The role of PIAS3, p-STAT3 and ALR in colorectal cancer: new translational molecular features for an old disease.

OBJECTIVE: Human colorectal cancer (CRC) is characterized by a sequence of biological events that determine its induction and progression. Gut microbiota has an important role in this multistep model of carcinogenesis, as well as constitutive activation of Signal Transducer and Activator Factors 3 (p-STAT3) and Protein Inhibitor of Activated STAT3 (PIAS3), which negatively controls STAT3. It has been reported that a liver growth factor, the Augmenter of Liver Regeneration (ALR), an anti-apoptotic, anti-metastatic factor, exerts protective/cell survival and anti-metastatic activities and has been detected highly expressed in neoplastic cells. PATIENTS AND METHODS: To evaluate, by immunohistochemistry, p-STAT3, PIAS3 and ALR expression in neoplastic human tissues from CRC patients, grouping the data in accordance with the histological alterations (G1, G2 and G3) and metastasis presence. Western blot (WB) analysis of ALR was also determined in neoplastic and surrounding tissues. Finally, cell proliferation (Ki-67) and apoptosis (Bcl-2) were determined. RESULTS: Colon cancer tissue samples showed: (1) ALR and p-STAT3 strongly over-expression in 100% of G1 tissue samples, reducing in G2 and G3 tissue samples; (2) PIAS3 immunological determination was poorly expressed in G1 tissue samples and highly expressed in the 100% of colorectal tissues from group G2 and G3. Ki-67 progressively increases with the importance of the anatomic-pathological alterations and Bcl-2 resulted higher in G3 tissue samples compared to G1 neoplastic tissues. WB data evidenced, in neoplastic tissues, compared to the tumour-surrounding tissues, ALR over-expressed in G1 neoplastic tissues and down-expressed in G3 neoplastic tissues. CONCLUSIONS: Our data demonstrate a different dynamism of the investigated factors in relation to the severity of CRC histological findings. We hypothesize that the positive expression of ALR and p-STAT3 in the neoplastic tissue samples from CRC G1 group, associated to the absence of PIAS3, could be useful marker to identify an early stage of the disease. Based on these data and on our previous studies on gut microbiota in precancerous intestinal lesions, we are confident that, after microbial priming, a cascade of molecular events is started. So, the detectable molecules acting in these initial steps should be considered for the study of CRC progression and therapy.

Orbital granular cell tumor in a patient with Churg Strauss syndrome: the importance of biopsy.

A 65-year-old woman presented with a long standing, progressive exophthalmos of the right eye. Her medical history was significant for Churg Strauss syndrome, and was treated with immunosuppressive therapy. She had undergone two previous orbital biopsies showing inflammatory reactive lymphoid hyperplasia. A diagnosis of orbital inflammation in Churg-Strauss syndrome was suspected, and the immunosuppressive therapy was increased. Because of the lack of response to therapy, a further biopsy was performed, by lateral orbitotomy approach. Biopsy of the mass revealed a granular cell tumor composed of S-100 positive cells with an acidophilic granular cytoplasm and peripheral lymphocytic infiltration. A granular cell tumor, which is very rare in the orbit, should be considered in the differential diagnosis of orbital tumors, and if suspected, an excisional biopsy must be undertaken. Typical histopathological aspect of the granular cell tumor is characterized by the presence of S-100 positive closely packed polygonal cells with a granular cytoplasm.

Hepatocellular Carcinoma Metastasis to the Orbit in a Coinfected HIV+ HBV+ Patient Previously Treated with Orthotopic Liver Transplantation: A Case Report.

Hepatocellular carcinoma rarely metastasizes to the orbit. We report a 45-year-old male, HBV+, HIV+, with a past history of a liver transplant for ELSD (end-stage liver disease) with hepatocellular carcinoma and recurrent HCC, who presented with proptosis and diplopia of the left eye. CT scans of the head revealed a large, irregular mass in the left orbit causing superior and lateral destruction of the orbital bone. Biopsy specimens of the orbital tumor showed features of metastatic foci of hepatocellular carcinoma. Only 16 other cases of HCC metastasis to the orbit have been described in literature, and this is the first case in a previously transplanted HIV+, HBV+ patient.

Airways humidification during mechanical ventilation. Effects on tracheobronchial ciliated cells morphology.

