Purpose Pain is the key symptom that distinguishes bladder pain syndrome/interstitial cystitis from overactive bladder syndrome but overlap occurs. To find a discriminating marker for these bladder ...diseases we examined sensory hyperinnervation and neurotrophin receptor expression in bladder biopsies as well as nerve growth factor levels in urine. Materials and Methods Bladder biopsies from patients with bladder pain syndrome/interstitial cystitis, including 12 with and 19 without Hunner lesions, 13 with overactive bladder syndrome and 12 healthy controls, were analyzed by immunohistochemistry with antibodies to the nerve cell marker PGP9.5 (neuron-specific protein gene product 9.5), p75NTR (p75 neurotrophin receptor), the B-lymphocyte marker CD20 and mast cell tryptase. Urinary nerve growth factor was quantified by enzyme-linked immunosorbent assay. Results Subepithelial sensory hyperinnervation on PGP9.5 staining had 97% sensitivity and 76% specificity, increased lymphocytic infiltration had 90% sensitivity and 80% specificity, and urothelial defects had 97% sensitivity and 76% specificity to distinguish bladder pain syndrome/interstitial cystitis with and without Hunner lesions from overactive bladder syndrome and healthy controls. Increased sensory innervation was associated with submucosal mast cell localization. Staining of p75NTR in basal urothelial cells was indicative of bladder pain syndrome/interstitial cystitis. Urinary nerve growth factor levels were below the detection level and did not differentiate bladder diseases from healthy controls. Conclusions Sensory hyperinnervation and basal urothelial p75NTR staining together with assessment of inflammatory lymphocytes and urothelial integrity allow for the differentiation of bladder pain syndrome/interstitial cystitis and overactive bladder syndrome even in the absence of Hunner lesions. Furthermore, these histopathological criteria enable the identification of early disease stages or oligosymptomatic/asymptomatic cases and may permit timely treatment to prevent disease progress.
Purpose
Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The ...Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion.
Methods
The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology.
Results
Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference.
Conclusions
In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.
To assess the morbidity after sentinel lymph node (SLN) biopsy compared with SLN and completion level I and II axillary lymph node dissection (ALND) in a prospective multicenter study.
ALND after ...breast cancer surgery is associated with considerable morbidity. We hypothesized: 1) that the morbidity in patients undergoing SLN biopsy only is significantly lower compared with those after SLN and completion ALND level I and II; and 2) that SLN biopsy can be performed with similar intermediate term morbidity in academic and nonacademic centers.
Patients with early stage breast cancer (pT1 and pT2 <or= 3 cm, cN0) were included between January 2000 and December 2003 in this prospective Swiss multicenter study. All patients underwent SLN biopsy. In all patients with SLN macrometastases and most patients with SLN micrometastases (43 of 68) or isolated tumor cells (11 of 19), a completion ALND was performed. Postoperative morbidity was assessed based on a standardized protocol.
SLN biopsy alone was performed in 449 patients, whereas 210 patients underwent SLN and completion ALND. The median follow-ups were 31.0 and 29.5 months for the SLN and SLN and completion ALND groups, respectively. Intermediate-term follow-up information was available from 635 of 659 patients (96.4%) of enrolled patients. The following results were found in the SLN versus SLN and completion ALND group: presence of lymphedema (3.5% vs. 19.1%, P < 0.0001), impaired shoulder range of motion (3.5% vs. 11.3%, P < 0.0001), shoulder/arm pain (8.1% vs. 21.1%, P < 0.0001), and numbness (10.9% vs. 37.7%, P < 0.0001). No significant differences regarding postoperative morbidity after SLN biopsy were noticed between academic and nonacademic hospitals (P = 0.921).
The morbidity after SLN biopsy alone is not negligible but significantly lower compared with level I and II ALND. SLN biopsy can be performed with similar short- and intermediate-term morbidity in academic and nonacademic centers.
Background
Previous studies using botulinum toxin type A (BT) to treat provoked vestibulodynia (PVD) reported conflicting findings, possibly attributable to singular injections or low doses. We ...assessed PVD treatment effectiveness with high-dose single injections of BT (50 or 100 units) versus placebo, and then repeat BT 100 U injections over 6 months.
Methods
This was a randomized, double-blind, three-arm, placebo-controlled study with 33 PVD patients. BT 50 U (arm A), 100 U (arm B) or saline (arm C) were injected subcutaneously into the dorsal vulvar vestibulum and pain was assessed after 3 months. The investigation proceeded as an unblinded exploratory analysis, in which symptomatic patients received a BT 100 U injection. Symptomatic patients in arm C received a second BT 100 U injection at the 6-month visit. Symptoms were measured at 3-month cycles using: (1) cotton swab-provoked visual analogue scale (VAS), (2) von Frey filaments, and (3) Marinoff dyspareunia scale.
Results
The three groups were comparable in terms of demographics and baseline clinical characteristics. Three months after the initial injection, no significant differences in pain were observed among the study arms, yet significant improvements occurred within all groups using the von Frey filaments test. Results from the exploratory analyses showed repeat injections of 100 U BT over 6 months led to significant pain reduction (VAS and von Frey filaments). Fifty-eight percent (7/12) of patients assessable after repeat injections were symptom-free or had ≥ 2 VAS reduction. Adverse events were minor and no serious adverse events occurred during the RCT or exploratory analysis.
