Extensive Lung Metastases Research Articles

A148 OSTEOSARCOMA GASTROINTESTINAL METASTASIS: A RARE ENTITY IN ADULTS

Abstract Background Osteosarcoma is highly aggressive and is the most common primary bone malignancy for both children and adults with a bimodal age distribution. The first peak coincides with pubertal growth spurt and the second is in the seventh and eighth decade of life. They frequently metastasize to the lungs. Metastasis to the gastrointestinal tract is extremely rare and to our knowledge, there have only been 15 cases reported in the literature since 1987, of those only three in the second peak. Aims Describe a case of 61-year-old female with periampullary metastatic osteosarcoma. Describe the demographics of osteosarcoma patients who develop gastrointestinal metastasis. Methods Search Pubmed using the terms: ("Osteosarcoma"[MeSH Terms] OR "Osteosarcoma"[Title/Abstract]) AND ("Gastrointestinal Tract"[MeSH Terms] OR "Gastrointestinal Tract"[Title/Abstract] AND "Case Reports"[Publication Type]. 113 articles were identified and screened by title. 15 articles were further screened by abstract or full text. 7 articles were identified. the remainder 7 articles were located by screening the references of the previously identified articles. Results A 61-year-old woman with a medical history significant for metastatic Osteosarcoma was referred to Gastroenterology clinic July 2023 for anemia investigation. Her Osteosarcoma was first diagnosed in the left femur in 2009. She was known for extensive bilateral lung metastasis, subcutaneous metastatic deposits, and distant bone metastasis. She had undergone over 37 surgeries and multiple sessions of radiotherapy. Aside from neoadjuvant and adjuvant chemotherapy for the primary tumor and the first occurrence of lung metastasis, she refused to undergo further cycles of chemotherapy. She had a 60 mg/dl hemoglobin drop from a previous one in December 2023 and intermittent melena. On gastroscopy, she was found to have a 2 cm bleeding mass in the periampullary area. The pathology report of the biopsies was consistent with metastatic osteosarcoma. It showed fragments of ampullary mucosa incorporating a malignant spindle cell neoplasm with a fascicular growth pattern, including scattered osteoclast-like giant cells, morphologically consistent with the known history of metastatic osteosarcoma. Of the 15 cases published, 9 were in patients 27 years old and younger, 3 were in patients 50 and older, and 3 were only available as titles. 50% of cases presented with intussusception while the rest had anemia or melena. The site of metastasis was the jejunum in the majority of patients (58%). Other sites included the ileum, stomach, colon, and esophagus. Only one other patient had periampullary metastasis. All patients had lung metastasis. Conclusions Gastrointestinal metastasis of osteosarcoma remains a rare occurrence. Our case report describes the second case reported in the literature of periampullary metastasis and the first case reported in older patients Funding Agencies None

Extensive metastatic ependymoma with long-term progression-free survival with capecitabine plus temozolomide combination chemotherapy: A case report

ABSTRACT We wanted to present a rare case of metastatic grade 2 spinal ependymoma with an atypical course at the time of diagnosis. Temozolomide plus capecitabine chemotherapy was started in May 2018 on a 30-year-old female patient with sacral ependymoma who had extensive lung metastases at the time of diagnosis. The patient remained in remission for approximately 29 months, and the current chemotherapy was continued until it progressed in November 2020. According to this case report, a combination of temozolomide and capecitabine may be the best treatment option for ependymoma patients.

Complete remission after primary single dose of radioactive iodine in metastatic papillary thyroid carcinoma: a case report

Background: Papillary thyroid cancer (PTC) accounts for 90% of the thyroid malignancies with predominance in females. Distant metastasis is usually seen in lungs and bones. The treatment of metastatic papillary cancer thyroid is total/near total thyroidectomy followed by radioactive iodine (RAI) ablation. Lung metastasis shows good response to RAI therapy. Case Presentation: We describe a case of 22-year-old female, referred to nuclear medicine department after surgery for RAI ablation. Patient was diagnosed case of PTC. First dose of 100 mCi of RAI under steroid cover was given. Post-therapy scan showed bilateral pulmonary metastasis. However, follow up I-131 whole body imaging after 2 years showed no evidence of functioning thyroid tissue/metastasis. Conclusion: PTC with lung metastasis has good prognosis and better survival in young patients treated with RAI. A single dose of RAI (I-131) may cure extensive lung metastasis.

