PubMed Health⌕ Search

Biomedical subjects

Piergiuseppe Colombo

Publications and source records attributed to Piergiuseppe Colombo.

16 recordsLinked to original sources

Administration of temozolomide during and after radiotherapy for newly diagnosed high-grade gliomas excluding glioblastoma multiforme.

Primary brain high-grade gliomas, excluding glioblastoma are rare and heterogeneous tumors, showing different characteristic mutations and a better prognosis than glioblastomas. The addition of chemotherapy to the radiotherapy in the newly diagnosed disease has not been established yet. We treated 9 patients with newly diagnosed tumors with temozolomide at 75 mg/m2 for 7 days a week during standard radiotherapy, followed by six cycles at 200 mg/m2 on days 1-5 every 28 days. Fluorescence in situ hybridization for the 1 p/19 q loss was performed in seven out of the 9 patients. With a median follow-up of 15 months (range, 8-50), eight patients are alive and one died from disease progression. Four patients had disease progression at 7, 15, 14 and 13 months from the diagnosis. The 1 p/19 q loss was found in 5 patients; three have no evidence of disease, one had partial disease remission and one disease progression. Toxicities included one discitis requiring treatment withdrawal and specific antibiotic therapy, and one transient grade 3 psoriasiform reaction. Based on this small series of patients, the addition of temozolomide to radiotherapy may be recommended.

Antineoplastic Agents↗

Early cytotoxic effects of ochratoxin A in rat liver: a morphological, biochemical and molecular study.

We characterized the overall early effect of chronic ochratoxin A (OTA) treatment on rat liver, analyzing different aspects related to: (i) fibrosis, by measuring collagen content and turnover, and alpha-smooth muscle actin (alphaSMA); (ii) oxidative stress and stress response, by analyzing protein carbonylation, superoxide dismutase (SOD) and heat shock protein (HSP70) gene expression; (iii) the possible tumor promoter effect, evaluating cadherin and connexin (CX) mRNA levels. Light microscopy analysis showed no histological differences in OTA-treated and control (CT) rats. Collagen content, determined by computer analysis of Sirius red-stained liver sections, was similar in both groups. In liver homogenates COL-I, COL-III, TIMP-1 and TGF-beta1 mRNA levels and alphaSMA were unaffected by OTA. Matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 protein levels were also similar in the two groups. Protein carbonylation, a marker of severe oxidative stress, was not evident in the homogenates of OTA-treated livers; superoxide dismutase (SOD) mRNA tended to be lower and HSP70 was strongly down-regulated. OTA reduced E-cadherin and DSC-2 transcription, and down-regulated liver CX26, CX32 and CX43. In conclusion, these in vivo results show that OTA-induced liver injury involves a reduction in the ability to counterbalance oxidative stress, maybe leading to altered gap junction intercellular communication and loss of cell adhesion and polarity. This suggests that mild oxidative damage might be a key factor, in combination with other cytotoxic effects, in triggering the promotion of liver tumors after exposure to OTA.

Animals↗

Sperm protein 17 is expressed in human nervous system tumours.

BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. METHODS: The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma). RESULTS: A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. CONCLUSION: The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells.

Aged↗

Spinal decompression and vertebroplasty in Paget's disease of the spine.

Paget's disease is an osteometabolic disorder affecting in particular long bones. The spine is the second most commonly involved site in Paget's disease. This pathology can cause low back pain, spinal stenosis, myeloradiculopathy, and vertebral collapse. Medical therapy is the first choice for the treatment of Paget's disease of the spine; in case of failure, surgery remains a valid option. In the present article, we report a case of a patient with leg disability due to myelopathy caused by spinal Paget's disease treated with spinal decompression and vertebroplasty. To our knowledge, this is the first case report in which these procedures have been performed together in the same operation to treat spinal pathologies due to Paget's disease.

Aged↗

Single small focus of prostate adenocarcinoma (< or = 1 mm and too small for grading) and clinical significant disease after radical prostatectomy.

