the metabolomic scent of cancer disease progression in soft tissue sarcoma a case report

Background: The purpose of this case report is to describe the potential that metabolomics breath analysis may have in cancer disease monitoring. The advances in mass spectrometry instrumentation allow the accurate real-time analysis of volatile metabolites exhaled in the breath. The application of such non-invasive devices may provide innovative and complementary monitoring of the physio-pathological conditions of cancer patients. Case presentation: A 59-year-old Caucasian woman with spindle cell malignant mesenchymal sarcoma of the presacral region started a first-line therapy with non-pegylated liposomal doxorubicin and ifosfamide associated with pelvic radiant treatment. After two cycles of chemotherapy plus radiotherapy, a significant pulmonary disease progression was reported. Thus, a second-line therapy with trabectedin was administered. However, after only two cycles of treatment a re-staging computed tomography scan reported further cancer disease progression of the target pulmonary lesions as well as occurrence of new satellite bilateral nodules. Real-time analysis of breath exhaled volatile organic compounds, performed by select ion flow tube mass spectrometry (SIFT-MS) during the follow-up of the patient, showed a specific metabolic pattern not observed in the breath of other soft tissue sarcoma patients who achieved clinical benefit from the treatments. Conclusions: This case report revealed the importance of the non-invasive real-time volatile organic compounds breath analysis to distinguish individual specific chemo-resistance phenotypes among soft tissue sarcoma patients. Such observation seems to suggest that breath metabolomics may be particularly useful for monitoring cancer disease progression in soft tissue sarcoma patients where only cost-effective diagnostic tools, such as positron emission tomography and computed tomography, are available

Association of the germline BRCA2 missense variation Glu2663Lys with high sensitivity to trabectedin-based treatment in soft tissue sarcoma

We report an interesting clinical case of a patient carrying a specific BRCA2 germline variant affected by bone and hepatic metastases from a high grade uterine stromal sarcoma who obtained a complete metabolic response after only 3 cycles of trabectedin treatment (1.5mg/m(2) given intravenously over 24hours every 21days). Molecular investigations linked this outstanding positive pharmacological response with the loss of heterozygosity (LOH) of the mutated BRCA2 gene. These data support the hypothesis that the response to trabectedin may be positively conditioned by the different DNA repair defects present in the neoplasm and that BRCAness tumor genotype is important in determining the efficacy of trabectedin-based chemotherapy

Weekly paclitaxel in heavily pretreated ovarian cancer patients: does this treatment still provide further advantages?

Objective: To evaluate the disease control rate (DCR) in heavily pretreated and relapsed ovarian cancer patients re-challenged with a weekly paclitaxel schedule and to establish whether a correlation between dose intensity, progression-free interval (PFI) and overall survival (OS) exists. Methods: Retrospective data were collected from 30 heavily pretreated metastatic ovarian cancer patients who received 80 mg/m(2)/week paclitaxel regimen. Results: The treatment was well tolerated and showed a DCR in 70% of the patients, with only one case of grade 3 hematological toxicity. One patient (3%) showed a complete response, 15 patients (50%) a partial response and five patients (17%) a stabilization of their disease. The regimen was mostly used as a fourth-line chemotherapy (range 2-7). The median dose intensity in responding patients was 57.5 mg/m(2)/week and in those with progressive disease 49.7 mg/m(2)/week. (p = 0.20). PFI and OS were increased in the responder patient groups with a log-rank test of 25.64 (p &lt; 0.001) and 15.10 (p = 0.0001), respectively. Conclusions: Weekly administration of paclitaxel was active and well tolerated as a salvage therapy for heavily pretreated ovarian cancer patients.</br

P16 immunostaining and HPV testing in histological specimens from the uterine cervix

