Botulinum toxin for the treatment of idiopathic and neurogenic overactive bladder: state of the art

The pharmacologic treatment of overactive bladder and detrusor overactivity, whether idiopathic or neurogenic, has centered around blocking muscarinic receptors on the detrusor muscle. Although newer agents have been developed with better tolerability and safety, the basic mechanism by which the "irritable" detrusor is treated has not changed in decades. Although effective in many cases of idiopathic and neurogenic detrusor overactivity and overactive bladder, antimuscarinic agents fall short in many other cases because of lack of efficacy and/or tolerability. For the past several years, there has been increasing evidence to support the use of botulinum toxin for the treatment of detrusor overactivity and overactive bladder syndrome not effectively treated by anticholinergics. From early open-label studies to the more recent randomized, controlled trials, efficacy and tolerability data have been very encouraging. Botulinum toxin is not yet approved by the US Food and Drug Administration for the treatment of detrusor overactivity and overactive bladder, but the positive results seen thus far cannot be ignored.     

Strains of genus Salmonella isolated from extraintestinal infections

Every year in Poland from tens to more than hundred bacteriologically verified extraintestinal infections caused by Salmonella species have been registered. These unusually located infections have substantially heavy course and in many cases hospitalisation and antibiotic therapy have to be involved. Cases of extraintestinal infections with these Gram-negative rods, which were described in the literature, concerned: pneumonias, lung abscesses and thoracic empyemas, and infections of: blood, bones and joints, wounds, fistulas and urinary tract. The aim of this study was to set extraintestinal Salmonella infections and to analyze a susceptibility of isolated strains to antimicrobial agents. Between 01.07.2002 and 31.12.2004 (30 months) 13 strains of Salmonella genus have been isolated, including 11 S. enteritidis and 2 S. Hadar. In general, with one exception, isolated strains were susceptible to tested antibiotics/chemotherapeutics. ESBL - positive strains were not detected. The tendency of Salmonella strains to cause extraintestinal infections has been noticed. The problem is still escalating, especially in group of patients chronically treated, with immunodeficiency and immunosuppression, after complicated medical procedures, also in the group of small children and aged persons. Therefore, it is necessary to evaluate a susceptibility to antibiotics/chemotherapeutics of every strain from confirmed case of Salmonella extraintestinal infection and it is important to apply a guided therapy.     

Urine cytology evaluation in cases of uretero-ileal cutaneous diversion

Cytological examination of urine from the ileal conduit in cases of bladder cancer treated by radical surgery can be an important and effective follow-up procedure. A total of 19 patients (18 males and one female) on whom radical cystectomy for cancer was performed were studied. Three urine specimens were examined in each case using routine cytological methods. Three cases of recurrent carcinoma (mainly of papillary type) were diagnosed cytologically before any clinical evidence of disease. the cytological examination of urine at 3-6 month intervals after cystectomy for bladder carcinoma is considered advisable in all cases, since the recurrence rate of transitional cell neoplasms in the upper urinary tract after cystectomy for transitional carcinoma is quite high.     

REPAIR OF VESICO-VAGINAL FISTULA

One hundred and thirteen patients with vesico-vaginal fistula were seen at the University of California Hospital from 1932 through 1959. The most common cause of fistula was trauma associated with pelvic operation, and the operation most often involved was total abdominal hysterectomy. Malignant disease of the pelvic organs was the second most common cause, while radiation therapy and obstetrical causes were next in the order of frequency.Three fistulas healed spontaneously. Twelve bladder by-pass operations were done and 54 repairs were carried out in 46 patients. Thirty-eight patients (82.6 per cent) were cured after one or more repair operations. A variety of operative approaches were used, selected in accordance with the needs of the individual case. Bladder distention postoperatively, due to a plugged catheter, was held responsible for failure of the repair in three cases, and this complication was considered preventable.Close attention to surgical technique, the recognition of bladder injury, and proper repair at the time of operation are prime factors in the prevention of vesico-vaginal fistula.     

