Development and feasibility of a telemedicine tool for patients with recurrent urinary tract infection: myRUTIcoach.

INTRODUCTION AND HYPOTHESIS: Patients with recurrent urinary tract infection (rUTI) have limited knowledge of preventive strategies to lower the risk of UTI. We aimed to develop and test the feasibility of an eHealth system for women with rUTI, named myRUTIcoach, and explored the facilitators and barriers related to its adoption. METHODS: We developed myRUTIcoach in a structured iterative process and tested its feasibility among 25 women with rUTI over 2 months. Subsequent questionnaires covered satisfaction, accessibility, and experiences with myRUTIcoach. A random selection of participants and relevant stakeholders took part in semi-structured interviews to explore adoption. Data were analyzed and elaborated using inductive and deductive approaches using the Non-adoption, Abandonment, Spread, Scale-up, and Sustainability (NASSS) framework. RESULTS: MyRUTIcoach was not only widely accepted but also facilitated communication with health care professionals (HCPs) and contributed to greater knowledge of rUTI. Women graded the system a mean of 8.0 (±0.6) out of 10, with 89% stating that they would recommend it to others. Patients indicated that self-management skills were the major facilitators and barriers related to adoption, whereas HCPs stated that the disconnect between myRUTIcoach and electronic health care records (EHRs) was the major barrier. CONCLUSIONS: This research describes the development and testing of myRUTIcoach for women with rUTI. Patients and HCPs reported high satisfaction and compliance with myRUTIcoach. However, adoption by the intended users is complex and influenced by all examined domains of the NASSS framework. We have already improved linkage to EHRs, but further optimization to meet patient needs may improve the effectiveness of this self-management tool for rUTI.

Assessment and treatment of recurrent urinary tract infections in women: development of a questionnaire based on a qualitative study of patient expectations in secondary care.

BACKGROUND: To develop a questionnaire to facilitate the inventorying of women's expectations for the assessment and treatment of recurrent urinary tract infection (UTI) in secondary care. METHODS: Semi-structured interviews were conducted among women with recurrent UTI referred to our urology department. The interviews were conducted by one interviewer, recorded, transcribed verbatim, and analyzed thematically by two researchers. We first developed 35 questions to identify potential themes, and we then tested them among women with and without recurrent UTI. Changes were made according to the feedback received. RESULTS: Six interviews were conducted before saturation was reached. Thematic analysis identified three themes: patient pathway, personal knowledge, and social implications. All respondents had received multiple antibiotic courses but no prophylactic antibiotic therapy, and although all were aware of some preventive measures, they wanted more information about their disease. However, some women were afraid to access information for fear of what they might learn. Recurrent UTI also significantly affected the daily lives all respondents. Some women expressed fears over frequent antibiotic use, and others felt that there must be something wrong with their body to have so many UTIs. Women expected the urologist to provide an explanation and to start adequate therapy for their recurrent UTI. We created a 32-item questionnaire based on these themes CONCLUSION: This study not only developed a questionnaire for use when assessing patient expectations of recurrent UTI management in secondary care but also provided novel insights into the thoughts, opinions, and expectations of women who are referred.

Recurrence of non-muscle invasive bladder carcinoma after transurethral resection with hexaminolevulinate photodynamic diagnosis or regular cystoscopy.

