Vascular endothelial growth factor expression in low and high grade B-cell non-Hodgkin's lymphomas.

OBJECTIVE: Angiogenesis is critical for the development of tumors. Although vascular endothelial growth factor is a well-known proangiogenic factor, its impact on B-cell non-Hodgkin's lymphoma is not clear. The aim of this study is to evaluate vascular endothelial growth factor expression in subtypes of B-cell non-Hodgkin's lymphoma. MATERIAL AND METHOD: Fifty-one patients with diagnoses of low and high grade B-cell non-Hodgkin's lymphoma were randomly selected and proper slides were immunostained with vascular endothelial growth factor antibody. The percentage of positive cells was recorded as the vascular endothelial growth factor score. A cut-off point was determined by using the median vascular endothelial growth factor score of all cases. The patients were subclassified as negative, weak or strong positive according to this cut-off point. RESULTS: The study cohort included 26 women and 25 men, aged 5 to 82 years. The number of low-grade patients diagnosed as grade I follicular lymphoma and small lymphocytic lymphoma were 7 and 6; while the number of high grade patients diagnosed as diffuse large B-cell lymphoma and Burkitt's lymphoma were 29 and 9, respectively. Twenty-five patients (49.0%) showed strong and 10 patients (19.6%) showed weak vascular endothelial growth factor immunoreactivity, while 16 patients (31.4%) showed no staining. No statistically significant difference was found for vascular endothelial growth factor expression between subtypes of B-cell non-Hodgkin's lymphoma; as well as between low and high grade groups. CONCLUSION: Further studies in large and specific series are needed to determine the role of vascular endothelial growth factor receptor related pathways in the development and progression of B-cell non-Hodgkin's lymphomas.

Treatment of Wilms tumor: a report from the Turkish Pediatric Oncology Group (TPOG).

AIM: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey. METHODS AND PATIENTS: Between 1998 and 2006, WT patients were registered from 19 centers. Patients <16 years with unilateral WT whose treatment started in first postoperative 3 weeks were included. Treatments were stage I favorable (FH) and unfavorable histology (UH) patients, VCR + Act-D; stage IIA FH, VCR + Act-D; stage IIB FH, VCR + Act-D + radiotherapy (RT); stage III-IV FH, VCR + Act-D + adriamycin (ADR) + RT; stages II-IV UH tumors, VCR + Act-D + ADR + etoposide + RT. RESULTS: 165/254 registered cases were eligible (bilateral, 5.9%) [median age 3.0 years; M/F: 0.99; 50/165 cases < or =2 years]. 9.7% cases had UH tumors. Disease stages were stage I 23.6%; IIA 36.4%; IIB 5.5%; III 22.4%; IV 12.1%. Cases >2 years had significantly more advanced disease. 1/11 cases with recurrent disease died; 2/165 had progressive disease, 2/165 had secondary cancers, and all 4 died. In all cases 4-year OS and EFS were 92.8 and 86.5%, respectively. Both OS and EFS were significantly worse in stage IV. CONCLUSIONS: Despite problems in patient management and follow-up, treatment results were encouraging in this first national experience with a multicentric study in pediatric oncology. Revisions and modifications are planned to further improve results and minimize short- and long-term side effects.

Comparison of pulse and oral steroid in childhood membranoproliferative glomerulonephritis.

BACKGROUND: There has been no controlled study comparing efficacy of pulse versus oral steroid therapy in childhood membranoproliferative glomerulonephritis (MPGN). This study aimed to compare these therapies and renal outcome over a long-term period for MPGN. METHODS: Outcome measures in 11 patients with MPGN treated with pulse methylprednisolone (MP) were compared with 8 patients with MPGN treated with oral prednisolone (P). RESULTS: Nineteen children with idiopathic MPGN (mean age 9.75 years, range 3.7-14 years) were followed for a mean period of 68.21 months (range 4-124 months). Both treatment groups were similar in demographic, clinical, laboratory and histopathological characteristics on presentation. In the pulse MP group, only 1 patient out of 11 progressed to end-stage renal failure (ESRF), compared with 4 patients out of 8 in the oral P group (p=0.041). For long-term renal survival, those patients with more than 8 years of follow-up were further evaluated. Twelve patients had completed 8 years of follow-up; in the pulse MP group, 1 of 7 patients, compared with 4 of 5 patients in the oral P group progressed to ESRF (p=0.039). Chronic damage in the presentation biopsy and lack of remission in patients with nephrotic syndrome (NS) were positively associated with adverse renal outcome (p=0.02, p=0.006, respectively). CONCLUSIONS: Pulse MP therapy may be superior to oral P therapy in children with MPGN in preserving renal function without any increase in steroid-related side effects. Chronic damage in the presentation biopsy and lack of remission of NS are adverse features.