Conclusions
PVD symptoms after one subcutaneous injection of BT (50 or 100 units) did not significantly differ compared to placebo, yet all three study arms experienced a reduction in pain 3 months after a single injection. Exploratory analyses indicated that repeat high-dose BT injections may significantly reduce pain over 6 months.
Trial registration
This trial was registered with the Swiss Medical Agency (reference number: 2007DR2102) in 2007.
Zielsetzung:
Blasenschmerzsyndrom/Interstitielle Cystitis (BPS/IC) und Reizblase (OAB) werden über die Schlüsselsymptome ‚Schmerz‘ respektive ‚Drang‘ definiert, aber die Zuordnung ist oft schwierig. ...Objektive molekulare Marker wären hilfreich. Wir untersuchten, ob der Blasenschmerz bei BPS/IC im Zusammenhang mit einer subepithelialen Hyperinnervierung steht. Zudem wurden auch weitere mögliche Unterscheidungs-Marker, wie die Lymphozyten- und Mastzell-Infiltration, die Urothel-Integrität und die Neurotrophin-Rezeptor-Expression (p75NTR) histopathologisch beurteilt, und der Nervenwachstumsfaktor (NGF) im Urin wurde quantifiziert.
Materialien:
Blasenbiopsien und Urin von BPS/IC-Patientinnen mit (12) und ohne (19) Hunnersche Läsionen, 13 Patientinnen mit OAB und 12 gesunden Kontrollen wurden untersucht. Die Patientinnen wurden aufgrund der Symptome und der zystoskopischen Befunde eingeschlossen.
Methoden:
Biopsieschnitte wurden mit Hämatoxylin-Eosin-Färbung und mit Immunhistochemie mit Antikörpern gegen PGP9.5, p75NTR, Mastzell-Tryptase und CD20 analysiert. ELISA-Experimente dienten zum NGF-Nachweis im Urin.
Ergebnisse:
Eine subepitheliale sensorische Hyperinnervierung (97% Sensitivität; 76% Spezifität), eine erhöhte Dichte von Entzündungsinfiltraten (90% Sensitivität; 80% Spezifität) und Urothel-Defekte (97% Sensitivität; 76% Spezifität) werden bei Patientinnen mit Blasenschmerz gefunden. Dank dieser Kriterien können BPS/IC mit und ohne Hunnersche Läsion von OAB und gesunden Kontrollen unterschieden werden. Die Hyperinnervierung assoziiert mit der Mastzellverteilung in der Submucosa, und die positive p75NTR-Färbung in basalen Urothelzellen ist hinweisend für BPS/IC. NGF konnte im Urin nicht nachgewiesen werden.
Zusammenfassung:
Die sensorische Hyperinnervierung in der Blasenbiopsie und weitere histopathologische Kriterien erlauben die Unterscheidung von BPS/IC und OAB, auch in Abwesenheit von Hunnerschen Läsionen. Damit wird auch die Diagnose von Frühstadien der BPS/IC und die Identifizierung von asymptomatischen Patientinnen ermöglicht. Eine früh eingeleitete Kausaltherapie kann das Fortschreiten der Krankheit verhindern.
Background: Routine adjuvant administration of trastuzumab (T) has been implemented in most centers, but its economic impact has not yet been well examined. Methods: A Markov model was constructed ...based on clinical data of the Herceptin Adjuvant (HERA) and the Finland Herceptin (FinHer) trials. Costs from the perspective of a Swiss health care provider were calculated based on resource use. Results: On the basis of HERA data, our model yielded an overall survival rate of 71.8% for the T group versus 62.8% for the control group risk ratio (RR) = 0.87) after 10 years and 62.9% versus 52.7% (RR = 0.84) after 15 years. Cost-effectiveness resulted in 40505 Euros (EUR) per life years gained (LYG) after 10 years and 19673 EUR per LYG after 15 years. For the FinHer regimen, overall survival after 10 and 15 years resulted in 81.8% versus 66.1% (RR = 0.81) and 73.6% versus 57.0% (RR = 0.77). Costs of 8497 EUR per patient could be saved after 10 years and 9256 EUR after 15 years compared with the control group. Conclusion: In a long-term perspective, adjuvant T based on the HERA regimen can be considered cost-effective. The regimen used in the FinHer trial is even cost saving, but estimations are based on a single small trial.
The aim of this study was to compare MRI of the breast with (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) in patients with suspected local or regional breast cancer recurrence ...or suspected contralateral breast cancer. Thirty-two patients (mean age 57.2 years, age range 32-76 years) with suspected loco-regional recurrence ( n=19), chest wall recurrence ( n=5), and suspected secondary tumor of the contralateral breast ( n=8) underwent MRI of the breast and FDG PET of the whole body and breast region. Cytology/histology ( n=17) or a clinical follow-up examination ( n=15) with additional imaging served as the standard of reference. A McNemar test was performed to compare PET and MRI, and kappa was determined to quantify agreement of both methods. Sensitivity was 79 and 100%, specificity was 94 and 72%, and accuracy was 88 and 84% for MRI and PET, respectively. Additional metastases outside the field of view of MRI were found in PET in 5 patients. In this study both imaging methods had comparable accuracy. The detection of distant metastases with whole-body PET imaging can influence patient management.
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