Unusual metastasis after radical cystectomy: case report.

Cutaneous metastasis of urothelial carcinoma after radical cystectomy is extremely rare. We present the case of a 57-year-old man who underwent a radical cystectomy with ileal conduit for the presence of a bladder tumor. He developed a cheek lesion after 2 months, which was diagnosed as a metastatic nodule along with bone metastases from high-grade bladder urothelial carcinoma. This nodule was treated with surgical removal with subsequent chemotherapy, but he succumbed after 10 months due to widespread metastatic disease.

Isolated diffuse intestinal ganglioneuromatosis presented as a redundant sigmoid colon: a case report.

Diffuse intestinal ganglioneuromtosis is a benign tumor of the enteric nervous system, that almost always occurs in children with systemic syndromes. Whereas isolated cases in adults are exceedingly rare. Case Presentation: A 38-year-old man presented with refractory chronic constipation. An abdominal computed tomography scan revealed a redundant sigmoid colon, then he underwent a sigmoid colectomy. Histopathologic examination showed diffuse ganglioneuromatosis. However, the patient was in good health 18 months after surgery. Clinical Discussion: Intestinal ganglioneuromas commonly occur in children with systemic syndromes such as multiple endocrine neoplasia type 2B and neurofibromatosis type 1. The most frequent symptoms are abdominal discomfort, constipation, ileus, weight loss, appendicitis, and obstruction in more severe cases. surgical resection is the standard management in diffuse ganglioneuromatosis. Conclusion: Although diffuse ganglioneuromatosis is uncommon, it should be considered in patients with refractory constipation.

Genome Sequence of Escherichia coli Stbl4, a Versatile Genetic Tool for Heterologous Expression.

Escherichia coli Stbl4 is widely used as a laboratory strain for heterologous expression of large gene clusters. Since no genome sequence has been publicly available, we here report the draft sequence of Stbl4, including its F-plasmid. It should serve as a useful reference for researchers working with Stbl4.

Proteomic analysis of Class IV lupus nephritis.

BACKGROUND: There have been several attempts to standardize the definition and increase reproducibility in classifying lupus nephritis (LN). The last was made by the International Society of Nephrology and Renal Pathology Society in 2003 where the introduction of Class IV subcategories (global and segmental) was introduced. METHODS: We investigated whether this subdivision is important using a proteomics approach. All patients with renal biopsies along with their clinical outcome of LN were identified and regrouped according to the above 2003 classifications. Fresh-frozen renal biopsies of Class IV LN (global and segmental), antineutrophil cytoplasmic antibody-associated vasculitis and normal tissue were analyzed using two-dimensional gel electrophoresis (2-DE) and mass spectrometry. Differentially expressed proteins were identified and subjected to principal component analysis (PCA), and post hoc analysis for the four sample groups. RESULTS: PCA of 72 differentially expressed spots separated Class IV global and Class IV segmental from both normal and antineutrophil cytoplasmic antibody-associated vasculitis (ANCA). The 28 identified proteins were used in a post hoc analysis, and showed that IV-global and IV-segmental differ in several protein expression when compared with normal and ANCA. To confirm the proteomic results, a total of 78 patients (50 Class IV-Global and 28 Class IV-Segmental) were re-classified according to 2003 classification. There was no difference in therapy between the groups. The renal survival and patient survivals were similar in both groups. CONCLUSIONS: There is no strong evidence to support a different outcome between the two subcategories of Class-IV LN and, they should thus be treated the same until further studies indicate otherwise.

Penile autotransplantation in rats: An animal model.

CONTEXT: Penile allotransplantation might be a viable option for patients who need penile reconstruction. AIMS: A successful autotransplantation rat model is the first step toward proceeding for allotransplantation. We herein evaluate autotransplantation following transaction of the rat penis just distal to the urethral bulb. SETTINGS AND DESIGN: Experimental animal study. MATERIALS AND METHODS: Five Sprague-Dawely rats weighing 520 g (SD 19) were used. Utilizing a magnification of 6-40, transection and immediate anastomosis of the tunica albuginea, urethra, dorsal vein and nerves were carried out. Vesicostomy was made to divert urine. The glandular skin was sutured to the perineum and the abdominal wall was closed in layers. STATISTICAL ANALYSIS USED: Descriptive statistics. RESULTS: Average surgery time was 8 h. The first two rats had no vesicostomy and died in the first postoperative day from retention. Three rats tolerated well the procedure and survived to the end point. One rat was sacrificed at day 10 and histopathology showed 30-50% necrosis of the implanted penis. Another rat was sacrificed at day 20 and showed normal cavernous tissue. The fifth rat was sacrificed 3 months postoperatively and showed evidence of moderate corporal fibrosis. Urethral fistula and necrosis of corpus spongiosum, dorsal nerve necrosis and dorsal vein occurred in all animals. CONCLUSIONS: Penile autotransplantation in rats is feasible and provides the basis for evaluation of the corpora cavernosa in an allotransplantation model. Long-term urethral continuity and dorsal neurovascular bundle survival in this model is difficult to establish.