Tibial nerve stimulation diminishes mast cell infiltration in the bladder wall induced by interstitial cystitis urine.

OBJECTIVES: To investigate whether the urine of interstitial cystitis (IC) patients has a toxic effect on the bladder wall, as determined by mast cell infiltration, and to evaluate the preventive effect of tibial nerve electric stimulation (TNES) on bladder mastocytosis induced by IC urine. MATERIAL AND METHODS: The bladders of female rats were catheterized and instilled with IC urine (Group IC; n=10) and normal urine (Group NU; n=5) obtained from humans, saline (Group S; n=5) and protamine sulphate (Group PS; n=10) for 6 weeks. Additionally, in five rats instilled with IC urine and five instilled with PS, TNES was also performed (Groups IC + TNES and PS + TNES). RESULTS: In the lamina propria of the bladder, the mean number of mast cells per square millimetre was significantly higher in Groups IC (32.5+/-12.3) and PS (39.4+/-11.1) than in Groups S (11.9+/-4.3) and NU (13.7+/-3.5). After TNES, the corresponding values were decreased significantly to 15.3+/-5.4 and 15.3+/-4.1 in Groups IC + TNES and PS + TNES, respectively (p<0.001). A significant reduction in mast cell infiltration in the detrusor was also determined after TNES compared with the value in Group IC (4.6+/-1.6 vs 12.1+/-3.0; p<0.001). CONCLUSIONS: We demonstrated that IC urine may result in increased mast cell infiltration in the bladder wall. TNES may play a therapeutic role by diminishing the mast cell count in the bladder wall, which has a strong relationship with nociceptive neural endings.

Reduced E-cadherin and alpha-catenin expressions have no prognostic role in bladder carcinoma.

In various human cancers, dysfunction of the E-cadherin-catenin complex is associated with a decrease in cellular and tissue differentiation, and with higher invasive and metastatic potentials. The objective of this study was to investigate E-cadherin and alpha-catenin expression in superficial noninvasive papillary TCC and invasive TCC, and correlate these results with pathological and clinical parameters. We have used immunohistochemistry to localize Ecadherin and alpha-catenin in 56 formalin-fixed, paraffin-embedded tissue blocks from 41 patients with superficial bladder cancer and 15 with invasive bladder cancer. The 46 male and 10 female patients had a mean age of 67 years, with range of 40 to 82 years. The mean follow-up time was 33.4 (range 5-120) months. Tumor grade 1:2:3 ratios were 5:32:19. In superficial bladder tumor, abnormal expression of E-cadherin and alpha-catenin was demonstrated in 37 and 71% of the tumors, respectively. In advanced bladder tumor, abnormal expression of E-cadherin and alpha-catenin was demonstrated in 80 and 100% of the tumors, respectively. Differences in expression of E-cadherin and alpha-catenin could be discerned between superficial and advanced bladder tumors (p=0.004, p=0.024, respectively). However, the association between E-cadherin and alpha-catenin expression and tumor grade was not statistically significant (p>0.05). In addition, the expression of E-cadherin and alpha-catenin did not correlate with tumor number and size (p>0.05). We have demonstrated that abnormal expression of E-cadherin and/or alpha-catenin occurs in more than 85% of bladder carcinomas and correlates significantly only with advanced stage. Nevertheless, these observations need to be confirmed in larger prospective clinical studies.

An atypical case of POEMS syndrome with IgG kappa M protein and end stage renal failure.

POEMS syndrome is a rare plasma cell dyscrasia which is characterized by small amounts of monoclonal protein, and a multisystem complex manifested by various combinations of polyneuropathy, organomegaly, endocrinopathy and skin changes. Here, we presented an atypical case of POEMS syndrome with IgG kappa monoclonal protein, chronic demyelinating polyneuropathy, hepatosplenomegaly, hypothyroidism, gynecomastia and severe renal impairment. The finding of IgG kappa type of monoclonal protein in our patient was interesting because the majority of cases were reported to have lambda light chain. Also, the absence of typical skin and bone lesions were atypical. Though speculative, these atypical features may account for the unusual presentation of this case. Our patient rapidly progressed to end-stage renal failure and died of cachexia. Renal involvement in POEMS syndrome is rare but may show substantial clinical and pathological variations. Proteinuria, hematuria, renal dysfunction and renal failure requiring hemodialysis can be seen. The pathogenesis of renal dysfunction is unclear. As a conclusion, POEMS syndrome may present with diverse clinicopathologic manifestations. In this syndrome, renal involvement may lead to end stage renal failure and the course may be fatal due to severe polyneuropathy and wasting.