吡柔比星预防浅表性膀胱癌术后复发的疗效观察

目的：比较吡柔比星与吉西他滨膀胱内灌注预防浅表性膀胱癌术后复发的疗效。方法：40 例浅表性膀胱癌患者根据随机抽 签法分为治疗组与对照组各20 例,所有患者都采用经尿道膀胱肿瘤电切方法,对照组用吉西他滨,治疗组用吡柔比星进行膀胱 灌注,比较两组患者术后复发率的不同。结果：所有患者都完成治疗,随访1 年,治疗组的复发率为5.0 %,对照组为25.0 %,治疗 组的复发率明显低于对照组,对比差异明显,有统计学意义(P<0.05)。经过观察,治疗组的膀胱刺激症状、骨髓抑制、尿道狭窄等不 良反应总体发生率明显少于对照组,两者比较有统计学意义(P<0.05)。结论：相对于吉西他滨,吡柔比星膀胱内灌注预防浅表性膀 胱癌术后复发有很好的效果,不良反应少,在临床上需要根据患者的实际情况来选择不同的灌注药物。     

Surgical closures of oropharyngocutaneous fistulas

Of the 146 patients undergoing surgery for oropharyngeal cancer in our institution, 12 (8.2 percent) developed fistulas. As a first line of therapy, conservative measures were used, which consisted of debridement, Xeroform gauze packing, and nasogastric feeding. Seven fistulas closed after conservative treatment. Of the five patients who required surgery for fistula closure, three had large (more than 20 mm) and two had mid-size (5- to 20-mm) fistulas. In all cases, internal flaps were prepared from the healthy viable tissues surrounding the fistula, and sternocleidomastoid-trapezius-platysma myocutaneous flaps were used for external closure. None of the closures failed, and we obtained good functional and aesthetic results.     

无环鸟苷抗乙型肝炎病毒复制长短程疗法随访观察

慢性乙型肝炎病毒感染s5例,随机分无环鸟苷长程组22例,短程组11例和对照组22例。经一年随访观察,无环鸟苷治疗组见血清HBeAg、DNA-P和HBV-DNA有规律性阴转,短程组于12个月又有部分指标阳转,长程组阴转较多,其血清HBeAg、DNA-P和HBV-DNA阴转率与短程和对照组比较有显著性差异。一年结果四项病毒复制指标全部阴转例数与对照组有显著性差异,结果表明,无环鸟苷长疗程是有较好疗效。     

Incidence of cleft palate fistula: an institutional experience with two-stage palatal repair.

The purpose of this study was to determine the incidence of cleft palatal fistula in a series of nonsyndromic children treated at the authors' institution. This retrospective analysis of 103 patients with cleft palate treated by five surgeons between 1982 and 1995 includes 60 boys and 33 girls, whose median age was 18.4 months at the time of surgery. The median length of follow-up was 4.9 years after primary palatoplasty. Cleft palatal fistula was defined as a failure of healing or a breakdown in the primary surgical repair of the palate. Intentionally unrepaired fistulas of the primary and secondary palate were excluded. Extent of clefting was described according to the Veau classification. Statistical examination of multiple variables was performed using contingency table analysis, multivariate logistic regression, and the Wilcoxon rank sum test. The incidence of cleft palatal fistula in this series was 8.7 percent. All of these fistulas were clinically significant. The rate of fistula recurrence was 33 percent. The incidence of cleft palatal fistula when compared by Veau classification was statistically significant, with nine fistulas occurring in patients with Veau 3 and 4 clefts and no fistulas occurring in patients with Veau 1 and 2 clefts (p = 0.0441). No significant differences between patients with and without fistulas were identified with respect to operating surgeon, patient sex, patient age at palatoplasty, type of palatoplasty, and use of presurgical orthopedics or palatal expansion. All three recurrent fistulas occurred in the anterior palate, two in patients with Veau class 3 clefts and one in a patient with a Veau class 4 cleft. The low rate of clinically significant fistula was attributed to early delayed primary closure, with smaller secondary clefts allowing repair with a minimum of dissection and disruption of vascularity.     

Diagnostic and therapeutic approach of congenital solitary coronary artery fistulas in adults: Dutch case series and review of literature

Background

Coronary artery fistulas (CAFs) are infrequent anomalies, coincidentally detected during coronary angiography (CAG).

Aim

To elucidate the currently used diagnostic imaging modalities and applied therapeutic approaches.

Materials and Methods

Five Dutch patients were found to have CAFs. A total of 170 reviewed subjects were subdivided into two comparable groups of 85 each, treated with either percutaneous ‘therapeutic’ embolisation (PTE group) or surgical ligation (SL group).

Results

In our series, the fistulas were visualised with several diagnostic imaging tests using echocardiography, multidetector computed tomography, and CAG. Four fistulas were unilateral and one was bilateral; five originated from the left and one originated from the right coronary artery. Among the reviewed subjects, high success rates were found in both treatment groups (SL: 97% and PTE: 93%). Associated congenital or acquired cardiovascular disorders were frequently present in the SL group (23%). Bilateral fistulas were present in 11% of the SL group versus 1% of the PTE group. The fistula was ligated surgically in one and abolished percutaneously in another. Medical treatment including metoprolol was conducted in two, and watchful waiting follow-up was performed in one.

