Carcinoma urotelial micropapilar de vejiga: reporte de un caso y revisión de la literatura / Micropapillary urothelial carcinoma of the bladder: a case report and literature review

El carcinoma urotelial micropapilar (CMP) de vejiga es una variante anatomopatológica infrecuente, de comportamiento agresivo. Se presenta habitualmente como carcinoma de alto grado, en estadios avanzados, sin signos clínicos distintos al del carcinoma vesical convencional. El tratamiento debe ser precoz y agresivo, fundamentalmente quirúrgico, dado que la radioterapia y la quimioterapia no han demostrado utilidad hasta el momento. Es necesario el reconocimiento de esta entidad pues su capacidad metástasica está asociada a una alta incidencia de mortalidad. Presentamos el caso de un varón de 64 años con hematuria de larga evolución diagnosticado de carcinoma micropapilar infiltrante de vejiga con compromiso de uréter.

Micropapillary urothelial carcinoma (MCP) of the urinary bladder is an rare anatomopathology variant aggressive behaviour. It is usually found as a high grade and stage carcinoma, and doesn't differ clinically from normal cell carcinoma of the bladder. Treatment should be early and aggressive, because radiotherapy and chemotherapy have shown limited results the therapy is surgically based. The diagnosis of this disease is required because its metastasic capacity is associate with a significantly increased mortality risk. In this study we report de case of a 64 years old man with a long development hematuria diagnosed of Micropapillary carcinoma infiltrating the bladder involving the ureter.

Use of coisogenic host blastocysts for efficient establishment of germline chimeras with C57BL/6J ES cell lines.

Gene targeting in embryonic stem (ES) cells allows the production of mice with specified genetic mutations. Currently, germline-competent ES cell lines are available from only a limited number of mouse strains, and inappropriate ES cell/host blastocyst combinations often restrict the efficient production of gene-targeted mice. Here, we describe the derivation of C57BL/6J (B6) ES lines and compare the effectiveness of two host blastocyst donors, FVB/NJ (FVB) and the coisogenic strain C57BL/6-Tyr(c)-2J (c2J), for the production of germline chimeras. We found that when B6 ES cells were injected into c2J host blastocysts, a high rate of coat-color chimerism was detected, and germline transmission could be obtained with few blastocyst injections. In all but one case, highly chimeric mice transmitted to 100% of their offspring. The injection of B6 ES cells into FVB blastocysts produced some chimeric mice. However; the proportion of coat-color chimerism was low, with many more blastocyst injections required to generate chimeras capable of germline transmission. Our data support the use of the coisogenic albino host strain, c2J, for the generation of germline-competent chimeric mice when using B6 ES cells.

Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning.

UNLABELLED: Several studies have found that administration of etidronate results in competitive interference with 99mTc-labeled bone scanning reagents. In contrast, in other studies this problem was not encountered with other bisphosphonates. METHODS: We prospectively studied 9 patients with hormone-refractory prostate cancer. 99mTc-methylene diphosphonate (MDP) bone scanning was performed before they received alendronate, and scanning was repeated a mean of 16.6 d afterward, when the patients had been receiving 40 mg alendronate daily for a mean of 6 d. In addition, 7 patients who underwent delayed scanning when they had been receiving alendronate for a mean of 111 d were also restudied. Quantitative whole-body bone scanning was performed, and radioactivity deposited in the bone metastasis was determined using region-of-interest analysis. RESULTS: A <6% increase in whole-body retention of 99mTc-MDP was seen on the initial postalendronate scan compared with the baseline scan. No significant differences in activity were seen in the bone lesion evaluated on the baseline and initial postalendronate studies. The delayed postalendronate scan generally showed similar or higher tracer accumulation compared with the baseline scan. CONCLUSION: Alendronate did not competitively inhibit uptake of 99mTc-MDP in the skeleton or tumor metastasis. Use of alendronate before bone scanning is unlikely to result in decreased detection of lesions or falsely decreased 99mTc-MDP activity at metastatic bone tumor sites.

Drug-induced lupus associated with COL-3: report of 3 cases.

BACKGROUND: Anti-angiogenesis is an exciting new approach to anticancer therapy. COL-3, a tetracycline derivative, is a novel anti-angiogenesis agent with potent preclinical anticancer activity. During the conduct of a phase 1 clinical trial for refractory metastatic cancer at the National Institutes of Health, we observed 3 individuals who developed phototoxicity followed by clinical and laboratory features of drug-induced lupus. OBSERVATIONS: Three of 35 patients treated with COL-3 developed sunburnlike eruptions accompanied by fever and a positive antinuclear antibody titer within 8 to 29 days of starting treatment. Two of 3 had positive antihistone antibody levels and arthralgia. One patient had marked systemic manifestations including pulmonary infiltrates and elevated erythrocyte sedimentation rate remittent for more than 1 year after discontinuing COL-3 treatment. The other 2 patients' symptoms and rash abated within 2 weeks of discontinuing therapy although the serologic markers remained abnormal for the duration of follow-up. CONCLUSIONS: COL-3 is the second tetracycline derivative to be implicated in the development of drug-induced lupus. A sunburnlike eruption immediately preceded or accompanied the systemic and serologic changes in these 3 patients. The rapid onset and the phototoxic appearance of the accompanying eruptions might suggest that damage to the keratinocytes caused the formation of neoantigens to which autoantibodies formed.