Clinical importance of circulating and cellular expression levels of Fas and Fas ligand in pediatric patients with lymphoproliferative malignancies.

Objectives of this study were to determine the extend of soluble Fas (sFas) and soluble FasL (sFasL) at the time of diagnosis and to evaluate its prognostic relevance under chemotherapy in childhood lymphoproliferative malignancies. The authors measured the circulating sFas and sFasL by ELISA in 25 children with newly diagnosed either ALL or NHL, as well as their expression of Fas and FasL at the time of diagnosis and remission. They did not observe any statistically significant difference between the patient group and age-matched healthy controls for sFas levels, whereas sFasL concentration in study population at the time of diagnosis was significantly higher than that in control subjects (1.05 +/- 1.46 vs. 0.36 +/- 0.18 ng/mL, p = .024). At remission the authors observed a significant decrease in the sFasL levels of all patients whose sFasL concentrations were above the minimal detectable level at the time of diagnosis (p = .008). sFasL and Fas/FasL immunohistochemical staining did not have an effect on survival. sFasL may be a marker in monitoring complete remission in children with LPM.

Posttransplant lymphoma in renal and heart allograft recipients: a single center experience.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with a reported incidence between 0.8% to 32%. Herein we retrospectively analyzed the patients who diagnosed as PTLD in Akdeniz University. Within the 782 (773 renal and 9 heart) transplant recipients six patients were diagnosed as PTLD (diffuse large B-cell lymphoma). Five of them had renal, one had cardiac transplantation. Three patients were diagnosed within the first year of transplantation. Five patients had abdominal disease one had central nervous system involvement. All patients had positive Epstein-Barr virus (EBV) and cytomegalovirus (CMV) IgG at the time of diagnose. EBV-DNA with polymerase chain reaction (PCR) was found to be negative in five patients. Only one patient was survived after the diagnosis of PTLD. In conclusion, even with treatment the mortality rate is high in patients with PTLD. In order to decrease the incidence of PTLD and related mortality, the risk factors should be evaluated with multicenter studies.

Cryptococcal mesenteric lymphadenitis: an unusual cause of acute abdomen.

Cryptococcal infection of intraabdominal organs or tissues is extremely rare. Herein we report a child with mesenteric cryptococcal lymphadenitis who presented with an acute abdomen misdiagnosed as acute appendicitis. Definitive diagnosis was established with 2nd look and lymph node biopsy. Clinicians should remember that cryptococcal infection of mesenteric lymph nodes may rarely mimic an acute abdomen and cause delay in diagnosis.

Bladder augmentation with an omental pedicled gastric seromuscular flap without the necessity of gastric resection.

Bladder augmentation using gastrointestinal segments requires gastric or intestinal resection. This has several risks. In a rat model, we aimed to test the efficacy of a new procedure in which a gastric seromuscular (GSM) flap is separated from the gastric mucosa without the necessity of gastric resection, and this GSM flap, based on an omentum pedicle, is transferred to the bladder. A GSM flap based on an omental leaf was dissected from the gastric mucosa and rotated 180 degrees counter-clockwise, after ligation of the vessels relating to the omentum, until the mid-duodenum. After urodynamic analysis for control levels of bladder capacity and pressure, the GSM flap was anastomosed to the bladder with a continuous suture. Because four rats died due to bladder calculi, only 21 of 25 rats were killed at 1 month (n = 10) and 4 months (n = 11) for histopathological and urodynamic evaluations of the augmented bladder. Bladder capacity increased significantly in the augmented bladders compared to preaugmentation (P < 0.001). There was no significant difference between end-filling pressures of the augmented bladders and preaugmentation. Histopathological findings demonstrated that the muscular surface of the flap was completely re-epithelialized in all rats. Squamous metaplasia was detected in 30% (3/10) of the 1 month group rats, and in 55% (6/11) of 4 month rats (P > 0.05). Gross calculi formation appeared in 20% (2/10) of the 1 month group rats, and in 34% (4/11) of 4 month rats (P > 0.05). Our data show that the use of the GSM flap in the bladder of a rat resulted in the complete re-epithelialization of the flap and sufficient bladder capacity. Despite significant complications such as death, metaplasia and calculi, this technique may be considered as an alternative experimental model to traditional full-thickness patching, which needs gastric or intestinal resection.