AIM: Airways humidification during mechanical ventilation (MV) can be performed by means of heat and moisture exchangers (HME). Good performance of selected hygroscopic HME was shown in terms of tracheal temperature and humidity control and low tube obstruction rates. However, few data are available on their effects on tracheobronchial ciliated cells. The purpose of this study was to evaluate the effects of 2 different HME on ciliated cell during MV. METHODS: Twenty consecutive patients undergoing elective surgery lasting <4 h were randomly assigned to be treated with Rusch (Group 1) or Mediflux (Group 2) hygroscopic HME. The morphology of tracheobronchial ciliated cells was evaluated from cytologic smears of endotracheal aspirate. Smears were prepared by using the thin-prep processor, stained using the Papanicolau method and examined in triplicate: recognizable respiratory cells were graded on a six-point scale, according to the normal appearance of cilia, cytoplasm and nucleus. RESULTS: In Group 1, 178.3+37 cells were retrieved from aspirates and , 155.6+58 in Group 2 (NS). The score was 739+241 in Group 1 and 617+329 in Group 2 (NS). Cilia and end plate were undamaged in 80+17% and 81+20% cells respectively in Group 1 and in 56+23% and 62+22% cells respectively in Group 2 (P<0.01 and <0.05). CONCLUSIONS: During MV epithelial tracheobronchial cells can be affected by the humidification device used. Our findings suggest that the 2 HME tested in the present study have a different impact on ciliated cells structure.

[Unusual presentation of metastatic osteosarcoma as a giant duodenal polyp. A case report]. / Osteosarcoma metastatico polipoide del duodeno. descrizione di un caso ad insolita presentazione.

INTRODUCTION: Osteosarcoma is a malignant bone neoplasm with an usually high metastatic potential. Besides the common metastatic sites such as lungs, bone, and pleura, metastases to unusual sites such as liver, brain and regional lymph nodes have also been reported with increasing frequency; among them, gastrointestinal metastases represent an extraordinarily rare event in the natural history of this neoplasia. MATERIALS AND METHODS: We describe a case of a 27 year old man, who was diagnosed with a grade IV osteoblastic osteosarcoma of the left tibia and submitted to 5 courses of pre-surgical chemotherapy; later he underwent tibial resection with implantation of a prosthesis, followed by 2 further courses of adjuvant chemotherapy. Five years after the patient presented with melena and acute anemia; during endoscopic examination, a large bleeding duodenal polyp was found, so a surgical resection of the gastric antrum, duodenum, head of the pancreas, main bile ducts and gallbladder was performed. The surgical specimen was formalin fixed and paraffin embedded, and sections obtained by the blocks were stained with haematoxylin-eosin; immunohistochemical and ultrastructural analysis were performed. RESULTS: Microscopically, the tumor mass showed a mostly fasciculated architecture, composed of spindle and epithelioid cells in a scarce fibromyxoid stroma, featuring large areas of coagulative necrosis and small foci of sclerohyalinosis. Tumor cells featured large vesciculous nuclei, with a few prominent nucleoli; no foci of osteoid matrix were detectable. The ultrastructural analysis revealed small calcified electron-dense depots both in the perinuclear cytoplasm and in the extracellular collagen matrix compatible with an "early osteoid formation". Due to alteration of the natural history of the tumor induced by multiagent chemotherapy, the rate of metastases of osteosarcoma to unusual sites has been increasing. We report the 9th case of a gastrointestinal metastasis of osteosarcoma reported thus far, and only the second one arising in the duodenum. Both the histological features and the immunohistochemical findings were not suggestive for osteosarcoma metastases because the tumor appeared dedifferentiated; in our case the combination of electron microscopy and clinical history played a pivotal role to establish the final diagnosis.

[Morphometric and histological evaluation of uterine leiomyomas treated with GnRH agonists or progestational agents]. / Valutazione istologica e morfometrica di leiomiomi dell'utero trattati con analoghi del GnRH o progestinici.

Both gonadotropin-releasing hormone (GnRH agonists) and progestational agents are commonly used in order to reduce the size of uterine leiomyomas before surgery. So far, little is known about the histologic changes underlying such shrinkage mechanism. Probably the conflicting data on this subject are due to the qualitative and subjective methods used by most previous reports. In this study we analyzed 42 leiomyomas from patients treated with GnRH agonists (14 different patient samples), patients treated with progestational agents (14 different patient samples) and age-matched control patients (14 different patient samples), using qualitative (light microscope analysis) and quantitative (morphometric analysis by a specific software) methods. We assessed the following parameters: areas of necrosis, areas of hyalinization, vasal density, vasal thrombi, thickness of vasal walls, size of vasal lumina, cell density, maximum nuclear diameter, maximum cytoplasmic diameter, mitotic index on each sample. The analysis showed that leiomyomas from women treated with GnRH agonist exhibited broader areas of necrosis, greater cell density, and wider vasal lumina, while those from women treated with progestational agents exhibited thicker vasal walls than the other two groups, respectively. In conclusion, our results suggest that vasal wall changes are the basis of leiomyomas shrinkage after GnRH agonist therapy.