Reversible sideroblastic anemia associated with the tetracycline analogue COL-3.

Eight of 35 patients with cancer receiving COL-3, a tetracycline derivative with antiangiogenic properties, developed anemia while on treatment. All of these patients were enrolled on an approved Phase I clinical trial at the National Cancer Institute. Three of these patients had bone marrow examinations that revealed ringed sideroblasts. This paper describes these cases. Am. J. Hematol. 67:51-53, 2001. Published 2001 Wiley-Liss, Inc.

Phase I clinical trial of oral COL-3, a matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer.

PURPOSE: This phase I clinical trial was designed to determine the maximum-tolerated dose and dose-limiting toxicities of the matrix metalloproteinase (MMP) inhibitor COL-3 in patients with refractory solid tumors. PATIENTS AND METHODS: Thirty-five patients with different cancer types were enrolled. COL-3 doses were escalated from 36 mg/m2/d in successive cohorts of at least three patients. Circulating levels of MMP-2, MMP-9, vascular endothelial growth factor, and basic fibroblast growth factor were assessed during treatment. Pharmacokinetic parameters were assessed for single and multiple doses of drug. RESULTS: Cutaneous phototoxicity was dose-limiting at 98 mg/m2/d. With the use of prophylactic sunblock, COL-3 was well tolerated at 70 mg/m2/d. The dose of 36 mg/m2/d was well tolerated without the use of sunblock. Other toxicities that did not seem to be related to dose or pharmacokinetics included anemia, anorexia, constipation, dizziness, elevated liver function test results, fever, headache, heartburn, nausea, vomiting, peripheral and central neurotoxicities, fatigue, and three cases of drug-induced lupus. Disease stabilization for periods of 26+ months, 8 months, and 6 months were seen in hemangioendothelioma, Sertoli-Leydig cell tumor, and fibrosarcoma, respectively. There was a potentially statistically significant relationship between changes in plasma MMP-2 levels and cumulative doses of drug when progressive disease patients were compared with those with stable disease or toxicity (P = .042). CONCLUSION: COL-3 induced disease stabilization in several patients who had a nonepithelial type of malignancy. Phototoxicity was dose-limiting. We recommend the dose of 36 mg/m2/d for phase II trials.

A pharmacokinetically guided Phase II study of carboxyamido-triazole in androgen-independent prostate cancer.

We conducted a Phase II clinical trial of the antiproliferative, antimetastatic, and antiangiogenic agent carboxyamido-triazole (CAI), using pharmacokinetic assessment to guide drug dosing. Fifteen patients who had stage D2 androgen-independent prostate cancer with soft tissue metastases were enrolled. Because CAI previously had been shown to decrease prostate-specific antigen secretion in vitro, this marker was not used to assess disease status. The dose of CAI used in this study was calculated so that plasma steady-state maximum concentrations between 2.0 and 5.0 microg/ml would be maintained. Following the initial dosage adjustment, 93% (14 of 15) of patients were within the predicted range. Fourteen of 15 patients were evaluable for response. All of the 14 evaluable patients demonstrated progressive disease at approximately 2 months. Twelve patients progressed by computed tomography and or bone scan at 2 months, whereas two patients demonstrated clinical progression at 1.5 and 2 months. One patient was removed from study at 6 weeks due to grade II peripheral neuropathy lasting >1 month. Although no clinical responses were noted, a 27.7% decrease in serum vascular endothelial growth factor concentration was observed. CAI does not possess clinical activity in patients with androgen-independent prostate cancer and soft tissue metastases. Pharmacokinetically guided dosing, although found to be feasible using a Bayesian approach, was not found to be of practical benefit. Although plasma CAI concentrations were maintained within the designated range, grade III toxicity requiring drug discontinuation was still observed.

Transvaginal ultrasound-guided oocyte retrieval following FSH stimulation of domestic goats.

The objectives of this study were to evaluate different ovarian stimulation protocols on donor goats and to develop a safe, repeatable method for harvesting oocytes from FSH-treated does (Experiment I). Based on the preliminary findings of the first experiment, 32 crossbred does were used in a second experiment (Experiment II), 16 that had not been previously aspirated and 16 that had undergone one previous aspiration, were used to fine tune the procedure. Females were randomly subjected to 1 of the 2 ovarian stimulation protocols: Treatment (A) does were implanted with a norgestomet ear implant. Starting 10 d post-implantation, does were administered FSH daily for 4 d. Does in Treatment (B) were treated similarly to those in (A) but were implanted for only 3 d before starting the FSH injections and implants were not removed prior to aspiration. Using a 2 x 2 factorial arrangement, fresh does (n=16), not previously aspirated, were then further randomly assigned to either a laparoscopic aspiration procedure (LAP) or a transvaginal ultrasound-guided aspiration procedure (TUGA). The LAP procedure was performed using a fiber optics. For the TUGA, the doe was placed in dorsal recumbency, and a 5 MHz human transvaginal transducer, attached to the ultrasound unit, was positioned vaginally for oocyte aspiration. In summary, there was no significant difference among treatment groups for parameters evaluated, with the exception of methods for oocyte collection. The number of follicles detected and oocytes harvested using TUGA (9.5 and 4.3, respectively) was less than for females obtained by LAP (17.4 and 14.4, respectfully). The percentage of oocytes recovered from does subjected to the TUGA (68%), however, was similar to those subjected to the LAP (69%). Unlike donor does subjected to a repeated LAP, there was no evidence of adhesions in donor does from the repeated TUGA group. The TUGA approach to oocyte collection should not be overlooked in an effort to decrease the chances of adhesions in valuable donor goats.