Conclusions

Several diagnostic imaging techniques are available for assessment of the anatomical and functional characteristics of CAFs.     

Disease-related lymphocyte cytotoxicity in vitro in patients with transitional cell carcinoma of the urinary bladder. Comparisons with other malignancies,acute cystitis,and healthy donors

Summary Blood lymphocytes from 100 patients with transitional cell carcinoma of the urinary bladder (TCC-bladder) were studied for their cytotoxicity in vitro against a panel of allogeneic tissue culture cell lines. Of the TCC-bladder patients, 45 were untreated for their disease, while 55 had been treated with local radiotherapy up to 12 years before testing. Control lymphocytes were obtained from (1) 45 untreated, age- and sex-matched patients with other neoplastic diseases, mainly urogenital cancers; (2) 19 patients with acute cystitis; and (3) 45 healthy donors. Lymphocytes from individual donors within all five groups were frequently cytotoxic to any one of the target cells. However, the lymphocytes from each of the two TCC-bladder groups were markedly more cytotoxic to two different bladder tumor targets than to control targets derived from normal bladder epithelium, from colon carcinoma, or from malignant melanoma. Similar comparisons made within each of the three control donor groups did not show this. The results indicate that the two bladder tumor targets were not more susceptible to lymphocyte-mediated lysis than the control targets. The mean cytotoxicity displayed by the lymphocytes from both TCC-bladder groups to the bladder tumor targets was significantly higher than that of the cancer control group and that of the healthy donors. No such elevation was seen when the cancer control group or the cystitis patients were compared with healthy donors. Although untreated TCC-patients with a larger tumor burden (stages T3–T4) appeared to be slightly less cytotoxic to all target cells than those with a smaller tumor burden (T1–T2), these differences were not statistically significant. On the other hand, among the treated TCC-patients, in the main those tested more than 1 year and up to 5 years after therapy exhibited a significantly elevated mean cytotoxicity to the bladder tumor targets. Within all five donor groups, the overall cytotoxicity to the bladder tumor targets and the normal bladder targets showed a statistically highly significant correlation. However, while there was no correlation for the untreated TCC-bladder patients and the clinical controls between cytotoxicity to the bladder tumor targets on one hand and non-bladder targets on the other, the cytotoxicity to the bladder tumor targets of the treated TCC-bladder patients was also correlated with that to the colon carcinoma and the melanoma targets. The results indicate that cytotoxicity in both TCC patients and controls reflects recognition by the lymphocytes of a variety of antigens, shared to different degrees by different groups of target cells. Furthermore, in TCC-bladder patients there is a superimposed cytotoxicity, which is related to their disease and which probably reflects reactions against one or several tumor-associated antigens.     

The association between -330T/G polymorphism of interleukin 2 gene and bladder cancer

Bladder cancer is one of the most common cancers in the world. Studies have shown that genetic factors may play important roles in the development of this disease. Interleukin-2 (IL-2) is a cytokine involved in the regulation of proliferation and functional activities of T- and NK-cell. Recombinant IL-2 has been shown to be a promising agent for the activation of immune response against tumors. The aim of this study was to examine the effect of -330T/G polymorphism of the IL-2 gene on the development of bladder cancer in the Chinese population. IL-2 -330T/G polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 365 bladder cancer cases and 390 age-matched healthy controls. Data were analyzed using the Chi-square test. Results showed that individuals with TG genotype or GG genotype had significantly increased susceptibility to bladder cancer (odds ratio [OR]=1.48, 95% confidence interval [CI]: 1.08-2.02, p=0.014 and OR=2.22, 95%CI: 1.35-3.68, p=0.002). Also, the frequency of the G allele was significantly higher in bladder cancer cases compared with healthy controls (OR=1.40, 95%CI: 1.14-1.73, p=0.002). In conclusion, IL-2 -330T/G polymorphism may be involved in the etiology of bladder in Chinese population.     

