Respiratory-gated 18F Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging in Evaluation of Primary Gastric Lesions and Gastric Lymph Nodes in Patients with Gastric Cancer.

AIMS: To evaluate the added value of respiratory-gated positron emission tomography (PET) in 18F fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) in the visual and semi-quantitative assessment of primary gastric lesions and gastric lymph nodes for patients with gastric cancer. MATERIALS AND METHODS: In total, 102 upper abdominal respiratory-gated and whole-body 18F FDG PET/MRI of 88 patients with gastric cancer were evaluated visually and semi-quantitatively. For 41 patients who underwent surgery, histopathological and PET findings were compared. Three PET images were obtained from upper abdominal PET data: non-Q static (non-QS) PET from all counts, respiratory-gated Q static (QS) PET from counts in the end-expiration phase of breathing, shortened 4 min (S4min) PET that was reconstructed to obtain similar counts to QS PET. The semi-quantitative parameters (standardised uptake values, metabolic tumour volume, total lesion glycolysis) of primary lesions for each PET image, the sizes of primary lesions and the patient's body mass index were recorded. According to lymph node stations, the presence and numbers of positive lymph nodes and visual scores of lymph nodes for each PET image were recorded. RESULTS: The patients with smaller gastric lesions (≤30 mm) or higher body mass index (>30) had significantly higher standardised uptake value percentage changes in QS PET compared with non-QS PET (all P < 0.05). The third (lesser curvature), fourth (greater curvature) and sixth (infra-pyloric) lymph node stations had significantly higher visual scores in the QS PET than in the others. The fourth lymph node station had a significantly higher number of FDG-positive lymph node in the QS PET than in the non-QS and the whole-body PET images. In the fourth station, sensitivity, positive predictive value, negative predictive value and accuracy increased in the QS PET compared with the others. CONCLUSION: Respiratory-gated PET/MRI was found to be significantly superior in the evaluation of especially the fourth lymph node station, smaller gastric lesions and in the patients with a higher BMI compared with the non-respiratory-gated PET images.

Assessment of concomitant versus sequential trastuzumab on radiation-induced cardiovascular toxicity.

There are limited data regarding effect of trastuzumab on radiation-induced cardiovascular toxicity when used sequentially or concomitantly. This experimental study aims to investigate effect of trastuzumab on radiation-induced cardiovascular toxicity with respect to the treatment sequence. One hundred and eight female Wistar albino rats were divided into six groups (G): G1 was control, G2 was trastuzumab, and G3 was radiotherapy (RT); G4 and G6 were sequential RT and trastuzumab; and G5 was concomitant RT and trastuzumab groups, respectively. Rats were killed at 6th h, 21st and 70th days after RT; thoracic aorta and heart samples were obtained. Transthoracic echocardiography and functional studies evaluating relaxation of thoracic aorta were performed. Subendothelial edema scores of thoracic aorta samples at 21st and 70th days were higher in RT groups (G3, G4, G5, and G6) ( p < 0.001). There was a deterioration of relaxation responses of thoracic aorta samples in RT groups ( p < 0.001). Cardiac fibrosis (CF) scores revealed detrimental effect of RT beginning from 6th h and trastuzumab from 21st day. RT groups showed further deterioration of CF at 70th day. Ejection fraction, left ventricular mass, and fractional shortening were significantly decreased in G4, G5, and G6. Trastuzumab may increase pathological damage in cardiovascular structures when used with RT regardless of timing.

The efficacy of minocycline against methotrexate-induced pulmonary fibrosis in mice.