The spectrum of glomerular diseases as studied by immunofluorescence microscopy a single center study in Iraq.

INTRODUCTION: Immunofluorescence (IF) microscopy is an important tool for the diagnosis of glomerular diseases. In this study, we focused on using IF technique together with light microscopy (LM) and clinical features in the diagnosis of different types of glomerulonephritis (GN). We aimed to evaluate the spectrum of glomerular diseases in our center and compare it with other centers in Iraq as well as in other countries. METHODS: We studied a total of 58 kidney biopsies taken between June 2010 and June 2012. All biopsies were examined by LM and 56 of them were examined by IF technique. Clinical information was recorded in a predesigned form before taking the biopsy. RESULTS: Nephrotic syndrome was the predominant clinical presentation in this study (75.9%). Focal segmental glomerulosclerosis (FSGS) was the commonest GN in this study (29.3%) followed by minimal change disease (20.7%) and membranous glomerulonephritis (13.8%). Immune deposition was observed in 37.5% of cases and the predominant deposit was immunoglobulin G (IgG). In all cases but one, deposition was granular and was found in the glomerular basement membrane (GBM) and/ or in the mesangium. In one case, IF showed dominant positive staining (3+) for complement factor 1q (C1q) in the glomerular mesangium and slightly positive staining for complement factor 3 (C3) in the same mesangeal areas. Two cases (3.4%) fulfilled the clinical, serological and histopathological criteria of lupus nephritis (LN). CONCLUSION: Nephrotic syndrome was the predominant clinical presentation and FSGS was the most commonly diagnosed GN in this study. Using IF technique and correlating it with LM, clinical, biochemical and serological markers was very useful for the correct diagnosis of glomerular diseases.

Tissue factor/factor VIIa pathway mediates coagulation activation in induced-heat stroke in the baboon.

OBJECTIVE: Excessive activation of coagulation, which can culminate in overt disseminated intravascular coagulation, is a prominent feature of heat stroke. However, neither the mechanism that initiates the coagulation activation nor its pathogenic role is known. We examined whether the tissue factor/factor VIIa complex initiates the coagulation activation in heat stroke and, if so, whether upstream inhibition of coagulation activation through its neutralization may minimize cellular injury and organ dysfunction. We also examined whether coagulation inhibition influences heat stroke-induced fibrinolytic and inflammatory responses. DESIGN: Randomized controlled study. SETTING: Comparative Medicine Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. SUBJECTS: Baboons (Papio Hamadryas). INTERVENTIONS: Twelve anesthetized baboons assigned randomly to recombinant nematode anticoagulant protein c2, a powerful inhibitor of tissue factor/factor VIIa-dependent coagulation (n = 6), or a control group (n = 6) were heat-stressed in a prewarmed neonatal incubator at 44-47°C until systolic blood pressure fell <90 mm Hg, signaling the onset of severe heat stroke. Recombinant nematode anticoagulant protein c2 was administered as a single intravenous dose of 30 µg/kg body weight at onset of heat stroke. The control group received an equivalent volume of sterile saline intravenously. MEASUREMENTS AND MAIN RESULTS: Heat stroke was associated with coagulation activation and fibrin formation as evidenced by the increased plasma thrombin-antithrombin complexes, endogenous thrombin potential, and D-dimer levels. Recombinant nematode anticoagulant protein c2 induced significant inhibition of thrombin generation and fibrin formation. Inhibition of coagulation in recombinant nematode anticoagulant protein c2-treated animals did not influence either fibrinolysis (assessed by tissue plasminogen activator, plasmin-α2-antiplasmin complexes, and plasminogen activator inhibitor) or the release of pro- and anti-inflammatory cytokines. No difference in markers of cell injury and organ dysfunction was observed between recombinant nematode anticoagulant protein c2-treated and control groups. CONCLUSIONS: Tissue factor/factor VIIa-dependent pathway initiates coagulation activation in induced-heat stroke in the baboon without an effect on fibrinolysis and inflammation. The findings suggest also that coagulation activation is not a prerequisite of cell injury and organ dysfunction.

Cyclooxygenase-2 inhibition inhibits PI3K/AKT kinase activity in epithelial ovarian cancer.