OBJECTIVES: To compare the recurrence of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection employing cystoscopy with hexaminolevulinate-based photodynamic diagnosis (PDD) or with standard white light. PATIENTS AND METHODS: We included patients with newly suspected NMIBC in this retrospective cohort study and compared those undergoing transurethral resection by white light cystoscopy (WLC) (2008-2010) and PDD (2010-2012). All patients were treated following established criteria for good quality resection. The primary outcome was the difference in the recurrence rate after 60 months' follow-up, but we also stratified recurrence by risk groups, as set by the European Organization for Research and Treatment of Cancer. The mean recurrence-free survival was compared between the cohorts. Odds ratios or hazard ratios are reported with their 95% confidence intervals. RESULTS: The WLC and PDD cohorts comprised 124 and 91 subjects, respectively. There were no significant differences in recurrence rates between the cohorts at 6 months (recurrence rate 9/123; 7.3%), 12 months (17/118; 14.4%) or 60 months (39/102; 38.2%), with odds ratios of 1.23 (CI 0.48-3.25), 1.32 (CI 0.67-2.62) and 1.12 (CI 0.70-1.79), in favour of WLC, respectively. Further analysis showed no significant effect of PDD on either recurrence by risk group or on mean recurrence-free survival (hazard ratio, 1.12 [CI 0.70-1.79]). CONCLUSION: We found no relevant differences in the recurrence of NMIBC after the introduction of PDD with hexaminolevulinate compared to standard WLC when used for transurethral resection in our single institution.

The Patient Pathway for Men with Chronic Urinary Retention: Treatments, Complications, and Consequences.

OBJECTIVE: To explore the treatment options for chronic urinary retention (CUR) in men, including treatment-related complications and consequences. METHODS: This retrospective cohort study included male patients diagnosed with a non-neurogenic, symptomatic and/or high-risk, CUR >150 mL in a large Dutch non-academic teaching hospital. Data for treatments, complications, and consequences (eg, diagnostics, additional treatments, and hospital contact) were recorded and incidence rate ratios (IRRs) were calculated. RESULTS: We enrolled 177 patients (median age, 77 years; range, 44-94) with a median follow-up of 68 months (range, 1-319) during which they had a median of 8 events (range, 1-51). Most patients initially received a urethral catheter (74%) and some form of catheterization as their final treatment (87%). Compared with non-surgical cases, catheterization was more likely to be stopped after de-obstructive prostate surgery (IRR, 4.18; P < 0.001). Urinary tract infection (IRR, 3.68; P < 0.001) and macroscopic hematuria (IRR, 5.35; P < 0.001) were more common with catheterization, but post-renal problems were more likely in patients with no catheterization (IRR, 25.36; P < 0.001). The lowest chance of complication was with clean intermittent catheterization, and complications were usually managed in outpatient (77%) or emergency (6%) departments, rather than by admission (17%). CONCLUSION: Most patients require catheterization for CUR, with clean intermittent catheterization preferred due to its comparatively lower complication risk. De-obstructive prostate surgery increases the chance of stopping catheterization and may be considered in suitable cases.

Scrotal necrosis after cobra (Naja annulifera) envenomation.

A 47-year-old man received a snouted cobra (Naja annulifera) snake bite to his genitals while on holiday in South Africa. His penis and scrotum were noted to be swollen, deep purple in color, and painful on hospital admission. Scrotal necrosis was diagnosed, and he received multiple doses of a non-specific snake venom antiserum and broad-spectrum antibiotics. Although no neurological sequelae developed, he did require hemodialysis due to acute kidney injury. After stabilizing, he was repatriated to the Netherlands for further treatment and has since made a full recovery.

A case of spontaneous urinary bladder rupture secondary to urinary retention due to an urethral stricture.

A spontaneous, non-traumatic, urinary bladder rupture is a rare condition. We describe a case of a 23-year-old male with a spontaneous bladder rupture secondary to urinary retention, due to an urethral stricture. He presented to the emergency department with voiding difficulties, severe abdominal pain and renal failure. Abdominal ultrasound revealed large amounts of ascites. After an unsuccessful attempt to place a Foley catheter a cystoscopy was performed which showed an urethral stricture. On CT-cystogram an intra-peritoneal bladder rupture was diagnosed and the patient underwent laparoscopic repair of the bladder wall. The postoperative course was uneventful.

Intratumoral distribution of two consecutive injections of chimeric antibody G250 in primary renal cell carcinoma: implications for fractionated dose radioimmunotherapy.

