In vitro toxicity evaluation of Ti(4+)-stabilized γ-Bi2O3 sillenites.

We report results regarding the in vitro toxicology of γ-Bi2O3 represented by its isomorphous phase Bi12TiO20 (γ-BTO). The γ-BTO microparticles were synthesized by two methods: coprecipitation from a bismuth nitrate-tetrabutyl titanate solution and solid state reaction of Bi2O3 and TiO2 oxides. The structural and morphological characteristics of the obtained materials were determined using X-ray diffraction (XRD), selected area electron diffraction (SAED), transmission (TEM) and scanning (SEM) electron microscopy. The elemental composition was investigated using energy dispersive spectrometry (EDS). The cytotoxicity and oxidative/nitrosative stress (intracellular reactive oxygen species (ROS) and nitric oxide (NO) release) induced by the studied microparticles in HepG2, SH-SY5Y and 3T3-L1 cell cultures were determined using the MTT, DCF-DA (2',7'-dichlorfluorescein-diacetate) and Griess methods respectively. Depending on the cell type and γ-BTO concentration, results showed only weak cytotoxic effects after 24h of γ-BTO exposure and cell proliferation effects for longer treatment times. Only reduced NO release increases (corresponding to high γ-BTO concentrations) were detected in case of SH-SY5Y and 3T3-L1 cells. The intracellular ROS production (higher for HepG2 cells) appeared inversely proportional to the γ-BTO concentration. The obtained results indicated a promising in vitro biocompatibility of γ-BTO and encourage further studies regarding its potential for biomedical applications.

Therapeutic approach in locally advanced colon tumours (T4NxM0) - clinical experience in 18 consecutive cases.

INTRODUCTION: Surgery holds a central seat in the treatment of colon cancer, its objective being R0 resection. Chemotherapy and an appropriate oncological follow-up complete the treatment. AIM: To establish an adequate therapeutic conduct in patients with advanced colon tumours, with no hepatic metastases. MATERIAL AND METHOD: retrospective study on a group of 150 patients with colon neoplasm treated in the First Surgery Clinic of the Bucharest Oncology Institute in Bucharest,between 01 01 2008 -01 03 2013. RESULTS: 18 patients presented locally extended colon tumours which required multivisceral resections. Patients with hepatic metastases were excluded from the study. The most frequently affected organs were: the small bowel and the internal genital organs, followed by the urinary bladder, spleen, duodenum and diaphragm muscle. Patients were oncologically followed-up according to current protocols and submitted to chemotherapy.When a maximum response was reached in R2 patients or when recurrence occurred in R0 and R1 patients, surgical intervention was required. When necessary, the operation was performed by multidisciplinary teams. 5 patients died due to local recurrence, disease progression, metastatic disease, and also due to comorbidities. CONCLUSION: Treatment applied by oncological committees and multidisciplinary surgical teams, along with correct oncological follow-up and surgical reintervention when maximum response to chemotherapy was reached in R2 or when recurrences occurred in R0 and R1 patients represents the adequate therapeutic conduct in patients with locally advanced colon tumours.

Risk stratification and consecutive prognosis progresses in childhood Wilms tumors. Two cases report.

