastases are promising, they are only feasible in selected patients. The mission of the MELACHONAT national network is to improve the management of patients regardless of the stage of the disease. The patient association ANPACO is dedicated to help uveal melanoma patients in their health care path and to promote knowledge dissemination within the patient community. The aim of this review is to focus on the local treatments of uveal melanomas as well as the management of their metastatic evolution., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Exosomes are now considered to be involved in mediating cell-to-cell communication to promote or inhibit tumor progression. However, the role and molecular mechanism of exosomes in promoting glioblastoma (GBM) metastasis remains elusive. Here, we found that circulating exosomal miR-148a levels were significantly higher in serum from GBM patients compared with serum from healthy volunteers. In T98G cells, inhibition of miR-148a suppressed cell proliferation and metastasis. In addition, we identified Cell adhesion molecule 1 (CADM1) as a target gene of miR-148a using luciferase reporter assay. Both protein and mRNA levels of CADM1 were decreased in tissues from GBM patients. There was a strong negative correlation between exosomal miR-148a and CADM1 mRNA levels in samples of patients. Moreover, miR-148a antagonist increased p-STAT3 protein level to activate STAT3 pathway. In conclusion, our findings indicated that miR-148a delivered by exosomes may promote cancer cell proliferation and metastasis via targeting CADM1 to activate STAT3 pathway, suggesting a predictor and therapeutic target role of exosomal miR-148a in GBM patients., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: The predictive value of systemic inflammatory markers has been explored in various types of cancer. In the present study, we aimed to investigate the association between pretreatment neutrophil/lymphocyte ratio (NLR) and tumor metastasis in pancreatic cancer, and the values of NLR as a prognostic factor of overall survival., Methods: Clinical and laboratory data from 256 consecutive pancreatic cancer patients were analyzed retrospectively. The NLR was recorded before treatment and analyzed along with clinicopathological characteristics and overall survival of pancreatic cancer patients., Results: Multivariate analysis revealed that pretreatment NLR (HR: 2.393; 95% CI: 1.326-4.320; P=0.004) was an independent risk factor for distant metastasis. Furthermore, COX regression analysis showed that in addition to pretreatment NLR (HR: 1.871; 95% CI: 1.413-2.477; P<0.001), metastasis and stage were independent prognostic factors., Conclusion: Pretreatment NLR values were significantly associated with distant metastasis in pancreatic cancer patients. Higher NLR values were detected in metastatic disease and may be an independent prognostic factor of overall survival in pancreatic cancer patients., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Epithelial-to-mesenchymal transition is a cellular process associated with cancer invasion and metastasis. However, the antimetastatic effects of chimaphilin remain elusive. In this study, we attempted to investigate the potential use of chimaphilin as an inhibitor of TGF-β1-induced epithelial-to-mesenchymal transition in U2OS cells. We found that TGF-β1 induced epithelial-to-mesenchymal transition to promote U2OS cell invasion and metastasis. Western blotting demonstrated that chimaphilin inhibited U2OS cell invasion and migration, increased the expression of the epithelial phenotype marker E-cadherin, repressed the expression of the mesenchymal phenotype marker vimentin, as well as decreased the level of epithelial-to-mesenchymal-inducing transcription factors Snail1 and Slug during the initiation of TGF-β1-induced epithelial-to-mesenchymal transition. In this study, we revealed that chimaphilin up-regulated the E-cadherin expression level and inhibited the production of vimentin, Snail1, and Slug in TGF-β1-induced U2OS cells by blocking PI-3K/Akt and ERK 1/2 signaling pathway. Additionally, the TGF-β1-mediated phosphorylated levels of Smad2/3 were inhibited by chimaphilin pretreatment. Above all, we conclude that chimaphilin represents an effective inhibitor of the metastatic potential of U2OS cells through suppression of TGF-β1-induced epithelial-to-mesenchymal transition.