Tumor uptake of the chimeric G250 (cG250) monoclonal antibody (mAb) in patients with primary renal cell carcinoma (RCC) is among the highest reported in solid tumors. However, as observed in other tumor types, the intratumoral distribution of the antibody is highly heterogeneous, which may limit the efficacy of radioimmunotherapy. A number of highly dynamic physiological factors have been postulated that may contribute to heterogeneous tumor uptake of antibodies. Their impact on tumor uptake of antibodies may vary from one tumor region to another as well as from one day to the next. Here, we report on a clinical study that was designed to investigate whether the pattern of mAb cG250 uptake within RCC tumors is altered with subsequent injections. Ten patients with a clinical diagnosis of primary RCC were studied. Nine days before surgery, patients received 125I-cG250 (5 mg of cG250, 50 microCi of 125I), followed by a second injection of 131I-cG250 (5 mg of cG250, 3.5 mCi of 131I) 4 days later. Postsurgery, the tumor was cut into (1-cm) thick slices. Slices were imaged on a gamma camera, and the slice with the most pronounced heterogeneity in 131I-cG250 distribution was selected and cut into 1-cm3 cubes. Each cube was analyzed for 121I-cG250 and 131I-cG250 uptake, and the 131I/125I ratio was determined. For each tumor slice, the distribution patterns of both isotopes were reconstructed and compared with each other. All tumors analyzed showed a heterogeneous distribution of both isotopes throughout the tumor slice; focal uptake in some areas of a tumor reached very high levels (up to 0.19% injected dose/g), whereas other tumorous areas of the same slice showed much lower uptake (as low as 0.0047% injected dose/g). Remarkably, in all tumors, the distribution pattern of both injections was identical: without exception, in all samples analyzed (n = 692), the uptake of 125I-cG250 was similar to 131I-cG250 uptake. Overall, the 131I/125I ratio was 1.64+/-0.31 (mean+/-SD). The constant 131I/125I ratios, observed in all tumor samples investigated, indicate that the tumor parameters governing cG250 mAb uptake were not altered significantly within the time period studied. In addition, the results of this study suggest that multiple radiolabeled antibody injections, administered within short time periods, will target the same areas within a tumor and, thus, will not solve the problem of heterogeneous tumor uptake of antibody.

Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250.

PURPOSE: Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody. PATIENTS AND METHODS: Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi 131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained of surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed. RESULTS: In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage of the injected dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250 uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients. CONCLUSION: 131I-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid tumors. Since tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250 are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC.

Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250.

Clinical tumor targeting studies with chimeric monoclonal antibody G250 (cG250) in renal cell carcinoma (RCC) patients indicated the potential use of this antibody for radioimmunotherapy. Here we report on a phase I activity dose escalation study to determine the safety, the maximum tolerable dose (MTD), and the possible therapeutic potential of 131I-labeled cG250 in patients with progressive metastatic RCC. All patients (n = 12) received a diagnostic i.v. infusion of 5 mg of cG250 labeled with 222 MBq of 131I. If accumulation of the antibody in metastatic lesions was observed, patients were hospitalized and a second, therapeutic, i.v. infusion of 5 mg of cG250 labeled with a high dose of 131I was administered (n = 8). Three patients per dose level were entered, starting at 1665 MBq/m2. If no dose-limiting toxicity occurred, the study continued at the next dose level (555 MBq/m2 increase). Most patients experienced mild nausea without vomiting. No other complaints were reported during hospitalization. In two of two patients who received a dose of 2775 MBq/m2, grade IV hematological toxicity was observed, which was defined as dose limiting. Thus, the MTD was set at 2220 MBq/m2. In one patient (2220 MBq/m2), stable disease (lasting 3-6 months) was achieved, whereas another patient (2220 MBq/m2) showed a partial response that is ongoing (>9 months). The minor responses observed in this phase I trial in patients with an advanced stage of RCC are encouraging and warrant further study in a phase II setting at the MTD to determine the efficacy of radioimmunotherapy for metastatic RCC.