OBJECTIVES: To determine whether a clinical significant adenocarcinoma of the cinoma (defined as a lesion < or =1 mm. and too small for grading) at needle biopsy, even repeated, and through prostate specific antigen (PSA), PSA density (PSAD) and free-to-total PSA ratio (f/t ratio). METHODS: Retrospectively 79/1610 consecutive patients undergoing prostatic needle biopsies presented one small focus of prostatic adenocarcinoma < or =1 mm and too small for grading. All patients underwent PSA, PSAD and f/t ratio to evaluate positive predictive value for clinically significant disease. All patients were submitted to radical retropubic prostatectomy (RRP) and were divided into three groups: group A (28/79 patients, 35.4%) submitted to RRP after diagnosis of just one small focus of adenocarcinoma at first biopsy; group B (26/79 patients, 32.9%) submitted to RRP after two successive diagnoses of small focus of adenocarcinoma; group C (25/79 patients, 31.6%) submitted to RRP after diagnosis of adenocarcinoma larger than 1 mm at successive biopsy in which Gleason score had been applied. RESULTS: The three groups resulted comparable for age, PSA, f/t ratio and PSAD. Clinically significant disease was found in 48 of 79 patients (60.7%); 16 patients of group A (33.3%), 15 patients of group B (31.2%) and 17 patients of group C (35.4%) respectively. Finally, PSA, f/t ratio, and PSAD showed no predictive value neither globally nor in the single groups. CONCLUSIONS: No selective criteria with consolidated predictive values emerge from our study and this is in agreement with data in the literature, where the risk to find no significant clinical disease is 9-48% approximately. The aim of this retrospective study is to analyze the correlation between a single small focus of adenocarcinoma by prostatic biopsy, even repeated, and the clinical significant disease on the following radical retropubic prostatectomy. Furthermore, we verified whether some preoperative parameters could be helpful to identify the subgroups of patients which could need a more or less aggressive and/or timely treatment. Our data show that 30-40% of patients did not harbor a clinically significant disease at the following RRP. Furthermore, the assumed predictive value of repeat biopsies has not been confirmed in these patients and no other preoperative predictive values can be helpful.

Adenocarcinoma↗

Oral ulcer as an exclusive sign of gastric cancer: report of a rare case.

BACKGROUND: The oral cavity is a rare but occasional target for metastases, which may masquerade as various benign and inflammatory lesions, and sometimes also be asymptomatic. Oral metastatic lesions have been described in various cancers, particularly lung, breast and kidney carcinoma. CASE PRESENTATION: We here describe an uncommon case of a hard palate mucosa and gingival metastasis from gastric carcinoma that was originally diagnosed as a periodontal disease. Histopathological examination of a biopsy of the lesion revealed a signet-ring cell carcinoma, and a subsequent biopsy of an ulcerated stomach lesion showed a poorly differentiated gastric carcinoma. The patient underwent gastric resection but died of heart failure on the tenth postoperative day; a post-mortem examination revealed a residual bilateral ovarian infiltration by gastric carcinoma (Krukenberg's tumor). CONCLUSION: An occult carcinoma of the stomach may rarely metastasise to the oral cavity even as a first and exclusive manifestation; it is important to bear this possibility in mind because such conditions may mimic a benign disease.

Biopsy↗

Localized intra-abdominal fibromatosis of the small bowel mimicking a gastrointestinal stromal tumor: a case report.

Intra-abdominal fibromatosis (IAF) is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor (GIST). This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor STI571 (imatinib mesylate) has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.

Diagnosis, Differential↗

Quantitative evaluation and modeling of two-dimensional neovascular network complexity: the surface fractal dimension.

BACKGROUND: Modeling the complex development and growth of tumor angiogenesis using mathematics and biological data is a burgeoning area of cancer research. Architectural complexity is the main feature of every anatomical system, including organs, tissues, cells and sub-cellular entities. The vascular system is a complex network whose geometrical characteristics cannot be properly defined using the principles of Euclidean geometry, which is only capable of interpreting regular and smooth objects that are almost impossible to find in Nature. However, fractal geometry is a more powerful means of quantifying the spatial complexity of real objects. METHODS: This paper introduces the surface fractal dimension (Ds) as a numerical index of the two-dimensional (2-D) geometrical complexity of tumor vascular networks, and their behavior during computer-simulated changes in vessel density and distribution. RESULTS: We show that Ds significantly depends on the number of vessels and their pattern of distribution. This demonstrates that the quantitative evaluation of the 2-D geometrical complexity of tumor vascular systems can be useful not only to measure its complex architecture, but also to model its development and growth. CONCLUSIONS: Studying the fractal properties of neovascularity induces reflections upon the real significance of the complex form of branched anatomical structures, in an attempt to define more appropriate methods of describing them quantitatively. This knowledge can be used to predict the aggressiveness of malignant tumors and design compounds that can halt the process of angiogenesis and influence tumor growth.

Computer Simulation↗

Calvarial metastases as clinical presentation of renal cell carcinoma: report of two cases and review of the literature.

Calvarium is a frequent target site of involvement for common neoplasms. Some cases of calvarial metastases have been reported in literature as secondary lesions from renal cell carcinoma (RCC), but only five cases have been described concerning calvarial mass as the first clinical presentation of this kind of tumor. In this report, we discuss the clinical aspects of two further cases we observed, in which the renal cell carcinoma was found thanks to the histological examination of a calvarial mass after surgery. We also briefly review the literature.