We report the case of a 57-year-old man, who is hospitalized for the surgery of a gallbladder mass associated by an increase in fluorodeoxyglucose-activity on positron emission tomography/computed tomography scan. This is an incidental finding occurring during monitoring of a skin melanoma. A cholecystectomy is performed. Microscopic examination identified an infiltration of the gallbladder wall by a proliferation of atypical pigmented spindled melanocytes with numerous mitoses. The immunohistochemical analysis confirmed the melanocytic nature of this proliferation with the staining of HMB-45, S100 protein and Melan-A. A complementary immunohistochemical (p16, desmin and BRAFV600E) and molecular (BRAF sequencing) study is performed. The results are consistent with the hypothesis of a gallbladder metastasis of a cutaneous melanoma is proposed. Gallbladder metastases of melanoma are exceptional. The aim of our work is to describe a new case with immunohistochemical and molecular characterization, to review the literature on this topic and to consider the main differential diagnosis (primary malignant melanoma of the gallbladder)., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

We report the case of a 33-year-old woman who went under surgery for a cystic mature teratoma. The histological exam found two cysts, one was a mature teratoma and the other was a struma ovarii with a papillary carcinomatous element. Struma ovarii cancerization is seen in 5 to 10% of the cases usually under a papillary carcinoma type. Diagnosis is rarely made before surgery, the patients exceptionally show thyroid symptoms. Histologically, the tumour presents the same way as the one seen in the thyroid gland and BRAF mutations have been reported. The problem concerns ovarian metastases of a thyroid cancer. A normal thyroid check up and normal thyroid tissue close to the tumor in the ovary are in favor for a cancerize struma ovarii. The therapeutic care is not consensual, going from an annexectomy to hysterectomy and bilateral annexectomy. The patients must be followed on long-term with thyroglobulin quantitative analysis for at least 10 years and whole body scintigraphy with iodine 123 to detect relapse or metastases. The prognosis is usually good but precise criteria are still to define., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The Oligopelvis 2 studies is based on the assumption that salvage pelvic radiotherapy may prolong the interval between the first and the second intermittent hormone therapy sequence in pelvic lymph node oligometastatic prostate cancer. This phase 3 study will compare intermittent hormone therapy (standard arm) alone or combined with salvage pelvic radiotherapy (experimental arm)., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

The goal of treatment of metastatic prostate cancer remains palliation. The oligometastatic state could be the right time to intensify therapy by introducing metastases directed treatments. The aim of this trial was to evaluate the benefit of radiotherapy to all macroscopic metastatic sites and to the primary disease in patients with hormone sensitive oligometastatic prostate cancer., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

A 41-year-old patient, with a medical history of embryonal carcinoma treated by orchidectomy at the age of 27, presented with abdominal pain. Serum alphafetoprotein, β-HCG and CEA levels were normal. MRI showed a cystic retroperitoneal lesion with septation, measuring 20cm. He underwent a surgical resection. Histology revealed an adenocarcinoma arising on a mature multitissular teratoma., (Copyright © 2016. Published by Elsevier Masson SAS.)