OBJECTIVES: In addition to its antimicrobial effects, inhibitory effects of minocycline have been demonstrated, including against inflammation, apoptosis, proteolysis, angiogenesis, and tumor metastasis. In this study, we aimed to determine the beneficial effects of minocycline on lung histology and its antioxidant activity in a murine model of pulmonary fibrosis. MATERIALS AND METHODS: Twenty-eight Swiss albino mice were randomly allocated into four groups of seven animals per group. Group I (control group) received intraperitoneal injection of saline. Group II (methotrexate group) received methotrexate orally 3 mg/kg for 28 days. Group III (minocycline group) received methotrexate orally 3 mg/kg and 15 mg/kg of intraperitoneally injected minocycline for 28 days. Group IV (minocycline group) received 15 mg/kg of intraperitoneally injected minocycline for 28 days. Twenty-eight days later, the animals were euthanized. Thereafter, lung tissue samples were harvested. Histological findings of airways were evaluated by light microscopy. The levels of malondialdehyde (MDA), the product of reactive oxygen in lung tissue, and catalase, an antioxidant enzyme, were also determined. RESULTS: In the light microscopic examination, the lung tissues of the control group showed normal histological features. In the methotrexate group, the degree of lung damage (grade 3 fibrosis) was higher than the control and other groups (p: 0.001). In the minocycline-treated group, improvement in lung tissue was noted (median fibrosis score: 3 (MTX group) vs 1 (MTX plus minocycline group); p: 0.001). Only the minocycline group showed normal histological features. Although minocycline reduced the MDA levels in lung tissue, an increase in catalase activity was detected (p: 0.018 and p: 0.014, respectively). CONCLUSIONS: The administration of minocycline may be effective in MTX-induced lung fibrosis in mice. However, further studies with high-dose and long-term treatments are needed.

How confocal laser endomicroscopy can help us in diagnosing gastric lymphomas?

Primary gastric diffuse large cell lymphoma is one of the most common extranodal lymphomas of the gastrointestinal system. Diagnosing gastrointestinal lymphomas can be difficult, since there is no pathognomonic sign in endoscopy to distinguish it from other malignancies. In some cases biopsy can be non-diagnostic. Therefore, multiple endoscopic examinations and biopsies can be necessary. With using confocal endomicroscopy, histology of the tissue can be seen in vivo and a range of diseases can be identified by using this technique. We are presenting a case, which is diagnosed as primary gastric diffuse large cell lymphoma during the evaluation of erythema nodosum etiology. We want to emphasize the role of confocal laser endomicroscopy for in vivo diagnosis of gastric lymphoma and directing the endoscopist for sampling the diseased mucosa. Confocal endomicroscopy decreases non-diagnostic rates in endoscopic biopsy and can be performed successfully in cases of gastric lymphoma. Pit patterns of gastric lymphoma, ring cell gastric carcinoma and gastric adenocarcinoma are similar. To best of our knowledge, this case is the fifth case of confocal laser endomicroscopy aided in diagnosing gastric lymphomas (Tab. 1, Fig. 2, Ref. 13).

Long term experience in high grade glial tumors with temozolomide.

PURPOSE: Temozolomide is used concurrently with radiotherapy (RT) and as consolidation therapy in high grade gliomas (HGGs). In the present study we present our experience of long-term efficacy and toxicity of temozolomide in HGGs. METHODS: After surgery, temozolomide was administered at 75 mg/m(2) daily concurrently with RT, followed by 6 courses of consolidation therapy (150-200 mg/m(2) for 5 days every 28 days). RESULTS: A total of 172 patients with either glioblastoma multiforme (GBM) (n= 142; 82.6%) or anaplastic astrocytoma (AA) (n= 30; 17.4%) were studied. The objective response rate (ORR) was 42.5%, including 12 (7%) complete responses (CRs) and 61 (35.5%) partial responses (PRs). In the GBM group, median progression free survival (PFS) and overall survival (OS) were 9 and 16 months, respectively. In the AA group, median PFS and OS were 16 and 24 months, respectively. Three-year OS was 18.2% for GBM, and 39.4% for AA. In elderly patients (14.5%), median PFS and OS were 8 and 11 months respectively for both HGGs. Serious toxicities were mainly hematologic. CONCLUSION: Temozolomide is an effective agent in HGGs with favorable outcome and low toxicity profile even in advanced age.

Prevalence, burden, and risk factors of atopic eczema in schoolchildren aged 10-11 years: a national multicenter study.

