'Very-low-risk' bladder tumours - a new entity?

OBJECTIVE: To evaluate the homogeneity of the 'low-risk' bladder cancer group in an attempt to optimise follow-up protocols. PATIENTS AND METHODS: Between June 1998 and December 2008, 211 patients (mean [sd] age of 66.7 [12.8] years) underwent transurethral resection of low-risk bladder cancer. Postoperative follow-up included cystoscopy at 3 and 12 months after surgery, then annually for a total of 5 years, and then annual ultrasonography indefinitely. RESULTS: After a median follow-up of 10 years, 65 patients (30.7%) developed tumour recurrence and three (1.4%) stage progressions. In all, 84 patients (40%) had tumours of ≤1 cm; these patients were significantly younger than patients with 1.1-3 cm tumours (64.6 vs 68.3 years, P = 0.03). Their 5-year recurrence-free survival rate was significantly higher (92% vs 70% in patients with larger tumours, P < 0.001). The median time to recurrence was 5.7 years in patients with smaller tumours and 3.6 years in patients with larger tumours (P = 0.03). Only 43.7% of the recurrences in patients with small tumours occurred within 5 years, compared to 75.5% in patients with larger tumours. CONCLUSIONS: Patients with low-risk bladder cancer make an inhomogeneous group. They can be stratified according to tumour size. Patients with tumours of ≤1 cm are younger, have lower risk of tumour recurrence, and most of their recurrences arise beyond the recommended 5-year surveillance period. It seems that these patients can be classified separately to a 'very-low-risk' group. Follow-up in these cases can be based on prolonged non-invasive evaluations.

Mixed high and low grade bladder tumors--are they clinically high or low grade?

PURPOSE: The pathological grade of bladder cancer has an immense impact on patient treatment and prognosis. While most bladder tumors show pure high or low grade patterns, some show a mixed pattern. We explored the incidence and clinical significance of this phenomenon. MATERIALS AND METHODS: A total of 642 patients with a mean age of 67.5 years underwent transurethral resection of nonmuscle invasive bladder tumors between June 1998 and December 2008, including 156 and 454 with low and high grade lesions, respectively. In 32 patients (5%) mixed grade tumors were found, defined as low grade tumors with 10% or less of a high grade component. All patients were followed a median of 60 months postoperatively. RESULTS: Mean age, the proportion of men and the proportion of stages Ta/T1 in patients with mixed grade tumors were between those of the high and low grade groups. Five-year recurrence-free survival was similar for high, low and mixed grade tumor types (56.9%, 63.8% and 66.4%, respectively, p=0.252). Five-year progression-free survival was significantly lower in patients with high grade disease (73.9%, p<0.0001) but similar in those with high and mixed grade tumors (99% and 96.9%, respectively, p=0.167). Similarly, disease specific survival was significantly worse in patients with high grade tumors (p<0.0001) but similar in those with high and mixed grade lesions (p=0.679). CONCLUSIONS: Mixed grade is found in about 5% of nonmuscle invasive tumors, representing a patient group with unique clinical features. The clinical course of patients with mixed grade tumors parallels that of patients with low grade tumors.

Intravesical administration of green tea extract attenuates the inflammatory response of bacterial cystitis--a rat model.

OBJECTIVE: To explore the effect of intravesical instillation of green tea extract (GTE) on a rat model of bacterial cystitis. MATERIALS AND METHODS: In vitro bactericidal properties of GTE were analysed by adding GTE to a suspension of uropathogenic E. coli (UPEC), streaking on MacConkey agar, and incubating overnight. In vivo effects of intravesical instillation of GTE on bacterial cystitis was analysed using a rat model of bacterial cystitis. In all, 42 female Sabra rats weighing 200-260 g were divided into five groups. Parameters measured were bladder weight (percentage of the total rat weight), dipstick urine analysis and histopathological changes in the bladder. Histological changes evaluated were degree of oedema, mixed inflammatory infiltration, urothelial epithelial invasion by neutrophils and reactive atypia. RESULTS: No in vitro bactericidal activity was detected for GTE. Intravesical instillation of GTE did not cause damage to the rat bladders. Intravesical instillation of GTE attenuated the inflammatory response to UPEC-SR71-induced bacterial cystitis in this rat model. CONCLUSIONS: Intravesical instillation of GTE attenuated the inflammatory response to UPEC-SR71-induced bacterial cystitis and is a novel approach to the treatment of bacterial cystitis. High concentrations of intravesical GTE did not cause histologically evident damage to the rat bladder. The results of this study are preliminary and further studies will be needed to explore the feasibility of using this approach in humans.