On the accuracy and reliability of predictions by control-system theory.

In three experiments we used control-system theory (CST) to predict the results of tracking tasks on which people held a handle to keep a cursor even with a target on a computer screen. 10 people completed a total of 104 replications of the task. In each experiment, there were two conditions: in one, only the handle affected the position of the cursor; in the other, a random disturbance also affected the cursor. From a person's performance during Condition 1, we derived constants used in the CST model to predict the results of Condition 2. In two experiments, predictions occurred a few minutes before Condition 2; in one experiment, the delay was 1 yr. During a 1-min. experimental run, the positions of handle and cursor, produced by the person, were each sampled 1800 times, once every 1/30 sec. During a modeling run, the model predicted the positions of the handle and target for each of the 1800 intervals sampled in the experimental run. In 104 replications, the mean correlation between predicted and actual positions of the handle was .996; SD = .002.

Use of the personal computer in clinical research.

Personal computers are quickly becoming items of everyday use. More physicians' offices are using computers for billing and patients' records. Others have purchased computers for their word processing capabilities. These computers can be used for archives of medical case records or to collect and collate data for clinical research. This article focuses on how we use a personal computer for organization and management of clinical research projects. Included is a description of how we organize a research project, gather data, write computer programs, enter data into the computer, and generate and display reports. The use of a template program and a personal computer permits creation of individual programs without the aid of a professional programmer. When a single data-management program is used, five or six research projects can be carried out at a cost comparable to that of one project using a large computer and professional programmers.

[Non-invasive explorations of the carotid arteries (author's transl)]. / Explorations no invasives des artères carotides.

For the non-invasive evaluation of patients suspected of having extracranial carotid artery disease, the non-invasive vascular laboratory at the Lahey Clinic, Boston, Massachusetts uses three tests. Carotid phonoangiography (C.P.A.) by itself is 60% accurate, the Kartchner-McRae Oculoplethysmograph (O.P.G.) by itself 80% accurate, and the Echoflow doppler arterial imager, by itself 90% accurate. These examinations are used for surveillance of high-risk patients and to determine the need for carotid arteriography. In a series of 94 patients, the combination of these non-invasive methods yielded one false negative and 2 false positive studies, for an overall accuracy of 95%.

Fibrinolytic therapy.

Fibrinolytic therapy is a useful addition to the armamentarium of most clinicians. Patients with fibrin-based intraluminal clots are seen by almost all physicians. With proper patient selection and careful physician adherence to dosage schedule and monitoring, the incidence of significant complications with fibrinolytic agents is about the same as with heparin therapy. Heparin stops the thrombotic process, whereas fibrinolytic therapy not only stops the thrombotic process, but often reestablishes a normal, hemodynamic state. Patients who undergo fibrinolytic therapy are spared long-term problems like amputation and the postphlebitic syndrome.

Clinical use of noninvasive evaluation of the carotid artery.

The noninvasive evaluation of carotid artery disease should include a battery of tests that includes one direct and one indirect assessment of the extracranial carotid arteries. The resulting data should be correlated with the clinical findings and the patient's general status so the risks and benefits of carotid endarterectomy may be determined. These studies are usually outpatient procedures and allow one to determine in the office which patients would benefit from carotid surgery and who should be followed serially. Carotid arteriography is reserved for those patients who will be subjected to surgery. In our hands, the combination of CPA, Kartchner-McRae OPG, and Echoflow fulfill these requirements. In a small number of patients the history, physical examination, and noninvasive studies are inconclusive. For most patients, we are able to make decisions as to the best therapy in the office and can discuss risks and benefits with patients and their families with an accuracy of approximately 95 per cent before hospitalization and arteriography are considered.

Femoral-to-femoral bypass graft.

Femoral-to-femoral bypass reconstructions were first described by Vetto in 1962. It is a low-stress, low-risk procedure with excellent long-term results. Its use need not be confined to high-risk patients with tissue necrosis; it can be offered to moderate-risk patients with unilateral disease and incapacitating claudication. Studies in the noninvasive vascular laboratory assist in the preoperative selection of patients as they determine if the iliac artery on the asymptomatic side is capable of acting as an inflow vessel. Noninvasive evaluation and monitoring at regular intervals after operation allow for early detection and correction of new disease.