In vivo and in vitro characterizations of three 99mTc-labeled monoclonal antibody G250 preparations.

UNLABELLED: In previous clinical studies, excellent visualization of tumor lesions has been observed with 131I-labeled monoclonal antibody (mAb) G250 in patients with renal cell carcinoma (RCC). In several cases, 131I-cG250 immunoscintigraphy disclosed tumor lesions that were not visualized by radiography or CT. To improve image quality, we aimed to develop a 99mTc-labeled mAb G250 preparation for radioimmunodetection of RCC. We studied in vitro stability, biodistribution and imaging potential of three 99mTc-labeled G250 preparations in nude mice with subcutaneous RCC xenografts.125I-G250 and the nonspecific mAb 131I-MN14 were used as control antibodies. METHODS: The mAb G250 was labeled with 99mTc according to three methods using: (a) S-hydrazinonicotinamide (HYNIC), (b) S-benzoylmercaptoacetyltriglycine (MAG3) and (c) a direct labeling method (Schwarz method). The stability of all preparations was tested in serum at 37 degrees C during 48 h. In addition, diethylenetriamine pentaacetic acid, cysteine and glutathione challenge assays were performed. RESULTS: All preparations showed good stability in serum during the 48-h incubation period. 99mTc-G250 (Schwarz) showed release of the radiolabel at a 100-fold or higher molar excess of cysteine and at a 10,000-fold or higher molar excess of glutathione. 99mTc-MAG3-G250 showed release of the radiolabel at a 10,000-fold molar excess of cysteine. 99mTc-HYNIC-G250 was stable under all conditions. Tumors were clearly visualized with all preparations. 99mTc-G250 (Schwarz) showed significantly lower blood levels (3.8 %ID/g) compared with all other preparations (11.2, 13.4 and 13.4 %ID/g for 99mTc-HYNIC-G250, 99mTc-MAG3-G250 and 125I-G250, respectively, 48 h postinjection). At 48-h postinjection, mean tumor uptake was very high with all mAb G250 preparations: 92.4 (99mTc-HYNIC-G250), 125.9 (99mTc-MAG3-G250), 29.4 (99mTc-G250 Schwarz) and 75.4 (125I-G250) %ID/g. Mean tumor uptake of the nonspecific 131I-MN14 mAb was 6.6 %ID/g. CONCLUSION: In this study, 99mTc-HYNIC-G250 showed excellent in vitro stability and tumor targeting. Moreover, this preparation could be labeled with high efficiency (>95%) at room temperature within 15 min. Therefore, 99mTc-HYNIC-G250 seems to be an ideal candidate for radioimmunodetection of RCC.

Immunohistochemical analysis of tumor antigen saturation following injection of monoclonal antibody G250.

Clinical tumor targeting studies with monoclonal antibody (mAb) G250 showed excellent targeting of primary renal cell carcinomas (RCC). However, tumor uptake decreased at higher mAb G250 doses, suggesting saturation of the G250 antigenic determinants. In this immunohistochemical study we investigated the saturability of G250 antigen sites after i.v. administration of mAb G250 at various protein doses in nude mice with RCC xenografts. Five groups of mice received five different protein doses (1, 3, 10, 30 or 100 micrograms) of murine mAb G250. Three days post injection mice were killed and the tumors were removed. Free G250 antigen sites, i.e., not targeted by the i.v. injected murine mAb G250 were determined by immunohistochemical staining with chimeric mAb G250. Distinct staining of the G250 antigen was observed only at the 1 and 3 micrograms dose whereas G250 antigen staining at higher doses was virtually negative. The results of this study indicate that saturation of antigen occurs at relatively low doses of i.v. administered mAb G250. Apparently, all antigenic determinants present on the RCC tumor cells were targeted, while previous preclinical studies suggested that i.v. administration of mAb G250 only saturated the accessible antigen sites.