The natural history of secondary muscle-invasive bladder cancer.

BACKGROUND: The management of patients with high-grade non muscle invasive bladder cancer (NMIBC) brings diagnostic and therapeutic challenges. In the current study, we sought to study the natural history of progression to "secondary" muscle-invasive bladder cancer (MIBC)-cancer that developed during follow up of patients presenting with non-muscle invasive bladder cancer (NMIBC). METHODS: Between 1998 and 2008, 760 patients were treated for bladder cancer. Primary MIBC (>=T2) tumors (present upon presentation) were diagnosed in 114 patients. All patients with high-grade NMIBC were treated with intravesical BCG. Mean follow-up was 44 months. RESULTS: Forty patients (6.1%) developed secondary MIBC after a mean period of 21 months from initial diagnosis of bladder cancer. The 2- and 5-year disease-specific survival rates were better for patients with secondary MIBC (90% and 56% compared to 69% and 42% for patients with primary disease, p=0.03). The Kaplan-Meier curves of the two groups were parallel but displaced by approximately 2 years. CONCLUSION: In the current series, MIBC progression occurred among initially presenting patients with NMIBC in 6.1%. In most patients, the initial diagnosis of NMIBC is correct and muscle invasion occurs after a mean period of about 2 years. This supports a non-radical approach in patients with high-grade T1, Ta or Tis. Meticulous follow-up with liberal biopsy of any suspicious lesion may provide early diagnosis of invasive disease.

Oct-3/4 is a dose-dependent oncogenic fate determinant.

The Oct-3/4 transcription factor sustains embryonic stem (ES) cell self-renewal and is a dose-dependent cell fate determinant. In the adult male, its expression is restricted to type A spermatogonia. We show that Oct-3/4 is expressed in all human testicular germ cell tumors (GCTs) tested, even in the early premalignant component. We demonstrate that Oct-3/4 dictates ES cells' oncogenic potential in a dose-dependent manner; high levels increase the malignant potential of ES cell-derived tumors while Oct-3/4 inactivation induces regression of the malignant component. Oct-3/4 expression in a heterologous cell system transforms nontumorigenic cells and endows tumorigenicity in nude mice. Our findings suggest that Oct-3/4 is not only a distinctive immunohistochemical marker for GCTs, but also plays a critical role in the genesis of these tumors.

Predicting the risk of high-grade bladder cancer using noninvasive data.

AIM: To examine the hypothesis that the risk of high-grade bladder cancer can be predicted using noninvasively obtained data. PATIENTS AND METHODS: We retrospectively analyzed the database of 431 patients that had transurethral resection of first-time bladder tumors between June 1998 and December 2009. Pre-operative parameters evaluated were: patients' age; gender; sonographic tumor diameter, number and location of tumor inside the bladder; presence of hydronephrosis, and results of urinary cytology. Parameters that showed significance in multivariate analysis were incorporated into the nomogram. RESULTS: Multivariate analysis of the data showed that patient's age, the presence of hydronephrosis, sonographic tumor diameter (risk of a high-grade tumor: 14, 29, 43.3, 55.7 and 69.4% at diameters: 0.5-1.5, 1.6-2, 2.1-2.5, 2.6-3 and >3 cm, respectively), location of tumor in the bladder (risk of high-grade tumor: 28.8, 47, 67.5 and 90.5% in the lateral walls, posterior/base, anterior and dome, respectively), and urinary cytology were all highly significant and independent predictors of high-grade tumors. A nomogram constructed using these variables scored an area of 0.853 in the ROC curve. CONCLUSIONS: The risk of high-grade bladder tumor can be accurately predicted using non-invasively obtained information. This prediction can help to triage patients with newly detected bladder cancer for biopsy.

Transjugular kidney biopsy: enabling safe tissue diagnosis in high risk patients.

