Acute hemolytic transfusion reactions can occur within minutes. Clinically they are characterized by chills, fever, urticaria, tachycardia, nausea and vomiting, lumbar pain, hemorrhage due to disseminated intravascular coagulation (DIC)..... We are told of a patient who, within minutes of starting a transfusion, presented with an acute and very serious condition (with shock). Such an acute and severe situation only fits option 4.

Acute hemolytic transfusion reactions can occur within minutes. Clinically they are characterized by chills, fever, urticaria, tachycardia, nausea and vomiting, lumbar pain, hemorrhage due to disseminated intravascular coagulation (DIC)..... We are told of a patient who, within minutes of starting a transfusion, presented with an acute and very serious condition (with shock). Such an acute and severe situation only fits [HIDDEN].

A 35-year-old patient who, due to hematemesis due to ulcus, receives a transfusion of 2 packed red blood cells. 5-10 minutes after starting the transfusion, she begins with fever, chills, hypotension and pain in the lumbar region. What would be the most likely diagnosis?

Febrile reaction secondary to transfusion.

Febrile reaction due to plasma contaminating red blood cells.

Blood transfusion

Acute hemolytic reactions are defined according to Serious Hazards of Transfusion (SHOT) as "fever and other symptoms/signs of haemolysis within 24 hours of transfusion; confirmed by one or more of the following: a fall of Hb, rise in lactate dehydrogenase (LDH), positive direct antiglobulin test (DAT), positive crossmatch" This is due to destruction of donor red blood cells by preformed recipient antibodies. Most often this occurs because of clerical errors or improper ABO blood typing and crossmatching resulting in a mismatch in ABO blood type between the donor and the recipient. Symptoms include fever, chills, chest pain, back pain, hemorrhage, increased heart rate, shortness of breath, and rapid drop in blood pressure. When suspected, transfusion should be stopped immediately, and blood sent for tests to evaluate for presence of hemolysis. Treatment is supportive. Kidney injury may occur because of the effects of the hemolytic reaction (pigment nephropathy). The severity of the

Acute hemolytic transfusion reaction

Signs and symptoms Early acute hemolytic transfusion reactions are typically characterized by fever, which may be accompanied by rigors (chills). Mild cases are also typically characterized by abdominal, back, flank, or chest pain. More severe cases may be characterized by shortness of breath, low blood pressure, hemoglobinuria, and may progress to shock and disseminated intravascular coagulation. In anesthetized or unconscious patients, hematuria (blood in the urine) may be the first sign of AHTR. Other symptoms include nausea, vomiting, and wheezing. Causes The most common cause of acute hemolytic transfusion reaction is ABO incompatibility, which is typically due to human error that results in a recipient receiving the incorrect blood product. Rarely, other blood type incompatibilities can cause AHTR, the most common of which is Kidd antigen incompatibility. Rh, Kell, and Duffy antigen incompatibility have also been implicated in AHTR.

Acute gram-negative urosepsis mimicking an acute hemolytic transfusion reaction.

The acute hemolytic transfusion reaction (AHTR) is one of the most feared complications of blood transfusion. Over the years, several clinical conditions, as well as errors in blood component preparation and administration, that mimic AHTR have been identified. This report describes a novel variation on the theme of pseudo-AHTR. A 47-year-old diabetic man with drug-induced pancytopenia suddenly manifested severe shaking chills, flank pain, and back pain during a red cell transfusion. The passage of bright red urine immediately after the transfusion virtually confirmed for the clinicians administering the transfusion that an AHTR had occurred. In the laboratory, the hematuria was shown to be due principally to red cells and not to free hemoglobin. Further posttransfusion work-up showed a urinary tract infection and overwhelming bacterial sepsis with Escherichia coli. As a pseudo-AHTR, gram-negative bacterial sepsis of urinary tract origin may surpass other forms of sepsis. Urosepsis should be considered in the work-up of a suspected AHTR in a pancytopenic patient with a urinary tract infection.

Yersinia septic shock following an autologous transfusion in a pediatric patient.

Although the literature on infections transmitted via transfused blood focuses on viruses, Yersinia enterocolitica can also cause severe infections in patients receiving transfusions. A 13-year-old patient developed severe sepsis after an autologous blood transfusion contaminated with Y. enterocolitica. The patient was an otherwise healthy female undergoing posterior spinal fusion for congenital scoliosis. Prior to surgery, the patient donated blood for perioperative and postoperative use. A few days before the donation, she had complained of abdominal pain and was experiencing mild diarrhea. The patient received four units of packed red blood cells (PRBCs) during the surgery. Intraoperatively, the patient developed fever up to 103.6 degrees F, became hypotensive requiring epinephrine and dopamine, and developed metabolic acidosis with serum bicarbonate concentration dropping to 16 mmol/l. The surgery team believed the patient was experiencing malignant hyperthermia and attempted to cool patient during the procedure. Postoperatively, the patient was transferred to the pediatric intensive care unit and treated for severe shock of unknown etiology. The patient further developed disseminated intravascular coagulation. The patient received supportive care and was started on ampicillin/sulbactam on postoperative day (POD) one which was changed to clindamycin, ciprofloxacin and tobramycin on POD two when blood cultures grew gram-negative bacilli. On POD three, cultures were identified as Y. enterocolitica and antibiotics were changed to tobramycin and cefotaxime based on susceptibility data. Sequelae of the shock included adult respiratory distress syndrome requiring intubation and a tracheostomy and multiple intracranial hemorrhagic infarcts with subsequent seizure disorder. Due to severe lower extremity ischemia, she required a bilateral below the knee amputation. The cultures of the snippets from the bags of blood transfused to the patient also grew Y. enterocolitica. This case illustrates the importance of considering transfusion related bacterial infections in patients receiving PRBCs. All patients in shock following any type of transfusion may require aggressive antibiotic therapy, until the diagnosis and etiology are known.

Transfusion reactions due to bacterial contamination of blood and blood products.

Bacterial infections transmitted by blood or blood products, although rare, remain a serious threat to the recipient of a transfusion. We report on five cases of adverse reactions due to bacterial contamination of blood products, and we review 76 similar cases reported in the English-language literature. Most cases (70%) have been reported from the United States. Various sources of contamination have been suggested, including infection in the donor and invasion of the blood product during the process of collection, preparation, and storage. Frequent clinical manifestations are fever (80%), chills (53%), hypotension (37%), and nausea or vomiting (26%). The overall mortality is 35% (28 of 81 patients). In 38 patients (47%) the adverse reactions have appeared during transfusion; in the others the interval between completion of the transfusion and appearance of symptoms has ranged from 15 minutes to 17 days. A wide spectrum of bacteria have been implicated as causes of adverse reactions, with Pseudomonas species involved in 28% of episodes. Many such reactions are probably misdiagnosed or overlooked, the result being underestimation of the extent of the problem.

Humoral immunity

An incompatible blood transfusion causes a transfusion reaction, which is mediated by the humoral immune response. This type of reaction, called an acute hemolytic reaction, results in the rapid destruction (hemolysis) of the donor red blood cells by host antibodies. The cause is usually a clerical error, such as the wrong unit of blood being given to the wrong patient. The symptoms are fever and chills, sometimes with back pain and pink or red urine (hemoglobinuria). The major complication is that hemoglobin released by the destruction of red blood cells can cause acute kidney failure. Antibody production In humoral immune response, the B cells first mature in the bone marrow and gain B-cell receptors (BCR's) which are displayed in large numbers on the cell surface.

Fever must be at least 38 °C/100.4 °F oral and a change of at least 1 °C/1.8 °F from pre-transfusion value OR chills and/or rigors must be present. The UK hemovigilance system (SHOT) categorizes the severity of the reaction. Mild Fever of at least 38 °C/100.4 °F oral and a change of between 1 and 2 °C from pre-transfusion values but no other symptoms or signs. Moderate Fever of at least 39 °C, OR a rise in temperature of at least 2 °C from pre-transfusion values AND/OR other symptoms or signs, including chills (rigors), painful muscles (myalgia), or nausea that are severe enough that the transfusion is stopped. Severe Fever of at least 39 °C, OR a rise in temperature of at least 2 °C from pre-transfusion values AND/OR other symptoms or signs, including chills (rigors), painful muscles (myalgia), or nausea that are severe enough that the transfusion is stopped AND requires immediate medical treatment, admission to hospital, or lengthens the duration of hospital admission.

Febrile transfusion reaction: what blood component should be given next?

