Noninvasive diagnostic imaging using machine-learning analysis of nanoresolution images of cell surfaces: Detection of bladder cancer.

We report an approach in diagnostic imaging based on nanoscale-resolution scanning of surfaces of cells collected from body fluids using a recent modality of atomic force microscopy (AFM), subresonance tapping, and machine-leaning analysis. The surface parameters, which are typically used in engineering to describe surfaces, are used to classify cells. The method is applied to the detection of bladder cancer, which is one of the most common human malignancies and the most expensive cancer to treat. The frequent visual examinations of bladder (cytoscopy) required for follow-up are not only uncomfortable for the patient but a serious cost for the health care system. Our method addresses an unmet need in noninvasive and accurate detection of bladder cancer, which may eliminate unnecessary and expensive cystoscopies. The method, which evaluates cells collected from urine, shows 94% diagnostic accuracy when examining five cells per patient's urine sample. It is a statistically significant improvement (P < 0.05) in diagnostic accuracy compared with the currently used clinical standard, cystoscopy, as verified on 43 control and 25 bladder cancer patients.

Devastating complications after brachytherapy in the treatment of prostate adenocarcinoma.

OBJECTIVE: To report a retrospective chart review of patients who developed recto-urethral fistula (RUF) or several bladder neck contracture (BNC) recurrences after brachytherapy for treating localized prostate cancer. PATIENTS AND METHODS: In the past 3 years 18 patients with devastating complications after prostate brachytherapy were referred to our centre (RUF in 11, BNC in seven; mean age 63 years, range 60-81). All patients with RUF initially underwent diverting colostomy (six cystoprostatectomy with closure of the fistula, omental interposition and urinary diversion; one prostatectomy, bladder neck closure, fistula closure with omentum flap and continent vesicostomy). Three patients had the fistula closed with gracilis muscle flap using the York-Mason approach (one had a bladder neck closure and suprapubic tube; one elected to have no treatment). All patients with BNC had received three or more procedures to resect or incise their contracture. Four had diversion with a catheterizable segment, two used an indwelling Foley catheter and one uses intermittent catheterization. RESULTS: All six patients who had cystoprostatectomy with urinary diversion have had no recurrence of their RUF. All three treated with the York-Mason procedure healed well. One developed recurrent prostate adenocarcinoma and two a secondary neoplasia in the prostate or rectum (leiomyosarcoma and neuroendocrine, respectively). The enterocystoplasty patient developed sepsis after colostomy reversal and subsequently died. In those patients with BNC, the four who underwent urinary diversion fared well; two tolerate the indwelling catheter poorly, and the seventh uses intermittent catheterization with occasional difficulty. CONCLUSIONS: Brachytherapy with or without external irradiation can be associated with severe complications. RUF managed with aggressive anterior pelvic exenteration and urinary diversion can be associated with excellent results. The York-Mason procedure in patients with an adequate urinary continence mechanism and bladder dynamics may provide good functional results. The presence of a secondary malignancy in patients deserves further investigation. Many recurrences of a BNC tend be refractory to transurethral resection/incision; indwelling catheters are then poorly tolerated and patients may require a major reconstructive procedure.

Contemporary management of superficial bladder cancer.

BACKGROUND: Bladder cancer is the second most common urologic malignancy after prostate cancer. Superficial bladder cancer presents as a heterogeneous group of tumors with variable biological potential. A significant percentage of patients diagnosed with superficial cancer will have multiple recurrences, and some will progress to invasive disease. METHODS: Patients are stratified into low- or high-risk for recurrence and progression. We review the most recent literature regarding intravesical therapy for superficial bladder cancer, and we summarize indications for the use of intravesical agents as well as their efficacy, toxicity, and cost. RESULTS: Several intravesical agents are available for the treatment of superficial bladder cancer. Patients may be identified as low- or high-risk for recurrence and progression. High-risk patients benefit from intravesical therapy. CONCLUSIONS: Superficial bladder cancer is a heterogeneous group of diseases. Treatment is effective in preventing recurrences and progression in the high-risk group.

B7-1 gene-modified autologous tumor-cell vaccines for renal-cell carcinoma.

In recent years, interest in the development of immunologic approaches to malignancies has increased, and there is good evidence that the growth of renal-cell carcinoma (RCC) can be modulated by the host's immune system. Indeed, use of the immunomodulatory cytokine interleukin-2 (IL-2) has been approved for the treatment for this disease. The efficacy of this approach remains low, and there is no other reasonable conventional therapy for patients with metastatic RCC. Therefore, there is a need for the development of novel treatment strategies. The development of autologous tumor-cell vaccines that have been genetically modified to become more immunogenic is an approach that is actively being studied. One of the genetic manipulations that is being employed by several groups is the induction of overexpression of B7-1 to provide costimulation to tumor-reactive T-cells. The rationale for this strategy is that T-cells need two signals before they can mount a cytotoxic response: the binding of the T-cell receptor (TCR) to an antigenic peptide presented on major histocompatibility complex (MHC) molecules and the binding of CD28 to B7-1. Since B7-1 is not normally expressed by RCC cells, the expression forced by transfection of an exogenous B7-1 gene could make the tumor cells more immunogenic. This has been shown to be the case in mice, in which the injection of tumor cells transfected with B7-1 can result in the T-cell-mediated rejection of unmanipulated parental tumor cells. We have applied this approach to the treatment of patients with metastatic RCC. Patients enrolled on our phase I protocol are treated with autologous tumor cells modified to express B7-1, which functions as a tumor vaccine. Primary tumors or metastases are resected from the patients. The tumor cells are adapted to in vitro culture, infected with a recombinant adenoviral vector containing human B7-1 cDNA driven by the cytomegalovirus (CMV) promoter, radiated, and stored in liquid nitrogen. Aliquots of the B7-1 gene-modified tumor cells are given to the patients as a vaccine at varying intervals according to a dose-escalation scheme. The patients also receive systemic IL-2 for the dual purpose of providing accepted therapy for this disease as well as expanding the tumor-reactive T-cells activated by the vaccine. The immunogenicity and toxicity of the vaccine as well as the clinical response are being assessed in three to five patients at each of three dose levels.

Adenocarcinoma in a continent colonic urinary reservoir.

We report the first case of an adenocarcinoma developing in a continent ileocolonic urinary reservoir. The tumor presented 7 years after the urinary diversion and more than 6 years after the resection of a Dukes' B lesion of the left colon. This report demonstrates that the colonic segment used for urinary diversion retains its malignant potential and that surveillance pouchoscopy should be performed in these patients.