Gastro-intestinal stromal tumor (GIST): case report.

Gastro-intestinal stromal tumors (GISTs), as currently defined, represent the largest category of primary non epithelial neoplasms of the gastrointestinal tract. They arise from mesenchymal cells located in the wall of the organ and show a remarkable variability in their differentiation pathways. For this reason there is relevant degree of confusion in their interpretation. On the basis of immunohistochemical and ultrastructural studies these neoplasms are divided into several categories: leiomyomas, schwannomas and less differentiated tumors referred as GIST. In the small bowel GIST are uncommon. Usually asymptomatic, they could be the cause of surgical emergencies like massive bleeding, obstruction, intussusception or perforation. Generally benign, an higher percentage of malignant cases are described in the small bowel. The Authors report a case of malignant GIST of the small intestine presented with bowel obstruction by ileal invagination. In this case, as usually it happens in malignant GIST, the final diagnosis was obtained by an abdominal surgical exploration.

[The Pap test in HIV-positive women]. / Il Pap test in donne HIV positive.

The aim of this work was to estimate the frequency of abnormal Papanicolau (Pap) smears in a group of HIV-infected women undergoing cervical screening. We re-examined 162 Pap smears from 118 patients infected with HIV. The patients were aged 23-55 years. A total of 108 smears (66.6%) from 80 patients were negative; 14 smears (8.6%) from 14 patients showed inflammation; 3 smears (1.8%) from 3 patients had atypical squamous cells of undetermined significance (ASCUS); 20 smears (13.5%) from 16 patients were abnormal for human papillomavirus (HPV); 13 smears (8.0%) from 9 patients revealed low-grade, squamous intraepithelial lesions; 10 smears (6.2%) from 7 patients were SIL-HG; the diagnosis of carcinoma was made in 3 cases (1.8%) and 2 smears from 2 patients were unsatisfactory. HIV-infected women have an increased rate of abnormal Pap smears for both HPV infections and cervical dysplasia. These results confirm the validity of cervical screening by Pap test.

Malignant fibrous histiocytoma of the larynx after radiotherapy for squamous cell carcinoma.

A few cases of malignant fibrous histiocytoma (MFH) of the larynx have been reported to date. All ages may be affected, but the tumor is more prevalent in the sixth and seventh decade of life. We describe a case of MFH in a 71-year-old Italian man who 8 years before underwent a right cordectomy and radiotherapy for squamous cell carcinoma. Recurrent tumor was found to be MFH. The clinico-pathological features of this tumor are presented and the possible relationship between radiotherapy and MFH discussed. The neoplasm was characterized by spindle-shaped atypical cells arranged in a diffuse storiform pattern. Mitoses were prominent, numerous, and often atypical. Immunohistochemically, neoplastic cells were strongly positive for vimentin and alpha1-antichymotrypsin but were negative for cytokeratins and S-100 protein. These findings confirmed the diagnosis and excluded possible sarcomatoid carcinoma, inflammatory pseudotumor, and a new carcinosarcoma. The risk of sarcoma after radiotherapy for squamous cell carcinoma in the larynx is very low when considering the frequent use of radiotherapy, but long follow-ups are required.

Down-regulated expression of transforming growth factor beta 1 mRNA in endometrial carcinoma.

Transforming growth factor beta1 (TGF-beta1) is a potent modulator of cell proliferation in vitro, and recent studies have demonstrated its overexpression in several different tumours; nevertheless, the molecular mechanisms of TGF-beta1 action on cell growth and differentiation have not been fully elucidated. To clarify the role of TGF-beta and its receptor in human endometrial proliferation and differentiation, TGF-beta1 expression at both the mRNA and protein levels has been evaluated by using Northern blotting and immunohistochemistry, in both normal (atrophic, proliferative and secretory) and neoplastic (adenocarcinoma) endometrial samples. This study demonstrates that TGF-beta1 mRNA expression is dramatically reduced in endometrial carcinomas with respect to non-neoplastic tissues, whereas the immunohistochemical expression of TGF-beta1 is enhanced in the epithelial component of endometrial carcinomas compared with non-neoplastic tissues. These data suggest that TGF-beta1 acts as a paracrine regulator of endometrial cell proliferation and that it may contribute to the carcinogenic mechanisms of endometrial carcinoma.