Cyclooxygenase-2 (COX-2) expression contributes to tumor growth and invasion in epithelial ovarian cancer (EOC). COX-2 inhibitors exhibit important anticarcinogenic potential against EOC, but the molecular mechanisms underlying this effect and relation with PI3-kinase/AKT signaling remain the subject of intense investigations. Therefore, the role of COX-2 in EOC and its cross talk with PI3-kinase/AKT pathway were investigated using a large series of EOC tissues in a tissue micro array (TMA) format followed by in vitro and in vivo studies using EOC cell lines and NUDE mice. Clinically, COX-2 was overexpressed in 60.3% of EOC and was significantly associated with activated AKT (p < 0.0001). Cox-1 expression was seen in 59.9% but did not associate with AKT. Our in vitro data using EOC cell line showed that inhibition of COX-2 by aspirin, selective inhibitor NS398 and gene silencing by COX-2 specific siRNA impaired phosphorylation of AKT resulting decreased downstream signaling leading to cell growth inhibition and induction of apoptosis. Finally, treatment of MDAH2774 cell line xenografts with aspirin resulted in growth inhibition of tumors in NUDE mice via down-regulation of COX-2 and AKT activity. These data identify COX-2 as a potential biomarker and therapeutic target in distinct molecular subtypes of ovarian cancer.

Culture-related service expectations: a comparative study using the Kano model.

OBJECTIVE: To compare service expectations between Arab and Austrian patients. METHODS: We used a Kano model-based questionnaire with 20 service attributes of relevance to the dialysis patient. We analyzed 530, 172, 60, and 68 responses from Saudi, Austrian, Syrian, and UAE patients, respectively. We compared the customer satisfaction coefficient and the frequencies of response categories ("must be," "attractive," "one-dimensional," and "indifferent") for each of the 20 service attributes and in each of the 3 national groups of patients. We also investigated whether any differences seen were related to sex, age, literacy rate, or duration on dialysis. RESULTS: We observed higher satisfaction coefficients and "one-directional" responses among Arab patients and higher dissatisfaction coefficients and "must be" and "attractive" responses among Austrian patients. These were not related to age or duration on dialysis but were related to literacy rate. CONCLUSION: We speculate that these discrepancies between Austrian and Arab patients might be related to underdeveloped sophistication in market competitive forces and to cultural influences.

Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy.

PURPOSE: To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response. PATIENTS AND METHODS: Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses. RESULTS: RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort. CONCLUSION: RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.

Sarcoidosis and immunoglobulin lambda II light-chain amyloidosis diagnosed after orthotopic heart transplantation: a case report and review of the literature.

Cardiac involvement by sarcoidosis and concomitant deposition of AL amyloid is an uncommon association. We describe the case of a 53-year-old African-American man with a 7-year history of dilated nonischemic cardiomyopathy and severe cardiac failure who underwent orthotopic heart transplantation. His prior cardiac biopsies had only mild myocyte hypertrophy and minimal interstitial fibrosis. After surgery, numerous sarcoid granulomas and amyloid deposition were identified in the native heart. Six days after the transplant the patient died due to aspiration bronchopneumonia and acute renal failure. At autopsy, both sarcoidosis and immunoglobulin (Ig) lambda light-chain amyloidosis were present in the native atria, lungs, thyroid, liver, spleen, and kidneys. Sarcoid granulomas alone were present in the parathyroids, lymph nodes, and bone marrow. Amyloid deposition alone was present in the aorta, stomach, large bowel, and urinary bladder. There was no evidence of plasma cell dyscrasia, or underlying gammopathy. This unusual association was described in only two other cases in the medical literature. However, this is the first case of sarcoidosis and AL amyloidosis with successful sequencing and identification of Ig lambda light-chain amyloid, and in which there was no evidence of plasma cell dyscrasia.

Cytologic features of renal medullary carcinoma.

BACKGROUND: Renal medullary carcinoma is a rare tumor that is most common in young black men with sickle cell disease or trait. Patients often present with advanced disease at the time of diagnosis, and their prognosis is poor, even with aggressive therapy. The clinical and pathologic features of renal medullary carcinoma have been described in several articles, but reports describing the cytologic features are rare. METHODS: In the current report, the authors describe the cytologic features of three cases of renal medullary carcinoma. The patients were young black men with sickle cell trait ages 20 years, 33 years, and 33 years. RESULTS: All three patients presented with hematuria, flank pain, and a renal mass. The cytologic specimens from all three patients showed primarily cohesive groups of cells with vacuolated cytoplasm that often displaced or indented the nuclei. The nuclei often had irregular membranes, coarse or vesicular chromatin, and prominent nucleoli. Both of the two patients who were tested with fluorescence in situ hybridization were negative for the bcr/abl rearrangement. CONCLUSIONS: Renal medullary carcinoma should be considered in the differential diagnosis of patients who present with hematuria or a renal mass, especially in young black men with sickle cell disease or trait. Cytologically, renal medullary carcinoma cells appear similar to the cells in high-grade carcinoma. Immunohistochemical studies can be helpful in distinguishing renal medullary carcinoma from other poorly differentiated kidney tumors, except for collecting duct carcinoma. The clinical findings are key to diagnosing renal medullary carcinoma.