Knockdown of Ki-67 by Dicer-Substrate Small Interfering RNA Sensitizes Bladder Cancer Cells to Curcumin-Induced Tumor Inhibition

Transitional cell carcinoma (TCC) of the urinary bladder is the most common cancer of the urinary tract. Most of the TCC cases are of the superficial type and are treated with transurethral resection (TUR). However, the recurrence rate is high and the current treatments have the drawback of inducing strong systemic toxicity or cause painful cystitis. Therefore, it would be of therapeutic value to develop novel concepts and identify novel drugs for the treatment of bladder cancer. Ki-67 is a large nucleolar phosphoprotein whose expression is tightly linked to cell proliferation, and curcumin, a phytochemical derived from the rhizome Curcuma longa, has been shown to possess powerful anticancer properties. In this study, we evaluated the combined efficacy of curcumin and a siRNA against Ki-67 mRNA (Ki-67-7) in rat (AY-27) and human (T-24) bladder cancer cells. The anticancer effects were assessed by the determination of cell viability, apoptosis and cell cycle analysis. Ki-67-7 (10 nM) and curcumin (10 µM), when treated independently, were moderately effective. However, in their combined presence, proliferation of bladder cancer cells was profoundly (>85%) inhibited; the rate of apoptosis in the combined presence of curcumin and Ki-67-7 (36%) was greater than that due to Ki-67-7 (14%) or curcumin (13%) alone. A similar synergy between curcumin and Ki-67-7 in inducing cell cycle arrest was also observed. Western blot analysis suggested that pretreatment with Ki-67-7 sensitized bladder cancer cells to curcumin-mediated apoptosis and cell cycle arrest by p53- and p21-independent mechanisms. These data suggest that a combination of anti-Ki-67 siRNA and curcumin could be a viable treatment against the proliferation of bladder cancer cells.     

Urodynamic findings in chronic retention of urine and their relevance to results of surgery.

Fifty-five consecutive male patients aged 18-77 with chronic retention of urine were investigated urodynamically. All were shown to have obstructed micturition. Inflow cystometry defined two groups, one with high-pressure and one with low-pressure filling. Recent-onset enuresis and upper-tract dilatation as seen on radiography were significantly associated with high-pressure bladder filling. Postoperative studies showed that patients with high-pressure filling on preoperative cystometryhad a better response to outflow-tract surgery. The poor response of the patients with low-pressure filling was due to a high incidence of inadequate detrusor contraction leading to persistent residual urine. Thus urodynamic studies may be used to indicate which patients are likely to benefit from prostatectomy and, after the operation, whether the obstruction has been relieved.     

Case report of isochromosome 17q in acute myeloid leukemia with myelodysplasia-related changes after treatment with a hypomethylating agent

Isochromosome 17q is a relatively common karyotypic abnormality in medulloblastoma, gastric, bladder, and breast cancers. In myeloid disorders, it is observed during disease progression and evolution to acute myeloid leukemia in Philadelphia-positive chronic myeloid leukemia. It has been reported in rare cases of myelodysplastic syndrome, with an incidence of 0.4-1.57%. Two new agents have been approved for treatment of myelodysplastic syndrome/chronic myelomonocytic leukemia. These are the hypomethylating agents, 5-azacytidine and decitabine, recommended by consensus guidelines for high-risk myelodysplastic syndrome patients not eligible for hematopoietic stem cell transplantation. We present a case of chronic myelomonocytic leukemia with normal cytogenetics at diagnosis treated with decitabine (with good response); however, the patient evolved to acute myeloid leukemia with i(17q) shortly after suspending treatment. To the best of our knowledge, this is the first report of acute myeloid leukemia with myelodysplasia-related changes with i(17q) after the use of a hypomethylating agent.     

Pleural Effusion with Pancreaticopleural Fistula

Three patients with pleural effusion were found to have pancreaticopleural fistulas passing through an opening in the diaphragm are reported. In one case the effusion was purulent and originated from an abscess of the pancreas. Retrograde pancreatography during operation defined the course of the fistula. In two other cases the fistula was demonstrated by radiography after intrapleural injection of contrast medium. The diagnostic importance of injecting contrast medium early into the pleural cavity in cases of effusion rich in amylase, before lung expansion obscures the fistula, is emphasized. Cases of pancreaticopleural fistula may be commoner than supposed.     

膀胱子宫内膜异位症的超声诊断(附三例临床分析及文献复习)

本文通过3例经活检和手术证实的膀胱子宫内膜异位症的超声图像分析,讨论了膀恍子宫内膜异位症的超声诊断价值。 半数以上的膀胱子宫内膜异位症有盆腔手术史。临床表现为月经期伴尿频尿急和尿痛等尿道刺激的症状,抗炎治疗常难奏效,而月经净后症状自行缓解和消退。 超声图见子宫峡部的前壁外缘有不规则的隆起,呈低回声区并向膀胱后壁突起。在月经来潮前和来潮时此隆起包块稍见增大饱满。用丹那唑或三苯氧胺治疗病灶将逐渐缩小。本文比较了膀胱镜检查的优越性及其局限性,认为超声检查可作为首选的检查方法进行早期诊断,尤其对需采取保守治疗的患者,超声检查可作定期随访以观疗效,而不需反复进行膀胱镜检。超声检查此症应与膀胱血管瘤,膀胱癌,息肉和炎症溃疡等鉴别。     

