The course of fatigue in patients with gynecologic and breast cancer

BACKGROUND: Hysterectomies are one of the most frequently performed surgical procedures in the United States. There are a wide variety of diagnoses that require a patient to obtain this procedure, but the majority of hysterectomies are performed for benign indications. Currently, gynecologists do not follow a standardized protocol surrounding postoperative laboratory ordering, and healthcare professionals can order a wide range of tests as often as they choose. Extraneous laboratory orders are disruptive to the patients’ well-being and risk their health following surgery. These orders are costly for hospital systems, take up precious time of hospital employees, and influence the course of patient treatment only in extremely rare circumstances. There are few studies that develop exclusion criteria for patients who may not require a laboratory test following surgery. Though systems to predict postoperative hematocrit have been created, they are complicated and difficult to use. The few studies that were performed are yet to be accepted by the medical community, in part because of their limited scope. This study will be the first to incorporate the results of robotic surgery in the analysis. OBJECTIVE: The purpose of this study is to determine concrete parameters to indicate that a patient is in need of postoperative laboratory work and at risk for anemia or transfusion. We aim to develop two comprehensive models that guide surgical practitioners to identify the cases which do not require laboratory data. METHODS: A total of 1027 gynecologic surgeries were performed at Saint Francis Hospital and Medical Center between April 1, 2014 and May 31, 2016. This retrospective study extracted data from EPIC EMR according to 42 variables preconceived to be the leading indicators of postoperative hematocrit and overall healing. Five healthcare professionals were surveyed to identify the variables that influence their postsurgical patient assessments and their decisions to order blood testing. This information was developed into score sheets with differing levels of stringency. Correlation highlighted 14 of the initial 42 variables as contributors to postoperative hematocrit and an equation model was built. Stepwise linear regression was used for univariate and multivariate analyses, from which we created our equation to predict all patients’ postoperative hematocrit. RESULTS: Out of the 1027 initial cases, a total of 602 cases were identified as hysterectomies for benign indications. Survey data gave the highest value to urine output and heart rate as key indicators of postoperative anemia. From the survey data, two clinical scoring sheets with differing stringency were created to guide practitioner laboratory ordering. These sheets gave parameters of heart rate and urine output the largest correlative weight in determining postoperative hematocrit. However, based on regression analysis, parameters of age (AGE), body mass index (BMI), preoperative platelet count (PPC), estimated blood loss during surgery (IO EBL), preoperative hematocrit (PHCT) and postoperative fluid bolus orders (POSTOP FB) proved to be the key variables impacting postoperative hematocrit (POSTOP HCT). These items were translated into the equation: POSTOP HCT = 22.51 – 0.40*POSTOP FB – 0.01*IO EBL + 0.25 PHCT + 0.09*BMI + 0.06*AGE – 0.01*PPC (R-squared = 0.310). CONCLUSIONS: This study aims to decrease superfluous laboratory testing, as well as to contribute to a larger conversation considering the potential merits of clinical judgement in a data-driven healthcare system. We have created a number of comparable strategies in order to reduce the number of unnecessary blood draws: two clinical scoring sheets and an equation. The score sheets indicate when to order additional testing. These sheets are representative of a range of surgical practitioners’ conventional clinical judgement. The equation serves as an evidence-based guide for determining postoperative hematocrit following benign gynecologic surgery. These predictive mechanisms will be validated and a superior method determined as our research continues with prospective application. We eventually expect to use the most accurate mechanism to reduce postoperative blood testing following all surgeries.