BACKGROUND: Even if Wilms' tumour is the commonest primary malignant neoplasia in children, it maintained a continuous interest due to actual therapeutic successes contrasting with the customary delayed diagnosis, malignancy and specific risk factors. PATIENTS AND METHODS: Two recent illustrative cases from our clinic are presented. The first one - a little girl of 22 months with repeated admissions for habitual constipation and psychomental disturbances revealed at abdominal ultrasonography a hypo-echoic mass at the superior pole of the right kidney. CT confirmed the presence of a solid homogeneous mass of 23/25 mm without node or distant metastases, suggestive for Wilms' tumour. Conforming to SIOP protocol she received chemotherapy and after 4 weeks a superior polar nephrectomy was performed. Pathology confirmed the diagnosis of triphasic nephroblastoma of intermediary risk. Postoperative chemotherapy according to the protocol SIOP assured the cure with a disease free period of 23 months. The second case - also a girl, of 3 years, is admitted for constipation, pain in the left flank and mental retard (QI=40). Ultrasonography determined a huge mass (Ø~6 cm) situated at the superior pole of the left kidney. CT attested a nonhomogeneous, encapsulated tumour image of 6.2/5.4/7.2 cm in large posterolateral contact with the renal parenchyma out of which it appears to be developed. The diagnosis of WT is strongly suggested and after chemotherapy a radical left nephrectomy with initial vessels ligature was performed. Pathology: stage IIb nephroblastoma with focal epithelial anaplasia. After surgery she continued the chemotherapy (HR regime), was cured and excepting a medullar aplasia is in a good health after 24 months. DISCUSSIONS: Our both cases were girls under 3 years, presenting nonspecific features: constipation and psychic troubles, the tumour being incidentally discovered by the abdominal ultrasonography. CT established the diagnosis. Conventional chemotherapy framing adapted to the tumour's stage and surgery conducted to a stable cure of about two years in both cases. CONCLUSIONS: Conforming to the SIOP protocols preoperative chemotherapy was applicable, well-tolerated and efficacious for two recent cases presented in our clinic, determining the shrinkage of tumour volume and stage and consecutive reduction of the surgical risks.

A primary hydatid cyst in the abdominal wall -- case report.

INTRODUCTION: A solitary primary hydatid cyst in the abdominal wall is an exceptional entity, even in countries where the Echinococcus infection has a high rate, being considered an endemic disease. CASE PRESENTATION: We report a case of a 70-year-old Caucasian man who presented to our clinic with a slow-growing painless parietal mass in the abdominal wall, right flank area. The diagnosis of cystic mass was established at the ultrasound exam. There were no findings that could describe a hydatic cyst. The punction at the surgical intervention revealed a "clear, stone liquid like"; due to the high risk of major injury of the abdominal wall, we performed partial resection of the outer cystic wall, proligerous membrane removal and drainage. The patient had an uneventful post-operative recovery. The histopathology confirmed the suspected diagnosis. CONCLUSION: Hydatid cyst should be considered in the differential diagnosis of every abdominal intraparietal cystic mass, especially in regions where the disease is endemic. The best treatment is the total excision of the cyst preserving an intact wall (complete cystectomy). Otherwise, removing the proligerous membrane with partial pericyst's resection (partial pericystectomy) and drainage should be considered.

Evaluating the treatment of metastatic colorectal cancer with monoclonal antibodies.

The ability to tailor biologic therapy based on the status of tumor biomarkers and monoclonal antibodies has become very important in the last years. The role of tumor biomarkers in treating colorectal cancer, specifically the K-RAS gene, was identified. K-RAS had a higher interest after Lievre and colleagues reported at the 2008 American Society of Clinical Oncology (ASCO) meeting, their analysis of K-RAS mutations in tumors from patients who did not appear to benefit from cetuximab therapy, providing additional data involving K-RAS mutant tumors and their lack of response to cetuximab, as part of first-line therapy for metastatic colorectal cancer. Furthermore, other trials evaluated the K-RAS status and the first-line treatment of metastatic colorectal cancer, the treatment of refractory metastatic cancer and dual-antibody therapy in the first-line treatment of colorectal cancer. Patients with mutant K-RAS colorectal tumors have no benefit from cetuximab, no matter the type of chemotherapy regimen.

Carcinogenicity of estrogens in human breast epithelial cells.