BACKGROUND: Little is known about the epidemiology of atopic eczema (AE), and studies from the Mediterranean region and the Middle East are limited. OBJECTIVE: We investigated the frequency, burden, and risk factors of AE in a developing country. METHODS: The International Study of Asthma and Allergies in Childhood Phase II questionnaire was used to survey a representative sample of 10 to 11-year-old children in Turkey. Children were examined by allergists, and parents completed standardized questionnaires. RESULTS: Among 6755 children, the prevalence of having eczema during one's lifetime or currently was 17.1% and 8.1%, respectively. The prevalence of visits to the doctor, nocturnal awakening, school absenteeism, and drug usage was 36.3%, 56%, 9.7%, and 28.7%, respectively. Associated factors were current rhinoconjunctivitis (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.99-3.21), current wheezing (OR, 2.10; 95% CI, 1.58-2.79), family history of allergic disease (OR, 1.62; 95% CI, 1.21-2.18), low birth weight (OR, 1.79; 95% CI, 1.08-2.94), and exposure to animals in the first year of life (OR, 1.47; 95% CI, 1.06-2.03). CONCLUSIONS: In a developing Mediterranean country, the prevalence of AE is comparable to that of developed countries in the same region and lower than that observed in developed countries elsewhere. The course of the disease and risk factors of AE probably differ in developing countries.

Efficacy and toxicity of preoperative chemotherapy with docetaxel and epirubicin in locally advanced invasive breast cancer.

PURPOSE: To investigate the efficacy and safety of neoadjuvant chemotherapy with docetaxel plus epirubicin with granulocyte colony-stimulating factor (G-CSF) support in locally advanced breast cancer patients. METHODS: We retrospectively evaluated the records of 39 patients with locally advanced breast cancer. All of them received neoadjuvant epirubicin 75 mg/m(2) plus docetaxel 75 mg/m(2) every 3 weeks with G-CSF support. Responding patients were subjected to breast-conserving or modified radical mastectomy. RESULTS: Four (10.3%) patients achieved clinical complete response (cCR) and 25 (64.1%) clinical partial response (cPR). Pathologic complete response (pCR) was observed in 4 patients with cCR. Ten (25.6%) patients achieved stable disease (SD), while no patient had progressive disease (PD). Grade 3 and 4 neutropenia was observed in 6 (15.3%) and 4 cases (10.3%), respectively. Febrile neutropenia was observed in 2 (5.1%) cases and anemia in 7 (17.9%) cases. Grade 1/2 mucositis was observed in 12 (30.7%) patients and grade 1/2 peripheral neuropathy in 7 (17.9%) patients. Dose reduction was necessary in 4 patients with grade 4 neutropenia. The median disease-free survival was 60 months (95% CI: 41-79 months). Median overall survival was not reached. Five-year overall survival was 64.2%. CONCLUSION: The combination of docetaxel plus epirubicin was active and tolerable in neoadjuvant treatment of locally advanced breast cancer.

Xelox (capecitabine plus oxaliplatin) as neoadjuvant chemotherapy of unresectable liver metastases in colorectal cancer patients.

Complete resection of liver metastasis may provide long term survival in patients with colorectal cancer. Increased number of studies on successful resection after neoadjuvant chemotherapy with initially unresectable liver metastasis has been reported. We evaluated retrospectively the results of 35 patients with unresectable liver only metastases from colorectal cancer treated with capecitabine plus oxaliplatin combination (XELOX). Treatment consisted of IV oxaliplatin 130 mg/m2 day 1 and oral capecitabine 1000 mg/m2 day twice daily on days 1 to 14 followed by 7 days of rest repeated every 3 weeks. After chemotherapy, 13 (37, 2 %) patients showed partial clinical response. Among them, 7 patients were considered suitable for surgery but 2 patients refused the surgery. While one of 5 patients had unresectable disease at surgery, the remaining 4 patients (11, 4 %) had a complete resection. There was one postoperative mortality due to sepsis within 2 months after surgery. Our data suggests that XELOX regimen seems to be useful in unresectable liver only metastases from colorectal cancer because of its activity, feasibility and tolerability. Further studies of XELOX in combination with bevacizumab and/ or cetuximab are warranted in this setting.

Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum.

