Defining prognostic parameters of well-differentiated gastric neuroendocrine tumors based on metastatic potential: a two-center experience.

Background: Gastric neuroendocrine tumors [gNETs] are heterogeneous tumors and we are still unable to predict the behavior of these tumors. We aim to define the prognostic parameters of well-differentiated gNETs based on metastatic potential and to evaluate the current classification systems. Patients and methods: We retrospectively retrieved 44 well differentiated gNET cases who underwent radical surgery between 2000-2015 at two tertiary-care centers. Results: Among the 44 well-differentiated gNET patients, 17 (38%) patients had metastatic disease to lymph nodes and/or distant sites, while 27 (62%) were confined to the stomach. Higher risk of metastasis was observed with increasing tumor size, grade, depth of invasion and with type-3 and solitary tumors. 30 (68%) patients had type-1 gNET and 14 (32%) had type-3 gNET. Majority of the type-1 cases (76,6%) were Grade 1 [G1] and type-3 cases (78,5%) were Grade 3 [G3]. Type-1 subgroup had no G3 tumor, and type-3 had no G1. Grade 2 [G2] tumors were more controversial, with metastatic and non-metastatic cases. G2 cases with a >10% Ki67 expression or type-3, had a worse prognosis. Although most of the type-1 gNETs had an indolent course, 6 of 30 (20%) patients had metastatic disease. Metastasizing type-1 gNETs were >10 mm in diameter or extended to/beyond the submucosa. Conclusion: Regarding our results, tumor type, grade, size, focality and depth of invasion are the prognostic parameters for gNETs, based on metastatic potential. Besides these parameters, a two-tiered grading system with a 10% Ki-67 proliferation index cut-off value could be considered for right treatment choice.

The frequency of HLA class I and II alleles in Turkish childhood acute leukaemia patients.

In this study, blood samples were taken from 200 patients with childhood acute leukaemias, including acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), and from 100 healthy volunteers (controls). The frequency of the human leucocyte antigen (HLA)-DRB1*04 allele was significantly higher, and the frequencies of the HLA-A23 and HLA-B7 antigens were significantly lower, in patients with ALL compared with controls. Among patients with AML, the frequency of the HLA-B49 antigen and the HLA-DRB1*15 allele were significantly higher, whereas the frequencies of the HLA-A11 and HLA-B38 antigens were significantly lower compared with controls. The frequency of the HLA-DRB1*04 allele was also significantly higher in male patients with ALL and AML, whereas the HLA-DRB1*13 allele was found significantly less frequently in male AML and female ALL patients than in controls. To date, this is the only study to evaluate the associations between HLA molecules and leukaemia in a Turkish population with acute childhood leukaemia.

A newborn with infantile fibrosarcoma of foot: treatment with chemotherapy and extremity-sparing surgery.

Infantile fibrosarcoma represents less than 1% of all childhood cancers, but it is the most common soft-tissue sarcoma in those under 1 year of age. We report an infant with congenital infantile fibrosarcoma diagnosed as hemangiopericytoma. He was treated with chemotherapy and extremity-sparing surgery. Amputation was avoided.

Differentiation-inducing liposoluble vitamin deficiency may explain frequent secondary solid tumors after hematopoietic stem cell transplantation: minireview.

Secondary cancers are among the most threatening long-term health problems of hematopoetic stem cell- transplant (HSCT) patients. There are several lines of evidence indicating the possibility of a prolonged Vitamin A deficiency for solid tumor-type secondary cancers: I- Solid tumors such as oral cavity, head/neck region squamous carcinomas, skin cancers and melanomas, where lowered Vitamin A concentrations and chemo-preventing activity of its derivatives (retinoids) are most explicitly proven, arise much more frequently than others. II- Early monitorings: A significant retinol deficiency in HSCT patients is detectable along with a severity of mucositis and the vulnerability to infection. III- Monitoring of other liposoluble vitamins: Vitamin D, a differentiation-inducing vitamin like Vitamin A, showed a sustained decrease. Another similarity of these two vitamins is that they also depend on intestinal absorption and are decreased due to bowel injury by conditioning agents and chronic graft-versus-host disease. IV- Peroxidative reactions and inflammation can directly exhaust retinol levels despite sufficient intake. Considering the similar inhibitory role of Vitamin D analogs (deltanoids) on squamous carcinomas, skin tumors and melanomas, we propose that animal studies and extended vitamin surveillance studies in HSCT patients may unfold a preventive strategy against long-term complications.