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子宮切除術是最常進行的婦科手術之一，據統計，美國每年平均錄得約600,000宗進行子宮切除術的病例。全腹腔鏡子宮切除術為子宮切除術的一種，在手術中，病人的子宮將經由完全使用腹腔鏡的模式被摘除。 / 在普遍全腹腔鏡子宮切除術的流程中，名為舉宮器的手術儀器會被應用於手術中，以改變病人子宮的位置及方向。手術室內，除了負責為病人摘除子宮的醫生外，還需額外一名負責操作舉宮器的醫生在場，以促進手術的進行。於手術的過程中，為使摘除手術能更有效及順利地進行，這名醫生需以人手操作舉宮器以控制病人體內子宮的方位。一般而言，這項工作都是枯燥而疲憊的。然而，在負責進行摘除手術的醫生眼中，縱子宮的方位已被調整，其方位仍然未如理想的情況亦不屬罕見。 / 故此，一個能勝任代替醫生負責操作舉宮器的機械人助手將會是可行的解決方案之一。與此同時，機械人亦能將病人子宮方位的控制權交回負責進行摘除手術的醫生手中。 / 本論文提出一套以把醫生從操作舉宮器的工作中釋放為目標，並使子宮方位操作變得更準確及穩定的機械人系統。機械人系統由兩個部分構成，分別為一支一個自由度的電動舉宮器以及一台三個自由度的舉宮器方位操作機械人。 / 舉宮器方位操作機械人旨在模仿以往醫生操作舉宮器的動作，以負責把固定在它身上的舉宮器移動到及固定在指定的位置。舉宮器方位操作機械人共有三個關節，分別為旋轉關節、滑動關節以及線性關節。關節的佈置滿足特定的幾何約束以構成遠程運動中心，使機械人能把手術儀器從細小的開口（例如：子宮頸）中進行操作。本論文提出的舉宮器方位操作機械人備有配適器以兼容不同款式的舉宮器，例如市場上現存的舉宮器以及本論文提出的電動舉宮器，均可應用在本系統中。 / 本論文提出的電動舉宮器為系統中可選擇性的元件，它是個一自由度附帶可轉動末端的裝置，旨在延伸機械人系統末端執行器的可到達範圍。 / 本論文將論述這套機械人系統的設計，包括其機械設計與電子系統的部分、運動學與及工作空間。一台實驗用的樣機已被建造以作驗證設計之用。該樣機以醫學人體模型為對象的實驗結果亦會在本論文中提出。 / Hysterectomy is one of the most frequently performed gynecologic procedures. In average, around 600,000 cases are recorded annually in the United States. Total laparoscopic hysterectomy (TLH) is one of the approaches of performing hysterectomy in which uterus of a patient is removed from an entirely laparoscopic approach. / In ordinary TLH procedures, a surgical apparatus, uterus manipulator, used for changing the position and orientation of the patient’s uterus is involved. In the operating theatre, apart from the primary surgeon who is responsible for the removal of uterus, an assisting surgeon is also involved for operating the uterus manipulator. Throughout the surgery, she/he has to manipulate the patient’s uterus using the uterus manipulator manually to facilitate the removal procedure. This task is generally tiring and boring. In addition, it is also common that the manipulated position is not satisfactory from the primary surgeon’s point of view. / Thus, a robotic assistant which is capable of taking up the task of this assisting surgeon as well as allowing the primary surgeon to have full control on the position of the patient’s uterus may be one of the potential solutions. / In this thesis, a robotic system aiming at providing more precise and stable manipulating motion and freeing the assisting surgeon who is responsible for operating the uterus manipulator is presented. The presented robotic system is composed of two parts, a motorized uterus manipulator of one degree of freedom and a robotic uterus manipulator positioner of three degrees of freedom. / Objective of the uterus manipulator positioner presented is to imitate what is doing by the assisting surgeon when operating the uterus manipulator. It holds and manipulates the uterus manipulator attached to it. The uterus manipulator positioner is a robotic system consisted of three joints, a revolute joint, a sliding joint and a translational joint. Arrangement of the joints is forced to satisfy specific geometric constraints so that a remote center of motion (RCM) is created to allow manipulation through small openings such as the cervix. Adaptors are included to enable the use of different uterus manipulators. Existing uterus manipulators and the