Reports of febrile, nonhemolytic transfusion reactions (FNHTR) occurring at hospitals served by a regional blood center supplying 99,658 units of blood during 1980 were analyzed to determine if leukocyte-poor red blood cells prepared by the inverted centrifugation technique (LP RBCs) were adequate to prevent subsequent reactions. FNHTR occurred following 0.5% of units transfused. The records of transfusions given to patients who had a FNHTR were reviewed in a subgroup of hospitals. Of 253 such patients, 161 received subsequent transfusions, 140 received red cells or LP RBCs without a reaction. The remaining 21 had a second reaction following transfusion of packed red cells. 12 of the 21 received further red cell transfusions. Only one experienced a third febrile reaction after receiving LP RBCs. We conclude that LP RBCs are adequate to prevent recurrence of FNHTR and question the need for costly saline-washed, leukocyte-poor red blood cells for this purpose.

Febrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reaction. It is a benign occurrence with symptoms that include fever but not directly related with hemolysis. It is caused by cytokine release from leukocytes within the donor product as a consequence of white blood cell breakdown .These inflammatory mediators accumulate during the storage of the donated blood, and so the frequency of this reaction increases with the storage length of donated blood. This is in contrast to transfusion-associated acute lung injury, in which the donor plasma has antibodies directed against the recipient HLA antigens, mediating the characteristic lung damage. Definition Symptoms must manifest within 4 hours of cessation of the transfusion, and should not be due to another cause such as an underlying infection, bacterial contamination of the blood component, or another type of transfusion reaction, e.g. acute hemolytic transfusion reaction.

Infectious Complications of Blood Transfusion -- Issues of Concern -- Bacterial Transfusion-Transmitted Infections

Regarding transfusion complications, bacterial septicemia remains the fourth leading cause of death in the United States. Presentation tends to be in the form of severe sepsis and usually presents as rapid onset fever and circulatory collapse. [4] Septic reactions should be suspected if the following occur: Temperature greater than 102 degrees Fahrenheit (or higher than 2 degrees Fahrenheit or 3 degrees Celsius above baseline temperature)* Chills Rigors* Tachycardia (heart rate greater than 40 beats over baseline)* Shock/falling systolic blood pressure (30 mm Hg below systolic) Backache Nausea/vomiting Unexplained bleeding from mucous membranes or the infusion site Renal failure may follow [7] [10] (*In 75% of cases, fever, rigors, or tachycardia were present within 4 hours of transfusion.) [3] The following steps should occur if suspected:

Surgery_Schwartz

resulting in tubu-lar necrosis and precipitation of hemoglobin within the tubules.Delayed hemolytic transfusion reactions occur 2 to 10 days after transfusion and are characterized by extravascular hemolysis, mild anemia, and indirect (unconjugated) hyperbili-rubinemia. They occur when an individual has a low antibody titer at the time of transfusion, but the titer increases after trans-fusion as a result of an anamnestic response. Reactions to non-ABO antigens involve immunoglobulin G-mediated clearance by the reticuloendothelial system.If the patient is awake, the most common symptoms of acute transfusion reactions are pain at the site of transfusion, facial flushing, and back and chest pain. Associated symptoms include fever, respiratory distress, hypotension, and tachycardia. In anesthetized patients, diffuse bleeding and hypotension are the hallmarks. A high index of suspicion is needed to make the diag-nosis. The laboratory criteria for a transfusion reaction are

First_Aid_Step2

Nonhemolytic febrile reactions: Involve cytokine formation during the storage of blood, and WBC antibodies. Minor allergic reactions: Involve antibody formation (usually IgA) against donor proteins. Usually occur following transfusion of plasma-containing product. Hemolytic transfusion reactions: Entail the development of antibodies against donor erythrocytes. Usually result from ABO incompatibility or from antibody against minor antigens. Nonhemolytic febrile reactions: Present with fever, chills, rigors, and malaise. Symptom onset is 1–6 hours following transfusion. Minor allergic reactions: Characterized by urticaria. Hemolytic transfusion reactions: Present with fever, chills, nausea, ﬂ ushing, apprehension, back pain, burning at the IV site, tachycardia, tachypnea, and hypotension. Symptoms begin following the transfusion of only a small amount of blood. Diagnosed by clinical impression.

Obstentrics_Williams

Of serious known risks, transfusion of an incompatible blood component may result in acute hemolysis. If severe, this can cause DIC, acute kidney injury, and death. Preventable errors responsible for most of such reactions frequently include mislabeling of a specimen or incorrectly transfusing a patient not slated for those products. The rate of such errors in the United States is estimated to be 1 in 14,000 units, but these events are likely underreported (Lerner, 2010). A transfusion reaction is characterized by fever, hypotension, tachycardia, dyspnea, chest or back pain, lushing, severe anxiety, and hemoglobinuria. Immediate supportive measures include stopping the transfusion, treating hypotension and hyperkalemia, provoking diuresis, and alkalinizing the urine.

Informed Consent -- Issues of Concern -- Informed Consent for Blood Transfusion

Acute hemolytic reaction The recipient's antibodies attack transfused red blood cells whether caused by a reaction to the ABO blood group or antibodies produced from previous transfusions. Acute hemolytic transfusions occur within 24 hours of transfusion. Symptoms include fever, nausea, vomiting, dyspnea, hypotension, bleeding, pain at the infusion site, oliguria, anuria, dyspnea, or chest or back pain.

Delayed hemolytic transfusion reaction

PROBABLE DIAGNOSIS Newly identified red blood cell alloantibody demonstrated between 24 hours and 28 days after cessation of transfusion BUT incomplete laboratory evidence to meet definitive case definition criteria. Epidemiology Delayed blood transfusion reaction occurs more frequently (1 in 20,569 blood components transfused in the USA in 2011) when compared to acute haemolytic transfusion reaction. References Transfusion reactions Complications of surgical and medical care Transfusion medicine

Transfusion reaction due to Yersinia enterocolitica and review of other reported cases.

A 26 yr old woman was transfused after her baby was delivered by Caesarian section. During transfusion of the second pack of concentrated erythrocytes, she became acutely febrile. She then became shocked and gravely ill. Yersinia enterocolitica serogroup O:3 was recovered by blood culture from the patient and from the remnant of the bag of blood (but not the segments). The blood donor had suffered no illnesses. The patient received intensive treatment including antibiotics and made a slow recovery. Yersinia enterocolitica contaminated blood is a rare cause of potentially fatal post transfusion septicemia. Prompt recognition of the endotoxemia with cessation of the transfusion of the contaminated blood, although desirable does not seem to alter the outcome. There is no known effective measure to prevent such reactions.

Noninfectious Complications of Blood Transfusion -- Clinical Significance -- Hemolytic Transfusion Reaction (HTR)

HTR can have a wide spectrum of symptoms, including fever, chills, rigors, chest/back/abdominal pain, infusion site pain, nausea/vomiting, shock, dyspnea, hemoglobinuria, oliguria/anuria, and diffuse bleeding. The severity of the reaction varies and can depend on the amount and how rapidly the incompatible blood is transfused. In severe cases, it can lead to acute kidney failure, shock, DIC, or death. Some of these symptoms are difficult to assess in certain populations, such as pediatric and unconscious patients. [2]

Escherichia coli sepsis from contaminated platelet transfusion.

Transfusion of pooled platelet concentrate (PC) caused a septic reaction characterized by sustained hypotension, high cardiac output, and low systemic vascular resistance. Investigation demonstrated the same strain of Escherichia coli in the patient's blood, the transfused pooled PC, and recalled packed red blood cells separated from the same unit of whole blood as one of the platelet units in the contaminated pool. Five hundred other units of PC from the same supplier were cultured prospectively, and 7% were bacterially contaminated. The level of contamination was 20 or fewer colony-forming units per milliliter in all except one unit, the only one associated with a febrile transfusion reaction. This episode illustrates the continuing importance of sepsis as a cause of platelet transfusion reactions and demonstrates the usefulness of appropriate cultures and epidemiologic information in assessing the source.

The first case of severe acute hemolytic transfusion reaction caused by anti-Sc2.

