Usefulness of the BTA STAT Test for the diagnosis of bladder cancer.

OBJECTIVES: To evaluate the usefulness of the Bard BTA stat Test in the diagnosis and follow-up of bladder cancer and to compare this test to cytologic analysis and cystoscopy, routine diagnostic methods. METHODS: Three hundred seventy-nine patients being followed up because of bladder cancer or with symptoms suggestive of bladder cancer underwent cystoscopy, cytologic analysis, and the BTA stat Test using a recently voided urine sample. In suspected cases, transurethral resection and histopathologic analysis were performed. RESULTS: Of the 379 patients, 235 proved to have bladder cancer and 144 did not. The sensitivity was 73.62% for the BTA stat, 61.70% for cytologic examination, and 99.57% for cystoscopy. The specificity was 83.33% for the BTA stat, 92.36% for cytologic analysis, and 85.42% for cystoscopy. The BTA stat Test's sensitivity for grades 1, 2, and 3 tumor was 47.27%, 69.15%, and 95.35%, respectively. The sensitivity of cytologic analysis was 30.91%, 55.32%, and 88.37%. The BTA stat Test's sensitivity for stage was 45.65% in Stage Ta, 75.52% in T1, and 95.56% in Stage T2-4; the cytologic results were 28.26%, 65.03%, and 84.44%, respectively. The combination of both tests improved the sensitivity and decreased the specificity slightly. CONCLUSIONS: The high sensitivity of the BTA stat Test, together with the data obtained from the parameters used for the evaluation of the test, demonstrate the better results of the BTA stat Test compared with cytologic analysis, making it a thoroughly valid diagnostic tool in the diagnosis of bladder cancer. In our opinion, the BTA stat Test can replace the use of cytologic analysis in the diagnosis of bladder cancer, but not the use of cystoscopy.

Amiodarone pulmonary, neuromuscular and ophthalmological toxicity.

Amiodarone is an iodinated benzofuran derivative class III antiarrhythmic that is highly effective in suppressing ventricular and supraventricular arrhythmias. It is also associated with an imposing side effect profile, which often limits its use. Numerous adverse effects have been documented including skin discolouration, photosensitivity, hepatitis, thyroid dysfunction, corneal deposits, pulmonary fibrosis, bone marrow suppression and drug interactions. These side effects are thought to be correlated with the total cumulative dose of amiodarone, but idiopathic reactions have been reported. The majority of adverse reactions resolve with discontinuation of the drug; however, rapid progression may occur, which may be fatal. The present report documents a patient who had a combination of serious amiodarone toxicities that, once recognized, were treated and eventually resulted in a good outcome.

Rat-to-mouse small bowel xenotransplantation: a novel model for studying acute vascular and hyperacute xenograft rejection and xenogenic cell migration.

The present study was undertaken to establish a rat-to-mouse vascularized small bowel xenotransplantation model to study acute vascular and hyperacute xenograft rejection, and xenogenic cell migration. Lewis rat small bowel grafts were transplanted heterotopically to group 1, Balb/c mice, and group 2, Balb/c mice pre-sensitized with a donor spleen cell injection. The grafts were examined by serial pathology and flow cytometry. In group 1, acute vascular rejection was present by the 5th post-operative day (POD). Immunohistology showed a strong endothelial deposition of IgG, IgM and C3, associated with a minimal lymphocytic infiltrate. There was a vigorous cell migration from the recipient to the graft, in which recipient origin cells comprised 80.1+/-6.9% of the graft mesenteric lymph node by POD 3. However, there was almost no cell migration from the graft to the recipient. The intestinal xenografts in the group 2 showed massive hemorrhage, fibrin deposition, vascular congestion and thrombosis 60 min after transplantation. IgG and C3 were present on the endothelium as early as 1 min after reperfusion. The vigorous humorally-mediated vascular damage and rapid elimination of donor cells seen with intestinal xenograft rejection are distinct from the usual picture of allograft rejection. Hyperacute rejection can be induced by recipient pre-sensitization with donor spleen cells. The potential advantages of studying xenotransplantation in this model include: (1) the wide range of immunologic reagents available for mice; (2) the opportunity to study the progression of vascular damage easily by performing serial biopsies in the same animal; and (3) the opportunity to study, in vivo, two-way cellular response by examining cell trafficking in the mesenteric lymph nodes.