motorized uterus manipulator presented in this thesis can be adapted to the system. / The motorized uterus manipulator presented in this thesis is an optional element of the robotic system. It is a device of one degree of freedom with a movable tip aiming at enhancing the reaching capability of the end-effector of the robotic system. / In this thesis, design of the robotic system in both mechanical and electronic aspects is presented. Kinematics and workspace of the system is also discussed. To verify the design, a prototype is built. Finally, verification experiments with the prototype on manikin are provided. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Yip, Hiu Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 96-98). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / Abstract --- p.i / 摘要 --- p.iv / Acknowledgement --- p.vi / Table of Contents --- p.viii / List of Figures --- p.x / Chapter Chapter 1. --- Introduction --- p.1 / Chapter 1.1. --- Total Laparoscopic Hysterectomy --- p.1 / Chapter 1.2. --- Existing Uterus Manipulators --- p.4 / Chapter 1.3. --- Existing Uterus Manipulator Positioners --- p.6 / Chapter 1.4. --- Existing Medical Robots --- p.9 / Chapter 1.5. --- Existing RCM Mechanisms --- p.11 / Chapter 1.6. --- Motivation and Contribution --- p.12 / Chapter Chapter 2. --- Conceptual Design --- p.15 / Chapter 2.1. --- Design Requirements --- p.15 / Chapter 2.2. --- Conceptual Design of Prototype --- p.16 / Chapter Chapter 3. --- Design of Prototype --- p.23 / Chapter 3.1. --- Mechanical Design of the Robotic System --- p.25 / Chapter 3.1.1. --- Design of the Robotic Uterus Manipulator Positioner --- p.25 / Chapter 3.1.2. --- Adaptor --- p.35 / Chapter 3.1.3. --- Design of the Motorized Uterus Manipulator --- p.36 / Chapter 3.2. --- Kinematics of the Robotic System --- p.38 / Chapter 3.2.1. --- Coordinates of Points on a Sphere --- p.39 / Chapter 3.2.2. --- The 2-DOF Uterus Manipulator Positioner --- p.40 / Chapter 3.2.3. --- The 3-DOF Uterus Manipulator Positioner --- p.42 / Chapter 3.2.4. --- The 4-DOF robotic system --- p.45 / Chapter 3.2.5. --- Velocity --- p.50 / Chapter Chapter 4. --- Design of Control System --- p.52 / Chapter 4.1. --- Robot Controlling Unit --- p.52 / Chapter 4.1.1. --- Size Reduced Controlling Unit --- p.53 / Chapter 4.2. --- User Interface --- p.62 / Chapter 4.2.1. --- Foot-Controlled Interface --- p.63 / Chapter 4.2.2. --- Hand-Controlled Panel --- p.68 / Chapter Chapter 5. --- Prototype and Experiments --- p.70 / Chapter 5.1. --- Developed Prototype --- p.70 / Chapter 5.2. --- Experiments --- p.72 / Chapter 5.2.1. --- Robot Controller --- p.73 / Chapter 5.2.2. --- Control Algorithm --- p.77 / Chapter 5.2.3. --- Experiment on the Prototype --- p.79 / Chapter 5.2.4. --- Experiment with Manikin --- p.87 / Chapter Chapter 6. --- Conclusion and Future Work --- p.90 / Chapter 6.1. --- Conclusion --- p.90 / Chapter 6.2. --- Robot Positioning Platform --- p.92 / Chapter 6.3. --- Reinforcement of the Robotic System --- p.94 / Chapter 6.4. --- Extension of User Interfaces --- p.95 / List of References --- p.96

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 4 uppsatser.