BACKGROUND: Transjugular kidney biopsy (TJKB) was first described in 1990. Indications for TJKB include uncorrectable bleeding disorders and conditions precluding the prone position. OBJECTIVES: To describe our initial experience with TJKB. METHODS: Between February 2008 and December 2009 all patients in whom percutaneous biopsy was contraindicated or unsuccessful underwent image-guided TJKB using a standard set with a 19 gauge core biopsy needle. Prospectively collected data included indication, number of needle passes, contrast dose, tissue yield, and complications. RESULTS: Twelve patients, age range 15-76 years (mean 55), underwent 14 TJKB procedures. Indications for the transjugular route included bleeding diathesis, dyspnea, ventral hernia, ascites, marked obesity, need for concomitant liver biopsy or concomitant insertion of tunneled dialysis catheter, discrepant kidney size, and failed percutaneous attempt. Thirteen biopsies were performed in 11 patients; in one patient TJKB was abandoned due to unfavorable renal vein anatomy. Four patients were premedicated with desmopressin and one with platelet transfusion due to prolonged bleeding time. Three to six passes (mean 3.8) were made per biopsy, with an overall yield of 9.6 +/- 8.2 glomeruli, providing a definite diagnosis in nine patients and a probable diagnosis in two. In two patients the first biopsy attempt yielded insufficient tissue, necessitating a repeat procedure. There were two minor bleeding episodes not requiring intervention. Serum creatinine was unchanged after the procedure and hemoglobin levels asymptomatically dropped by 0.3 +/- 1.0 g/dl within 48 hours, requiring no treatment. CONCLUSIONS: TJKB appears to safely allow adequate tissue diagnosis in patients at increased risk for complications from or contraindications to percutaneous renal biopsy.

Hyper-Interleukin-6 Protects Against Renal Ischemic-Reperfusion Injury-A Mouse Model.

Background: Most of the ischemia-reperfusion injury (IR-I) occurs during reperfusion and is mediated by the immune system. In this study we determined whether immunomodulation with hyper-Interleukin-6 (a recombinant designer cytokine composed of interleukin-6 linked to its soluble receptor) is protective against IR-I in mice kidneys. Methods: Hyper-Interleukin-6 (HIL-6) was administered by in vivo plasmid DNA transfection to 10 male mice. Twenty-four hours later, unilateral nephrectomy was done. IR-I immediately followed by closure of the remaining kidney vascular pedicle for 40 min. Seven mice transfected with non-coding control plasmid served as the control group. The functional and morphological effects of IR-I and its effect on mice longevity were explored. This was done by serial blood tests and by histopathology done upon sacrifice of the animals at post-operative day 7. Findings: Mice pretreated with HIL-6 had a mean creatinine level at post-operative day 1 of 35.45 ± 4.03 µmol/l and mean Urea level was 14.18 ± 2.69 mmol/l, whereas mean creatinine was 89.33 ± 69.27 µmol/l (P = 0.025), and mean urea was 38.17 ± 20.77 mmol/l (P = 0.0024) in the control group. Histological changes in the control group included inflammatory infiltration, tubular damage, and architectural distortion. These were not seen in the treatment group. Seven days post-operatively the survival rate of treated mice was 100% compared to 50% in the control group (P = 0.015). Interpretation: In this single kidney mouse model, pretreatment with HIL-6 administration effectively protected against IR-I both morphologically and functionally. Further studies are needed to better understand the mechanism and feasibility of using this immunomodulator.

Prostatic urothelial carcinoma: is transurethral prostatectomy necessary before bacillus Calmette-Guérin immunotherapy?

OBJECTIVE: To evaluate the efficacy of transurethral prostatectomy (TURP) followed by bacillus Calmette-Guérin (BCG) immunotherapy in patients with prostatic urothelial carcinoma (PUC) and compare the results of studies using combined TURP and BCG with studies in which TURP was not performed. PATIENTS AND METHODS: Patients with bladder cancer and PUC were treated with TURP followed by six weekly intravesical instillations of BCG. Response was determined and monitored by periodic bladder and prostatic urethra biopsies and urinary cytology. Also, the outcome of previous series using similar methodology was compared with the outcome of studies in which TURP was not performed. RESULTS: In all, 20 patients with PUC were treated with TURP followed by intravesical instillations of BCG. The median follow-up was 52.5 months. All patients had an initial complete response (CR). The prostatic urethra 5-year recurrence-free survival rate was 90%. However, bladder and prostatic urethra 5-year recurrence-free survival rate was only 30%. Five patients (25%) died from urothelial carcinoma (UC) after a median period of 58.5 months (two from bladder cancer metastases and three from upper tract metastases). The long-term prostatic urethra CR rate in studies using TURP before immunotherapy was significantly higher than the CR rate in studies using immunotherapy alone (P < 0.001). However, there was no difference when bladder and prostatic urethra CR rates were considered together (P = 0.54). CONCLUSION: In patients with PUC, TURP before BCG immunotherapy eliminates PUC in most cases, and is probably the preferred treatment for this disease. The risk of UC-specific mortality in these patients is high.