Alloantibodies to the low-frequency antigen Scianna-2 (Sc2) have been implicated in cases of hemolytic disease of the fetus and newborn but never in hemolytic transfusion reactions (HTRs); thus, the clinical significance of anti-Sc2 has yet to be fully addressed. A 26-year-old woman with thalassemia presented rigors, fever, nausea, abdominal pain, and hemolytic biochemistry after exposure to 75 mL of plasma-reduced red blood cells (RBCs). The RBC unit was issued by electronic crossmatch but was 3+ incompatible on recrossmatch by gel indirect antiglobulin test (IAT). The patient had anti-Sc2 previously identified, but considered to be clinically insignificant. The transfusion history was reviewed and a monocyte monolayer assay (MMA) was performed. The patient was investigated for a RBC reaction 9 years prior, when she developed symptoms of HTR. The RBC unit was crossmatched by immediate spin due to consistent screen negativity. Full crossmatch found the RBC 1+ incompatible by gel IAT with both pre/post samples, while direct antiglobulin test was negative (pre) and 1+ immunoglobulin G positive (post). The antibody remained unidentified and she was committed to gel IAT crossmatch. Two-years later, the specificity to Sc2 was deduced when one RBC unit was found 3+ incompatible. Finally, the transfusion reaction reported herein occurred when she received by happenstance RBCs from the same donor who was associated with the remote reaction 9 years earlier. MMA yielded highly positive phagocytic indices only for Sc2+ RBCs, including the donor's RBCs that triggered the severe HTR. This is the first case of HTR caused by anti-Sc2 confirmed by clinical findings and MMA.

Managing Fresh-Frozen Plasma Transfusion Adverse Effects: Allergic Reactions, TACO, and TRALI -- History and Physical

Hemolytic transfusion reactions can manifest with a range of symptoms, including fever, abdominal pain, and the presence of red or brown-colored urine. Patients experiencing these reactions may also exhibit chills, hypotension, and back pain. In severe cases, patients may exhibit signs of renal failure or disseminated intravascular coagulation, reflecting the systemic consequences of red blood cell destruction and hemoglobin release. Early recognition and immediate intervention are essential to prevent further complications in these cases. [24]

Two septic transfusion reactions presenting as transfusion-related acute lung injury from a split plateletpheresis unit.

We report two simultaneous cases of Staphylococcus aureus sepsis initially consistent with and diagnosed as transfusion-related acute lung injury. The sepsis in both cases resulted from transfusion of two split products from a single contaminated plateletpheresis unit. In each case, the platelets were given along with numerous other blood products during posterior spine surgery. The discussion includes presentation, clinical course, diagnosis, and similarities between sepsis and transfusion-related acute lung injury. The cases and discussion highlight the importance of considering sepsis as part of the differential for any patient believed to have transfusion-related acute lung injury with clinical features of sepsis. Data were collected from the patients' electronic medical records and the hospital laboratory medicine database. Our cases highlight the importance of vigilant investigation in patients suspected of transfusion-related acute lung injury, as septic transfusions are easily missed and may mimic or coexist with transfusion-related acute lung injury. Sepsis should be strongly considered whenever clinical features such as hypotension, leucopenia, and fever are noted in patients with suspected transfusion-related acute lung injury. In comparison to patients receiving red blood cells or plasma, platelet transfusion recipients are at a greater risk for sepsis from a contaminated unit. Patients developing sepsis from a contaminated blood product may meet the clinical definition of transfusion-related acute lung injury. In such cases, if the clinical syndrome is attributed solely to transfusion-related acute lung injury and bacterial sepsis is not suspected, the correct diagnosis may be missed or delayed. Consequently, appropriate treatment for sepsis would also be delayed or not provided and likely result in increased morbidity and mortality.

Mechanisms of severe transfusion reactions.

Serious adverse effects of transfusion may be immunologically or non-immunologically mediated. Currently, bacterial contamination of blood products, particularly platelets, is one of the most significant causes of transfusion-related morbidity and mortality. Septic transfusion reactions can present with clinical symptoms similar to immune-mediated hemolytic transfusion reactions and transfusion-related acute lung injury. Extremely high fever and/or gastrointestinal symptoms, in a transfusion recipient, may be indicative of sepsis. The diagnosis is based upon culturing the same organism from both the patient and the transfused blood component. Numerous organisms have been implicated as the cause of septic transfusion reactions. Due to different storage conditions, gram negative organisms are more often isolated from red blood cell components; gram positive organisms are more often isolated from platelets. Prevention of septic transfusion reactions is primarily dependent on an adequate donor history and meticulous preparation of the donor phlebotomy site. Visual inspection of blood components prior to transfusion is also vital to preventing these reactions. Several methods of detection of bacterial contamination and inactivation of pathogens are currently under active investigation.

Immediate Hypersensitivity Reactions -- Complications -- Post-Transfusion Reaction

This is a hypersensitivity reaction that occurs within 24 hours of a blood transfusion. Hemoglobinuria that appears during or after the procedure becomes an alarming sign. Other manifestations include back pain, fever, chills, dizziness, and dyspnea. [44]

Treatment Paracetamol has been used in treatment, and leukoreduction of future transfusions is sometimes performed. References External links Transfusion reactions Complications of surgical and medical care Transfusion medicine

Blood transfusion

Febrile nonhemolytic reactions are, along with allergic transfusion reactions, the most common type of blood transfusion reaction and occur because of the release of inflammatory chemical signals released by white blood cells in stored donor blood or attack on donor's white blood cells by recipient's antibodies. This type of reaction occurs in about 7% of transfusions. Fever is generally short lived and is treated with antipyretics, and transfusions may be finished as long as an acute hemolytic reaction is excluded. This is a reason for the now-widespread use of leukoreduction – the filtration of donor white cells from red cell product units.

A multistate cluster of red blood cell transfusion reactions associated with use of a leucocyte reduction filter.

In 2000, the American Red Cross (ARC) received reports of unusual transfusion reactions of unknown aetiology among patients receiving leucocyte-reduced (LR) red blood cell (RBC) units in multiple distribution regions. We evaluated potential risk factors of reactions among patients who received LR-RBC transfusions. A case-patient was defined as any patient with onset of back pain while receiving an LR-RBC transfusion from 1 January to 25 May 2000. Controls were chosen randomly and selected in a 1:3 case : control ratio from healthcare facilities in which case-patients were transfused. Product-specific risk factors of reactions were further determined through nested case-control study, procedural review of blood collection facility and quality-control-testing record review of product processing. Reaction incidence rates were determined through ARC blood product distribution data by region of blood collection and processing. There were 29 reactions detected in patients who received transfusions in 13 healthcare facilities in five states. Eighteen case-patients and 78 controls were included in the case-control study. In univariate analysis, case-patients were more likely than controls to have a haematologic malignancy, to have received the transfusion as an outpatient, to have received an RBC transfusion within the previous 3 months, to have received medication used to prevent reactions or to diminish their intensity upon transfusion (i.e. premedication) or to have received LR-RBC units prepared with the HemaSure r\LS System(HS) rather than two other filters used. In multivariate analysis limited to recipients of HS-filtered RBC units, transfusion premedication [adjusted odds ratio (AOR) = 7; 95% confidence interval (CI) 1.4-37; P = 0.02] and transfusion as an outpatient (AOR = 5; 95% CI 1.1-20; P = 0.03) were independently associated with reactions. The rate of reported transfusion reactions was 2.0 reactions per 10 000 RBC units distributed. A multistate cluster of transfusion reactions was significantly associated with leucocyte filtration of RBC units prepared with a specific product, the HS filter. The reactions also were independently associated with premedication and transfusion as an outpatient; these may be surrogates for an increased risk of reaction or for greater likelihood of detection. The mechanism for these reactions has not been elucidated. This cluster of reactions underscores the importance of surveillance efforts to detect adverse events after transfusion, particularly when new methods to modify blood products are introduced.

Beta thalassemia

Long-term transfusion therapy (in those with transfusion dependent beta thalassemia) is a treatment used to maintain hemoglobin levels at a target pre-transfusion hemoglobin level of 9-10.5 g/dL (11-12 g/dL in those with concomitant heart disease). To ensure quality blood transfusions, the packed red blood cells should be leucoreduced. By having leucoreduced blood packets, the patient is at a lower risk to develop adverse reactions by contaminated white cells and preventing platelet alloimmunisation. Patients with allergic transfusion reactions or unusual red cell antibodies must receive washed red cells or cryopreserved red cells. Washed red cells have been removed of plasma proteins that would have become a target of the patient's antibodies allowing the transfusion to be carried out safely. Cryopreserved red cells are used to maintain a supply of rare donor units for patients with unusual red cell antibodies or missing common red cell antigens. These regular transfusions promote

Massive Transfusion -- Complications -- Additional Complications

Acute hemolytic transfusion reaction: This reaction is characterized by symptoms such as fever, chills, flank pain, and oozing from IV sites, resulting from acute intravascular hemolysis of transfused red blood cells. The leading cause is typically ABO incompatibility or a reaction to other RBC antigens. Transfusion-associated sepsis: This sepsis occurs when a patient is transfused with blood containing a microorganism, causing symptoms such as fever, chills, and hypotension. Anaphylactic transfusion reaction: This is a severe allergic reaction characterized by angioedema, wheezing, and hypotension.