Tumor retention of 186Re-MAG3, 111In-DTPA and 125I labeled monoclonal antibody G250 in nude mice with renal cell carcinoma xenografts.

UNLABELLED: In radioimmunotherapy of solid tumors substantial gain might be achieved by carefully selecting the radionuclide and the linker connecting it to the antibody. In contrast to 131I, radiometals such as 90Y and 111In may be retained in the tumor cell after internalization of the antibody, thereby enhancing the radiation dose to the tumor. The physical properties of 186Re with 1.08 MeV beta-emission (71%) and 137 keV gamma-emission (10%) seem ideal for radioimmunotherapy. In this study we investigated in nude mice with s.c. renal cell carcinoma xenografts the biodistribution and the retention in the tumor of 186Re-MAG3 labeled monoclonal antibody (mAb) G250 as compared to 111In-DTPA-G250, to 125I-G250 and to 131I-MN14 (non-specific control mAb). Radiolabeled antibody preparations were i.v. injected. Seventy two hours p.i. the biodistribution of the radiolabel was determined. Blood levels of all mAb G250 preparations were remarkably low (mean: 2.38, 1.40 and 1.43% ID/g for 125I, 111In and 186Re respectively) whereas blood levels of mAb MN14 were significantly higher (mean: 12.3% ID/g), indicating tumor processing of mAb G250. Retention of 111In in the tumor was significantly higher than of 186Re and 125I whereas retention in the tumor of 186Re and 125I did not differ significantly. CONCLUSION: In contrast to other radiometals such as 111In and 90Y, 186Re is not retained in the tumor cell. Therefore 186Re has no additional advantage for radioimmunotherapy with respect to retention in the tumor.

131 I-cG250 monoclonal antibody immunoscintigraphy versus [18 F]FDG-PET imaging in patients with metastatic renal cell carcinoma: a comparative study.

The aims of this study were to establish the percentage of metastatic renal cell carcinoma (RCC) lesions detected by radioimmunoscintigraphy (RIS) with the chimeric monoclonal antibody 131I-cG250 versus positron emission tomography (PET) with 18F-labelled deoxyglucose ([18F]FDG), and to evaluate the use of these radionuclide imaging modalities compared with routinely used imaging techniques. Twenty patients with metastatic RCC disease were examined with [18F]FDG-PET and 131I-cG250 RIS within 1 week. Total body gamma camera images were obtained up to 120h after injection of 232MBq 131I-cG250. Total body PET scanning was performed 45-60 min after intravenous injection of 370MBq [18F]FDG. Nuclear medicine techniques were compared to routine imaging procedures. Routine imaging modalities revealed a total of 79 metastases. [18F]FDG-PET and 131I-cG250 RIS detected 33 previously unknown metastases, of which 32 were [18F]FDG positive and seven were 131I-cG250 positive. Of the 112 tumour lesions that were documented, [18F]FDG-PET detected 69% (77 out of 112), whereas 131I-cG250 RIS detected only 30% (34 out of 112). In conclusion, [18F]FDG-PET is superior to 131I-cG250 RIS in detecting metastases in patients with metastatic RCC, and therefore seems a promising tool for (re)staging patients with RCC. The usefulness of RIS with a diagnostic dose of 131I-cG250 seems to be restricted to selecting patients for radioimmunotherapy with 131I-cG250.

[Paraneoplastic syndromes in three patients with renal cell carcinoma]. / Paraneoplastische verschijnselen bij 3 patiënten met een niercelcarcinoom.