Fatal nephrotic syndrome complicating allogeneic stem cell transplantation: a case report.

Disturbed kidney function is a common occurrence after bone-marrow transplantation. Sepsis, nephrotoxic medications, thrombotic microangiopathy and injury related to haemodynamic alterations are frequently accountable. Recently, attention has been given to immune-mediated glomerular damage, related to graft-versus-host disease. Herein we describe the fatal course of a nephrotic syndrome complicating allogeneic stem cell transplantation in a young woman with long-standing paroxysmal nocturnal haemoglobinuria. A post-mortem kidney biopsy revealed amyloidosis of the AA type. Physicians should be aware of the possibility that infections and inflammation accompanying the post-transplantation period may rarely promote the development of systemic amyloidosis or exacerbate silent pre-existing disease.

The natural history of bladder carcinoma in situ after initial response to bacillus Calmette-Gúerin immunotherapy.

OBJECTIVES: To explore patterns of recurrence, muscle invasion, and disease specific mortality in patients with bladder carcinoma in situ (CIS) who responded to an induction course with intravesical bacillus Calmette-Gúerin (BCG) immunotherapy. METHODS: Between June 1985 and December 2003, 104 patients (mean age 67 years) were diagnosed with either pure (38 patients) or concomitant (66 patients) CIS. Patients who responded to one (92 patients) or two (12 patients) induction courses of intravesical BCG instillation were included in the study. Response was determined and monitored by routine periodic bladder biopsies. Outcome of patients and the effect of various prognostic parameters were assessed after a median follow-up of 75 months. RESULTS: The 5- and 10-year recurrence-free survival rates were 63% and 54%, respectively. The 5- and 10-year muscle-invasive-free survival rates were 79% and 77%, and the 5- and 10-year disease-specific survival rates were 90.5 and 85.8%, respectively. Median time to recurrence, muscle invasion, and disease-specific mortality was 18, 19, and 40 months, respectively. Pure and concomitant CIS were associated with a similar outcome. The recurrence of nonmuscle-invasive tumor did not increase the risk for muscle invasion or mortality. CONCLUSIONS: Pure and concomitant bladder CIS share similar biologic behavior. Muscle-invasive disease is expected in about 25% of the BCG responders followed for long time periods and disease-specific mortality in 15%. Tumor recurrence, whether nonmuscle-invasive or muscle-invasive, follows a similar time table suggesting that these are not sequential but parallel and independent processes.

IL-6/IL-6R axis plays a critical role in acute kidney injury.

The response to tissue injury involves the coordination of inflammatory and repair processes. IL-6 expression correlates with the onset and severity of acute kidney injury (AKI), but its contribution to pathogenesis remains unclear. This study established a critical role for IL-6 in both the inflammatory response and the resolution of AKI. IL-6-deficient mice were resistant to HgCl2-induced AKI compared with wild-type mice. The accumulation of peritubular neutrophils was lower in IL-6-deficient mice than in wild-type mice, and neutrophil depletion before HgCl2 administration in wild-type mice significantly reduced AKI; these results demonstrate the critical role of IL-6 signaling in the injurious inflammatory process in AKI. Renal IL-6 expression and STAT3 activation in renal tubular epithelial cells significantly increased during the development of injury, suggesting active IL-6 signaling. Although a lack of renal IL-6 receptors (IL-6R) precludes the activation of classical signaling pathways, IL-6 can stimulate target cells together with a soluble form of the IL-6R (sIL-6R) in a process termed trans-signaling. During injury,serum sIL-6R levels increased three-fold, suggesting a possible role for IL-6 trans-signaling in AKI. Stimulation of IL-6 trans-signaling with an IL-6/sIL-6R fusion protein activated STAT3 in renal tubular epithelium and prevented AKI. IL-6/sIL-6R reduced lipid peroxidation after injury, suggesting that its protective effect may be largely mediated through amelioration of oxidative stress. In summary, IL-6 simultaneously promotes an injurious inflammatory response and, through a mechanism of trans-signaling, protects the kidney from further injury.

Brain metastases: a rare initial presentation of prostate cancer.

Although brain metastases are common in cancer patients, carcinoma of the prostate rarely metastasizes to the brain. Cerebral metastases as an initial clinical presentation of prostate carcinoma are extremely rare. We report a patient, who presented with confusion and behavioral changes. Cranial magnetic resonance imaging revealed a large right temporal lobe lesion. The pathological diagnosis of the tumor was consistent with metastatic prostate carcinoma. Further evaluation revealed widespread bony metastases by technetium 99 bone scan and high level of prostate-specific antigen.