Epidemiological and clinical evidences indicate that breast cancer risk is associated with prolonged ovarian function that results in elevated circulating levels of steroid hormones. Principal among these is estrogen, which is associated with two important risk factors, early onset of menarche and late menopause. However, up to now there is no direct experimental evidence that estrogens are responsible of the initiation of human breast cancer. We postulate that if estrogens are causative agents of this disease, they should elicit in human breast epithelial cells (HBEC) genomic alterations similar to those exhibited by human breast cancers, such as DNA amplification and loss of genetic material representing tumor suppressor genes. These effects could result from binding of the hormone to its nuclear receptors (ER) or from its metabolic activation to reactive metabolites. This hypothesis was tested by treating with the natural estrogen 17beta-estradiol (E2) and the synthetic steroid diethylstilbestrol (DES) MCF-10F cells, a HBEC line that is negative for ER. Cells treated with the chemical carcinogen benzo (a) pyrene (BP) served as a positive control of cell transformation. BP-, E2-, and DES-treated MCF-10F cells showed increases in survival efficiency and colony efficiency in agar methocel, and loss of ductulogenic capacity in collagen gel. The largest colonies were formed by BP-treated cells, becoming progressively smaller in DES- and E2-treated cells. The loss of ductulogenic capacity was maximal in BP-, and less prominent in E2- and DES-treated cells. Genomic analysis revealed that E2- and DES-treated cells exhibited loss of heterozygosity in chromosomes 3 and 11, at 3p21, 3p21-21.2, 3p21.1-14.2, and 3p14.2 14.1, and at 11q23.3 and 11q23.1-25 regions, respectively. It is noteworthy that these loci are also affected in breast lesions, such as ductal hyperplasia, carcinoma in situ, and invasive carcinoma. Our data are the first ones to demonstrate that estrogens induce in HBEC phenotypic changes indicative of cell transformation and that those changes are associated with significant genomic alterations that might unravel new pathways in the initiation of breast cancer.

[Case of cystic metastasis of the liver]. / Un caz de metastaze chistice hepatice.

The report is about a patient clinic of Iassy from oncologic clinic. He had pain in the right, back and inferior hypocondrium, with irradiation, vomitings, pain less (7 kg in 2 months), weekness. The echography shows three years ago, hepatic cysts (the patient refused the admitted in hospital). Computed tomographic (CT) exam made in jan. 1996 shows three cystic hepatic tumors (2 in right and 1 in left lobes). The CT function revealed sterile biliohematic liquid. The laparotomy made the sharp diagnosis--cephalic pancreatic tumor with cystic metastatic hepatic tumors. The surgical treatment was partial resection of pancreatic tumor and drainage of hepatic cysts, with good postoperator evolution. The intraoperative histological exam found the same kind of malignant tumor in the pancreas and liver. We present the case for his rarity.

[Morphological study of osteosarcomas in children]. / Studiu morfologic privind osteosarcoamele la copil.

Osteosarcoma is the most frequent primary osteal tumor in children. Our study evaluates morphological aspects of osteosarcomas during last 20 years. We present the results of study that includes 32 cases of classical osteosarcomas that had been diagnosed and treated at the "Sf. Maria" Hospital from Iasi (Romania). The diagnosis is based on usually histopathological methods applied to bioptic and surgical exeresis pieces. Male sex is most involved (56%). Patients' age is between 12-15 years in 68% of total cases. In 50% cases the tumour was localized in distal femoral metaphysis. Histological forms were: osteoblastic (66%), chondroblastic (18%), fibroblastic (16%). Enneking's staging was: II A (6.25%), II B (81.25%), and III (12.5%). Metastasis appeared in 75% cases' evolution. Concluding, 25% of studied patients had a favourable evolution during a 5 years period. Survival rate at 2 years was 39%.

[Laparoscopic cholecystectomy in non-lithiasis cholecystopathies]. / Colecistectomia laparoscopica în colecistopatiile nelitiazice.