[Hemovigilance: State 2007-2013 Tunis].

Despite its lifesaving role, blood transfusion still has risks associated with it. Hemovigilance is a set of surveillance procedures of the transfusion chain intended to promote safe and effective use of blood components. This work aims to present a descriptive analysis of adverse reactions, which were notified over a period of 5 years (incidence and etiology); to identify malfunctions and to propose corrections. All transfusion adverse reactions accidents reported to the blood bank of the hospital La Rabta (n=120) are explored (clinical and laboratory tests). The average age of patients with transfusion reaction was 51.2 years (25 days to 89 years). The transfusion accident rates ranged from 0.59 to 2.19 accidents/1000 labile blood products (LBP) distributed. The investigations were used to classify 71 % of accidents in different categories. The most prevalent reaction is the hemolytic reaction, n=24 (19.8 %), followed by allergic reactions, n=21 (17.5 %) and non-hemolytic feverish reaction, n=19 (15.8 %). Transfusion reactions of grade 1 severity were the most frequent (n=94); followed by those of grade 3 severity (n=16), accidents grade 4 (n=4) including two cases of acute pulmonary edema, one case of hyperkalemia, and the last case classified undetermined. These data are particularly rich in learning lessons. This study identified several levels failures: under-reporting of certain transfusion accidents, malfunctions at certain stages of the transfusion chain. In order to achieve an accurate statement of each transfusion reaction, it is important to plan in-service training.

ABO Blood Group System -- Clinical Significance

A hemolytic transfusion reaction is one type of reaction that can occur with the transfusion of blood products. Acute hemolytic transfusion reactions most commonly occur with transfusion of red blood cells, although they can develop with transfusions of other blood products. An acute hemolytic transfusion reaction occurs within 24 hours of the transfusion. Acute hemolytic reactions are most often caused by incompatibility between the donor product and recipient blood group system, most commonly the ABO blood group system. The classic presentation of acute hemolytic transfusion reaction includes fever, red/brown urine, and back/flank pain. However, not all patients will present in this way; other symptoms that may be noted include hypotension, chills, renal failure, and disseminated intravascular coagulation. [17]

Delayed hemolytic transfusion reaction

A delayed hemolytic transfusion reaction (DHTR) is a type of transfusion reaction. According to the Centers for Disease Control's (CDC) National Healthcare Safety Network's (NHSN) Hemovigilance Module, it is defined as: Mechanism If a person without a Kidd blood antigen (for example a Jka-Jkb+ patient) receives a Kidd antigen (Jka-antigen for example) in a red blood cell transfusion and forms an alloantibody (anti-Jka); upon subsequent transfusion with Jka-antigen positive red blood cells, the patient may have a delayed hemolytic transfusion reaction as their anti-Jka antibody hemolyzes the transfused Jka-antigen positive red blood cells. Other common blood groups with this reaction are Duffy, Rhesus and Kell.

Is it an acute pain transfusion reaction?

A 40-year-old male patient presented to the emergency department with complaints of anasarca, mild dyspnea, orthopnea, vomiting, and decreased urine output. A provisional diagnosis of chronic kidney disease was made and planned for hemodialysis. In view of severe anemia, 1 packed red blood cell (PRBC) was requested and after pretransfusion testing one unit of buffy coat-poor, nonleucofiltered, coombs cross-match compatible, fresh (<7-days old) saline-adenine-glucose-mannitol PRBC unit was issued. After transfusion of around 20 ml of red cells patient developed sudden onset of excruciating pain in the lower back and hip joints, tachypnea, and breathlessness with oxygen saturation dropping to 82%. Vitals were normal and patient remained afebrile. After stopping transfusion, supplemental oxygen and opioid analgesic were given. Once the symptoms subsided, transfusion was completed. A complete work-up was done to rule out other adverse reactions. Thus, this patient experienced what is known as an acute pain transfusion reaction.


All breast carcinomas should be accompanied by the study of hormone receptors and HER-2 for the prognostic implications of the tumor, as well as the adequacy of the treatment of the same, since depending on the result will apply some drugs or others. The study of relatives and the BCRA gene is not indicated since she does not have a family history of neoplasia.

[HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN] [HIDDEN].

67-year-old woman diagnosed with an infiltrating ductal carcinoma of the breast and no family history of neoplasia. What additional studies should be performed on the tumor for its clinical-therapeutic implications?

Complete phenotypic study by flow cytometry.

Study of hormone receptors, e-cadherin and study of first-degree relatives.

BRCA 1-2 study and study of first-degree relatives.

The significance of family history for patients with carcinoma of the breast.

Since the risk of carcinoma of the breast is increased in women with a family history of the disease, new primary carcinomas of the breast may be increased after treatment. Women with several relatives with carcinoma of the breast are thought to be at higher risk of having a second primary carcinoma of the breast develop and mastectomy is more frequently recommended. The computerized registry of the Mount Sinai Medical Center Breast Service was used to identify 1,337 patients with complete information concerning family history. Three hundred fifty-nine patients with a family history of carcinoma of the breast were compared with women with no family history. Compared with patients with no family history of carcinoma of the breast, patients with a family history of carcinoma of the breast were significantly younger (54.0 versus 55.8 years of age, p < 0.01), were significantly more likely to have used oral contraceptives (26 versus 13 percent, p < 0.001), had significantly more ductal carcinoma in situ (10 versus 4 percent, p < 0.01), and were significantly more often treated with breast conservation (42 versus 31 percent, p < 0.001). Simultaneous contralateral carcinoma of the breast was diagnosed more frequently in patients with a family history (3 versus 1 percent, p < 0.025), but metachronous contralateral carcinomas were not increased. In comparing the two groups, there were no significant differences in proportion premenopausal, parity, use of postmenopausal hormones, tumor size, tumor differentiation, nodal involvement, TNM stage, estrogen receptor status, or use of adjuvant radiation, chemotherapy, or tamoxifen. Complete five-year follow-up evaluation for 748 patients, 179 with a family history, found no differences in local, distant, or disease-free survival rates for mastectomy or breast conservation in relation to family history. Outcome for patients with first-degree affected relatives and those with more than one affected relative was the same as those with no family history. These results indicate that women with a family history of carcinoma of the breast should be treated no differently than women with no family history.

Clinical features and first degree relative breast cancer, their correlation with histological tumor grade: a 5-year retrospective case study of breast cancer in Mizoram, India.

The aim was to assess the association of histological tumor grade with other clinical features and epidemiological factors of women with invasive breast carcinoma. A retrospective study of 103 Mizo breast cancer patients visiting hospitals was made in Aizawl, Mizoram, Northeast India. With a prior consent, information on epidemiological factors and family history in relation to cancer was obtained. Clinical reports were obtained from their medical records. The frequency of distribution was calculated for age at diagnosis and tumor characteristics. Statistical analysis for different variables was done using a chi-square test. p < 0.05 was considered significant. The histological tumor grades in our studies were found to be associated with lymph node invasion (p < 0.021), different subtype of hormone receptor such as ER status (p < 0.004), ER/PR status (p < 0.007), HER2/neu status (p < 0.014), and ER/PR/HER2 status (p < 0.025). A patient with a family history of breast cancer in their 1st degree relative is also seen to have association in determining the tumor grade (p < 0.003). Reproductive history, lifestyle and dietary habits, tobacco, and alcohol consumption were found to have no influence on breast cancer tumor grade. Our results showing significant correlation between status of lymph node, ER, PR, and HER2/neu oncoprotein and family history with 1st degree relative breast cancer are the first time report to target and focus on the possible role of biomarkers for diagnosis among the Mizo tribal breast cancer patients.

