A Pilot Study of Functional Brain Magnetic Resonance Imaging in BPS/IC Patients: Evidence of Central Sensitization.

Bladder pain syndrome/Interstitial cystitis (BPS/IC) is characterized by increased activity in bladder afferent pathways, recruitment of silent nociceptive neurons, and sensitization of the brain areas responsible for pain amplification. Default mode network (DMN) is a set of regions activated during the resting state, which reflect the brain's intrinsic activity. Conversely, the sensorimotor network (SMN) plays a key role in structural neuroplasticity. This study aimed to evaluate DMN and SMN activity in BPS/IC patients, both with and without bladder noxious stimulus, using functional brain magnetic resonance imaging (MRI). Six BPS/IC female patients underwent 3 Tesla fMRI brain scanners. Acquisitions consisted of 10-minute blood oxygen level-dependent echo-planar imaging. The first acquisition was with an empty bladder, painless, and the second was with suprapubic pain. Data were processed using the independent component analysis method with the MELODIC tool from the functional brain MRI of the Brain Software Library (FSL). A semi-quantitative analysis was performed afterward. The patients' age was 42.6 ± 5 years, pain intensity was 7 ± 0.7 (0-10), day and night frequency were 9.2 ± 2.2 and 2.8 ± 1.0, and maximal bladder capacity was 260 ± 54 mL. One patient was unable to complete the study. All patients showed a comparable DMN activation in both empty and full bladder states, and all presented high SMN activation whether the bladder was empty or full. The activation of DMN at both bladder states, empty and full, and constant SMN activation without and with pain supports the role of these networks in BPS/IC. Similar findings have been reported in other chronic pain syndromes.

What is in the pipeline for new treatments for bladder pain syndrome/ interstitial cystitis?

PURPOSE OF REVIEW: Despite available treatments, many bladder pain syndrome/interstitial cystitis (BPS/IC) patients continue to have poor quality of life. Thus, there is an urge for new therapies. Our manuscript aims to review papers about BPS/IC treatments published in the last 2 years. RECENT FINDINGS: During this period, several treatments were tested, most of them new and others combining treatments already used. Pentosan polysulfate, interleukin 1 antagonist, low energy shock wave, physical therapy, hypnosis, acupuncture, clorpactin, dimethyl sulfoxide and hyaluronic acid plus botulinum toxin-A showed positive results. ASP3652 and lidocaine-releasing intravesical systems failed to prove their efficacy. SUMMARY: Validation of these studies is arduous due to the broad spectre of BPS/IC phenotypes, small number of patients enrolled, distinct outcome measures and short-term follow-up. It is also important to highlight that some authors combined therapies, and others split central and peripheric phenotypes before treatment. Therefore, soon, phenotyping and combining therapies with a step-by-step approach will be needed in BPS/IC treatment.

The Role of Urinary VEGF in Observational Studies of BPS/IC Patients: A Systematic Review.

BACKGROUND: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic pain condition, often underdiagnosed, with an important impact on patient quality of life. More recently, an association between VEGF and its receptors has been suggested in BPS/IC pathophysiology, due to their role in promoting angiogenesis and inflammation, which can enhance bladder pain. Eventually, VEGF may be used as a biomarker for the diagnosis and prognostication of BPS/IC. To further clarify this issue, this review aims to critically summarize the available information, giving rise to a solid starting point for future studies. METHODS: We systematically searched PubMed and Embase, using the queries "urinary VEGF", "urinary VEGF" AND "pain", "urinary VEGF" AND "lower urinary tract symptoms" and "urinary VEGF" AND "LUTS" from January 2016 to February 2022. RESULTS: A total of 1026 papers were identified from which 7 articles were included in this study, which assessed 1036 participants. Regarding VEGF levels, overactive bladder (OAB) and healthy patients were used for comparison with BPS/IC patients. VEGF concentration seems to be higher when compared to healthy patients and overactive bladder (OAB) patients. Higher levels of VEGF were associated with pain severity, while a decrease in VEGF concentration was associated with pain and symptom improvement in women. However, these findings were not constant in all studies. CONCLUSIONS: There is a trend toward a relevant association between increased VEGF levels and pain or symptom severity in BPS/IC patients. Although there are some discrepancies among the studies and the number of patients included is small, VEGF and its receptors should be considered for future studies regarding its use in BPS/IC pathophysiology, diagnosis and prognostication.