Background: The cellular tumor suppressor protein p16INK4a (p16) has been identified as a biomarker for transforming human papilloma virus (HPV) infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell cycle and cell proliferation by inhibiting cell cycle G1 progression. Purpose of the study: To confirm the role of p16 as biomarker for transforming HPV infections and possible clinical applications in histological samples from the uterine cervix. Materials and Methods: The subject of this study included 56 biopsies of the cervical canal collected from January 2012 to September 2012 in the Institute of Pathology of the University of Sassari. The search for HPV immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while for the detection of p16 was used CINtecTM p16 (INK4a) histology kit. Results: In 56 biopsies performed in women aged between 23 and 69 years, the authors highlighted, by histological analysis, 24 cases of low-grade squamous intraepithelial lesion (LSIL) - cervical intraepithelial neoplasia (CIN1) and 31 cases of high-grade squamous intraepithelial lesion (HSIL) - CIN2/3); 15 CIN2, 14 CIN3, and two cervical squamous cell carcinoma in situ (SCIS). One case was an infiltrating squamous cell carcinoma (ISC). In 24 CIN1, there was a 16.67% positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2 the percentage of positivity for p16 was considerably increased (73.33%), unlike the search for HPV which had a positivity rate of 20%. Finally, in 14 cases of CIN3, and in three carcinomas, the positivity for p16 was equal to 100%, however the search for HPV positivity was between 0% and 7.14%. Conclusions: These results demonstrated that p16 was a highly sensitive marker of cervical dysplasia. The authors have shown that p16 overexpression increased with the severity of cytological abnormalities and that had a greater ability to identify the viral infection compared to the classical immunohistochemical staining for HPV

A new mutation of the CDH1 gene in a patient with an aggressive signet-ring cell carcinoma of the stomach

Germline mutations in CDH1, the gene coding for the E-cadherin adhesion protein, are known to cause hereditary diffuse gastric cancer. We identified a new truncating germline mutation (p.Asp538Thrfs*19) in exon 11 of the CDH1 gene in a 41-year-old male with a diffuse gastric cancer. Although he had no parental history of gastric cancer, the co-segregation study in the family detected the same mutation in his healthy 31-year-old brother. The mutation affects one of the extracellular repeat (CAD repeats) domains which is essential for the homophilic binding specificity that directs E-cadherin to bind with itself each others. In this case, immunohistochemical analysis showed no expression of E-cadherin in the tumor sample and was a useful prescreening tool to genetic testing. This finding was associated with a poor response to trastuzumab-based treatment

Fulminant liver failure in a patient affected by polycystic liver disease and liver metastases from breast carcinoma

Background. Polycystic liver disease (PLD) is a rare, congenital, benign condition characterized by the presence of multiple bile-duct-derived epithelial cysts in the liver parenchyma. The disease is usually asymptomatic, but cyst growth can result in complications such as ascites, esophageal varices, jaundice and hepatic failure. The exact mechanism leading to cyst growth is unclear, but estrogenic stimulation and paracrine action of vascular endothelial growth factor (VEGF) are thought to play a role in the growth of cyst epithelium. Case report. We report a case of acute liver failure in a young woman with PLD and liver metastases from breast carcinoma. Results. No data are available in the literature about metastatic liver involvement in PLD patients affected by breast cancer. The prognosis of patients with liver metastases is generally poor but fulminant liver failure is a very rare occurrence. Estrogen stimulation seems to be a risk factor for breast cancer and severe PLD. In the reported case, the presence of either the cysts or the metastatic lesions may have resulted in more extensive liver damage. Conclusions. The adoption of drugs selected in relation to their hepatic toxicity together with careful monitoring of liver function is warranted in the management of breast cancer patients affected by PLD, in order to reduce the risk of liver failure

Small cell lung cancer in a young patient with osteopetrosis

BACKGROUND: Osteopetrosis or Albers-Schönberg's disease is a heterogeneous group of rare hereditary troubles of the bone characterized by bone sclerosis due to an alteration of the bone reabsorption mediated by osteoclasts. The defect in the osteoclastic activity is responsible for complete or partial medullary cavities occlusion, with consequent reduced hemopoiesis, and for the excessive fragility of the affected bone segments. CASE REPORT: We reported the case of a young man of 31 years affected by osteopetrosis in which a small cell lung cancer developed. RESULTS: Small cell lung cancer is a particularly rare neoplasm in the young, and even though it is highly sensitive to chemotherapeutic treatment its prognosis remains poor. The greatest clinical problem connected with chemotherapeutic treatment of patients affected by osteopetrosis is the variability of the reduction of their bone marrow reserve, which could expose them to an excessive hematological toxicity caused by the therapy. CONCLUSIONS: The adoption of suitable prophylactic measures, such as the use of growth factors and drugs selected in relation to their toxicity or given in reduced doses, should be appropriately considered in these subjects.</br