Notch1 inactivation promotes invasion and metastasis of nasopharyngeal carcinoma cells partly through Slug activation.

Nasopharyngeal carcinoma (NPC) is a rare form of the head and neck cancer of the epithelial lining of the nasopharynx and exhibits the highest metastatic rate among head and neck cancers. Underlying mechanisms of metastasis remain largely unknown. Here, we explored whether Notch1 affects the invasion and metastasis of NPC cells. In vitro migration and invasion capacities were evaluated after the knockdown of Notch1 expression in NPC cells. To investigate the role of Notch1 in in vivo metastasis, we examined the metastatic ability to the lungs following administration of cancer cells via mouse tail vein. The expression of epithelial-mesenchymal transition (EMT) markers associated with Notch1-mediated metastasis was investigated, and their roles in metastasis and relationship with Notch1 expression were investigated. Suppression of Notch1 expression increased the ability of NPC cells to invade Matrigel in vitro. Knockdown of Notch1 expression in NPC cells resulted in extensive lung metastasis in a mouse model and increased the mRNA expression of Slug in NPC cells. Slug-specific RNA interference resulted in the loss of the metastatic and invasion capacities in Notch1-suppressed NPC cells. These findings show that Notch1 has a significant suppressive role in the regulation of metastasis in NPCs, suggestive of its prudent use in clinical trials.

Establishment of syngeneic murine model for oral cancer therapy

Oral carcinoma (OSCC) is one of the most important causes of cancer death worldwide. OSCC cell lines and preclinical rodent models are crucial to addressing the mechanisms of OSCC and helping the development of new therapeutic strategies and interventions. The establishment of murine OSCC cell lines and syngeneic models are necessary to allow concordant investigation of both in vitro and in vivo pathogenesis. In this study, we established two murine tongue squamous cell carcinoma cell lines, designated MTCQ1 and MTCQ2, from 4NQO-induced OSCC using C57BL/6 mice. These cell lines express a variety of epithelial markers but produce only a tiny amount of E-cadherin. The expression of mesenchymal and stemness regulators are evident, and this is associated with the high mobility in these cell lines. MTCQ1 also shows high Ki67 and PCNA expression, and complicated alterations in p53 expression, which may underlie its high clonogenic potential and rapid orthotopic tumor induction. Using the MTCQ1 cell subclone tagged with GFP (MTCQ1-GFP), extensive neck nodal metastasis and lung metastasis were identified by immunostaining and fluorescence imaging. Inhibition of oncogenic miRNAs, particularly miR-134, was able to attenuate the oncogenicity of MTCQ1-GFP. Cisplatin treatment inhibited both in vitro and in vivo growth of MTCQ1-GFP, and it was found to decrease miR-134 expression in this subclone. The anti-PD-L1 treatment enhanced the inhibitory effects of cisplatin against tumorigenesis. This syngeneic preclinical model should help provide valuable mechanistic insights into OSCC, as well as helping with the development of new approaches to treating this disease.

Tetrac Delayed the Onset of Ocular Melanoma in an Orthotopic Mouse Model.

Ocular melanoma research, the most common primary intraocular malignancy in adults, is hindered by limited in vivo models. In a series of experiments using melanoma cells injected intraocularly into mouse eyes, we developed a model for ocular melanoma. Inoculation of 5 × 105 B16F10 cells led to rapid tumor growth, extensive lung metastasis, and limited animal survival, while injection of 102 cells was sufficient for intraocular tumors to grow with extended survival. In order to improve tumor visualization, 102 melanoma cells (B16F10 or B16LS9) were inoculated into Balb/C albino mouse eyes. These mice developed intraocular tumors that did not metastasize and exhibited extended survival. Next, we studied the therapeutic potential of inhibitor of the thyroid hormones-αvβ3 integrin signaling pathway in ocular melanoma. By utilizing tetraiodothyroacetic acid (tetrac), a thyroid hormone derivative, a delay in tumor onset in the B16F10 (integrin+) arm was observed, compared to the untreated group, while in the B16LS9 cells (integrin–) a similar rate of tumor onset was noticed in both experimental and control groups. In summary, following an optimization process, the mouse ocular melanoma model was developed. The models exhibited an extended therapeutic window and can be utilized as a platform for investigating various drugs and other treatment modalities.