Clinical importance of vascular endothelial growth factor (VEGF) for papillary thyroid carcinomas.

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and may be produced by some cancer cells. Several recent reports have documented that increased expression of VEGF is associated with risk of recurrence or decreased recurrence-free survival in papillary thyroid cancers (PTC). The aims of this study were to determine whether immunohistochemical expression of VEGF is related to local and distant recurrence of PTC and to evaluate the relationship between hypervascularization and VEGF expression in papillary thyroid carcinomas. VEGF expression was examined immunohistochemically in 48 papillary carcinomas. Ten normal thyroids were used as controls. Patients were followed for 61.7 (range 24-143) months. Twelve of the patients had local and distant recurrences. VEGF immunostaining, blinded for clinicopathological data, was evaluated semiquantitatively by two pathologists. The difference between the recurrent (n:12) and nonrecurrent (n:36) carcinomas was statistically significant (p:0.001). VEGF expression was also stronger in papillary thyroid carcinomas than in normal thyroid tissues. The mean microvascular densities were significantly higher than in normal thyroid tissues. These data indicate that VEGF staining is strongly associated with increased frequency of local and distant recurrence in PTC and that the immunohistochemical profile of the expression may be used as a marker for predicting which tumors have metastatic potential.

Visceral Kaposi's sarcoma with intracranial metastasis: a rare complication of renal transplantation.

The incidence of Kaposi's sarcoma (KS) has increased in solid organ transplantation recipients. This type of KS tends to be aggressive, involving lymph nodes, mucosa and visceral organs in about half of patients, sometimes in the absence of skin lesions. Brain involvement of KS has rarely been reported. A 16-yr-old Turkish boy underwent renal transplantation from his mother. The immunosuppressive regimen included prednisolone, cyclosporin A and azathioprine. Fourteen months later the azathioprine was changed to cyclophosphamide (3 mg/kg/day) because of the development of a nephrotic syndrome. After 12 weeks, the cyclophosphamide was changed to mycophenolate mofetil (MMF) to control the nephrotic syndrome. At this time his serum creatinine level rose to 2.1 mg/dL. Polyclonal or monoclonal antibodies were never given. Multiple intra-abdominal lymphadenopathy was detected on abdominal tomography at the 32nd month after renal transplantation. Kaposi's sarcoma was diagnosed via laparotomy and biopsy. He had a generalized tonic and clonic seizure and contrast enhanced cranial tomography showed two intracranial masses which had an abundant vascular component which caused a mild shift. One of the masses was removed via a burr-hole with the aim of diagnosis and treatment of the shift. A pathologic examination of the intracranial lesion was also reported as Kaposi's sarcoma. Herpes virus-8 DNA was detected by PCR in the intracranial lesion.

Medullary thyroid carcinoma, follicular variant.

We report here a 48-yr-old woman presenting with a solitary thyroid nodule in the left lobe of the thyroid. The aspiration cytology of the nodule was reported as follicular neoplasia and she underwent surgery. Frozen section was suspicious for medullary thyroid carcinoma and a total thyroidectomy was performed. The pathology report revealed medullary thyroid carcinoma, follicular variant. Immunohistochemical analysis was negative for thyroglobulin and positive for calcitonin. A few patients with this variant have been reported in the literature, mainly diagnosed by immunohistochemical features of the tumor. In light of the limited information we have obtained from the literature, it is reasonable to emphasize that these cases should be distinguished from the mixed medullary- follicular thyroid carcinomas and medullary carcinomas with entrapped follicles. Immunohistochemical examination with calcitonin and thyroglobulin is also essential.

Expression of extracellular matrix proteins and vimentin in testes of azoospermic man: an immunohistochemical and morphometric study.