Dieulafoy's lesion in the cecum: A rare case report presentation.

INTRODUCTION AND IMPORTANCE: Dieulafoy's lesion is a rare entity, normally present in the stomach and more rarely in the colon, and it is responsible for 1% to 5% of acute gastrointestinal bleeding cases. Its true incidence may be underrated, since most cases are asymptomatic and difficult to diagnose despite endoscopic advances. We present a clinical case of acute gastrointestinal bleeding due to Dieulafoy's lesion in the cecum. CASE PRESENTATION: An 85-year-old woman presented with a clinical condition of haematochezia associated with anaemia and haemodynamic instability, needing blood transfusion. Colonoscopy demonstrated a Dieulafoy's lesion in the cecum with active bleeding, and haemostasis was performed successfully with localized adrenaline injection and haemostatic clip placement. Hospitalization occurred without further complications. DISCUSSION: The diagnosis of Dieulafoy's lesion is difficult because it is a rare condition and thus, usually not included in the differential diagnosis of gastrointestinal bleeding. Its endoscopic diagnostic and therapeutic approach is the standard method in the event of an acute gastrointestinal bleeding episode, with greater efficiency with the combined use of haemostatic techniques. Surgery is necessary in less than 5% of cases when bleeding is not effectively controlled by endoscopic or angiographic techniques. CONCLUSION: It is essential to be aware of this lesion as a possible cause of gastrointestinal bleeding and differentiate it from other causes. Advances in endoscopy have increased the rate of diagnosis of these lesions and reduced their associated mortality.

Intratrigonal OnabotulinumtoxinA Improves Bladder Symptoms and Quality of Life in Patients with Bladder Pain Syndrome/Interstitial Cystitis: A Pilot, Single Center, Randomized, Double-Blind, Placebo Controlled Trial.

PURPOSE: We compared the efficacy and safety of trigonal injections of onabotulinumtoxinA and saline in patients with bladder pain syndrome/interstitial cystitis. MATERIALS AND METHODS: This phase II study enrolled women who had had bladder pain syndrome/interstitial cystitis for more than 6 months and pain for 4 months or longer on a visual analogue scale of 0 to 10, which were refractory to common treatment. OnabotulinumtoxinA 100 U in 10 or saline as placebo in 9 was administered as 10 trigonal injections of 1 ml. The primary study end point was the change from baseline pain intensity reported at week 12. Additional end points included O'Leary-Sant scores, micturition frequency, quality of life at week 4, 8 and 12, and the treatment benefit scale at week 12. Safety assessments included urinary tract infection, post-void residual urine and the initiation of clean intermittent catheterization. RESULTS: At week 12 onabotulinumtoxinA had significantly reduced pain compared with saline (mean ± SD -3.8 ± 2.5 vs -1.6 ± 2.1, p <0.05). The proportion of patients who achieved a 50% or greater reduction in the pain visual analog scale was 60% for onabotulinumtoxinA vs 22% for placebo. OnabotulinumtoxinA significantly improved O'Leary-Sant scores and quality of life over placebo at weeks 4, 8 and 12. Important numerical reductions in voiding frequency were also observed with the toxin. OnabotulinumtoxinA was well tolerated. Urinary tract infections developed in 3 patients who received onabotulinumtoxinA vs 2 who received saline. Mean post-void residual urine at week 12 was 5 ± 13 ml for onabotulinumtoxinA vs 0 ml with saline. This study had the limitations inherent to a single center trial with a small number of patients enrolled. CONCLUSIONS: OnabotulinumtoxinA 100 U caused significant and clinically relevant improvements in bladder pain and quality of life in patients with bladder pain syndrome/interstitial cystitis refractory to common therapy. It was also well tolerated.

Extraocular Muscles Involvement as the Initial Presentation in Metastatic Breast Cancer / 한국유방암학회지

Orbital metastasis is a rare event, and metastatic disease affecting the extraocular muscles is an even less frequent complication of solid tumors. Herein, we report an unusual case of ptosis as the initial presentation of an invasive breast cancer. A 68-year-old woman presented with III and VI partial nerve paresis, secondary to a compressive retrobulbar mass. Magnetic resonance imaging revealed an infiltrative lesion involving the extraocular muscles. Tissue biopsy yielded a result compatible with metastasis to the orbit, with immunohistochemistry analysis suggesting breast as the primary organ. Mammography identified an area of architectural distortion; stereotactic wire-guided biopsy confirmed the result of the previous orbital biopsy. A positron emission tomography scan demonstrated disseminated disease. Palliative chemotherapy with bone-modulating agents and subsequent hormonal therapy was proposed. Unfortunately, the patient did not respond to therapy and died 38 months after diagnosis.