Diagnostic role of fine-needle aspiration of pancreatic allograft to detect rejection.

The purpose of this study was to assess whether the same principles to evaluate renal transplant by fine-needle aspiration (FNA) for rejection could be applied to pancreatic allograft. Between 1996-1998, 25 ultrasound-guided FNAs on 13 patients with pancreatic allograft were performed and ThinPrep made. The percentage of lymphocytes, lymphoblasts, monocytes, eosinophils, plasma cells, immunoblasts, and macrophages were calculated. Simultaneous peripheral smear was obtained and "total corrected increment" score calculated. Subsequent core biopsy was available in six patients. A total of seven FNAs on three patients were inadequate because of insufficient epithelial cells. No evidence of rejection reported in nine patients was confirmed on biopsy in five patients. One patient reported as suspicious later showed rejection on biopsy. Thus, FNA may be used to monitor the graft status with faster turnaround times. Rejection may be a focal process and FNA may be used for sampling multiple sites. Cytologic diagnosis fairly accurately detects early rejection. Core biopsies are warranted in unsatisfactory specimens and when FNA is suspicious for rejection.

Anaplastic T large cell lymphoma diagnosed by exfoliative cytology in a post renal transplant patient.

In the last two decades posttransplant lymphoproliferative disorders (PTLDs) have been recognized as a complication of organ transplantation with immunosuppression. The reported incidence of PTLDs in renal transplant patients ranges between 0.3-3% (Birkeland et al., Transplantation 1999;67:876-881). In contrast to the reported incidence of PTLDs in post bone marrow transplant, it is 1% in HLA-matched recipients and up to 20% in HLA mismatched T-cell depleted bone marrow recipients (Curtis et al., Blood 1996;94:2208-2216). In cardiac transplant recipients the reported incidence of PTLDs is between 1.8-9.8 (Mihalov et al., Clin Transplant 1996;10:248-255). PTLDs are predominately extranodal. They have varied morphologic patterns and clonality, but almost all are associated with Epstein-Barr virus (EBV). The vast majority are of B cell lineage; only about 10% are of T-cell origin. We report a T-cell anaplastic large cell lymphoma (ALCL) presenting with bilateral pleural effusion and liver involvement in a renal transplant recipient.

Diagnostic role of fine-needle aspiration of bone lesions in patients with a previous history of malignancy.

At the present time fine-needle aspiration (FNA) is considered a routine diagnostic procedure in evaluating neoplastic vs. nonneoplastic lesions in many organs, with high sensitivity and specificity. The purpose of this study was to assess the utility of FNA in areas of diagnostic difficulty and its limitations in evaluating bone lesions in patients with a previous history of malignancy. From 1989 to 2000, 249 CT-guided FNAs of bone lesion were performed at our institutions; 187/249 (75.1%) patients had a previous history of malignancy. Aspirated material was air-dried for Diff-Quik stain or fixed in ethanol for Papanicolaou staining. Subsequent surgical tissue was available in 69/187 (36.9%) of the cases. There were 114 males and 73 females, ages 14-86 yr (mean, 64 yr). The primary tumor site was lung 49, genitourinary 46, breast 31, gastrointestinal 28, hematopoietic 26, soft tissue/skin 5, and thyroid 2. There were 125 FNAs of the vertebral spine, 19 from the pelvis, 11 from the ribs, 9 from the sternum, 5 from the femur, and 18 from miscellaneous bone sites. Out of 187, 166 (88.7%) were malignant aspirates confirming the patients' primary malignancies. The most common malignancy encountered was adenocarcinoma, 126/187 (67.4%). Surgical tissue was available for review in 69 patients and the results were in agreement with the FNAs diagnosis in all cases. Nine out of 187 (4.8%) cases were diagnosed as marrow elements on cytological material. These patients have been followed for 1-9 yr and have failed to reveal signs or symptoms of clinical recurrence. Three out of 187 (1.6%) cases showed osteomyelitis. Nine out of 187 (4.8%) were unsatisfactory specimens, with biopsy follow-up available in four cases, showing three metastatic tumors and one case of osteomyelitis. FNA of metastatic bone lesions is a major step in pretreatment diagnosis. On satisfactory specimens, the cytological diagnosis viewed in the clinical-radiological context proves to be similar to surgical diagnosis. FNA is an excellent technique with a high accuracy rate in assessing metastatic bone lesions.