FISH detection of chimerism in pediatric hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established curative therapy for various malignant and non-malignant diseases. Successful outcome after allogeneic HSCT has been associated with donor chimerism (DC). However, the detection of residual host cells or mixed hemopoietic chimerism (MC) has indicated that donor chimerism is not obligatory following HSCT. More recently, fluorescence in situ hybridization (FISH) analysis has been applied to engraftment studies for the identification of polymorphic or sex chromosomes. In this study, chimerism status was evaluated in 48 sex-mismatched HSCT pediatric patients (17 women/31 men, mean age: 9.02 +/- 3.95 years, range: 2-19) by FISH and the effect of DC or MC on outcome and long-term disease-free survival was documented. The stem cell source was bone marrow in all cases. All of the donors were human leucocyte antigen-identical siblings. FISH was performed on 156 specimens between days +13 and +1878. Donor chimerism was found in 47.9% (23/48) and MC was found in 52.1% (25/48) of the patients. Fifteen of 48 (31.25%) patients died, of whom 12 (80%) were MC and three patients (20%) were DC. The difference in chimerism status (MC or DC) was statistically significant between those patients who died and those still alive (chi(2) = 6.813; P = 0.009).

Capsaicin in albino rats prevents contralateral testis from the damaging effects posed by ipsilateral testis that underwent torsion.

OBJECTIVE: To evaluate the effect of capsaicin, a powerful neurotoxin selective to afferent nerves, on contralateral testicular damage in ipsilateral testicular torsion. METHODS: Forty male albino rats were randomly allocated into five groups. No operation was performed in group one. After intraperitoneal administration of 0.9% NaCl, rats underwent a sham operation in group 2 and testicular torsion in group 3. In groups 4 and 5 rats underwent sham operation and testicular torsion, respectively after intraoperitoneal capsaicin injection. Contralateral testes were harvested on the fifteenth day of the experiment and mean seminiferous tubular diameters and mean testicular biopsy scores were recorded for each testis. The values were compared through analysis of variance (ANOVA) with Turkey-Kramer multiple comparisons test and p values less than 0.05 were considered to be significant. RESULTS: Mean testicular biopsy scores and mean seminiferous tubular diameters of group 5 was significantly higher than the group 3. There was no difference between the groups 1, 2, 4, and 5 when these two parameters are concerned. CONCLUSION: Capsaicin effectively prevents contralateral testicular damage encountered following ipsilateral testicular torsion. The inhibition of afferent impulses from the ipsilateral testis under distress prevents contralateral testicular injury, and provides additional data to support the role of an autonomic reflex arc in contralateral testicular injury.

Fibrocartilaginous mesenchymoma of the distal femur: case report and literature review.

A case of a 9-year-old boy with fibrocartilaginous mesenchymoma located in the distal femur is presented. Fibrocartilaginous mesenchymoma is a rare tumor. There have been 17 cases reported since 1984. The presenting complaint was pain and local discomfort. Radiological examination showed lytic and sclerotic lesions located in the distal femur. Magnetic resonance imaging showed that there was no soft tissue expansion. Differential diagnosis included fibrocartilaginous dysplasia, dedifferentiated chondrosarcoma, desmoplastic fibroma, fibrosarcoma and low-grade osteosarcoma. The diagnosis of the tumor in a state hospital would not have been possible. Wide resection of the tumor and resection arthrodesis with an intramedullary nail has yielded good results. The patient has been disease free for 4 years. Pathological diagnosis of this very rare tumor may be challenging; the treatment should be wide resection of the tumor.

The effect of calcitonin on osseous healing in guinea pig mandible.

Calcitonin (CT) is reported to be an effective medication for the treatment of inflammatory root resorption and to be capable of stimulating osteoblast proliferation in cell culture studies. In this study the effect of CT on the healing of osseous defects was evaluated in the mandibles of guinea pigs. After raising tissue flaps two experimental cavities were created on both sides of the corpus mandible of 33 guinea pigs. CT was applied into cavities either in hydroxypropyl methycellulose (HPMC) gel or gelatin as carrier. HPMC and gelatin alone and an empty cavity were also examined as control groups. Histopathological examinations under light microscopy were performed on weeks 1, 3, and 6. At week 1 in CT+gelatin and CT+HPMC groups, prominent osteoblastic activity was observed when compared with control groups. At week 3 the presence of woven bone in the experimental cavity areas reflected the increased osteoblastic activity in all groups. At the end of week 6 woven bone was gradually replaced by osteogenic tissue undergoing remodelization with Haversian systems in all groups. It is suggested that the osseous healing of the experimental cavity was enhanced by CT application in early stages (i.e. at week 1). However there was no significant difference of osteogenic activity between the control and CT-treated groups at the end of weeks 3 and 6.