The course of fatigue in patients with gynecologic and breast cancer

La chimiothérapie systémique par voie intraveineuse, essentiellement réservée aux cancers avancés, n'est pas ciblée sur la tumeur, il est très difficile d’atteindre des niveaux thérapeutiques en intra tumoral, et ses effets secondaires et sa toxicité sont doses-limitantes.La chimiothérapie localisée pourrait permettre :1) la stabilisation des molécules médicamenteuses incorporées une seule administration médicamenteuse,2) une libération prolongée et contrôlée du médicament pour assurer une diffusion adéquate et l'absorption par les cellules cancéreuses sur plusieurs cycles de division cellulaire 3) le chargement de molécules de chimiothérapie insolubles dans l’eau, 4) l’apport direct au site de la maladie, 6) des effets secondaires diminués en évitant la circulation systémique,7) des résections chirurgicales moindres en traitant les marges de la tumeur. Nous nous sommes plus particulièrement intéressés aux cancers gynécologiques. Nous avons étudié les effets pharmacologiques et cliniques de microsphères chargées en doxorubicine (Doxo) sur un modèle de carcinose péritonéale et de tumeur de glande mammaire, et étudié le profil de diffusion ganglionnaire de divers implants non chargés. 12 jours après injection laparoscopique de tumeurs VX2 sur les ligaments larges droits et gauches de lapines WNZ 12 une injection laparoscopique de 0,5 ml de microsphères chargées ou non de Doxo (respectivement DM, groupe 1 et BM, groupe 2) a été réalisée de façon aléatoire d’un côté ou de l’autre, en sous péritonéal, au site tumoral. 7 jours après les ligaments larges, l’utérus, les ovaires, les orifices de trocarts, les intestins, la vessie, le foie et les poumons ont été examinés en macroscopie et microscopie. Le volume tumoral était plus faible dans le groupe 1 (3,6 ± 3,2 cm) par rapport au groupe 2 (8,9 ± 5,4 cm) (MW, p = 0,0179). La nécrose a été observée autour de toutes les DM, sans nécrose autour des BM. La concentration de Doxo était de 2,1 ± 2,7 uM aux limites tumorales, au-dessus du niveau thérapeutique de 1,0 uM. Sur un autre modèle, 19 jours après injection locale de suspensions tumorales de VX2 sur la deuxième glande mammaire de lapines WNZ chaque glande a été aléatoirement traitée par injection locale de 0,5 ml de microsphères chargées ou non de Doxo (HSDOXO, Groupe1, et HS, groupe 2).Pour les tumeurs de moins de 5 cm3 ou 2 cm de diamètre avant traitement, le volume final était plus faible dans le groupe 1 par rapport à groupe2 (respectivement p<0.008 et p<0.3, MW)et la croissance tumorale a été diminuée après injection de HSDOXO par rapport à HS. En microscopie une nécrose tissulaire a été observée autour des HSDOXO en extratumoral, sans nécrose autour des HS.Nous avons enfin étudié la diffusion de particules de diverses tailles, non chargées, au ganglion sentinelle d’une tumeur de glande mammaire . Les animaux ont été répartis en trois groupes de trois, chacun d'eux recevant des particules de 100 nM, 1 uM ou 10 uM. Cinq jours après traitement, l'intensité de fluorescence a été évaluée par lampe UV. Le ganglion sentinelle a été disséqué selon la technique du bleu, avant curage complet. Les premiers résultats montrent la capture de particules de 1 et 100µm par les ganglions tumoraux mais aussi dans les ganglions sains, ce qui permettrait d’envisager un traitement ganglionnaire préventif et curatif.De plus en plus de tumeurs seront décelées au stade local. Par ailleurs l'identification des phénotypes génomiques permettra un traitement personnalisé « à la carte ». On pourrait envisager un dispositif de délivrance programmable traitant tous les aspects de la maladie, de l'inhibition de la croissance tumorale et de l'angiogenèse à la promotion de la cicatrisation des tissus normaux. / Systemic chemotherapy is mainly reserved for advanced cancers, is not targeted to the tumor, it is very difficult to achieve intratumoral therapeutic levels and its side effects and toxicity are dose-limiting.Local chemotherapy may have several advantages:1) stabilization of embedded drug molecules and preservation of anticancer activity,2) controlled and prolonged drug release to ensure adequate diffusion and uptake into cancer cells over many cycles of tumor cell division, 3) loading and release of water-insoluble chemotherapeutics, 4) direct delivery to the site of disease, 5) one-time administration of the drug, 6) diminished side effects due to the avoidance of systemic circulation of chemotherapeutic drugs.We were particularly interested in gynecological cancers. We studied the pharmacological and