A working group classification of focal prostate atrophy lesions.

Focal atrophy is extremely common in prostate specimens. Although there are distinct histologic variants, the terminology is currently nonstandardized and no formal classification has been tested for interobserver reliability. This lack of standardization hampers the ability to study the biologic and clinical significance of these lesions. After informal and formal meetings by a number of the authors, focal atrophy lesions were categorized into 4 distinct subtypes as follows: (i) simple atrophy, (ii) simple atrophy with cyst formation, (iii) postatrophic hyperplasia, and (iv) partial atrophy. In phase 1 of the study, pathologists with varying levels of experience in prostate pathology were invited to view via the Internet a set of "training" images with associated descriptions of lesions considered typical of each subtype. In phase 2 of the study, each participant provided diagnoses on a series of 140 distinct "test" images that were viewed over the Internet. These test images consisted of the 4 subtypes of atrophy and images of normal epithelium, high grade prostatic intraepithelial neoplasia, and carcinoma. The diagnoses for each image from each pathologist were compared with a set of "standard" diagnoses and the kappa statistic was computed. Thirty-four pathologists completed both phases of the study. The interobserver reliability (median kappa) for classification of lesions as normal, cancer, prostatic intraepithelial neoplasia, or focal atrophy was 0.97. The median kappa for the classification of atrophy lesions into the 4 subtypes was 0.80. The median percent agreement with the standard diagnosis for the atrophy subtypes were: simple 60.6%, simple with cyst formation 100%; postatrophic hyperplasia 87.5%; partial atrophy 93.9%. The lower percentage for simple atrophy reflected a propensity to diagnose some of these as simple atrophy with cyst formation. Seven pathologists completed the phase 2 analysis a second time, and their intraobserver reproducibility was excellent. Three of 4 pathologists with low agreement with the standard diagnosis for simple atrophy improved their scores after repeating the analysis after re-examination of the "training set" of images. In conclusion, these criteria for variants of focal prostate atrophy may facilitate studies to examine the relation between various patterns of prostate atrophy and prostate cancer.

Identification of a novel functional androgen response element within hPar1 promoter: implications to prostate cancer progression.

Human protease-activated receptor-1 (hPar1) plays a role in malignant and physiological invasion processes. We have identified a functional androgen response element (ARE) located in the hPar1 promoter upstream of the transcription start site at -1791 to -1777. Dihydrotestosterone treatment of the prostate cancer cell line LNCaP increased endogenous hPar1 mRNA levels, consistent with the threefold increase in promoter activity of hPar1-luciferase reporter construct. Specific binding of the hPar1-derived ARE to LNCaP nuclear extracts was demonstrated by electrophoretic mobility shift assay. This binding was abrogated by antiandrogen receptor (anti-AR) antibodies or excess cold oligonucleotide but not by a mutated oligonucleotide. Moreover, using chromatin immunoprecipitation assays, we confirm the in vivo interaction between the AR and ARE domain of the hPar1 promoter. In parallel, we show that hormone ablation therapy markedly reduces the otherwise high hPar1 expression levels in prostate cancer biopsy specimens. We suggest that the hPar1 gene is regulated transcriptionally by androgens, representing one of several target genes effectively reduced during hormone ablation therapy. A major limitation of hormonal deprivation is that it causes only a temporary remission, and the cancer eventually reappears in a more malignant, androgen-independent form. hPar1 is also overexpressed in CL1 cells, an aggressively metastasizing, hormone-independent subclone of LNCaP, and in PC3 prostate adenocarcinoma lacking AR in a mechanism yet to be fully elucidated. These data may imply that hPar1 expression correlates with prostate cancer progression in androgen-dependent and -independent phases and therefore, provides an instrumental, therapeutic target for treatment in prostate cancer.

Puerperal renal rhabdomyosarcoma: case report and review of the literature.

Renal rhabdomyosarcoma is a rare malignant mesenchymal tumor with an aggressive clinical course. We describe the case of a 39-year-old woman with a large rhabdomyosarcoma of the left kidney serendipitously discovered ultrasonographically subsequent to cesarean section. To our knowledge, this is the first reported case of renal rhabdomyosarcoma during pregnancy. The importance of ultrasound examination in the differential diagnosis of gestational flank pain is discussed.

The Response of Variant Histology Bladder Cancer to Intravesical Immunotherapy Compared to Conventional Cancer.