Importance of proliferation markers in gastrointestinal carcinoid tumors: a clinicopathologic study.

BACKGROUND/AIMS: Carcinoid tumors are common tumors in the gastrointestinal tract. Certain criteria such as the depth of invasion, the localization, the tumor size, the mitotic index and the pattern of ploidy are used to determine the potential biological behavior of these tumors some of which might be malignant. The goal of this study was to assess the prognostic significance of proliferation markers (Ki67 and PCNA) in carcinoid tumors by using immunohistochemistry. METHODOLOGY: An immunostaining in 37 carcinoid tumors arising in various locations of the gastrointestinal tract was performed. The best stained area was selected and 1000 neoplastic cells were counted in order to determine the proliferation index in each case. RESULTS: The results of proliferation index were compared with the depth of invasion, the embryologic type, the tumor size, the presence of metastases and disease-free survival by using statistical methods. The Ki67 tumor proliferation index in the tumors > 2.1 cm was significantly different from the tumors < or = 2 cm (P = 0.032). CONCLUSIONS: The presence of significant correlation between Ki67 positivity and the tumor size might suggest that Ki67 antibody can be useful for the determination of potential behavior of gastrointestinal carcinoid tumors.

Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.

Effects of abdominal location and epididymal or vasal obstructions either individually or in association on ipsilateral and contralateral testes. A histologic and DNA flow cytometric analyses.

OBJECTIVE: An experimental study was conducted to evaluate the damages in ipsilateral and contralateral testes in individual or associated presences of abdominal location and vasal or epididymal obstructions. METHODS: Six groups each consisting of 8 rats were established. The groups included sham operation, ligation of the vas deferens, detachment of the epididymis from testis, abdominal placement of the testis, abdominal placement of the testis with vas deferens ligation, and abdominal placement of the testis with detachment of epididymis from testis. After 30 days, bilateral orchidectomy was performed. Mean seminiferous tubular diameters (MSTD) and mean testicular biopsy scores (MTBS) were obtained for each testis. Relative proportions of haploid, diploid and tetraploid cells were determined by DNA flow cytometry. MSTD, MTBS and the proportions of haploid cells were compared through one-way analysis of variance. RESULTS: While vas deferens ligation has diminished MSTD only in the contralateral testes, abdominal testis and detachment of epididymis have diminished MSTD in both ipsilateral and contralateral testes. MTBS were depressed only in the ipsilateral testes in groups of abdominal testis, vas deferens ligation and detachment of epdidymis. However, ratios of haploid DNA were depressed in both ipsilateral and contralateral testes. Abdominal testis together with vas ligation or detachment of epididymis has further depressed the ratios of haploid DNA in both ipsilateral and contralateral testes. CONCLUSION: Compared to their individual presence, the associated presence of abdominal testis and vasal or epididymal obstructions may augment the damages encountered within the ipsilateral and contralateral testes.

Spleen damage in endotoxaemic mice: the involvement of nitric oxide.

The association between Escherichia coli endotoxin-induced organ damage and nitric oxide-related mechanisms was investigated in the spleen of male Swiss albino mice (20-40 g) by using (1) Pt/Ir electrochemical sensor connected to an amperometric detection system (NO-501, InterMedical Co., Japan), (2) nitrotyrosine immunohistochemistry, (3) conventional light microscopy and (4) immunoblotting techniques in parallel. 1 h before endotoxin injection, animals were pretreated with either nitric oxide synthase inhibitor, L-N(G)-nitroarginine methyl ester (L-NAME, 20 mg kg(-1), i.p.) or inducible nitric oxide synthase expression inhibitor, dexamethasone (5 mg kg(-1), i.p.) or the inhibitor of murine inducible nitric oxide synthase in vivo, 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT, 1 mg kg(-1), i.p.). 5 h after endotoxin treatment, electrochemically detected concentration of nitric oxide was significantly elevated (nM, endotoxin: 716.6 +/- 178.2, n = 10 vs saline: 209.4 +/- 127.8, n = 9, P = 0.0312, unpaired Student's t-test) and remained so throughout the 30 min monitorization period. Neither dexamethasone nor AMT blocked the endotoxin-induced overproduction of nitric oxide indicating that the enhanced inducible nitric oxide synthase activity cannot be the only explanation. When dexamethasone and L-NAME combination was used to block both the constitutive and the inducible isoforms, nitric oxide production was virtually abolished, indicating a significant contribution from the constitutive isoform of nitric oxide synthase. The results of nitrotyrosine immunohistochemistry and the conventional light microscopy were also in agreement with the amperometric method while immunoblotting revealed the expression of both the endothelial and the inducible isoforms of nitric oxide synthase were induced endotoxaemic animals. Thus, conclude that endotoxin-induced splenic damage in endotoxaemia can be explained by enhanced production of nitric oxide due to the induction of both endothelial and inducible nitric oxide synthases while causal relationship and the roles of other deleterious mediators such as oxygen-derived free radicals are yet to be established.