Portuguese Version of the EORTC QLQ-OES18 and QLQ-OG25 for Health-Related Quality of Life Assessment.

INTRODUCTION: Health-related quality of life assessment is increasingly important as it can help both clinical research and care for patients, particularly among oncological patients. Quality of Life Questionnaire - OES18 (esophageal module) and Quality of Life Questionnaire - OG25 (esophagogastric module) are the European Organization for Research and Treatment of Cancer modules for the evaluation of quality of life in patients with esophageal and esophagogastric cancers, respectively. The aim of our study was to translate, to culturally adapt and to perform a pilot testing to create the Portuguese version of both questionnaires. MATERIAL AND METHODS: The European Organization for Research and Treatment of Cancer guidelines were followed for translation, cultural adaptation and pilot testing of Quality of Life Questionnaire - OES18 (esophageal module) and Quality of Life Questionnaire - OG25 (esophagogastric module). The Quality of Life Questionnaire - OG25 (esophagogastric module) went through a process of forward (English → Portuguese) and backward (Portuguese → English) translation, by independent native speaker translators. After review, a preliminary version was created to be pilot tested among Portuguese patients. As a Brazilian version was already available for Quality of Life Questionnaire - OES18 (esophageal module), the questionnaire was simply culturally adapted and pilot tested. Both cancer and non-cancer patients were included. RESULTS: Overall, 30 patients completed the Portuguese version of each questionnaire. Afterwards, a structured interview was conducted to find and report any problematic items. Troublesome items and wording were changed according to the pilot testing results. The final versions were sent to the European Organisation for Research and Treatment of Cancer Quality of Life Group and approved. CONCLUSION: The Portuguese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - OES18 (esophageal module) and OG25 (esophagogastric module) questionnaires are useful, reliable and valid tools for measuring health-related quality of life in patients with esophageal and esophagogastric cancers, respectively. They can now be used in clinical setting and for scientific purposes.

Introdução: A avaliação da qualidade de vida relacionada com a saúde é cada vez mais importante, já que pode beneficiar a investigação clínica e os cuidados prestados aos doentes, particularmente entre doentes oncológicos. O Quality of Life Questionnaire ­ OES18 (esophageal module) e o Quality of Life Questionnaire ­ OG25 (esophagogastric module) são módulos da Organização Europeia para a Investigação e Tratamento do Cancro para avaliação da qualidade de vida em doentes com neoplasia esofágica e/ou esofagogástrica, respetivamente. O objetivo do nosso estudo foi traduzir, adaptar culturalmente e realizar um ensaio-piloto para criar a versão portuguesa de ambos os questionários. Material e Métodos: Foram seguidas as orientações da Organização Europeia para a Investigação e Tratamento do Cancro para tradução, adaptação cultural e ensaio-piloto do Quality of Life Questionnaire ­ OES18 (esophageal module) e Quality of Life Questionnaire ­ OG25 (esophagogastric module). O Quality of Life Questionnaire ­ OG25 (esophagogastric module) passou por um processo de tradução (inglês → português) e tradução-reversa (português → inglês), por tradutores independentes falantes nativos. Após revisão, uma versão preliminar for criada para ensaio-piloto entre doentes portugueses. Uma vez que já estava disponível uma versão brasileira do Quality of Life Questionnaire ­ OES18 (esophageal module), o questionário foi apenas adaptado culturalmente e alvo de ensaio-piloto. Foram incluídos doentes com e sem neoplasia. Resultados: No total, 30 doentes preencheram a versão portuguesa de cada questionário. No final, foi conduzida uma entrevista estruturada para detetar e documentar quaisquer tópicos problemáticos. Tópicos e enunciados problemáticos foram alterados, conforme os resultados do ensaio-piloto. As versões finais foram enviadas para o grupo de Qualidade de Vida da Organização Europeia para a Investigação e Tratamento do Cancro e foram aprovados. Conclusões: As versões portuguesas dos questionários da Organização Europeia para a Investigação e Tratamento do Cancro Quality of Life Questionnaire ­ OES18 (esophageal module) e OG25 (esophagogastric module) são instrumentos úteis, fidedignos e válidos para aferição da qualidade de vida relacionada com a saúde em doentes com neoplasia esofágica e/ou esofagogástrica, respetivamente. Podem agora ser utilizados em contexto clínico e para fins científicos.