clinical effects of doxorubicin-loaded microspheres (Doxo) in a model of peritoneal carcinomatosis,a model of mammary gland tumor, and studied the diffusion profile of various micro and nanoparticles in tumoral and non tumoral lymph nodes.12 days after laparoscopic injection of VX2 tumors on the right and left broad ligament of WNZ rabbits laparoscopic injection of 0.5 ml of microspheres loaded or not with Doxo (DM or Group 1, BM Group 2 respectively) was conducted randomly to one side or another, at the sub peritoneal tumor site. 7 days after the broad ligaments, uterus, ovaries, trocars, bowels, bladder, liver and lungs were examined macroscopically and microscopically. The tumor volume was lower in group 1 (3.6 ± 3.2 cm) compared with group 2 (8.9 ± 5.4 cm) (MW, p = 0.0179). Necrosis was observed around all DM without necrosis around the BM. Doxo concentration was 2.1 ± 2.7 µM at the tumor margins, above the therapeutic level of 1.0 uM.On another model, 19 days after local injection of VX2 tumor suspensions in the second mammary gland of WNZ rabbits each gland was randomly treated by local injection of 0.5 ml of microspheres loaded or not with Doxo (HSDOXO, Group1, and HS Group 2).For tumors less than 5 cm3 or 2 cm in diameter before treatment, the final volume was lower in group 1 compared to Group 2 (p <0.008 and p <0.3, MW) and tumor growth was reduced after HSDOXO injection compared to HS. Microscopic tissue necrosis was observed around extratumoral HSDOXO without necrosis around the HS.We finally studied the diffusion of unloaded particles of various sizes on the lymph nodes of a mammary gland tumor. The animals were divided into three groups of three, each receiving particles of 100 nm, 1 µm or 10 µm. Five days after treatment, the fluorescence intensity was measured by UV lamp. The sentinel lymph node was dissected according to the technique of blue dye.The first results show the capture of 1 μm and 100μm particles by the tumoral and non tumoral lymph nodes, which would consider a preventive and curative treatment of the nodes.Since more and more tumors are detected at the local stage and with the identification of genomic phenotypes, a personalized local chemotherapy could be the next step of cancer therapy. One could imagine a programmable controlled drug delivery device dealing with all aspects of the disease, inhibition of tumor growth and angiogenesis, while promoting the healing of normal tissues.

Actuellement les gynécologues sont en France les professionnels de santé les plus impliqués dans le dépistage des cancers gynécologiques, mais les généralistes, qui voient l’ensemble de la population, sont les mieux placés pour dispenser des soins préventifs à tous et de façon équitable.Ce travail visait à comprendre la variabilité des pratiques de dépistage des cancers gynécologiques (par le frottis cervico-utérin et la mammographie) chez les femmes consultant en médecine générale, en fonction notamment de la position sociale des patientes et de l’organisation du cabinet de leur médecin.Il s’intègre dans une étude menée en 2005-06 sur les principaux soins préventifs destinés aux adultes des deux sexes. Sur une période de deux semaines, toutes les patientes de 50 à 69 ans de 59 généralistes franciliens tirés au sort (taux de participation des généralistes : 39 %) ont été incluses au fil des consultations. Les données ont été recueillies auprès des patients par téléphone et auprès des médecins en face-à-face à leur cabinet. L’essentiel des analyses a été réalisé avec des modèles logistiques mixtes à intercept aléatoire pour tenir compte de la structure hiérarchique des données.Au total, 66,7 % des patients éligibles (n=4106) ont participé à l’étude, sans différence selon le sexe des patients.Même parmi des femmes utilisant le système de santé, on observe des inégalités sociales, mais uniquement concernant le frottis (n=858). Un gradient de dépistage défavorable au bas de la hiérarchie sociale existe pour la profession (indice relatif d’inégalité = 2,3), le niveau d’études (IRI = 2,0) et les revenus (IRI = 3,0). L’analyse des contributions à ces gradients de diverses dimensions de la position sociale (logement, quartier, richesse du foyer, statut vis-à-vis de l’emploi, relations sociales et assurance santé) montre que la richesse du foyer, les caractéristiques du quartier et le type d’assurance santé expliquent entre 20 et 60 % de ces inégalités.L’investissement des généralistes dans le dépistage semble restreint comme en témoignent les taux de renseignement d’une date de dernier frottis ou de dernière mammographie dans les dossiers médicaux (23 % pour le cancer du col utérin et 38 pour le cancer du sein). Les praticiens semblent mieux renseigner les dossiers des patientes du bas de la hiérarchie professionnelle et les dossiers des femmes dont ils savent qu’elles ne sont pas suivies par un gynécologue.L’organisation des consultations apparaît centrale dans notre enquête. La participation des patients à l’étude était meilleure parmi les médecins proposant des consultations sur rendez-vous (OR = 2,12 pour les patients hommes et 3,38 pour les femmes). Cette organisation jouerait aussi sur les pratiques de soins : les médecins ayant des consultations plus courtes s’impliquent moins dans le dépistage du cancer du sein (n=898, OR = 0,65). Ces aspects organisationnels permettent d’expliquer environ un quart de la variabilité des pratiques entre les médecins.Ces résultats devraient inciter les généralistes à investir davantage les dépistages des cancers gynécologiques et peut-être à opérer des changements organisationnels. Ce travail, au croisement de la recherche en médecine générale et de l’épidémiologie sociale, a fait émerger une réflexion sur l’analyse de données provenant de patients suivis sur le long cours par des professionnels de santé. Il ouvre aussi des perspectives sur la mise en place d’interventions pour réduire les inégalités sociales observées dans les patientèles. / Currently gynecologists are the healthcare professionals most involved in screening for gynecologic cancers in France, but general practitioners, who see the entire population, are best placed to provide preventive care equitably and to all.The aim of this work was to understand the variability in practices of screening for gynecologic cancers (by Pap smears and mammography) among women seeing general practitioners, especially as a function of the patient's social position and the organization of their doctor's office.It was included as part of a study conducted in 2005-06 of the principal types of preventive care for adults of both sexes. Over a two-week period, this study included all consecutive patients aged 50-69 years seen by 59 randomly drawn general practitioners in the Paris metropolitan region (participation rate of general practitioners: 39%). Data were collected from the patients by telephone and from the physicians in face-to-face interviews in their office. Most of the analyses were performed with mixed logistic models with a random intercept to take the hierarchical structural of the data into account.Overall, 66.7% of the eligible patients (n=4106) participated in the study; this rate did not differ by sex.Social inequalities were observed even among women who use the health-care system, but only for the Pap smear (n=858). A gradient with screening lowest at the bottom of the social hierarchy was observed for occupation (relative index of inequality = 2.3), educational level (RII = 2.0), and income (RII = 3.0). Analysis of the contributions to these gradients of diverse dimensions of social position (housing, neighborhood, household wealth, employment status, social relations, and health insurance) showed that household wealth, neighborhood characteristics, and type of health insurance explain between 20 and 60% of these inequalities.General practitioners' investment in screening seems limited, as shown by the rates of information in the medical files about the date of the last Pap smear (23%) or the last mammography (38%). Physicians appear to keep this information better for women at the bottom of the occupational hierarchy and women whom they know are not seeing a gynecologist.The organization of doctors' consultations appeared central in our survey. Patient participation in this study was best among the physicians who offered appointments for consultations (OR = 2.12 for male patients and 3.38 for the women). This organization also appeared to play a role in care practices: physicians with shorter consultations were less involved in screening for breast cancer (n=898, OR = 0.65). These organizational aspects explained approximately a quarter of the variability of practices between physicians.These results should encourage general practitioners to spend more time in screening for gynecologic cancers and perhaps to modify the organization of their practice. This study, at the intersection between research in general practice and in social epidemiology, leads to a discussion about the different strategies for analysis of data from patients followed over the long-term by healthcare professionals. It also opens up perspectives for interventions to reduce social inequalities in patient lists.