Capsaicin effectively prevents apoptosis in the contralateral testis after ipsilateral testicular torsion.

OBJECTIVE: To evaluate the effect of afferent nerve blockage by administration of capsaicin on apoptotic changes in the contralateral testis in rats undergoing ipsilateral testicular torsion. MATERIALS AND METHODS: Twenty male albino rats were randomly divided into four groups. In groups 1 and 2, rats underwent a sham operation and testicular torsion, respectively, after the intraperitoneal administration of 0.9% NaCl. Similarly, in groups 3 and 4 the rats underwent a sham operation and testicular torsion, respectively, after an intraperitoneal capsaicin injection. The testes were untwisted 24 h later and the contralateral testes harvested. Apoptosis was assessed in paraffin-embedded sections stained for nuclear DNA fragmentation. Fifteen cells were counted in each seminiferous tubule and the apoptotic cells recorded. A score was calculated for each group and the results compared using the Kruskal-Wallis analysis of variance and Mann Whitney U-tests, with P<0.05 considered to be significant. RESULTS: The mean apoptotic score of group 2 was significantly higher than that of the other groups. There was no difference between the apoptotic scores of groups 1 and 3, 1 and 4, and 3 and 4. CONCLUSION: Capsaicin effectively prevented apoptosis in the contralateral testes of rats that had undergone testicular torsion.

Congenital infantile fibrosarcoma of the thigh in a newborn.

Congenital/infantile fibrosarcoma occurs frequently in the first year of life and differs from fibrosarcoma in adulthood. The clinical course of congenital/infantile fibrosarcoma is more favorable and metastatic spread is rare. While adult fibrosarcomas are common in the thigh, congenital/infantile fibrosarcomas affect chiefly the distal portions of the extremities. Standard treatment is primarily wide surgical excision. Chemotherapy may be given as neoadjuvant or adjuvant treatment in order to avoid the morbidity associated with wide excision. In this case report we present our experience of a newborn affected by congenital/infantile fibrosarcoma of the left thigh.

Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of relapsed or poor risk childhood acute leukemia.

The prognosis of relapsed acute leukemia or chronic leukemia in acute blast crisis is poor and new chemotherapeutic regimens could be useful for these patients. Six relapsed acute lymphoblastic leukemia (ALL), nine relapsed acute myeloblastic leukemia (AML), one chronic myelomonocytic leukemia (CMML) and one chronic myeloid leukemia (CML) in acute blast crisis between three to 18 years (median 10 years) received fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) chemotherapy (CT). Five of the AML relapses were after bone marrow transplantation (BMT) and four were recurrent relapses. At the end of the second course only three patients (2 AML, 1 ALL) were in complete remission (CR). Of the three patients in CR, one patient with AML had her first donor lymphocyte transfusion (DLT) on the 7th day of the second FLAG-IDA course and she is disease-free on the 30th month of the second remission. The remaining two patients were transplanted from unrelated donors in a BMT center abroad on the 5th and 8th month of the last remission and both died with BMT-related complications. Out of 25 courses, seven resulted in fatal infections. The regimen was ineffective in B-cell ALL as in acute blastic crisis of CMML and CML. We could not evaluate the remission-inducing effect accurately in most of the patients due to induction failure. FLAG-IDA appears to be a myelotoxic therapy for relapsed or poor risk leukemia in a developing country. It is not cost-effective; dose modifications or a regimen without IDA may be tried if there is an available marrow donor.