AIM: To investigate the changes in the extracellular matrix protein expression and the morphology of seminiferous tubules in the testis of 88 azoospermic men. METHODS: The patients were of the following categories: (1) 22 cases of Sertoli-cell-only syndrome, (2) 20 cases of spermatogenic arrest, and (3) 46 cases with hypospermatogenesis. Testicular sections were immunohistochemically stained for fibronectin, vimentin, laminin and collagen type IV. The seminiferous tubular diameter and the connective matrix zone (CMZ, the acellular zone between the basement membrane [BM] and the peritubular cells) thickness were measured. Seminiferous tubules were typed according to the thickness of the connective matrix in the lamina propria. The predominant tubule type and the Johnsen and Silber scores were determined. RESULTS: The mean tubular diameter were 119 +/- 27, 117 +/- 20, and 140 +/- 38 microm for Groups 1, 2, and 3, respectively. Both the laminin and the type IV collagen were localized to the epithelial BM and peritubular cells. In most of the tubules, BM and peritubular cells were separated by a homogenous acellular layer, the CMZ, in which laminin, type IV collagen, fibronectin and vimentin were not present. It is perceived that the worse the testicular histology, the higher the thickness of the CMZ. CONCLUSION: In testis with no or low sperm production, the diameter of the seminiferous tubules is decreased, the thickness of the seminiferous tubular wall is increased and a CMZ is formed between the peritubular cells and the BM. The thickness of CMZ is increasing with the advancement of testiclar deterioration. The most important morphologic predictive factor for spermiogenesis is the predominant

Androgen receptor levels in the sebaceous glands of papulopustular lesions from patients with Behçet's disease and acne vulgaris: a controlled study.

AIMS: Male sex and a younger age of onset in Behçet's disease (BD) are associated with more severe disease. Eye diseases, folliculitis and thrombophlebitis are also more common among males. The disease rarely developes before puberty or after the age of 50. Clinical manifestations of BD, with the exception of eye symptoms, tend to get better with time. Clinical and histological pattern of the papulopustular lesions (PPL), the most common type of skin lesions in BD and the difference from ordinary acne is contradictory. Therefore, BD may be androgen driven to some degree. In the present study, using acne vulgaris (AV) as a prototype of an androgen driven disease, we investigated such a possibility between PPL and androgen receptor (AR) levels in the sebaceous glands (SG) of PPL from patients with BD and AV. METHODS: Eighteen patients with BD (10 women, 8 men; mean +/- SD age, 34 +/- 11 years), 16 patients with AV (10 women, 6 men; mean +/- SD age, 25 +/- 6.2 years), and 10 healthy volunteers (5 women, 5 men; mean +/- SD age, 36 +/- 12 years), were included in this controlled study with blind histological study. Biopsies of the PPL and adjacent (approximately 2 cm distant) normal-appearing skin in patients with BD and AV, and of the normal-appearing skin from healthy volunteers were performed from the interscapular region, thus minimizing differences in androgenic activity. Follicle-based acneiform lesions were excluded for biopsies from patients with BD. Nuclear AR levels of SG were studied by an immunohistochemical technique, using monoclonal antibodies. The percentage of positively staining cells were recorded as the androgen receptor index (ARI). MAIN RESULTS: The lesional skin of the patients with BD showed a higher ARI than non-lesional skin of those patients (34.3% and 23.82%), or the healthy controls (21.37%). AR levels in the lesional skin of active patients was also higher than inactive patients (39.82 and 27.12%), but the differences were not statistically significant. ARI values in the lesional skin (78.58%) of acne patients were found to be significantly higher as compared with non-lesional skin (38.88%) and other groups (p<0.01). CONCLUSION: Our findings indicate that androgens may play a role at least in the formation of PPL and disease activity in patients with BD. Androgen metabolism takes place peripherally in the SG, being indipendent of the central endocrine regulation. Target organ sensitivity and excess number of nuclear AR seem to be responsible for the development of AV.

Clinicopathologic evaluation of CDw75 antigen expression in colorectal adenocarcinomas.

CDw75, a B lymphocyte surface antigen, is a sialylated carbohydrate epitope, which is generated by the enzyme beta galactosyl alpha 2,6 sialyltransferase (Sia-T1). In colon carcinomas, although higher levels of Sia-T1 has been described and found to be correlated with metastatic potential of tumor cells, the expression of CDw75 antigen still remains unknown. To address this issue, we investigated immunohistochemically CDw75 antigen expression in 195 colorectal adenocarcinomas and their nodal metastases. The correlation between CDw75 antigen expression with selected clinicopathologic variables was analyzed by using Chi-square and Fisher s exact tests. Positive staining was observed in 101 cases. Non-neoplastic mucosa was negative consistently. The frequency of positivity was decreased according to the degree of differentiation (p<0.001). Antigen expression was found to be associated with deeper penetration (p<0.006), positive lymph nodes (p<0.001), distant metastases (p<0.006) and advanced stage (p<0.001). Same relationships were detected in well and moderately differentiated tumors when CDw75 immunoreactivity was evaluated in each histologic grade separately. Our findings indicate that CDw75 antigen expression may be a good indicator of the biological aggressiveness of colorectal adenocarcinomas especially in tumors with well and moderately differentiated morphology.