Tracheobronchial Polyflex stents for the management of benign refractory hypopharyngeal strictures.

AIM: To describe a modified technique for placement of a tracheobronchial self-expanding plastic stent (SEPS) in patients with benign refractory hypopharyngeal strictures in order to improve dysphagia and allow stricture remodeling. METHODS: A case series of four consecutive patients with complex hypopharyngeal strictures after combined therapy for laryngeal cancer, previously submitted to multiple sessions of dilation without lasting improvement, is presented. All patients underwent placement of a small diameter and unflared tracheobronchial SEPS. Main outcome measurements were improvement of dysphagia and avoiding of repeated dilation. RESULTS: The modified introducer system allowed an easy and technically successful deployment of the tracheobronchial Polyflex stent through the stricture. All four patients developed complications related to stent placement. Two patients had stent migration (one proximal and one distal), two patients developed phanryngocutaneous fistulas and all patients with stents in situ for more than 8 wk had hyperplastic tissue growth at the upper end of the stent. Stricture recurrence was observed at 4 wk follow-up after stent removal in all patients. CONCLUSION: Although technically feasible, placement of a tracheobronchial SEPS is associated with a high risk of complications. Small diameter stents must be kept in place for longer than 3 mo to allow adequate time for stricture remodeling.

Web-based system for training and dissemination of a magnification chromoendoscopy classification.

AIM: To evaluate the use of web-based technologies to assess the learning curve and reassess reproducibility of a simplified version of a classification for gastric magnification chromoendoscopy (MC). METHODS: As part of a multicenter trial, a hybrid approach was taken using a CD-ROM, with 20 films of MC lasting 5 s each and an "autorun" file triggering a local HTML frameset referenced to a remote questionnaire through an Internet connection. Three endoscopists were asked to prospectively and independently classify 10 of these films randomly selected with at least 3 d apart. The answers were centrally stored and returned to participants together with adequate feedback with the right answer. RESULTS: For classification in 3 groups, both intra- [Cohen's kappa (kappa) = 0.79-1.00 to 0.89-1.00] and inter-observer agreement increased from 1st (moderate) to 6th observation (kappa = 0.94). Also, agreement with reference increased in the last observations (0.90, 1.00 and 1.00, for observers A, B and C, respectively). Validity of 100% was obtained by all observers at their 4th observation. When a 4th (sub)group was considered, inter-observer agreement was almost perfect (kappa = 0.92) at 6th observation. The relation with reference clearly improved into kappa (0.93-1.00) and sensitivity (75%-100%) at their 6th observations. CONCLUSION: This MC classification seems to be easily explainable and learnable as shown by excellent intra- and inter-observer agreement, and improved agreement with reference. A web system such as the one used in this study may be useful for endoscopic or other image based diagnostic procedures with respect to definition, education and dissemination.

Tabagismo em empresas-uma nova forma de abordagem

A abordagem dos tabagistas e as constantes queixas dos fumantes passivos em seus ambientes de trabalho, ganharam conotaçöes bastante abrangentes com as recentes divulgaçöes científicas sobre o assunto. No Ambulatório Médico da sede da CPFL foi desenvolvido um esquema de acompanhamento clínico e espirográfico em empregados fumantes, sintomáticos ou näo, nos anos de 1985 e 1986. Entre estes tivemos uma alteraçäo das provas funcionais em 27,8%. Paralelamente, desenvolveu-se um trabalho de conscientizaçäo de toda a populaçäo de empresa no sentido de se assegurar ao näo fumante a privatizaçäo do seu ambiente sem a presença do fumante ativo. A comparaçäo entre as provas funcionais, realizados em intervalos anuais, foi fator decisivo, tanto na conscientizaçäo do tabagista em abandonar o hábito quanto em sensilizar os órgäos diretivos da empresa em resguardar os direitos dos fumantes passivos, possibilitando o desencadeamento de uma campanha anti-tabagismo por solicitaçäo da imensa maioria dos empregados