Purpose: Bilateral pulmonary radiotherapy in children and young adults aims to reduce the recurrence of lung metastases. The radiation field includes liver tissue, which is sensitive to even low radiation doses. We investigated the feasibility of respiratory gating radiotherapy using voluntary deep inspiration breath hold and its toxicity in these patients., Patients and Method: A retrospective clinical review was conducted for all patients who had undergone bilateral pulmonary radiotherapy, with or without deep inspiration breath hold, treated in our institution between October 1999 and May 2012. A dosimetric study was conducted on seven consecutive children using 4D-scan data on free-breathing and a SpiroDyn'RX-system-scan on deep inspiration breath hold. A radiation treatment of 20Gy was simulated., Results: Concerning the clinical study, seven patients of mean age 11.9 years (range: 4.9-21.1 years) were treated with free-breathing and ten patients of mean age 15.6 years (range: 8.6-19.7 years) were treated with deep inspiration breath hold for mainly Ewing sarcoma and nephroblastoma. Within six months of radiotherapy, all patients experienced mild liver toxicity (grade 1 or 2 altered levels of alanine/aspartate aminotransferase [n=8 of 9] or cholestasis [n=1 of 9]), which resolved completely with no difference between deep inspiration breath hold and free-breathing technique. Over a median follow-up of 2.6 years (range: 0.1-9.3 years), four patients died from disease progression (mean 1.5 years post-radiotherapy [range: 1.1-1.6 years]) and three experienced grade III-V lung toxicity. Concerning the dosimetric study, the irradiated liver volume was significantly lower with deep inspiration breath hold than free-breathing, for each isodose (V5: 73.80% versus 86.74%, P<0.05; V20: 5.70% versus 26.44%, P<0.05)., Conclusions: The dosimetric data of respiratory-gated bilateral pulmonary radiotherapy showed a significantly spare of normal liver tissue. Clinical data showed that this technique is feasible even in young children. However, no liver toxicity difference between deep inspiration breath hold and free-breathing was shown., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Meningiomas represent the most common tumours of the central nervous system in adults. Risk factors include ionizing radiation, female hormones exposure, head trauma, cell phone use, breast cancer and family history of meningioma. Despite complete surgical resection, natural history of meningiomas often includes local recurrence but very few metastatic meningiomas have been reported. Here, we report the case of a metastatic meningioma. A 43-year-old woman was firstly treated for a symptomatic parietal meningioma WHO grade II by surgical resection followed by an irradiation of the surgical bed. After surgical resection and irradiation, the patient recovered incompletely. Two months after the end of the radiation treatment, the patient presented at the emergency unit for sciatic pain revealing bone metastases that has been histologically confirmed. Moreover, imaging led to the diagnosis of liver and lungs metastasis. Despite lack of guidelines for metastatic meningioma, few treatments have been used and published for recurrent and multiple meningioma management. In case studies, some partial responses have been seen with mifepristone and improved progression-free survival rates have been obtained with hydroxyurea and sunitinib. Metastasis in meningioma is very uncommon and no specific management has been described. Hydroxyurea, sunitinib and mifepristone could be options if no clinical trial data is available., (Copyright © 2017. Published by Elsevier SAS.)

Initial staging is a key part of the initial evaluation of non-small cell lung cancer. It relies on the 7th edition of the TNM classification. Proposals have been recently developed for the 8th edition of the classification, which is due to be enacted in early 2017. Among these proposals, the weight of tumor size has been increased and new N descriptors have been introduced to further describe N category depending on the number station involved. Regarding M descriptors, oligometastatic disease is distinguished from multiple distant extrathoracic metastases., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate local control and adverse effects after postoperative hypofractionated stereotactic radiosurgery in patients with brain metastasis., Methods: We reviewed patients who had hypofractionated stereotactic radiosurgery (7.7Gy×3 prescribed to the 70% isodose line, with 2mm planning target volume margin) following resection from March 2008 to January 2014. The primary endpoint was local failure defined as recurrence within the surgical cavity. Secondary endpoints were distant failure rates and the occurrence of radionecrosis., Results: Out of 95 patients, 39.2% had metastatic lesions from a non-small cell lung cancer primary tumour. The median Graded Prognostic Assessment score was 3 (48% of patients). One-year local control rates were 84%. Factors associated with improved local control were no cavity enhancement on pre-radiation MRI (P<0.00001), planning target volume less than 12cm 3 (P=0.005), Graded Prognostic Assessment score 2 or above (P=0.009). One-year distant cerebral control rates were 56%. Thirty-three percent of patients received whole brain radiation therapy. Histologically proven radionecrosis of brain tissue occurred in 7.2% of cases. The size of the preoperative lesion and the volume of healthy brain tissue receiving 21Gy (V 21 ) were both predictive of the incidence of radionecrosis (P=0.010 and 0.036, respectively)., Conclusion: Adjuvant hypofractionated stereotactic radiosurgery to the postoperative cavity in patients with brain metastases results in excellent local control in selected patients, helps delay the use of whole brain radiation, and is associated with a relatively low risk of radionecrosis., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients. The cellular mechanisms of therapy resistance in CSCs are ascribed to several factors including a state of quiescence, an enhanced DNA damage response and active repair mechanisms, up-regulated expression of drug efflux transporters, as well as the activation of pro-survival signaling pathways and inactivation of apoptotic signaling. Understanding the mechanisms underlying the acquisition of resistance to therapy may hold the key to targeting the CSC population.