Effect of major histocompatibility complex expression on murine intestinal graft survival.

BACKGROUND: Clinical intestinal transplantation has been plagued by frequent and severe graft rejection. It has been proposed that the major histocompatibility complex (MHC) antigens might play a critical role in this process owing to their extensive expression on enterocytes and mucosa-associated immune cells. METHODS: The present study examined the role of MHC antigens in intestinal graft rejection using MHC class I-deficient and MHC class II-deficient donors. RESULTS: Grafts with normal MHC expression were rejected by 9 days, whereas survival was prolonged to 14 days in the MHC class II-deficient grafts (P=NS) and to 20 days in the MHC I-deficient grafts (P<0.002). In all groups, early rejection was characterized by (1) increased crypt cell apoptosis, as detected by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique of in situ labeling; and (2) the increased expression of perforin and a CD8 phenotype in the graft-infiltrating cells. CONCLUSIONS: These data suggest that MHC antigens, CD8-positive T cells, and perforin-expressing cells contribute to intestinal graft rejection. Apoptosis of the progenitor epithelial crypt cells during early intestinal rejection may impair the gut's ability to regenerate and repair mucosal damage.

Cytologic diagnosis of a primary pure oat cell carcinoma of the bladder in voided urine. A case report.

BACKGROUND: The urinary bladder is an uncommon site for primary oat cell carcinoma, with as few as 30 histologically diagnosed cases described in the literature. The first reported cytologic diagnosis was made in 1991. CASE: A 76-year-old female presented with gross hematuria. Voided urine cytology showed small, dark cells with little visible cytoplasm and coarse chromatin. Subsequent histopathologic, immunopathologic and electron microscopic studies confirmed the diagnosis of primary oat cell carcinoma. CONCLUSION: The diagnosis of oat cell carcinoma is well recognized in respiratory cytology. The same cells found in a urinary specimen may suggest a primary oat cell tumor in conjunction with negative clinical and radiologic investigations for a primary tumor elsewhere.

Key features distinguishing post-transplantation lymphoproliferative disorders and acute liver rejection.

Post-transplantation lymphoproliferative disorder (PTLD) and acute rejection are two serious complications of orthotopic liver transplantation that can have a similar histologic appearance. We undertook the present study to assess the best way to distinguish these two entities. We studied histologic features, immunophenotyping, and Epstein-Barr virus (EBV) status, as assessed by immunohistochemical stain and in situ hybridization (ISH), in three groups: Group I, 8 cases of PTLD post-orthotopic liver transplantation with liver involvement; Group II, 15 cases diagnosed with acute liver rejection (control group); and Group III, a subset of 6 biopsy specimens from 4 patients of Group I whose graft rejection was diagnosed within the 2 months preceding the diagnosis of PTLD. The mean proportion of plasma to plasmacytoid cells in most cases from Group I was more than 40%, whereas from Group II it was less than 25% (P = .0001). There was a higher number of B lymphocytes than T lymphocytes in Group I. The numbers of mitotic figures and immunoblasts were significantly different in the two groups (P < .0001 and P = .0005, respectively), being higher in the patients with PTLD. EBV immunostain was most specific for the diagnosis of PTLD (75% positive in Group I, negative in Group II). ISH for EBV-encoded RNA was positive in 87% of cases in Group I and only 6.6% of cases in Group II (P = .0005). In Group III, four of the six liver biopsy specimens had a low plasma cell count and were negative for EBV studies. The other two biopsy specimens in this group had 70 to 80% plasma cell infiltrate, in addition to positive EBV immunostain and ISH in one, for which tissue was available for study. We conclude that viral studies and assessment of the number of plasma cells and B lymphocytes can help to distinguish between acute rejection and early PTLD.