We made a study in 1st Surgery Clinic of Iassy between March 93--November 98, with 2246 laparoscopic cholecystectomies. The reason was to define the place and role of laparoscopy in non-lithiasis cholecystopathies (81 cases). In the same period were operated classically 888 calculous cholecystitis and 38 non-lithiasis cholecystitis. The laparoscopy has a major role in diagnosis to the patients with many abdominal symptoms. We discovered pericholecystic adherences, hepatic cirrhosis, acute appendicitis, etc. Sometimes, the laparoscopy was made for "second look" after surgical treatment for neoplasia, the metastasis diagnosis, for tumors visible echographically. In many situations the laparoscopic cholecystectomy may be considered like a preventive operation. The easy postoperative evolution is an argument to enlarge the indication for laparoscopic cholecystectomy in alithiasis cholecystitis.

[Association between phakomatosis and neoplasia in children pathology. IV Pediatric Clinic experience]. / Asocierea între facomatoze neurocristopatice si neoplazii în patologia copilului. Experienta clinicii pediatrie IV.

The risk to developing a neoplasm is increased when associated to a patient phakomatosis (Recklinghausen neurofibromatosis, Bourneville's tuberous sclerosis). We analysed 6 cases with phakomatosis and tumours, admitted in the Department of Oncopediatry, between 1993-1998; five of these children had neurofibromatosis and one Bourneville's disease. The associated tumours were hematologic malignancies (juvenile myeloid chronic leukemia) and solid tumors (rhabdomyosarcoma, hepatic carcinoma, CNS tumour, NHL optic glioma). The diagnosis was confirmed by microscopic examination of the bioptic material in all cases. Tumoral staging was performed by clinics, biology and imagistic investigations. All cases had extensive and aggressive tumours at the moment of diagnosis, We noticed a poor response and an early relapse after chemotherapy. A special follow-up and a different management has to be established for the patients with phakomatosis, in order to have a good oncological prophylaxis.

Functional roles of chromosomes 11 and 17 in the transformation of human breast epithelial cells in vitro.

Genomic alterations in primary breast cancer play a role in the initiation and progression of the disease. We have analyzed the molecular events involved in the initiation and progression of the neoplastic process in an in vitro experimental system. Immortalization of human breast epithelial cells (HBEC) is associated with 3:9 translocation, p53 mutation and microsatellite instability (MSI) of chromosomes 11p13, and 17p. BP1-E cells, derived from the immortalized MCF-10F cells transformed by the carcinogen benzo(a)pyrene (BP), express in vitro growth advantage, anchorage independence, enhanced chemoinvasiveness, loss of ductulogenic capabilities and tumorigenesis in a heterologous host. This neoplastic progression is also associated with mutations and/or amplification of c-H-ras, int-2, c-neu, c-myc and MDM2, MSI at 11q25 and 13q12-q13 and loss of heterozygosity at 17p. In order to test whether chromosomes 11 or 17 play a functional role in the phenotypic expression of transformation of BP1E cells, we utilized microcell-mediated chromosome transfer (MMCT) technique for inserting the corresponding normal chromosomes to these transformed cells. BP1E cells were transfected with PsV2neo plasmid and fused with microcells obtained from the mouse cell line A9, containing a normal chromosome 11 or 17 (A9-11neo and A9-17neo cells, selected in G418 and cloned. Sixteen primary microcell hybrids from each chromosome transfer, designated BP1E-11neo and BP1E-17neo survived selection in G-418 containing medium. A single clone from each group, BP1E-11neo #145 and BP1E-17neo D100, survived subcloning and were utilized for a detailed panel of analyses. The presence of a donor chromosome was confirmed by dual color fluorescence in situ hybridization (FISH), southern blot analysis of the marker vector pSV2neo, and microsatellite polymorphism analysis. The transfer of the normal chromosomes 11 and 17 resulted in a 50% and 90% inhibition of cell growth respectively, and reduced both colony efficiency and colony size. Telomerase activity was significantly reduced only by chromosome 17 insertion, providing a possible explanation for the more significant senescence observed in BP1E-17neo D100 cells. Microsatellite polymorphism analysis revealed that three loci, 11q13-23, 11q23.1, and 11q23.3 (markers D11S911, DRD2, and D11S29) were retained in BP1E-11neo #145 cells, and two, 17q24.2-25.2, 17q25.2 (markers D17S515 and D17S785 were retained in BP1E-17neo D100 cells. We conclude that the specific regions of normal chromosomes 11 and 17 transferred play a functional role in the expression of immortal and transformed phenotypes of HBEC in vitro.