Breast tumor cell-specific knockout of Twist1 inhibits cancer cell plasticity, dissemination, and lung metastasis in mice

Twist1 is an epithelial-mesenchymal transition (EMT)-inducing transcription factor (TF) that promotes cell migration and invasion. To determine the intrinsic role of Twist1 in EMT and breast cancer initiation, growth, and metastasis, we developed mouse models with an oncogene-induced mammary tumor containing wild-type (WT) Twist1 or tumor cell-specific Twist1 knockout (Twist1TKO). Twist1 knockout showed no effects on tumor initiation and growth. In both models with early-stage tumor cells, Twist1, and mesenchymal markers were not expressed, and lung metastasis was absent. Twist1 expression was detected in ∼6% of the advanced WT tumor cells. Most of these Twist1+ cells coexpressed several other EMT-inducing TFs (Snail, Slug, Zeb2), lost ERα and luminal marker K8, acquired basal cell markers (K5, p63), and exhibited a partial EMT plasticity (E-cadherin+/vimentin+). In advanced Twist1TKO tumor cells, Twist1 knockout largely diminished the expression of the aforementioned EMT-inducing TFs and basal and mesenchymal markers, but maintained the expression of the luminal markers. Circulating tumor cells (CTCs) were commonly detected in mice with advanced WT tumors, but not in mice with advanced Twist1TKO tumors. Nearly all WT CTCs coexpressed Twist1 with other EMT-inducing TFs and both epithelial and mesenchymal markers. Mice with advanced WT tumors developed extensive lung metastasis consisting of luminal tumor cells with silenced Twist1 and mesenchymal marker expression. Mice with advanced Twist1TKO tumors developed very little lung metastasis. Therefore, Twist1 is required for the expression of other EMT-inducing TFs in a small subset of tumor cells. Together, they induce partial EMT, basal-like tumor progression, intravasation, and metastasis.

Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc.

Metastatic Giant Cell Tumor of Bone: A Case Report

Giant cell tumor of bone is a relatively rare primary bone neoplasm. It was originally classified as benign tumor; however, it rarely presents as aggressive disease with the potential to distant metastasis mainly in lung. The objective of this study was to present and discuss a case of metastatic giant cell tumor. A young female patient with a recent history of resected bone lesion, hospitalized with dyspnea, was investigated and extensive lung metastasis was found. She received one cycle of chemotherapy until availability of molecular targeted therapy; however, she died due to disease complications 1 day after introduction of denosumab. This rare neoplasm is slightly predominant in females, typically occurring during the third or fourth decades of life, when bone maturity is reached. Accurate diagnosis is given by histopathological analysis. Microscopically the neoplasm is characterized by the presence of multinucleated giant cells of osteoclast type amid a richly vascular stroma of mononuclear cells. The standard treatment is curettage, filling with cement (polymethylmethacrylate) or bone graft. The possibility of recurrence is significant, and 15-50% of cases are treated with simple curettage. In cases where surgery is not possible, the systemic treatment can be attempted. The choice of the treatment regimen is based on case reports or series of cases. Recently a promising targeted therapy emerged, denosumab, a monoclonal antibody directed to the RANK ligand-L. In our case, besides the severity of the disease, inadequate follow-up after surgery and delayed access to specialized services may have contributed to the outcome. J Med Cases. 2014;5(11):557-560 doi: http://dx.doi.org/10.14740/jmc1947w

Abstract 2365: Defining the role of Akt activation in melanoma development and progression