Introduction: Spinal metastasis are getting more frequent. This raises the question of pain and neurological complications, which worsen the functional and survival prognosis of this oncological population patients. The surgical treatment must be the most complete as possible: to decompress and stabilize without delaying the management of the oncological disease. Minimal invasive surgery techniques are by definition, less harmful on musculocutaneous plan than opened ones, with a comparable efficiency demonstrated in degenerative and traumatic surgery. So they seem to be applicable and appropriate to this patient population., Material and Methods: We detailed different minimal invasive techniques proposed in the management of spinal metastasis. For this, we used our experience developed in degenerative and traumatic pathologies, and we also referred to many authors, establishing a literature review thanks to Pubmed, Embase., Results: Thirty eight articles were selected and allowed us to describe different techniques: percutaneous methods such as vertebro-/kyphoplasty and osteosynthesis, as well as mini-opened surgery, through a posterior or anterior way., Discussion: We propose a surgical approach using these minimal invasive techniques, first according to the predominant symptom (pain or neurologic failure), then characteristics of the lesions (number, topography, type…) and the deformity degree. Whatever the technique, the main goal is to stabilize and decompress, in order to maintain a good quality of life for these fragile patients, without delaying the medical management of the oncological disease., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Fundamental Basis of Metastatic Process: Metastatic process is described as a "dissemination of neoplastic cells in a distant secondary site, in which cells proliferate to develop a mass of cells partially differentiated". The vast majority of death in solid cancers is the consequence of metastasis development which lead to vital organ dysfunction. In the present review, either recent discoveries or controversial subjects associated with metastasis process will be discussed. Indeed epithelia-mesenchymal transition (EMT), circulating tumor cells, tumor dormancy, colonization in distant organ and cancer stem cells are tackled., (© 2016 Société Française du Cancer. Publié par Elsevier Masson SAS.)

Cystic pancreatic neoplasms concern 1 to 2% of the pancreatic tumours. The serous ones are considered benign tumours but since 1989, several pancreatic serous cystadenocarcinomas (SCAC) cases have been reported. We report the case of a SCAC with a particular pattern. An 80-year-old female patient presented a 4-cm tumour in the neck of the pancreas associated with liver lesions evoking, on imagery exams, focal nodular hyperplasia nests. A cephalic duodenopancreatectomy and a resection of the liver lesions were carried out. The gross exam showed a tumour with a pattern mostly solid and an area made of cysts. The microscopic exam displayed two patterns: the solid one, predominant, made of mild atypical clear cells, and the cystic one. The liver lesions revealed solid pattern similar to the pancreatic tumour one. The tumoral cells were cytokeratin 7, AE1/AE3 and inhibin positives. The Periodic-acid Schiff showed cytoplasmic granulations, which were digested after diasatasis. Only the presence of metastases allows distinguishing a pancreatic serous cystadenoma from a SCAC. To date, thirty cases of pancreatic SCAC have been reported. Immunohistochemistry cannot confirm the malignancy nature of the lesion but it needs to be done in order to cross out the differential diagnosis, that is pancreatic metastatic clear cell renal carcinoma. Nevertheless, it remains a pathology with good prognosis. Only two cases have been reported but ours case a predominant solid pattern., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)