Renal cell carcinoma was diagnosed in three male patients, 45, 53 and 52 years of age. In addition, they had paraneoplastic symptoms: hypercalcaemia, hyperglycaemia and elevated hepatic enzyme levels, respectively. All three patients underwent tumour nephrectomy, after which the paraneoplastic symptoms disappeared. The first patient died 16 months postoperatively, while the other two were alive and free of symptoms after a follow-up of nine months and four years, respectively. Many patients with renal cell carcinoma remain asymptomatic for a long period of time and 30% of all patients have metastatic disease at the time of diagnosis. The classic triad of flank pain, haematuria and an abdominal mass occurs in only 10% of all cases. However, 20-40% of all patients present with signs of a paraneoplastic syndrome, of which anaemia (20-40%), fever (30%), hypertension (24%), hypercalcaemia (10-15%) and hepatic dysfunction (3-6%) are the most common.

Chronic scrotal and inguinal pain after orchidopexy in a 13-year-old boy, treated by pulsed radiofrequency of the dorsal ganglia.

Chronic scrotal pain can be a difficult clinical entity to treat. Many different treatment options have been proposed. We describe the case of a young boy with chronic scrotal and inguinal pain on the right side, following two orchidopexies. After many therapies had failed, we treated the dorsal root ganglia of thoracic 12, lumbar 1 and lumbar 2 with pulsed radiofrequency, finally resulting in alleviation of his pain.

Value of fluorodeoxyglucose positron emission tomography in women with breast cancer.

BACKGROUND: The aim of this prospective study was to evaluate the role of fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging of high-risk women with primary or recurrent breast cancer. METHODS: FDG-PET was performed in 42 women with a primary breast cancer and unfavourable characteristics, or who had a suspected relapse. FDG-PET and conventional staging methods were compared. In case of abnormality on FDG-PET, confirmation was always attempted. RESULTS: Increased uptake was found in five of 17 women with a primary cancer. In the 25 women with a suspected relapse, FDG-PET showed increased uptake in 43 areas, 22 correctly confirming the area of suspected relapse and 21 indicating other sites of metastases. Compared with conventional imaging, FDG-PET revealed additional (confirmed) lesions in two women with primary cancers and three with relapse. Patient management was changed for five women. CONCLUSION: FDG-PET is a sensitive diagnostic method for the detection of distant metastatic disease. Its exact role in women with breast cancer remains to be defined.

Immunohistochemical analysis of intratumoral heterogeneity of [131I]cG250 antibody uptake in primary renal cell carcinomas.

In previous studies, highly heterogeneous uptake of 131I-labelled chimeric monoclonal antibody G250 ([131I]cG250) in primary renal cell carcinomas has been observed (intratumoral differences > factor 100). In this study, we investigated a possible correlation between intratumoral antibody uptake and four immunohistochemically determined parameters: G250 antigen expression, blood vessel density, neovascularization and percentage of viable tumour cells. Whole tumour slices of four different tumours were cut into 1-cm3 cubes, and in each cube the [131I]cG250 uptake was determined. The correlation between [131I]cG250 uptake and each individual parameter was determined in a multiple regression analysis. Additionally, the data were reanalysed after introducing arbitrary cut-off values for each parameter. If a sample showed expression of a parameter above the introduced threshold value, this sample fulfilled one condition. Subsequently, the Pearson correlation coefficients were calculated from [131I]cG250 uptake and the number of fulfilled conditions (0-3). All tumour samples with high [131I]cG250 uptake [> 0.1% of the injected dose per gram (ID g(-1))] showed high antigen expression (> 50%). However, not all samples with high antigen expression displayed high uptake. A statistically significant correlation between [131I]cG250 uptake and antigen expression was found (beta = 0.44, 0.69 and 0.74) in three out of four tumours analysed. Of the other determined parameters, no consistent correlation with [131I]cG250 uptake was found; only the percentage of viable tumour cells correlated significantly in two out of four tumours (beta = 0.80 and 0.26). Calculation of the Pearson correlation coefficients showed a statistically significant correlation between [131I]cG250 uptake and an increased number of fulfilled conditions in all tumours, indicating that each of the individual parameters contribute to the uptake of [131I]cG250. These observations indicate that high antigen expression is a prerequisite for high antibody uptake. However, regional differences in antibody uptake within a tumour cannot be explained by antigen expression alone.