[Operational models in the histopathological examination of liver puncture biopsies]. / Modele operationale în examenul histopatologic al punctiei biopsie hepatice.

The main goal of this paper is to give an overview of the personal experience in the investigation of the hepatic biopsy. There were analyzed liver specimens from 26 children hospitalized in Clinical Hospital "Sf. Maria" Iasi. The first clinic diagnosis was post-viral chronic hepatitis and most of the cases provided the serologic markers. Histopathological exam revealed 2 cases of active chronic hepatitis and 24 cases of persistent chronic hepatitis. The interpretation of the lesions relied on Ludwig and Metavir scoring systems. The significance of these scores is very important because they allow one to identify the grading of the necro-inflammatory/histological activity and the staging of fibrosis. Thus, the result of these scoring systems make it possible to classify the cases into aggressivity based forms, indicate the therapy approach and estimate the prognosis as well as the clinical course.

Ultrastructural aspects of the alveolar wall in SIDS.

The aim of this study is to make a comparative analyse between light and ultrastructural lesions of the alveolar wall in SIDS. The study was made on lung specimens collected from autopsy of infants with sudden unexplained death. There were studied histopathologically 10 cases of sudden death. Only in 3 cases were made electron microscopically studies. At light microscope, there were put in evidence interstitial and intra-alveolar oedema and the presence of many parietal and intra-alveolar macrophages. There is a good correlation between light and ultrastructural aspects.

Etiological, clinical and pathomorphological aspects of acute respiratory distress syndrome in children.

Acute respiratory distress syndrome (ARDS) is the result of severe injuries of different etiologies of the capillary system in patients with previously healthy lungs, resulting in noncardiogenic pulmonary edema. The authors studied 42 infants in whom the histopathologic aspects were suggestive for ARDS. The etiologic factors of this syndrome were: severe gastroenteritis with hypovolemic or endotoxic shock (13 cases), sepsis (9 cases), fulminans purpura (2 cases), severe neurological disorders (13 cases), pulmonary infections (5 cases). In such conditions, if the infant presents hyperpnea followed by generalised cyanosis, refractory to oxygen therapy, and if there are clinical and radiologic signs of acute pulmonary edema, the diagnosis of ARDS must be considered and a complete intensive care therapy is compulsory in order to alleviate the severe prognosis of this syndrome.

New trends in "mystery SIDS" research.

The aim of this study is to suggest some new trends of research in SIDS, leaving from the pathologist's observations of the presence of unusual lesions in SIDS. The histopathological study was made on 27 cases of SD, representing 1996 SIDS cases registered to hospital. There were put in evidence the oesophageal inflammation, the hyperplasia of submucosal laryngeal glands, different grades of bronchiolar mucous hypersecretion and reducing of elastic lung tissue and the hypertrophy of muscular lung small arteries. This lesions are frequently encountered to SIDS cases.

[3 cases of malignant immunoblastic lymphomas]. / Trei cazuri de limfoame maligne imunoblastice.

Immunoblastic malignant lymphomas belong to the high-grade malignant lymphomas and can be classified into B and T types, according to the origin line of the proliferating cells. This paper presents three cases of immunoblastic malignant lymphomas, exhibiting fairly close morphological aspects. The morphological diagnosis based on standard methods using conventional dyes was supplemented by immunohistochemical diagnosis with monoclonal antibodies. Thus, the cellular line of the proliferating cells has been identified. A brief overview of the theoretical criteria requested for defining and differentiating the two types of immunoblastic lymphomas is also formulated.