This study is an examination of ovarian and uterine cancer patients’ perceptions of chemotherapy-induced alopecia and how it impacts quality-of-life over the course of chemotherapy. The chapters in this dissertation address the following research questions: How do ovarian and uterine cancer patients communicate about their experiences of alopecia over the course of chemotherapy? How does chemotherapy-induced alopecia influence patients’ understandings of quality-of-life? Longitudinal interviews were conducted with a patient population of twenty-three, and each patient was interviewed at least twice over the course of chemotherapy. The data set was composed of fifty-five interviews, and a thematic analysis was performed across interview transcripts. Analysis of the data revealed four themes: 1) chemotherapy-induced alopecia and quality-of-life; 2) the “mirror moment”; 3) performance of social roles; and 4) gendered visibility. Data indicate ovarian and uterine cancer patients experienced substantial daily distress related to chemotherapy-induced alopecia. The ability to perform social roles deemed important to patients’ quality-of-life such as the familial roles of partner and mother/grandmother were negatively impacted by hair loss. Patients’ distress concerning alopecia was strongly connected to the ability to function in the public sphere without feeling approachable or being approached by “strangers” because of their alopecia. Clinicians might consider repeatedly asking about chemotherapy-induced alopecia over the course of chemotherapy, both because it could help patients cope with the side effect and because it may generate dialogue related to other important concerns late-stage cancer patients may feel are too trivial to mention in clinical discussions. Women’s social and familial roles may be impacted by alopecia and chemotherapy in unique ways that deserve additional study.

INTRODUÇÃO: O câncer constitui-se na principal causa de mortalidade entre indivíduos de 45 a 84 anos, configurando-se em um dos principais problemas de saúde pública dos países em desenvolvimento. As reações de hipersensibilidade aos quimioterápicos têm aumentado, impedindo muitas vezes a utilização de terapias de primeira linha no tratamento de neoplasias primárias ou recidivantes. O procedimento de dessensibilização é uma abordagem alternativa, por meio do qual o paciente passa a tolerar a medicação que antes desencadeava reações potencialmente letais. Quimioterápicos do grupo das platinas são exemplos de drogas passíveis de readministração por meio do processo de dessensibilização, no entanto faltam biomarcadores preditivos de reações durante o procedimento. OBJETIVOS: O objetivo principal do estudo foi avaliar o papel do teste de ativação de basófilos (BAT) como biomarcador para reações de hipersensibilidade ocorridas durante a dessensibilização em pacientes alérgicas às platinas. Como objetivo secundário, avaliou-se a prevalência e o impacto da mutação dos genes BRCA 1 e 2 em pacientes com hipersensibilidade imediata à carboplatina submetidas à dessensibilização. MÉTODOS: Padronizou-se o BAT, com análise da expressão de CD63 e CD203c na superfície de basófilos de pacientes com hipersensibilidade imediata às platinas submetidas à dessensibilização. Foram realizados BATs em 15 pacientes portadoras de neoplasias malignas submetidas a 27 dessensibilizações devido à anafilaxia a quimioterápico do grupo das platinas e em 12 indivíduos de dois grupos controle (Grupo 1: seis pacientes tolerantes às platinas e Grupo 2: seis voluntários sadios que nunca foram expostos às platinas). Os resultados dos BATs foram comparados entre os três grupos. Correlacionou-se o BAT com a ocorrência ou não de reação durante a dessensibilização e com os níveis de triptase sérica. Para análise da prevalência e impacto da mutação dos genes BRCA 1 e 2 nas dessensibilizações, realizou-se análise retrospectiva de prontuários de 138 portadoras de neoplasias malignas ginecológicas submetidas à dessensibilização à carboplatina. RESULTADOS: O BAT foi positivo em 11 das 15 pacientes alérgicas (n= 11; 73,3%), com aumento de expressão de CD203c e CD63 em 11 (73,3%) e 