Abstract We have developed a somatic cell gene delivery mouse model of human melanoma that allows for rapid validation of genetic alterations identified in this disease. A major advantage of this system is the ability to model the multi-step process of carcinogenesis in immune-competent mice using retroviral-mediated gene delivery. Mutant BRaf has been demonstrated to cooperate with Pten loss to induce metastatic melanoma in mice but the role of Akt in this context has not been evaluated. This is relevant because ∼60% of human melanomas contain amplification and activation of AKT. In this study, we evaluated the role of mutant Braf in melanoma initiation in the context of Ink4a/Arf loss and Akt activation. Ink4a/Arflox/lox mice expressing the viral receptor TVA specifically in melanocytes under control of the dopachrome tautomerase (DCT) promoter were crossed to Ptenlox/lox mice and mice carrying a conditional BrafV600E allele, which can be activated by Cre expression (BrafCA). Cohorts of newborn mice were injected subcutaneously with retroviruses containing Cre recombinase. Melanoma developed in 100% (8/8) of the DCT-TVA/BrafCA mice following Cre mediated Braf activation combined with Pten and Ink4a/Arf loss; median survival was 62 ± 6.7 days in this cohort. The incidence was reduced to 43% (6/14) if Pten was retained (Pten+/+ mice); median survival of tumor bearing mice in this group was 72 ± 6.7 days. Kaplan Meier survival analysis revealed a highly significant difference between these cohorts (P = 0.01). Interestingly, Akt expression could substitute for Pten loss in this context. Melanoma developed in 88% (15/17) of the DCT-TVA/BrafCA mice following viral delivery of activated Akt and Cre, which mediated Braf activation combined with Ink4a/Arf loss; median survival of tumor bearing mice in this group was 60 ± 6.6 days. Kaplan Meier survival analysis revealed that there was no significant difference between cohorts with Pten loss or Akt expression (P = 0.658). Expression of virally delivered Akt in the absence of Cre did not lead to tumor formation in control cohorts (0/7) and no uninfected mice developed melanoma (0/14). Histological examination of the tumors generated in the BrafCA mice with delivery of Cre and Akt viruses demonstrated that they were very similar to tumors lacking Pten. Importantly, the tumors were similar to human melanoma consisting primarily of short spindle cells exhibiting high grade nuclear features and prominent nucleoli. Mitotic figures were abundant, and some tumors possessed giant cells with epitheliod features. Occasional neoplasms exhibited regions of necrosis. Extensive lung metastases were evident following Pten loss or Akt expression, but not in tumors lacking activation of Akt, confirming a role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in melanoma progression and metastasis. Our ongoing experiments seek to further characterize the role(s) of the PI3K/AKT pathway in melanoma progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2365. doi:1538-7445.AM2012-2365

Bevacizumab plus chemotherapy as salvage treatment in chemorefractory patients with metastatic colorectal cancer: A retrospective analysis.

e14095 Background: The combination of chemotherapy and bevacizumab (beva), a monoclonal antibody targeting VEGF, is consistently being used as first- and second-line treatment in patients with metastatic colorectal cancer (mCRC). There is little data on activity of beva in advanced lines. The aim of this retrospective single center study is to evaluate the activity of beva combined with chemotherapy in patients with beva-naïve chemorefractory mCRC. Methods: Forty six consecutive patients treated in the University Hospital Gasthuisberg Leuven (Belgium) receiving beva in advanced lines following failure of conventional chemotherapy were included in this study. All patients failed under a chemotherapy with fluoropyrimidines plus irinotecan and/or oxaliplatin and/or cetuximab and received bevacizumab (5mg/kg) in combination with either FOLFOX or FOLFIRI. Tumor response was assessed by central review by use of RECIST guidelines; PFS and OS were calculated since start of treatment with beva. Results: Beva plus chemotherapy was used in third line in eight (17.4%) patients and in fourth line or more in the other 38 patients (82.6%). All patients previously failed irinotecan based chemotherapy, 44 (95.7%) failed oxaliplatin based regimens and 40 (87%) failed treatment with cetuximab. Median time on treatment since diagnosis of metastatic disease was 34.7 months. Beva was given in combination with irinotecan based chemotherapy in 36 patients while 9 patients received it in combination with oxaliplatin based chemotherapy and 1 patient in combination with single agent 5-FU. Objective response was demonstrated in 10 patients (21.7%) and disease control in 38 (82.6%) with a median PFS of 8.9 months and a median OS of 13.8 months. Only 4 patients experienced grade 3 and above bevacizumab related toxicity; in two patients with very extensive lung metastasis hemoptysis resulted in death. Conclusions: Taking into account the retrospective nature of the study which can influence the selection of patients, bevacizumab given in advanced lines after failure of conventional chemotherapy and anti-EGFR agents in beva-naïve patients can result in high disease control rates in selected patients.

Poor prognosis nonseminomatous germ-cell tumours (NSGCTs): should chemotherapy doses be reduced at first cycle to prevent acute respiratory distress syndrome in patients with multiple lung metastases?