Mycobacterium cell wall: an alternative to intravesical bacillus Calmette Guerin (BCG) therapy in orthotopic murine bladder cancer.

PURPOSE: The antitumor effect of intravesical mycobacterium cell wall (MCW) therapy on orthotopic and heterotopic bladder tumors in the mouse was assessed with magnetic resonance imaging (MRI). MATERIALS AND METHODS: The live bacillus Calmette Guerin (BCG) organism was replaced with a cell wall extract derived from the outer capsule of Mycobacterium phlei. This alternative form of intravesical therapy was used with the aim of reducing the toxicity associated with the live mycobacterium organism without compromising efficacy. Response to multiple doses of intravesical MCW and BCG was assessed in mice with established MBT-2 tumors after transurethral tumor implantation. RESULTS: Serial MRI of BCG-treated mice revealed significant tumor regression. The MR images correlated well with the corresponding histology of the whole mount bladder sections. Treatment with MCW also resulted in significant inhibition of tumor growth compared with control untreated animals (p < 0.05) although the antitumor effect was less pronounced than that of live BCG. Treatment was well tolerated in the MCW group with no apparent ill effects. Flow cytometric (FCM) analysis of bladder washings with phenotype-specific monoclonal antibodies revealed predominantly a CD3+ T cell infiltrate in the control and BCG-treated as well as the MCW-treated mice. The CD4+ (helper/inducer) subset of T cells predominated over the CD8+ (suppressor/cytotoxic) subset in both the BCG- and MCW-treated animals, and the CD4+/CD8+ ratio in both of the treated groups differed significantly from that of the control untreated groups. CONCLUSION: Intravesical MCW appears to invoke a similar inflammatory response in the mouse bladder mucosa as the live BCG organism and retains an antitumor action. It deserves further evaluation as a potential antitumor agent against bladder cancer. A Phase II clinical trial is now underway.

Surgical biopsy findings in patients with atypical hyperplasia diagnosed by stereotaxic core needle biopsy.

PURPOSE: To correlate the stereotaxic core needle biopsy results with those of surgical biopsy in patients with atypical lobular or ductal hyperplasia (atypical hyperplasia) diagnosed at stereotaxic core needle biopsy (SCNB). METHODS: We retrospectively reviewed the mammograms and pathology reports of 358 consecutive SCNBs performed in 323 patients. The results of SCNBs of 22 lesions reported as atypical hyperplasia were correlated with histologic findings at surgical biopsy. RESULTS: A histologic diagnosis of atypical hyperplasia at SCNB was found to be a poor predictor of the final surgical results. In the 19 patients with 22 lesions, surgical biopsy and SCNB results were in disagreement in 16, partial agreement in two, and complete agreement in only four lesions. Furthermore, five cases of atypical hyperplasia were shown to have invasive carcinoma on open biopsy, and five had ductal carcinoma in situ in the surgical biopsy, none of which was present on SCNB. CONCLUSION: Given the frequent occurrence of malignancy in patients diagnosed with atypical hyperplasia by SCNB, it is recommended that all such patients undergo excisional biopsy.

Prevention and reversal of renal allograft rejection by antibody against CD45RB.

Rejection continues to be the single largest impediment to successful organ transplantation. Antilymphocyte globulin, which contains antibodies that react with the leukocyte common antigen known as CD45, has proved to be one of the most effective agents for preventing rejection. We have shown earlier that a monoclonal antibody directed against the RB isoform of CD45 substantially inhibits the alloreactivity of human CD4+ lymphocytes in vitro. Here we investigate whether CD45RB could be an appropriate target for preventing renal allograft rejection in mice. Mice treated with two injections of a monoclonal antibody (MB23G2) raised against CD45RB protein all survived and had normal renal function. Furthermore, this antibody reversed acute rejection when therapy was delayed until day 4, and the mice survived for their natural lifespan. The immunosuppression achieved may find application in the prevention and treatment of transplant rejection in man.