[The morphopathological aspects at autopsy of HIV infection in children]. / Aspecte morfopatologice necropsice ale infectiei cu HIV la copii.

Aspects of HIV infection and AIDS in childhood have been reported since 1982. Pathological features are due to direct action of HIV, opportunistic infection and some tumoral processes. This report presents our own experience resulted from 27 cases of necropsy of patients diagnosed with AIDS or seropositive for HIV. Emphasize is placed on microscopic changes in different systems and organs (central nervous system, heart, lung, gastrointestinal tract, liver, lymphoid organs, kidney), by comparing our results with those described in literature.

[The anatomicopathological considerations in the clinical study of malignant non-Hodgkin's lymphomas in children]. / Consideratii anatomo-patologice pe marginea studiului clinic al limfoamelor maligne non-hodgkiniene la copil.

There have been studied 78 cases with abdominal LMNH diagnosis, treated at the "Sf. Maria" Hospital of Iasi, during the period 1970-1994. The microscopic exam has placed emphasis on the following two important aspects: (i) morphological diagnosis based on standard morphological methods, using conventional staining; (ii) immunohistochemical diagnosis, using monoclonal antibodies CD20, CD3; CD68, E29--for 18 cases. The cases investigated immunohistochemically permitted the identification of the lymphoid tumoral cells for the B/T line and tumoral macrophages, as well as the differential diagnosis with undifferentiated carcinomas. A direct correlation between a certain symptom and the disease could not be determined, although all the gastro-intestinal symptomatic elements have been taken into account. This fact reconfirmed the important role played by the anatomo-pathological exam in establishing the diagnosis and stage of the disease. Consequently the gastro-intestinal lymphomas are particular clinical entities, the investigation of which requires an interdisciplinary approach.

[Helicobacter heilmanii gastritis: the bacteriological, endoscopic and histopathological considerations in 18 cases of infection in children]. / Gastrita cu Helicobacter heilmanii: consideratii bacteriologice, endoscopice si histopatologice privind 18 cazuri de infectie la copil.

The investigations on the presence of Helicobacter pylori in gastric mucosa biopsy specimens have evidenced another morphologically distinct spiral bacterium, Helicobacter heilmanii, which is associated with histopathological lesions of antral gastritis. The authors found 18 cases of such infection in a number of 1508 children with dyspeptic manifestations examined endoscopically. While H. pylori-associated infection was detected in 48.7% of the cases, H. heilmanii-associated gastritis had a much lower prevalence, 1.1%. The diagnosis was made by microscopic examination of the gram fuchsin-stained smear from a biopsy fragment, the urease test being more commonly erratic or late positive. In 10 cases, the endoscopic examination of gastric mucosa revealed nodularity of antral mucosa, in one of these cases a ulcer lesion at the level of the great curvature being also associated. Histopathological changers of active chronic gastritis have been found but in 4 out of children, the examined fragments of gastric mucosa being collected in most cases from the fundic area: in the child with gastric ulceration the histopathological lesions were of antral acute gastritis. Clinical, bacteriological, endoscopic and histological cure of H. heilmanii gastritis is possible by therapy with bismuth compounds alone.

Comparative behaviour of antithrombin III antigen and antithrombin III activity in cardiovascular patients.

Antithrombin III-functional (AT III F) and immunoprotein (AT III I) assessed by two comparative methods in various cardiovascular conditions, showed significant differences between the two parameters, namely: a simultaneous decrease of both AT III F and AT III I during acute embolic episodes of only AT III F in transient ischemic attacks (with normal level of AT III I) and increase of AT III I (with apparently normal AT III F) in patient with mitral valve prosthesis. It is considered that in condition of "hypercoagulability" various patterns of AT III F/AT III I ratio can be obtained: decompensated, compensated and hypercompensated consumption.