BackgroundPatients with extensive lung metastases from nonseminomatous germ-cell tumours (NSGCTs) and dyspnoea at presentation are at high risk of acute respiratory distress syndrome (ARDS) and death within the first weeks after chemotherapy induction. This syndrome is linked to acute intra-alveolar haemorrhage related to early tumour necrosis, which in turn, can be complicated by pulmonary infection promoted by neutropenia. The management of these patients was modified at Institut Gustave Roussy in 1997 to try to avoid this complication. Patients and methodsData concerning all patients with lung metastases from NSGCT and dyspnoea or a partial pressure of oxygen (pO2) <80 mmHg treated from 1980 to 2006 in our institution were collected. Patients were treated in a specialised intensive care unit. From 1980 to 1997, the first chemotherapy cycle consisted in a full-dose regimen. After 1997, a 3-day reduced induction regimen of EP (cisplatin 20 mg/m2/day and etoposide 100 mg/m2/day) was used, with bleomycin and two additional days of EP being postponed to day 15, with the regular BEP regimen being started at day 21. ResultsTwenty-five patients with poor-risk disseminated NSGCT according to the International Germ Cell Consensus Classification Group had extensive lung metastases plus dyspnoea at presentation (n = 6), a pO2 <80 mmHg (n = 2), or both criteria (n = 17). Median human chorionic gonadotrophin was 200000 UI (range 11–8920000), and 18 of 25 (72%) patients also had nonpulmonary visceral metastases. During the 1980–1997 period, 13 of 15 patients (87%) developed ARDS, 10 of whom died, and only 4 of 15 (27%) patients were long-term survivors. In contrast, during the 1997–2006 period, only 3 of 10 patients (30%) developed ARDS (P = 0.01), 2 of whom died, and 4 of 10 (40%) eventually survived. ConclusionInitial reduction of chemotherapy doses during the first cycle of chemotherapy for poor prognosis NSGCT with extensive lung metastases seems to prevent the risk of early death due to ARDS.

KITENIN represents a more aggressive phenotype in a murine model of oral cavity squamous carcinoma

Objective To investigate the tumor invasiveness and early lung metastasis associated with KITENIN in a murine model of oral cavity squamous carcinoma. Study Design Cross-sectional study with planned data collection. Setting Department of Otolaryngology–Head and Neck Surgery, Medical Research Center for Gene Regulation, and Pathology, Chonnam National University Medical School and Hwasun Hospital. Subjects and Methods The cDNA of KITENIN and vector only were transfected into the SCC VII (murine squamous cell line) cells. The suspension of 5 × 10 5/mL viable KITENIN- or vector-transfected SCC VII cells was injected into the floor of the mouth of C3H/HeJ syngeneic mice, deep into the mylohyoid muscle via the intraoral approach. From the first to the sixth week after injection, tumor, lung, liver, and brain tissues were obtained. Results For all groups, the tumor invaded the superficial musculature of the floor of the mouth, the deep musculature of the floor of the mouth, the salivary glands, perineural tissue, bone, and skin, sequentially. Lung metastases developed multiple focal nodular patterns at first and then became more extensive. Earlier and more aggressive tumor invasion into the deep floor of the mouth musculature, salivary glands, perineural tissue, bone, and skin was observed in the KITENIN-transfected group compared to the vector-only group. An earlier and more extensive lung metastasis was observed in the KITENIN group. Conclusion An antisense KITENIN strategy might inhibit distant metastasis and the progression of head and neck squamous cell carcinoma.

379 Hyaluronic acid versus simple emollient for the management of radio-induced skin toxicity: results of an open-label, phase III trial

To investigate the tumor invasiveness and early lung metastasis associated with KITENIN in a murine model of oral cavity squamous carcinoma.Cross-sectional study with planned data collection.Department of Otolaryngology–Head and Neck Surgery, Medical Research Center for Gene Regulation, and Pathology, Chonnam National University Medical School and Hwasun Hospital.The cDNA of KITENIN and vector only were transfected into the SCC VII (murine squamous cell line) cells. The suspension of 5 × 105/mL viable KITENIN- or vector-transfected SCC VII cells was injected into the floor of the mouth of C3H/HeJ syngeneic mice, deep into the mylohyoid muscle via the intraoral approach. From the first to the sixth week after injection, tumor, lung, liver, and brain tissues were obtained.For all groups, the tumor invaded the superficial musculature of the floor of the mouth, the deep musculature of the floor of the mouth, the salivary glands, perineural tissue, bone, and skin, sequentially. Lung metastases developed multiple focal nodular patterns at first and then became more extensive. Earlier and more aggressive tumor invasion into the deep floor of the mouth musculature, salivary glands, perineural tissue, bone, and skin was observed in the KITENIN-transfected group compared to the vector-only group. An earlier and more extensive lung metastasis was observed in the KITENIN group.An antisense KITENIN strategy might inhibit distant metastasis and the progression of head and neck squamous cell carcinoma.