6 (40%) pacientes, respectivamente. Todos os participantes dos grupos controles apresentaram testes negativos. Maior expressão de CD63 foi observada em pacientes com reações iniciais mais graves. O BAT foi positivo em 92,3% das reações ocorridas durante as dessensibilizações (n=12/13), sendo positivo em todas as reações que apresentaram aumento concomitante de triptase sérica (n=5). Com relação à mutação dos genes BRCA 1 e 2, sua prevalência foi de 34% nas pacientes com hipersensibilidade às platinas (n=47/138), sendo que 51% das portadoras reagiram durante a dessensibilização. CONCLUSÕES: O BAT positivo, com aumento da expressão de CD63 e/ou CD203c na superfície do basófilo, identificou pacientes alérgicos às platinas com especificidade de 100% e sensibilidade de 73,3%. O BAT e a mutação dos genes BRCA 1 e 2 identificaram pacientes mais propensos a reagir durante o procedimento de dessensibilização. A utilização de biomarcadores preditores de reações durante a dessensibilização aos quimioterápicos do grupo das platinas pode aumentar a segurança do procedimento e auxiliar na manutenção do esquema quimioterápico de primeira linha do paciente / INTRODUCTION: Cancer is the leading cause of death in the age group of 45 to 84 years, and one of the main public health issues in developing nations. Hypersensitivity reactions to chemotherapeutic agents have been increasing, sometimes hindering the use of first-line therapies in the treatment of primary or relapsed tumors. Rapid drug desensitization (RDD) is an alternative approach, through which a patient becomes tolerant to the medication that once triggered a potentially lethal hypersensitivity reaction. Platinum-based compounds are examples of drugs that can be readministered through the desensitization procedure, but currently there are no known biomarkers that could help predict reactions during RDD. OBJECTIVES: The main goal of our study was to assess the basophil activation test (BAT) as a biomarker of breakthrough reactions occurred during RDD in patients allergic to platinum-based agents. As a secondary goal, we evaluated the prevalence and impact of the BRCA 1/2 mutation in carboplatin-allergic patients undergoing RDD. METHODS: We standardized the BAT by evaluating CD63 and CD203c expressions on the basophils of patients with immediate hypersensitivity reactions to platinum-based agents undergoing RDD. We analyzed BATs of 15 patients with malignant neoplasms who had undergone 27 RDD procedures due to anaphylaxis to platinum-based agents, and of 12 control subjects (Group 1: six patients tolerant to platinum-based agents, and Group 2: six healthy volunteers who had never been exposed to platinum-based agents). BAT results were compared among the three groups. We correlated BAT results with the occurrence of breakthrough reactions during RDD and with serum tryptase levels. To conduct the analysis of the BRCA 1/2 mutation prevalence and its impact on RDD, a retrospective review of 138 medical records of patients with gynecological malignancies who underwent RDD to carboplatin was performed. RESULTS: BAT was positive in 11/15 allergic patients (73.3%), with increased expression of CD203c and CD63 in 11 (73.3%) and 6 (40%) patients, respectively. All control subjects presented negative BATs. A higher CD63 expression was observed in patients with severe initial reactions. BAT was positive in 92.3% of the breakthrough reactions occurred during RDD (n=12/13), and in all reactions with concomitant increased tryptase levels (n=5). Regarding the BRCA1/2 mutation, its prevalence was 34% in patients allergic to platinum-based agents (n=47/138), and 51% of the mutation carriers had breakthrough reactions during RDD. CONCLUSIONS: A positive BAT, with an increased expression of CD63 and/or CD203c, identified patients allergic to platinum-based agents with a specificity of 100% and a sensitivity of 73.3%. The BAT and the BRCA 1/2 mutation helped identify patients at risk of breakthrough reactions during RDD. The use of predictive biomarkers of breakthrough reactions during RDD to platinum-based agents might enhance RDD safety and help maintain a patient`s first-line treatment