We report successful treatment of a refractory myelodysplastic syndrome-associated pyoderma gangrenosum with the combination of thalidomide and interferon-alpha2a in a single patient. A non-healing wound developed on a 40-year-old woman's left thumb after minor trauma. Massive ulcerovegetative lesions developed after reconstruction surgery. Histopathological examination of the bone marrow and cytogenetic studies revealed an atypical myeloproliferative/myelodysplastic syndrome. The skin lesions resolved dramatically after two months of thalidomide and interferon-alpha2a combination therapy and the haematological status improved.

Tonsillar abscess formation due to herpes simplex type-1 in a severely immunocompromised stem cell transplant patient with chronic myeloid leukemia.

Herpes simplex virus (HSV) causes life-threatening infections in immunocompromised patients such as transplant recipients and patients with hematologic malignancies. We herein describe the case of a patient with chronic myeloid leukemia blastic transformation who developed severe herpetic tonsillitis complicated by tonsillar abscess formation. Abscess formation was determined by computed tomography, whereas tonsillitis due to HSV was confirmed by pathologic and immunohistochemical examinations of the tonsillar biopsy. For molecular confirmation, HSV DNA was amplified by LightCycler PCR and type (HSV-1) determined by melting point analysis. The patient responded promptly to antiviral treatment and there were no signs of recurrent infection at the follow-up. To our knowledge, this case is unique for being the first case of tonsillar abscess formation due to HSV-1, also emphasizing the importance of herpetic infections in the differential diagnosis of oropharyngeal small-sized lesions in the immunocompromised patient population.

The ability of 67Ga scintigraphy to detect the lesions of Echinococcus multilocularis infection: preliminary results.

AIM: To assess the ability of 67Ga scintigraphy to detect the lesions of Echinococcus multilocularis (EM) infection. MATERIALS AND METHODS: An animal model of EM infection was developed. The infected tissues taken from stock infection were placed into the abdominal cavity of uninfected animals operatively. The success of implantation was controlled 20-25 days after implantation. Five infected and 2 healthy animals were studied. All of the animals were examined by ultrasound before the scintigraphic evaluation. After the injection of 7.4 MBq (200 microCi) 67Ga citrate intravenously, static images from the whole anterior thorax and abdomen were obtained at 24, 48 and 72 hours. Visual and semiquantitative analyses were performed. In semiquantitative analysis, an irregular region of interest was drawn over the thorax as the background, excluding the heart and a second region of interest was drawn over the abdomen, excluding the liver and spleen. Abdomen/ background ratios were calculated using the mean counts. RESULTS: In the visual evaluation, it was noticed that there was considerably increased 67Ga uptake in the abdomens of the infected animals. In infected animals, mean abdomen/background ratios at 48 and 72 hours (3.76 +/- 1.04, 4.13 +/- 0.72, respectively) were increased compared with mean abdomen/background ratios at 24 hours (2.94 +/- 0.77). These increases in abdomen/background ratios were statistically significant at 72 hours (p = 0.04). Between the infected animals and control group, mean abdomen/background ratios were compared, and statistically significant differences were found in the images obtained at 48 and 72 hours. CONCLUSION: Imaging at 72 hours seems to be more suitable imaging time for the diagnosis of alveolar echinococcosis. 67Ga scintigraphy may successfully demonstrate the lesions of EM infection localized intraperitoneally. The method of 67Ga scintigraphy is useful because it is simple, non-invasive and relatively safe.

Behaviour of Toxoplasma gondii RH Ankara strain tachyzoites during continuous production in various cell lines.