BRCA mutation

Relative indications for testing for a mutation in BRCA1 or BRCA2 for newly diagnosed or family members include a family history among 1st (FDR), 2nd (SDR), or 3rd(TDR) degree relatives usually on the same side of the family but not limited: A known mutation (BRCA1 or BRCA2) in a cancer susceptibility gene within the family Women affected with any breast cancer diagnosed under the age of 30 Women affected with triple negative breast cancer (TNBC) (estrogen receptor negative, progesterone receptor negative, and HER2/neu negative) under the age of 50 Two relatives (FDR/SDR) diagnosed under the age of 45 Three relatives (FDR/SDR) diagnosed with average age of 50 or less Four relatives at any ages Ovarian cancer with either an additional diagnosed relative or a relative with male breast cancer A single family member with both breast and ovarian cancer Male breast cancer Pancreatic cancer with breast or ovarian cancer in the same individual or on the same side of the family

Influence of young age at diagnosis and family history of breast or ovarian cancer on breast cancer outcomes in a population-based cohort study.

The objective of this study was to examine the association of: (i) diagnosis at age </=35, (ii) first-degree family history of breast or ovarian cancer (BOC) and (iii) a research based definition of genetic risk, with tumor characteristics, treatment and survival in breast cancer (BC). Consenting female participants in the population-based Ontario Familial Breast Cancer Registry diagnosed with primary invasive BC between 1996 and 1998 were followed prospectively until 2005. Among 967 women, 105 were </=35 years old at diagnosis and 686 were classified as genetic risk cases, including 349 with a first-degree family history. Individuals diagnosed at age </=35 were more likely to self-detect tumors, to present with inflammatory BC, to have invasive ductal carcinoma of no special type, high T stage, and tumors with lymphovascular invasion (LVI), high grade and negative estrogen receptors. Younger women were more likely to receive chemotherapy and less likely to receive hormonal therapy. Diagnosis </=35 years old was associated with significantly reduced distant recurrence free survival, an effect that did not persist after adjustment for tumor and treatment related variables. Poor outcomes were restricted to younger women with hormone responsive BC. Family history was associated with increased rates of mammographic detection of BC, lower tumor stage and less frequent inflammatory BC, but had no association with BC outcomes. Women diagnosed with BC at age </=35 have more aggressive tumors; these adverse tumor characteristics, rather than age, lead to poor outcomes. Family history was not associated with survival.

Four new cases of double heterozygosity for BRCA1 and BRCA2 gene mutations: clinical, pathological, and family characteristics.

Double heterozygosity (DH) for BRCA1 and BRCA2 mutations is a very rare finding, particularly in non-Ashkenazi individuals, and only a few cases have been reported to date. In addition, little is known on the pathological features of the tumors that occur in DH cases and on their family history of cancer. Four carriers of pathogenic mutations in both BRCA1 and BRCA2 were identified among women who underwent genetic counseling for hereditary susceptibility to breast and ovarian carcinoma at three different Italian institutions. Clinical, pathological, and family history data were collected from medical records and during genetic counseling sessions. All identified DH cases developed breast carcinoma and three of them were also diagnosed with ovarian carcinoma. Mean ages of breast and ovarian cancer diagnosis were 42.7 and 48.6 years, respectively. The majority of breast cancers showed a BRCA1-related phenotype, being negative for hormone receptors and HER2. Two cases reported different gastrointestinal tumors among relatives. Although the individuals described in this study show more severe clinical features in comparison to previously reported BRCA1 and BRCA2 DH cases, our observations support the hypothesis of a non specific phenotype of DH cases in terms of age of disease onset. In addition, our observations indicate that in DH patients breast carcinogenesis appears to be driven mainly by the mutations in BRCA1. The possible association of DH for BRCA gene mutations with gastrointestinal tumors is in keeping with previous reports, but needs to be confirmed by further analyses.

Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk.

Triple-negative breast cancer accounts for less than 20% of breast cancers overall, but is the predominant subtype among carriers of mutations in BRCA1. However, few studies have assessed the association between breast cancer family history and risk of triple-negative breast cancer. We examined the relationship between having a family history of breast cancer in first-degree relatives and risk of triple-negative breast cancer, and risk of two other breast cancer subtypes defined by tumor marker expression. We evaluated data collected by the Breast Cancer Surveillance Consortium from 2,599,946 mammograms on 1,054,466 women, among whom 15% reported a first-degree family history of breast cancer. Using Cox regression in this cohort, we evaluated subtype-specific associations between family history and risk of triple-negative (N = 705), estrogen receptor-positive (ER+, N = 10,026), and hormone receptor-negative/HER2-expressing (ER-/PR-/HER2+, N = 308) breast cancer among women aged 40-84 years. First-degree family history was similarly and significantly associated with an increased risk of all the subtypes [hazard ratio (HR) = 1.73, 95% confidence interval (CI): 1.43-2.09, HR = 1.62, 95% CI: 1.54-1.70, and HR = 1.56, 95% CI: 1.15-2.13, for triple-negative, ER+, and ER-/PR-/HER2+, respectively]. Risk of all the subtypes was most pronounced among women with at least two affected first-degree relatives (versus women with no affected first-degree relatives, HR(triple-negative) = 2.66, 95% CI: 1.66-4.27, HR(ER+) = 2.05, 95% CI: 1.79-2.36, HR(ER)-(/PR)-(/HER2+) = 2.25, 95% CI: 0.99-5.08). Having a first-degree family history of breast cancer was associated with an increased risk of triple-negative breast cancer with a magnitude of association similar to that for the predominant ER+ subtype and ER-/PR-/HER2+ breast cancer.

Cancer biomarker

Similarly, additional laboratory research has shown that tumor cells undergoing apoptosis can release cellular components such as cytochrome c, nucleosomes, cleaved cytokeratin-18, and E-cadherin. Studies have found that these macromolecules and others can be found in circulation during cancer therapy, providing a potential source of clinical metrics for monitoring treatment. Recurrence Cancer biomarkers can also offer value in predicting or monitoring cancer recurrence. The Oncotype DX® breast cancer assay is one such test used to predict the likelihood of breast cancer recurrence. This test is intended for women with early-stage (Stage I or II), node-negative, estrogen receptor-positive (ER+) invasive breast cancer who will be treated with hormone therapy. Oncotype DX looks at a panel of 21 genes in cells taken during tumor biopsy. The results of the test are given in the form of a recurrence score that indicates likelihood of recurrence at 10 years.

Negative/low HER2 expression alone or combined with E-cadherin positivity is predictive of better prognosis in patients with breast carcinoma.

The loss of E-cadherin expression leads to absence of tissue integrity, an essential step in tumor progression. Methylation of CpG islands in the promoter region of the CDH1 gene coding E-cadherin might be an alternative for gene silencing. In the present study, we investigate the expression of E-cadherin and hormone receptors in invasive ductal breast carcinoma (IDCs). Protein expression was analysed immunohistochemically in 87 cases, including 26 familial tumors. The most interesting results revealed a significantly reduced E-cadherin expression in cases with familial history compared to sporadic tumors (p=0.009), as well as with tumors ≤5 cm (p=0.022). Moreover, HER2 over-expression was associated with distant metastasis (p=0.011) and overall survival (p log rank=0.028). Tumors displaying negative/low HER2 expression combined with E-cadherin positivity confer better patient survival (p=0.052). Triple Negative tumors (TN) were more frequently found in patients with advanced grade (GIII) (p=0.001) and TNM (III+IV) (p=0.018) which supports the aggressive behavior of TN tumors. On the other hand, hypermethylation of CDH1 gene promoter was observed in 46% of hereditary cases and strongly associated with loss of E-cadherin expression (p=0.002). Furthermore, patients with unmethylated CDH1 pattern have a better 5-year disease free survival (p=0.021). In conclusion, in patients with hereditary breast cancer, the CpG methylation event contributes to the loss of E-cadherin expression. On the other hand, HER2 over-expression is predictive of worse prognosis, either alone or combined with loss of E-cadherin expression in Tunisian patients with breast cancer.

Seven-year survey of classical and pleomorphic invasive lobular breast carcinomas in women from southeastern Serbia: Differences in clinicopathological and immunohistochemical features.