BACKGROUND: High-grade urothelial carcinomas (UCs) often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with bacillus Calmette-Guerin (BCG). We compared the response, to treatment with BCG, of UC containing glandular, squamous, nested, and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade UC. METHODS: A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. Forty-one patients with Ta or T1, confirmed by second look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation, 13 patients with squamous differentiation, 9 patients with glandular differentiation, and 7 patients with nested variants. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly. FINDINGS: Patients with variant tumors had similar clinical features to patients with conventional disease, including age, male to female ratio, stage, the presence of Tis, and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC, including 5-year recurrence-free survival (63.5 Vs. 71.5%, p = 0.05), 5-year progression (≥T2)-free survival (60 Vs. 82.5%, p = 0.002), 5-year disease-specific survival (73 Vs. 92.5%, p = 0.0004), and overall survival (66 Vs. 89.5%, 0.05). INTERPRETATION: A patient with variant bladder cancer treated with intravesical immunotherapy has a 27% chance of dying from this disease within 5 years compared to 7.5% chance for a patient with conventional high-grade UC.

Effect of KRN7000 on induced graft-vs-host disease.

OBJECTIVE: Graft-vs-host disease (GVHD) is a serious complication of allogeneic stem cell transplantation (SCT) and donor lymphocyte infusion (DLI), for which no effective therapy exists. In our study, KRN7000, a synthetic analog of alpha-galactosylceramide, known for its ability to activate natural killer T cells, was tested for its ability to prevent onset of GVHD in a murine model of haploidentical major histocompatible (MHC) mismatched hematopoietic cells. METHODS: Irradiated (BALB/cXC57BL/6)F1 mice were inoculated with parental C57BL/6 splenocytes with or without SCT. KRN7000 was given intraperitoneally as single or multiple doses at 100 microg/kg/dose and mice were followed up for GVHD clinical symptoms and for survival. The effect of KRN7000 treatment was also tested in vitro for the induction of suppression of alloreactivity in mixed lymphocyte reaction (MLR). RESULTS: KRN7000 prevented development of GVHD symptoms in almost all mice and 52/53 mice maintained a healthy profile for more than 235 days. Most vehicle-treated mice or untreated controls died of GVHD within a median of 3 weeks. KRN7000 treatment did not prevent engraftment of donor cells following sublethal total-body irradiation (TBI) and allowed durable persistence of donor cells following lethal TBI and SCT. Splenocytes derived from KRN7000-treated mice suppressed efficiently mixed lymphocyte reaction (MLR) in vitro. CONCLUSION: GVHD induced by alloreactive lymphocytes can be prevented by KRN7000. GVHD prevention may be accomplished by regulation of T cell function and might thus provide a new modality for safer SCT and DLI.

Multiple myeloma involving the thyroid cartilage: case report.

Multiple myeloma involving the thyroid cartilage is exceedingly rare. We describe a patient with progressive airway obstruction due to diffuse involvement of the thyroid cartilage with multiple myeloma. CT revealed a conglomerate of calcifications of the thyroid cartilage. Additional classic lytic lesions of multiple myeloma were subsequently found in the bones, without associated calcifications. Calcified matrix in multiple myeloma involving the thyroid cartilage should now be included as an additional manifestation of extraosseous multiple myeloma.

Expression of the h19 oncofetal gene in premalignant lesions of cervical cancer: a potential targeting approach for development of nonsurgical treatment of high-risk lesions.

Background. Recent data suggest a role for H19 gene in promoting cancer transformation and progression. Cervical cancer, progresses from high-grade lesions (CIN3). At present, it is unclear if CIN lesions express H19. Objectives. To determine H19 expression in patient samples of CIN3 as well as the ability of a construct in which the promoter from the H19 gene drives expression of the diphtheria toxin A chain (DTA) to inhibit cervical cancer cell growth in vitro. Methods. H19 transcript levels were evaluated on 10 biopsies of CIN3 using in situ hybridization. PCR was used to examine H19 expression in cervical cancer cell lines and in two samples from a patient with cervical carcinoma. Cell lines were transfected with H19-DTA to determine its impact on cell number. Results. H19 gene was expressed in the area of CIN3 in 9 out of 10 samples. RT-PCR indicated expression of H19 in cervical cancer samples and in one of the three cell lines examined. Transfection of all cell lines with H19-DTA vector resulted in inhibited cell growth. Conclusions. H19 is expressed in the majority of CIN3 samples. These results suggest that most CIN3 lesions could be targeted by H19-DTA. Further in vivo preclinical studies are thus warranted.