Toxoplasma gondii is an obligate intracellular protozoan parasite. The objective of the present study was to examine the behaviour of Toxoplasma gondii RH Ankara strain tachyzoites in a cell culture environment. The study represents the first step in determining whether T. gondii RH Ankara strain tachyzoites, grown in cell culture, are of sufficient quality to allow cessation of in vivo tachyzoite production for diagnostic assays. In the present study, T. gondii RH Ankara strain tachyzoites were continuously produced in myeloma X63.Ag8.653, HeLa, Hep-2, and Vero cell cultures for 2 months. The average size of the tachyzoites was 3 x 5.7 microm prior to the first inoculation but after continuous production, a marked decrease was noted in average tachyzoite size. The smallest tachyzoite size, was 1 x 2.1 microm after 2 months, in myeloma cell cultures even though the yield of tachyzoites increased. With other cell cultures, tachyzoite yields were not as high as myeloma cell culture although decrease in size was less. The smallest decrease in tachyzoite size, averaging 2 x 3.8 microm after 2 months, was observed in tachyzoites produced in HeLa cell cultures. A virulence assay in small groups of BALB/c mice, using tachyzoites derived from cell cultures, was also conducted. The preliminary results of the virulence assay suggest that as the size of the tachyzoites decreased, the virulence in mice decreased. Future research will focus on the effect of the size of cell culture-derived T. gondii RH Ankara strain tachyzoites on the virulence, protein expression, and the reliability of diagnostic assays. Ultimately, the behaviour of tachyzoites from various T. gondii strains will be observed in cell culture to determine if size is altered.

Enhanced expression of the local haematopoietic bone marrow renin-angiotensin system in polycythemia rubra vera.

Local bone marrow (BM) renin-angiotensin system (RAS) affects physiological and pathological haematopoiesis, including erythropoiesis. In this study, quantitative expression of the messenger RNAs of the major RAS components--angiotensin-converting enzyme (CD143), renin and angiotensinogen--were measured in BM samples by quantitative real-time polymerase chain reaction, to evaluate the activity of local BM RAS in polycythemia rubra vera (PV) in comparison with normal erythropoiesis. The presence of CD143 was also investigated in the same BM samples by flow cytometry. Increased local synthesis of the major RAS components has been identified by demonstrating corresponding mRNAs in the BM of the patients with PV. Our findings indicate up-regulation of local BM RAS, together with down-regulation of the cell surface angiotensin-converting enzyme receptors, in the autonomous neoplastic clonal erythropoiesis of PV.

Vascular endothelial growth factor, c-erbB-2 and c-erbB-3 expression in colorectal adenoma and adenocarcinoma.

AIM: To analyze vascular endothelial growth factor (VEGF), c-erbB-2 and c-erbB-3 expression and to evaluate their relation to clinicopathologic parameters and pathogenesis of colorectal carcinoma. METHODS: Sections of adenoma, intramucosal carcinoma and adenocarcinoma were evaluated by immunohistochemistry in 85 malignant and 37 benign colorectal neoplasms for the expression of VEGF, c-erbB-2 and c-erbB-3 considering clinicopathological variables. RESULTS: VEGF was detected in comparable percentages of all neoplasm types while c-erbB-2 expression was detectable more frequently in adenoma than adenocarcinoma cases (65% vs 43%). Except for the correlation of c-erbB-3 expression with Dukes' staging, there was no correlation between the studied markers and grade of differentiation, Dukes' stage and localization of colorectal adenocarcinoma. c-erbB-3 expression was seen more frequently in tubular adenomas, while c-erbB-2 expression was higher in tubulovillous and villous types. These differences were not statistically significant. The presence of distant metastasis and angiolymphatic invasion were identified as independent predictors of survival. A positive correlation was found between VEGF expression and lymphatic vessel invasion and regional lymph node involvement. CONCLUSION: These results suggest that VEGF, c-erbB-2, c-erbB-3 expression does not have prognostic value in colorectal cancer. VEGF expression may be implicated in the lymph node metastasis.

Gastrointestinal involvement in POEMS syndrome: a novel clinical manifestation.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is characterised by a rare multisystem disorder of unknown pathogenesis. Although its pathophysiology is not well understood, overexpression of proinflammatory cytokines has been implicated. Gastrointestinal system disorders have not been reported among the components of the syndrome. A case is reported of POEMS syndrome with gastrointestinal involvement shown by gastrointestinal endoscopy.

Colonic metastasis from squamous carcinoma of the lung: report of a case and review of the literature.

We describe a rare case with metastatic involvement of the gastrointestinal tract (colonic metastasis) secondary to lung cancer. After diagnostic work-up, a left hemicolectomy was performed. Patient has been alive and healthy 9 months after operation. We report the first case with the longest survival period after the diagnosis of metastasis, although the symptomatic gastrointestinal metastases from lung cancer generally follow a poor prognosis because of their advanced state and multiplicity.