Aged↗

Immunohistochemical profile and c-kit mutations in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are low-grade sarcomas arising from the interstitial cells of Cajal, harboring mutation of c-kit. We investigated the morphological, immunohistochemical, and molecular profile of 55 GISTs to establish the prevalence of mutations, their clinical significance, and diagnostic utility. c-kit mutations were investigated by evaluating the entire coding sequence of the gene with non-radioisotopic PCR-SSCP, and characterized with fluorescent cycle sequencing. Mutations were detected in 39 tumors (71%), the majority (67%) involving exon 11. Two tumors showed exon 9 mutations (one tumor located in the small intestine and one in the stomach), whereas two cases showed a polymorphism at the splicing site of exon/intron 1 present in healthy blood donors with a 3% frequency. CD117 was expressed in 53 tumors (96%); CD34 was positive in 42 cases (76%); 42 cases (76%) expressed both CD117 and CD34. c-kit mutations were similarly distributed in stromal tumors at low risk of aggressive behavior (78%), intermediate risk (66%), and high risk (71%). Fifteen tumors expressing CD117 showed wild-type kit gene, and on histological grounds, they were equally distributed among epithelioid and spindle cell morphology. One case neither expressed CD117 nor did it show c-kit mutation. Data suggest that both immunohistochemical and molecular evaluation may be useful in tumors likely to be classified as GISTs; molecular analysis appears valuable to support the diagnosis and to identify cases that can benefit from recent novel therapeutic tools.

Adolescent↗

Unusual cytogenetic findings in a synovial sarcoma arising in the paranasal sinuses.

A fresh specimen from an intracranial tumor, which was histopatologically classified as a synovial sarcoma, was investigated cytogenetically. The direct method failed to give any information due to a lack of mitotic cells after treatment with 70% acetic acid, whereas 6-day cultures showed a 45,XY,del(6q),-10 karyotype. The histologic evaluation was consistent with a synovial sarcoma, which is well characterized from a cytogenetic perspective and involves a t(X;18)(p11;q11) in more than 95% of cases. Reverse-transcription polymerase chain reaction analysis did not show the presence of the SYT-SSX chimeric gene.

Adult↗

Acinar cell cystadenocarcinoma of the pancreas: report of rare case and review of the literature.

Most exocrine pancreatic tumors are of ductal origin, whereas acinar cell adenocarcinomas are unusual (1% to 2% of all exocrine pancreatic neoplasms). We recently found a cystic adenocarcinoma of the pancreatic body whose cells had the characteristics of acinar cells, which we term acinar cell cystadenocarcinoma. Macroscopically, this tumor consists of a large multilocular cystic mass with a pseudocapsule and a spongy appearance on the cut surface. Microscopically, the cysts are lined by a single layer of cuboid/columnar cells. The cytoplasm has the characteristics of acinar cells, with eosinophilic granules in the apex and prominent nucleoli. Immunohistochemically, the cells express alpha1-antitrypsin, trypsin, and lipase in their cytoplasm, thus confirming the acinar origin of the tumor. A review of the literature revealed only 5 other cases of this tumor reported since its first description in 1981. Follow-up data are available for 4 of these; all of the affected patients had metastases at presentation or a few months later, and 2 died of the disease, at 13 and 37 months after diagnosis. Although this variant of adenocarcinoma of the pancreas is not prognostically different from the classic solid type (few patients survive more than 5 years), we believe that it is important because of its extreme rarity.

Aged↗

Sperm protein 17 is expressed in human somatic ciliated epithelia.

It was once believed that sperm protein 17 (Sp17) was expressed exclusively in the testis and that its sole function was to bind to the oocyte during fertilization. However, immunohistochemistry of the human respiratory airways and reproductive systems show that it is abundant in ciliated cells but not in human cells with stereocilia and microvilli. The high degree of sequence conservation throughout its N-terminal half, and the presence of an A-kinase anchoring protein (AKAP)-binding motif within this region, suggest that Sp17 plays a regulatory role in a PKA-independent AKAP complex in both male germinal and ciliated somatic cells.

Antigens, Surface↗

Aspergillus left ventricular assist device endocarditis.

Left ventricular assist device (LVAD) support is an established therapy for patients with end-stage heart failure as a bridge to transplant; its usage as an alternative for those patients not eligible for transplant is not an established therapy yet. A 68-year-old male had a Thoratec-Heartmate LVAD implanted as destination therapy. After an uneventful (apart from early fever) recovery in the intensive care unit, the patient developed an intractable high temperature, and generalized sepsis and died 21 days following implant. The white cell blood count never exceeded the guard limits, and the patient succumbed with severe LVAD valve malfunction. At post-mortem examination friable material consisting of fungal hyphae was found on the inflow and outflow valves. According to published clinical trials, infection accounts for more than 40% of mortality in LVAD supported patients. Fungal LVAD endocarditis is a particularly deadly disease. Successful management requires a high level of suspicion and timely institution of antifungal therapy to control the infection. This has led some authors to recommend empiric antifungal therapy in LVAD recipients with culture-negative sepsis unresponsive to broad-spectrum antibiotics.

Aged↗