Cortisol secretory patterns in Cushing's disease and response to cyproheptadine treatment.

To investigate whether cortisol secretory patterns are associated with a response to cyproheptadine treatment in Cushing's disease, we studied two patients with a hyperpulsatile pattern and one patient with a hypopulsatile pattern before and during chronic cyproheptadine therapy (24 mg daily). In the two patients with a hyperpulsatile cortisol secretory pattern, pituitary magnetic resonance imaging with gadolinium did not reveal a pituitary adenoma, whereas in the patient with a hypopulsatile cortisol secretory pattern, a microadenoma was identified. Plasma cortisol levels were measured every 30 min for 24 h. In the two patients with a hyperpulsatile cortisol secretory pattern, chronic treatment with cyproheptadine resulted in sustained clinical and biochemical improvement and normalization of the median of absolute and relative increments in cortisol spikes. In the patient with a hypopulsatile cortisol secretory pattern, only a reduction of cortisol spikes was noticed during treatment. These results suggest that patients with Cushing's disease who are characterized by a hyperpulsatile cortisol secretory pattern and in whom no pituitary lesion can be identified by magnetic resonance imaging, cyproheptadine treatment may be useful.

Altered gene expression of cytokine, ICAM-1, and class II molecules precedes mouse intestinal allograft rejection.

Rapid and severe rejection remains a major obstacle to successful clinical intestinal transplantation (IT). The aggressive nature of rejection in IT has been attributed to the increased massive immune stimulus provided by large numbers of resident lymphocytes, antigen presentation capacity of enterocytes, and graft damage mediated by luminal microflora. Early small bowel expression of proinflammatory cytokines, MHC class II, and adhesion molecules may also promote IT rejection, but the lack of a mouse model has hampered extensive studies of gene expression in IT. Using a recently developed surgical model, we examined the temporal pattern of gene expression in CB6F1 (H-2b/d) vascularized, heterotopic intestinal allografts transplanted into BALB/c (H-2d) mice. Although histological evidence of rejection was not present until day 7 in allografts, Northern blot analysis demonstrated increases in TNF alpha gene transcripts as early as day 3, followed by the expression of IL-1 beta, intercellular adhesion molecule-1, and MHC class II by day 5. Using reverse-transcriptase polymerase chain reaction, IFN-gamma was detected in allografts by day 3 and persisted to day 10. In contrast, IL-2, IL-4, IL-5, and IL-6 mRNA transcripts peaked by day 5 and then decreased, suggesting that both Th1 and Th2 subsets are involved in the rejection of unmodified small bowel allografts. The early and progressive expression of TNF alpha and IL-1 beta as well as IFN-gamma, intercellular adhesion molecule-1, and MHC class II in IT rejection may contribute to the difficulty in controlling IT rejection with present immunosuppression.

Treatment with FK506 prevents rejection of rat colon allografts.

Colon transplantation has been proposed as a method to improve the function of an intestinal allograft. The present study examined the risk of colon rejection and the effect of FK506 on colon rejection in BN-->LEW rats with orthotopic bowel transplants. The first 4 groups included rats with untreated allografts (group 1), rats with isografts treated with 0.6 mg/kg FK506 (group 2), rats with allografts treated with 0.6 mg/kg FK506 (group 3), and rats with allografts treated with 0.4 mg/kg FK506 (group 4). In each of these groups (10-12 rats), half of the animals received a small bowel graft only (SB), while the other half received a small bowel, ascending colon, and cecum graft (SBC). The animals were followed daily until they died or were killed at 4 weeks. In group 5, an additional 18 untreated rats with SBC allografts were randomly killed on the third, fifth, seventh, and tenth postoperative days to study the sequential histopathologic and immunopathologic changes of colon rejection. There was no difference in survival, body weight, nutritional parameters, or bacterial contamination after SB and SBC transplantation. Intestinal transit was slower after SBC than SB transplantation (P < 0.05). Sequential histopathologic studies revealed that (1) the severity and time course of colon rejection was similar to small intestine rejection, and (2) the features of colon rejection were similar to ulcerative colitis. There was no evidence of graft-versus-host disease after SBC transplantation. In summary, adding a segment of large bowel to a small bowel allograft does not increase the risk of rejection or surgical complications. The transplanted colon slows intestinal transit. Treatment with FK506 effectively prevents colon rejection. These data suggest that adding a colon graft may improve the outcome of clinical small bowel transplantation.