A Case of Hepatocellular Carcinoma with Pulmonary Metastases Treated Successfully with a Combination of Repeated Hepatic Arterial Infusion Epirubicin and Cisplatin Chemotherapy and Systemic Low-Dose Infusion of 5-Fluorouracil

We report a case of hepatocellular carcinoma (HCC) with pulmonary metastases treated with repeated hepatic arterial infusion chemotherapy (HAIC) comprising epirubicin and cisplatin, and systemic infusion of 5-fluorouracil (a modified EC/F protocol), which led to complete remission. A 49-year-old man with compensated liver cirrhosis experienced intrahepatic recurrence of HCC with extensive lung metastases. The modified EC/F therapeutic protocol, which was applied at the tenth cycle every 4-5 weeks, resulted in disappearance of the pulmonary metastases and normalization of serum α-fetoprotein levels. A single small HCC lesion was found in the left lobe of the liver 13 months after the final chemotherapy session. HAIC with the same regimen was conducted again, followed by percutaneous intratumoral chemoinjection therapy with 5-fluorouracil and interferon-γ. Thereafter, there was no evidence of recurrence in either the liver or the lung, as evidenced by image analysis and expression of tumor markers. The disease-free intervals for the liver and lung were 41 and 54 months, respectively.

Chemotherapy for poor prognosis non seminomatous germ cell tumors (NSGCT): Should doses be reduced at first cycle to prevent acute respiratory distress syndrome (ARDS) in patients with multiple lung metastases?

5087 Background: Patients with multiple lung metastases from NSGCT and dyspnea at presentation are at high risk of ARDS and death in the first days after chemotherapy induction. This entity has been designated the “choriocarcinoma syndrome” or “very high risk NSGCT”. It is linked to acute intra-alveolar hemorrhage related to early tumor necrosis, which in turn, may be complicated by pulmonary infection promoted by neutropenia. To try to avoid this complication, The policy to manage these patients was changed at Institut Gustave Roussy in 1997. Methods: Data from all patients with lung metastases from NSGCT and dyspnea or a pO2 &lt; 80 and treated between1980–2006 in our institution were collected. Patients were treated in a specialized intensive care unit. From 1980–1997, the first cycle of chemotherapy consisted in a full dose regimen. After 1997, it consisted in a 3-day reduced induction regimen of EP (cisplatin 20 mg/m2/day and etoposide 100 mg/m2/day), with bleomycin and two additional days of EP being postponed to day 15, and the regular BEP regimen being started at day 21. Results: 25 patients with a poor risk NSGCT according to the IGCCCG classification had extensive lung metastases plus either dyspnea at presentation (n=6) or a pO2&lt;80 (n=2), or both criteria (n=17). Median age was 30 years (range 18–49). Median hCG was 200,000 UI (range 11–8,920,000) and 18/25 (72%) patients also had non-pulmonary visceral metastases. During the 1980–1997 period, 13/15 patients (87%) developed ARDS, of whom 10 died, and only 4/15 (27%) patients were long-term survivors. In contrast, during the 1997-2006 period, only 3/10 patients (30%) developed ARDS, of whom 2 died, and 4/10 (40%) survived. Conclusions: Reducing doses of chemotherapy during the first cycle of chemotherapy for poor-prognosis NSGCT with extensive and symptomatic lung metastases seems to prevent the risk of early death due to ARDS and should therefore be recommended. No significant financial relationships to disclose.

Papillary thyroid carcinoma producing granulocyte-macrophage colony-stimulating factor is associated with neutrophilia and eosinophilia