The occurrence of different variants of invasive lobular carcinoma (ILC) of the breast is variable. For example, the pleomorphic variant of ILC has an incidence of around 5%; however, the number of analyzed cases of ILC is shadowed by the number of ductal type carcinoma (IDC). Thus, we aimed to analyze the classical and pleomorphic ILCs in women from southeastern Serbia. Analyzed were 296 cases (11.91%) diagnosed with ILC, out of 2486 cases of all breast cancers (BCs), during a 7-year period (2005-2011) from southeastern Serbia. The differences in clinicopathological and immunohistochemical features (estrogen receptor/ER, progesterone receptor/ PR, HER-2, Ki-67, BRCA-1, p53 and E-cadherin) of these cases of ILCs were assessed and compared. Pleomorphic ILC occurred relatively rarely compared to other variants, however almost one fifth of the ILC cases were pleomorphic. No statistically significant correlation was found between patient age, tumor stage and the presence/absence of multifocality (MFC), multicentricity (MCC) and bilaterality (BL) on one side, and ILC variant on the other. Only the expression of two prognostic and predictive immunohistochemical markers, important for endocrine therapy, ER and PR, showed significant correlation with the ILC variant. Although higher tumor stage, incidence of multicentricity, overexpression of HER2 and higher p53 positivity were deemed to be characteristic of pleomorphic ILC, in our study that included a much larger number of cases than previous studies did, such correlations were not observed. Thus, it appears that the only two features of pleomorphic ILCs is absence of ER and PR positivity.

Breast cancer and family history: a multivariate analysis of levels of tumor HER2 protein and family history of cancer in women who have breast cancer.

The HER2 gene, located on the long arm of chromosome 17, codes for a protein with the characteristics of a growth factor receptor. In a preliminary study, we reported that high levels of tumor HER2 (erbB-2/neu) protein are associated with a family history of breast cancer (that is, one or more female blood relatives with breast cancer). We have now collected a larger number of subjects (94) and performed a multivariate analysis of the independent variables family history of breast cancer, tumor estrogen receptor, age, and tumor DNA index. Family history of breast cancer was assessed by questioning the patient, in many cases by telephone. HER2 levels were significantly higher in women with a family history of breast cancer (p = 0.015, two-tailed t-test). The 27 women with family history were predominantly postmenopausal, mean age 61 +/- 2.3 (mean +/- SEM), versus a mean age of 56 +/- 1.7 for the 67 women with no family history. Of the 27 women with a family history of breast cancer, 13 had a first-degree relative (mother or sister) with the disease. The remaining 14 women had other relatives (grandmothers, aunts, cousins, or a niece) with breast cancer. The results of multiple linear regression analysis, with HER2 as the dependent variable, showed that family history of breast cancer was significantly associated with elevated HER2 levels in the tumors (p = 0.0038), after controlling for the effects of age, tumor estrogen receptor, and DNA index. The association of family history of breast cancer and elevated tumor HER2 protein suggests that postmenopausal familial breast cancer may be associated with altered HER2 expression.

BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations. A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR). (a) Of 325 patients (with or without invasive cancer), 19.1% (62/325) tested positive for BRCA1/BRCA2 mutations. And 18.4% (9/49) was positive for BRCA1/BRCA2 mutations in DCIS, compared with 19.2% (53/276) in IDC (p = 1.000). Among BRCA mutations, 14.5% (9/62) had DCIS compared with nonmutations (15.2%, 40/263). Incidence of DCIS was 3.0% (1/33) of BRCA1 mutations and 27.5% (8/29) of BRCA2 mutation (p = 0.009). (b) Median age of diagnosis in BRCA mutation carriers was 39 years, compared with 46 years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between BRCA mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX ≥ 2 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266-20.763; p = 0.022), age at diagnosis ≤35 years (OR 0.149, 95% CI 0.023-0.954, p = 0.045) and ER+/HER2+ status (OR 5.034, 95% CI 1.092-23.210, p = 0.038) remained as independent significant predictors for BRCA mutation. Ki67 index (cut off by 14% or 30%) did not differ between BRCA mutation carriers and noncarriers (p = 0.459 and p = 0.651). (c) There was a significant difference in ER-positive tumors among BRCA2 carriers and noncarriers (p = 0.042). Subgroup analysis showed BRCA2 carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+/PR+ (p = 0.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) BRCA mutation was not associated with an increased risk of IBTR and CBTR. DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX ≥2, age at diagnosis ≤35 years and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing.

Basal-like carcinoma

The most common histopathological type is invasive ductal carcinoma. It can also be metaplastic carcinoma, medullary carcinoma and adenoid cystic carcinoma, with high grade, high mitosis count. Central necrosis, apoptotic cells, and stroma lymphocyte reaction and a small amount of interstitial components can be seen through microscopic examination. In BLBC, p53 mutations are usually found and the expression epidermal growth factor receptor (EGFR or HER-1) and c-kit are usually positive. Through the genetic hybridization techniques, BLBC is verified to have the most complex gene phenotypes. The relationship between BLBC and familial BRCA1-associated breast cancer has been discussed in recent years. Several studies have demonstrated that BRCA1-associated breast cancer is more likely to be a BLBC. However, there are few BRCA1 mutations in BLBC, indicating that it is likely to be epigenetic changes. Studies have reported that the negative regulatory factor of BRCA1 gene, ID4, is often

Metaplastic carcinoma

Metaplastic carcinoma, otherwise known as metaplastic carcinoma of the breast (MCB), is a heterogeneous group of cancers that exhibit varied patterns of metaplasia and differentiation along multiple cell lines. This rare and aggressive form of breast cancer is characterized as being composed of a mixed group of neoplasms containing both glandular and non-glandular patterns with epithelial and/or mesenchymal components. It accounts for fewer than 1% of all breast cancer diagnoses. It is most closely associated with invasive ductal carcinoma of no special type. (IDC), and shares similar treatment approaches. Relative to IDC, MCB generally has higher histological grade and larger tumor size at time of diagnosis, with a lower incidence of axillary lymph node involvement. MCB tumors are typically estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER-2) negative, meaning hormone therapy is generally not an effective treatment option, which correlates to

Breast cancer expression of E-cadherin does not differ between patients with positive and negative oncological history.

The question of whether or not non-sporadic breast malignancies have different immunohistochemical features than sporadic malignancies has not been investigated previously. Consequently, the purpose of this study was to compare the expression of E-cadherin (EC) in breast cancer patients with positive and negative oncologic histories. The study included 98 breast cancer patients divided into two groups: 1) without the personal or familial history of previous malignancies, and 2) with the personal history of previous malignancies and/or with the data on cancer episodes in first- and/or second-degree relatives. There were no significant differences in the expression of EC between breast malignancies of the two groups. Moreover, statistical relationships were not observed between the positive or negative oncologic history, the age, and the menopausal status of patients, or histological tumor grade. Although the results of our series revealed no significant differences in the expression of EC between assumed sporadic and assumed non-sporadic malignancies, there is a need for further comparative studies on the immunohistochemistry of both the breast carcinoma types in order to find the other biological markers that could suggest or exclude cancer susceptibility in a given patient. Nevertheless, the results of our study suggest that EC immunohistochemistry cannot be used as a surrogate marker for screening for hereditary breast cancer.

Male Breast Cancer -- Etiology

Similarly to women, males have a higher risk of breast cancer if they have a first- or second-degree relative with breast cancer. Studies have shown that an affected sibling or parent of either gender may increase the risk of breast cancer in either the males or females in the family. Bevier et al. (2012) noted in their study that the relative risk (RR) of breast cancer was similar in either offspring when the father or mother was affected (RR = 1.73 and 1.74, respectively), but the risk was slightly higher in the females when the brother is affected as opposed to when the sister is affected (RR = 2.48 and 1.39, respectively). [3] Also, in addition to a family history of breast cancer, males with a BRCA mutation appear to have increased risk for breast cancer as well. Although rare for a male to have a BRCA mutation, those with BRCA2 carrier mutation have a 6% increased risk and BRCA1 with a 4% risk of developing the disease. [4] Other genetic disorders have been implicated in increasing the risk of MBC, including Klinefelter syndrome (47, XXY), Cowden syndrome ( PTEN tumor suppressor gene), Li-Fraumeni syndrome ( TP53 ), Lynch syndrome ( PALB2 and mismatch repair genes). [2] [4]

Somatostatin receptor 2

other components of the endocrine system and nervous system, so it can be drawn that the receptor family has great influence among these systems. The family was first discovered in a segment of a rat's pituitary gland known as the tumor cell line. A cell line is grown as a culture under controlled conditions, so the first discovery was found by culturing these cells in controlled conditions and in an environment outside of its norm. There, researchers found that the tumor cell line expresses a cell dividing inhibitor known as the transforming growth factor beta (TGF-beta) and also acts as an inhibitor to the milk producing hormone in female mammals, prolactin, and growth hormones. Researchers studied the activity of the receptors by conducting an assay with Ligand binding studies, which basically means they were conducting studies to see how prevalent the binding of the receptors occurred. Differences in how prevalently they receptors bonded revealed the existence of multiple

Does family history influence survival in breast cancer cases?