Transplantation of segmental rat intestinal grafts including the ileocecal value and the ascending colon.

Extrinsic denervation and lymphatic disruption impair nutrient absorption after small bowel transplantation. The present study was undertaken to determine whether adding the ileocecal valve with or without the ascending colon would improve the function of a segmental intestinal graft. Five groups of Lewis rats (n = 10/group) were studied. Group I had a sham laparotomy. Groups II, III, IV, and V had the native jejunum, ileum, and cecum replaced with a graft. Inbred Lewis rats were used as isogeneic donors for the transplants to avoid the confounding effect of graft rejection. Group II had the entire jejunum and ileum transplanted. Group III had 20 cm of terminal ileum transplanted. Group IV had 20 cm of the terminal ileum including the ileocecal valve transplanted. Group V had 20 cm of the terminal ileum, the ileocecal valve, and the ascending colon transplanted. The terminal ileum-transplanted and terminal ileum/ileocecal valve-transplanted groups lost more than 25% of their preoperative weight by the end of the second postoperative week; most of these animals were killed because of inanition. In contrast, the sham laparotomy, jejunum/ileum-transplanted, and ascending colon-transplanted groups remained healthy until completion of the study on the 28th postoperative day. The ascending colon-transplanted group had slower intestinal transit and less bacterial contamination of the terminal ileum compared with the terminal ileum-transplanted and terminal ileum/ileocecal valve-transplanted groups (P < 0.05). Transplantation of the ascending colon and the ileocecal valve significantly improves the function of segmental small bowel isografts in rats. These data suggest that adding a colonic segment may be a simple method to improve the function of short-segment cadaveric and living-related intestinal grafts in humans.

Human orthotopic small intestine transplantation: radiologic assessment.

The authors describe the postoperative anatomy and review the radiologic examinations of five patients who underwent orthotopic small intestine or combined orthotopic liver and small intestine transplantation. Mucosal thickening of the transplanted intestine was demonstrated on the first postoperative contrast material-enhanced images and was due to submucosal edema. This resolved within 2 weeks in the long-term survivors. Bowel peristalsis appeared normal as early as 31 days after transplantation. Contrast-enhanced examinations of the intestine were useful to exclude surgical complications such as anastomotic leaks or strictures, but were insensitive for biopsy-proved cytomegalovirus enteritis or rejection.

Fine needle aspiration cytologic characteristics of hyalinizing trabecular adenoma of the thyroid.

The cytologic characteristics of a histologically proven hyalinizing trabecular adenoma are presented. The solitary thyroid nodule was diagnosed cytologically as benign and histologically as malignant. Cytologically, the fine needle aspirate showed increased cellularity, with mild nuclear atypia and eosinophilic nuclear pseudoinclusions. Collections of an amorphous colloidlike material were noted surrounded by follicular cells. Inflammatory cells in the background suggested the possibility of a thyroiditis. Since the patient's antibodies were negative, a hemithyroidectomy was performed to rule out a neoplasm. The frozen section was interpreted as suggestive of medullary carcinoma since the tumor showed a poorly differentiated pattern of cells with marked nuclear atypia and abundant fibrous stroma (thought to be amyloid) separating the cells. The results of immunopathology and electron microscopy ruled out a medullary carcinoma. Upon review of the histology at a later date, the case was recategorized as a hyalinizing trabecular adenoma, proving the negative cytologic diagnosis to be correct.

An unusual complication of polymorphic reticulosis: a case presentation.

The authors present a case of polymorphic reticulosis which responded to radiotherapy, but had a fatal complication with the development of a tracheoesophageal fistula.