Thyroid tumors producing colony-stimulating factors associated with neutrophilia and/or eosinophilia are very rare and almost all of them concern anaplastic thyroid cancer. Only one case of papillary thyroid carcinoma associated with neutrophilia and one case of medullary thyroid carcinoma associated with eosinophilia have been reported. In this report a 72-year old male patient with metastatic papillary thyroid carcinoma associated with neutrophilia and eosinophilia is described. While investigating the cause of neutrophilia and eosinophilia, a blind bone marrow biopsy of the posterior iliac crest was performed, which showed infiltration by papillary thyroid carcinoma. High blood levels of granulocyte-macrophage colony-stimulating factor (GM-csF) were found using an enzyme-linked immunosorbent assay. As other causes of neutrophilia and eosinophilia were excluded, we assumed that these were paraneoplastic manifestations induced by GM-csF produced by the thyroid tumor. the disease progressed rapidly, despite appropriate treatment which included thyroidectomy and postoperative radioactive (131)I administration. the patient died 11 months after diagnosis because of extensive lung metastasis. Neutrophilia and eosinophilia were stable findings, while serum thyroglobulin levels remained elevated throughout the follow-up period. to our knowledge, this is the first report of a patient with metastatic papillary thyroid carcinoma in whom neutrophilia and eosinophilia associated with high circulating levels of GM-csF were detected.

Spindle-cell ameloblastic carcinoma: A case report with immunohistochemical, ultrastructural, and comparative genomic hybridization analyses

Spindle-cell ameloblastic carcinoma is a classification proposed for a group of rare odontogenic carcinomas with sarcomatoid components and is distinguished from odontogenic carcinosarcoma. We report a case of spindle-cell ameloblastic carcinoma of the right mandible that occurred in a 67-year-old Japanese man. Growth of the tumor was destructive, there was extensive lung metastasis, and the outcome was unfavorable. Ultrastructural and immunohistochemical examination showed the spindle-cell component of the tumor to be epithelial in character. A gain of 5q with amplification of 5q13 was detected in the tumor by comparative genomic hybridization.

High-malignancy orthotopic nude mouse model of human prostate cancer LNCaP.

An animal model of human prostate cancer LNCaP demonstrating high rates of spontaneous metastasis from the orthotopic site after tumor implantation would be very valuable for mechanistic and drug discovery studies. We previously developed microsurgical techniques to implant histologically intact tumor tissues orthotopically in nude mice in order to develop high metastatic mouse models of human cancer. Intact tissue of the androgen-dependent human prostate cancer cell line, LNCaP, was implanted on the ventral lateral lobes of the prostate gland by surgical orthotopic implantation (SOI) in a series of 20 nude mice. Mice were autopsied, and histopathological examination of primary tumors and relevant organs was done to identify and quantitate micrometastasis. Eighteen of 20 animals transplanted with LNCaP by SOI had tumor growth. Mean primary tumor weight in the prostate was 9.24 g at time of necropsy. Sixty-one percent of the transplanted animals had lymph node metastasis. Forty-four percent had lung metastasis. Mean survival time was 72 days, indicating a high degree of malignancy of the tumor. The extensive and widespread lung metastasis as well as lymph node metastasis following orthotopic implantation of LNCaP in nude mice and the short survival time provide a high-malignancy nude model of the LNCaP human prostate tumor.

Transcatheter arterial chemoembolization in the treatment of hepatoblastoma

Background: The prognosis of hepatoblastoma is poor unless the tumor is completely resected. Various types of chemotherapy have been developed to increase its resectability. Recently, transcatheter arterial chemoembolization (TACE) has been developed for the treatment of unresectable adult hepatoma with favorable results. The authors applied this procedure to hepatoblastoma in infants and children. Methods: TACE was performed in eight hepatoblastoma cases. After an intraarterial catheter was inserted into the main feeding artery of the tumor, injection of adriamycin or THP-adriamycin (20 to 30 mg/m 2) dispersed in lipiodol and cisplatin (40 to 60 mg/m 2) followed by embolization using Gelfoam pieces was performed. Effects of TACE were evaluated according to shrinkage of tumor mass on imaging examinations, alpha-fetoprotein (AFP) levels, and pathological findings of the surgical specimens 4 weeks after TACE. Results: A marked reduction in tumor size associated with a decrease in AFP level occurred 1 month after the treatment. Tumor shirinkage ranged from 0.9% to 45.0% with a mean value of 25.8%. AFP levels decreased by 0.2% to 11.9% with a mean level of 4.6% from initial levels. In addition, there was no marked chemotherapeutic agent-induced toxicity noted during the observation period. Resection of the tumors was performed safely after TACE in all cases. Pathological examination showed massive necrosis in the surgical specimens, and the mean percentage of necrotic area within the tumor was 71.1%. Two patients died of extensive lung metastasis 2 months and 3 years after the operation, respectively. The remaining six were doing well and free of disease at a mean follow-up period of 50 months. Conclusion: TACE is an effective, safe, and useful method for the initial treatment of hepatoblastoma.