A few studies have suggested a relatively better prognosis for breast cancer (BC) cases reporting a positive family history (FH). We aimed at comparing the survival of patients according to FH in a large hospital-based series of 1,278 BC cases. Information on FH for BC was obtained at diagnosis by interview. All cases reporting a first- or second-degree FH for breast carcinoma were compared with cases without FH. Overall survival was estimated using a product-limit method. Hazard ratios (HRs) and the corresponding 95% confidence intervals (95% CIs), adjusted for confounding factors, were computed using proportional hazard models. Overall, 240 (18.8%) cases reporting, at diagnosis, a positive FH (156 with at least 1 first-degree relative and 84 with at least 1 second-degree relative) were compared with 1,038 patients without FH for BC. No significant differences were found in terms of distribution of age at diagnosis, tumor stage, nodal involvement, receptor status and histology. Cumulative survival rates at 5 years for cases without FH and with first-degree and second-degree FH for BC were 79.8 (95% CI 77.0-83.0), 78.6 (95% CI 70.0-88.0) and 80.2 (95% CI 68.0-92.0), respectively (log-rank test, chi(2) (2) = 0.02, p = 1.0). After adjustment for age, pathologic size and nodal involvement, the HR among cases of invasive cancer with a first-degree FH of BC was 0.91 (95% CI 0.55-1.48); however, the HR for cases with second-degree FH was 1.18 (95% CI 0.62-2.25) compared to cases without FH. Our study, based on a large series of consecutive invasive BC cases, did not find any significant survival differences associated with a positive FH for breast carcinoma, suggesting the existence of a large heterogeneity among BC cases with FH.

Combined small-cell lung carcinoma

Pemetrexed has been shown to improve survival in non-squamous cell NSCLC, and is the first drug to reveal differential survival benefit in large cell lung carcinoma. C-SCLC appear to express female hormone (i.e. estrogen and/or progesterone) receptors in a high (50–67%) proportion of cases, similar to breast carcinomas. However, it is at present unknown whether blockade of these receptors affects the growth of c-SCLC. Prognosis Current consensus is that the long-term prognosis of c-SCLC patients is determined by the SCLC component of their tumor, given that "pure" SCLC seems to have the worst long-term prognosis of all forms of lung cancer. Although data on c-SCLC is very sparse, some studies suggest that survival rates in c-SCLC may be even worse than that of pure SCLC, likely due to the lower rate of complete response to chemoradiation in c-SCLC, although not all studies have shown a significant difference in survival.

Clinical characteristics of breast cancer patients with family history.

This study was conducted to acquire information as to the clinicopathological characteristics of breast cancer patients with family history. Of 583 patients with breast cancer, 60 (10.3%) had family history in at least one relative within the second-degree. The affected family member was most frequently a sister (43%), followed by the mother (23%) and an aunt (20%). Comparison of the data for the patients between with and without family history revealed no significant differences for any of mean age, menopausal status, histological type, histological staging, and estrogen receptor status. Although the sample size was small, neither the survival rate nor the bilaterality of disease was influenced by the family history of breast cancer.

Selective estrogen receptor modulator

Tamoxifen is a first-line hormonal treatment of ER-positive metastatic breast cancer. It is used for breast cancer risk reduction in women at high risk, and as adjuvant treatment of axillary node-negative and node-positive, ductal carcinoma in situ. Tamoxifen treatment is also useful in the treatment of bone density and blood lipids in postmenopausal women. Adverse effects include hot flushes and more serious is two to three times higher relative risk of developing endometrial cancer compared to women of an age-matched population. Toremifene, a chlorinated tamoxifen derivative, causes fewer DNA adducts in liver than seen with tamoxifen in preclinical studies and was developed to avoid hepatic carcinomas. It is used as endocrine therapy in women with ER/PR-positive stage 4 or recurrent metastatic breast cancer and has demonstrated similar efficacy compared to tamoxifen as adjuvant treatment of breast cancer and in the treatment of metastatic breast cancer.

Prognosis of breast cancer patients with familial history classified according to their menopausal status.

Breast cancer patients were classified in the family history positive (FHP) group when they had at least one second-degree relative who was a breast cancer patient. The results of a comparative study with patients classified in the family history negative (FHN) group showed the prognosis of the FHP group was significantly better than that of the FHN group. However, when those patients were classified according to their menopausal status at onset, there were no significant differences in survival rates between the FHP and FHN groups with onset before menopause, whereas the survival rate of the FHP group was significantly higher than that of the FHN group with onset after menopause. The same results were found when the FHP group was subgrouped into the FHP group with first-degree relatives and the FHP group with second-degree relatives. Further investigations on background factors revealed that the patients with onset before menopause showed no significant differences between the FHP and FHN groups in age at surgery, diameter of the tumor, histologic grade, the number of metastatic lymph nodes, body weight, estrogen receptor (ER) status, and the values of CEA and CA15-3 before surgery. On the other hand, the FHP patients with onset after menopause showed significantly lower numbers of metastatic lymph nodes and trends showing higher ER values and lower CA15-3-values. Therefore the favorable prognosis in the FHP group seems to be attributable to the higher survival rate of the FHP patients with onset after menopause.

Parathyroid hormone 1 receptor

Interactions Parathyroid hormone 1 receptor has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2 and Sodium-hydrogen antiporter 3 regulator 1. Model organisms Model organisms have been used in the study of PTH1R function. A conditional knockout mouse line called Pth1rtm1a(EUCOMM)Hmgu was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping See also Parathyroid hormone receptor References Further reading External links G protein-coupled receptors

Karen E. Knudsen

Research Knudsen is an oncology researcher whose studies are focused on precision medicine in advanced prostate cancer, with an emphasis on understanding therapeutic relapse and designing new means of clinical intervention. Her translational studies have resulted in new clinical trials targeting DNA repair, cell cycle, and hormonal regulation pathways in patients with advanced disease. Knudsen and her colleagues discovered the mechanisms by which androgen signaling impacts cancer cell proliferation and DNA repair processes, and identified novel strategies for therapeutic intervention. Notable discoveries include identification of RB tumor suppressor loss as a major mechanism of therapeutic bypass, discovery of the androgen-DNA repair axis, and elucidation of androgen receptor function in the mitotic cell cycle. Her discoveries were amongst the first to propose utilization of PARP 1/2 inhibitors for advanced disease, now an FDA-approved agent for selected prostate cancers.

A clinicopathological analysis of breast cancer in patients with a family history.

A study was conducted to investigate the clinical and pathological characteristics of breast cancer in patients with a family history (FH). Among 4,481 primary breast cancer patients, 394 (8.8%) had families which included two or more breast cancer patients within three generations (FH(+)group). This group was compared with the remaining 3,969 patients (FH(-) group) with the following results: (1) The tumor diameter in the FH(+) group was slightly less than that in the FH(-) group [not significant (NS)], with fewer lymph node metastases (P < 0.05); (2) the positive rates for the estrogen receptor were 52% (138/266) and 49% (1,216/2,481), respectively (NS); (3) expression of the c-erbB-2 protein was observed in 14 out of 40 (35%) and 32 out of 100 cases (32%), respectively (NS); (4) the relative risk of bilateral occurrence in the FH(+) group was 1.4, with a 95% confidence interval of 0.9-2.4; (5) the 15-year survival rate was 72% and 60%, respectively, suggesting a better prognosis for the FH(+) group (P < 0.01); and (6) multivariate analysis showed that the contribution of FH to postoperative survival was marginal (P = 0.07). Factors related to the hormonal environment such as age at menarche (P = 0.08) and age at menopause (P = 0.08) made a greater but non-significant contribution to the prognosis of the FH(+) group than to that of the FH(-) group. However, further genetic and molecular biological analyses of familial breast cancer are needed in order to clarify the mechanisms of cancer accumulation within families.