Benign squamous cells with pleomorphic microvilli in urine or bladder washings

Exfoliated cells in catheterized urine or bladder washings from 40 patients were observed by light microscopy (LM) and by scanning electron microscopy (SEM). The specimens from seven of these patients (six postmenopausal females and one 85-year-old male) contained squamous cells with pleomorphic microvilli (PMV) on their surfaces. Four of these cases had no bladder lesions by cystoscopic examination. Three patients had recurrent papillary transitional-cell carcinoma of the bladder, and the cytologic specimens from two of them contained transitional cells with PMV. The distinction between squamous and transitional cell is readily made by SEM, based primarily on cell shape and thickness. The presence of PMV on otherwise-benign-appearing squamous cells in urine or bladder washing specimens may be a source of confusion in the interpretation of SEM findings. The presence of PMV on exfoliated squamous cells in cytologic material from the human urinary tract does not seem to have the same diagnostic and prognostic significance as the presence of PMV on transitional cells.     

Survival with bladder cancer,evaluation of delay in treatment,type of surgeon,and modality of treatment.

OBJECTIVE--To determine whether length of delay before treatment; specialty and grade of the surgeon; and use made of surgery, radiotherapy, and chemotherapy influenced the survival of patients with cancer of the bladder, after adjusting for case severity. DESIGN--Retrospective cohort study. SETTING--South East and South West Thames health regions. PATIENTS--609 men aged under 75 resident in the South Thames regions who had been registered as new cases of bladder cancer in 1982, 35 of whom were excluded, leaving 574 eligible patients. Analysis was based on 75% retrieval rate for case notes. MAIN OUTCOME MEASURES--Duration of survival from date of diagnosis of the bladder tumour. RESULTS--10 prognostic variables were used to adjust for case severity. The median delay from referral to first treatment was 48 (interquartile range 27-84) days. Treatment after a short delay was associated with shorter survival because of the early treatment of more severe cases. Consultants treated 68% of patients, trainee surgeons treated less severe cases. Initial treatment was by a urologist in 67% of cases, but the specialty of the surgeon was not associated with prognosis. The associations of radiotherapy, cystectomy, and systemic chemotherapy with survival were interpreted in terms of selection bias as well as therapeutic effect. CONCLUSION--Case severity was the most important influence on survival and influenced length of delay before treatment, grade and specialty of the surgeon, and main treatment allocation. After adjusting for case severity variations in these processes of care were not strongly associated with variations in survival.     

Persistent Tn polyagglutination syndrome during febrile neutropenia: a case report and review of the literature

Introduction

Crohn's disease is a chronic inflammatory bowel disease of unknown etiology which may affect any part of the bowel. Fistulas are a common and often serious complication of Crohn's disease. The treatment for fistulizing Crohn's disease can be medical, surgical or a combination of the two. Recently, adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, has been suggested as a safe and effective treatment for the induction and maintenance of remission in adult patients with moderate to severe Crohn's disease, who are refractory to conventional therapy or intolerant to infliximab. However, large studies focusing on evaluating the efficacy of adalimumab in fistulizing Crohn's disease have not yet been published.

Case presentation

We report the cases of three patients, of European Caucasian ethnicity and Greek nationality, with active luminal and fistulizing Crohn's disease. All of the cases were treated successfully with adalimumab. Patient 1 (a 44-year-old man) and patient 2 (an 18-year-old woman) developed early post-surgical enterocutaneous fistulas, while patient 3 (a 20-year-old woman) had peri-anal fistulizing Crohn's disease. Adalimumab treatment (160 mg subcutaneously at week zero, 80 mg at week two, and 40 mg every other week) was used for three different indications: (1) after the failure of other conservative medical treatments for Crohn's disease (patient 1); (2) as a monotherapy in treating a naive patient (patient 2); (3) after an intolerance to infliximab (patient 3). A remission of the active luminal and fistulizing disease was achieved soon after the initiation of adalimumab and sustained thereafter with maintenance doses. No further surgical intervention was required and no adverse effects were observed in any of the cases.

Conclusions

Fistulizing Crohn's disease remains a challenge in clinical practice. Adalimumab seems to be an effective, well-tolerated and safe treatment option for the induction and maintenance of remission in patients with moderate to severe peri-anal fistulizing Crohn's disease. Furthermore, adalimumab seems to be a promising treatment option for patients with moderate to severe fistulizing Crohn's disease with enterocutaneous fistulas. However, this clinical observation needs to be investigated in further clinical trials.