Abemaciclib

As of early 2016, abemaciclib was involved in 3 Phase III clinical trials: The JUNIPER Study is comparing abemaciclib against erlotinib in patients with stage IV non-small-cell lung carcinoma Due to collect data until September 2017. The MONARCH 2 study is investigating the effectiveness of abemaciclib in combination with fulvestrant for women with breast cancer. It is due to end in Feb 2017. In March 2017, Eli Lilly announced that it had met its primary endpoint of superior progression-free survival (PFS) over placebo plus fulvestrant in patients with estrogen receptor positive and HER2 negative advanced or metastatic breast cancer. This result led to the September 2017 FDA approval. The MONARCH 3 study is investigating the effectiveness of abemaciclib, plus either anastrozole or letrozole, as a first-line treatment for women with breast cancer. The trial is expected to end in June 2017.

Retrospective analysis of clinicopathological characteristics and family history data of early-onset breast cancer: a single-institutional study of Hungarian patients.

Patients at young age (≤ 35 years) diagnosed with breast cancer (BC) are considered to have poor prognosis. The aim of the present study was to retrospectively analyse clinicopathological characteristics and prognosis in a group of young BC patients. We included women diagnosed with invasive breast carcinoma younger than/or at the age of 35 years. Between 1999 and 2009, 107 women with early-onset BC were selected from the database of the 2nd Department of Pathology at Semmelweis University. For clinicopathological comparison, 55 women (36-45 years), 214 women (46-65 years), 110 women (66-75 years) and 58 women (76 ≤ years) were also included in the analysis. Family history, clinicopathological and follow-up data were analysed. The tissue specimens were reviewed for histological type, nuclear grade, and estrogen receptor (ER), progesterone receptor (PgR), Ki67 and HER2 status (IHC4). The mean age in the study group was 31.6 years at the time of diagnosis. Histology showed a high incidence of grade III tumours in this group of patients (67.9 %), while only four cases (3.8 %) were considered grade I. According to the immunohistochemical results, 35.3 % of the study cases were considered as Luminal B (LumB: either being higly proliferative or co-expressing HER2) and 33.3 % as triple negative breast carcinomas (TNBC). The detailed questionnaire related to family history was completed and received in 49/107 cases (45.8 %). Analysis of these data revealed an affected family history of breast or ovarian carcinoma in first and second degree relatives in 51.0 %. A high proportion (52.0 %) of TNBC was observed among young women with a family history of the disease. Survival analysis of the 107 patients showed that 25 (23.3 %) women died until 31 December 2012. No significant difference in survival was detectable considering the regimen of systemic treatment (p = 0.188). Regarding clinicopathological parameters, the immunophenotypes, grade, pT and pN values differred substantially between the age groups (p = 0.001, for all), and the shortest relapse-free survival was seen among the youngest BC patients. This analysis illustrates that breast cancer arising in young women is characterized by the presence of less favorable subtypes such as LumB and TNBC. The increased proportion of TNBC was especially remarquable in the group of patients presenting with family history of the disease. The fact that a high rate of death occurred and no significant difference in OS were notable regarding the scheme of systemic therapies (neoadjuvant vs. adjuvant) highlight the necessity of the development of new treatment strategies.

Dynamic angiothermography

DATG is able to detect changes in blood flow that are indicative of breast cancer, may be used for younger patients, is completely non-invasive (no need for radiation or contrast agent, no need for compression of the breast) and is lower cost than alternatives requiring minimal facilities. This technology, performed quickly (5–6 minutes for visit) and very precise, is useful for screening and is also able to detect precancerous lesions. Studies have been conducted that have shown how it is possible, by means of this methodology, to diagnose invasive ductal carcinoma and infiltrating lobular carcinoma with the same accuracy. DATG can be strategic for young patients, or patients with dense breasts where the contrastive performance of mammography is challenged. Another application of DATG is the monitoring of at-risk patients with increased changes of breast cancer who take hormone replacement therapy (sometimes taken to reduce menopause symptoms) and participate in in-vitro

Prevalence of BRCA1 and BRCA2 mutations in women diagnosed with ductal carcinoma in situ.

The distribution of BRCA1 and BRCA2 mutations in women diagnosed with noninvasive breast carcinoma is unknown. To estimate the BRCA1 and BRCA2 mutation prevalence in women with ductal carcinoma in situ (DCIS), unselected for age, family history, or ethnicity. The data were 369 DCIS cases diagnosed among female residents aged 20 to 79 years from the state of Connecticut between September 15, 1994, and March 14, 1998. These women were participants in a large population-based case-control study of breast carcinoma in situ. Telephone interviews were used to collect risk factor information and blood or buccal specimens were collected for BRCA1 and BRCA2 mutation testing. Prevalence of disease-associated mutations of BRCA1 and BRCA2 in women diagnosed with DCIS. Three (0.8%) and 9 (2.4%) of 369 DCIS cases had disease-associated mutations in BRCA1 or BRCA2, respectively. One woman had a mutation in both genes (BRCA1 W321X and BRCA2 3398del5). Carriers were significantly more likely than noncarriers to report a first-degree (mother, sister, or daughter) family history of breast cancer (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.1-12.4), as well as a personal history of ovarian cancer. In addition, carriers were more likely than noncarriers to be diagnosed at an early age (<50 years) (OR, 3.4; 95% CI, 1.0-11.7), as well as to report at least 1 first-degree relative diagnosed with breast cancer before 50 years (OR, 10.6; 95% CI, 3.0-37.0). Ductal carcinoma in situ is a part of the breast/ovarian cancer syndromes defined by BRCA1 and BRCA2, with mutation rates similar to those found for invasive breast cancer. These findings suggest that patients with breast cancer with an appropriate personal or family history of breast and/or ovarian cancer should be screened and followed according to high-risk protocols, regardless of whether they are diagnosed with in situ or invasive breast cancer.

Family History and Risk of Second Primary Breast Cancer after <i>In Situ</i> Breast Carcinoma.

<bBackground:</b Incidence rates of <iin situ</i breast carcinomas have increased due to widespread adoption of mammography. Very little is known about why some women with <iin situ</i breast cancer later develop second primary breast cancers.<bMethods:</b In this population-based nested case-control study among <iin situ</i breast cancer survivors, including 539 cases with a second primary breast cancer and 994 matched controls, we evaluated the association between first-degree family history of breast cancer and risk of developing a second primary breast cancer.<bResults:</b First-degree family history of breast cancer was associated with an increased risk of developing a second primary breast cancer among women with a previous <iin situ</i breast cancer [odds ratio (OR) = 1.33, 95% confidence interval (CI), 1.05-1.69] and those with two or more affected first-degree relatives had an even higher risk (OR = 1.94; 95% CI, 1.15-3.28). Those whose relative was diagnosed at less than 50 years old were more likely to develop a second primary breast cancer (OR = 1.78; 95% CI, 1.24-2.57). No difference in risks associated with number or age of affected relatives was observed by menopausal status.<bConclusions:</b Results from this study suggest that first-degree family history of breast cancer may be an important risk factor for development of a second primary breast cancer among women with a previous <iin situ</i breast cancer.<bImpact:</b Given the growing population of <iin situ</i breast cancer survivors, a better understanding of risk factors associated with development of a second primary breast cancer is needed to further understand risk. <iCancer Epidemiol Biomarkers Prev; 27(3); 315-20. ©2018 AACR</i.

Linking Histopathology and Family History in Breast Cancer.

In order to assess the prognostic value of family history (FH) of malignancies in patients afflicted with breast cancer (BC), we examined FH and histopathologic characteristics of 542 Iranian primary BC patients. Cases with distant metastasis at the time of diagnosis were excluded. Mean age of the studied population was 49 and the most common presenting stage was stage IIA followed by stage IIB. Data on a total of 6089 relatives (1st to 4th generations with the assumption of probands as the 3rd generation) were gathered. FH of BC and other malignancies (OM) was positive in 29 and 54% of cases, respectively. The most common OM's were gastric (67), lung (52) and uterus (47) cancers. We found that a FH of BC does not have any significant correlation with proven prognostic factors but a history of BC among relatives at or before the age of 36 is associated with more aggressive tumours. On the other hand, although FH of OM was associated with an older age of the probands (which is generally associated with a favourable prognosis), tumours of the cases with FH of OM had higher grades, lymphatic invasion being detected more frequently. Also we noted that the younger the age of the relatives diagnosed with cancer, the higher the stage of the probands themselves. All together our study indicates the possibility of a relation between FH of BC and OM, and histopathologic characteristics of the probands' tumours which would put forward FH as a prognostic factor rather than a simple risk factor in BC.

CDH1 (gene)

Clinical significance Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis. E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane and invade surrounding tissues. E-cadherin is also used by pathologists to diagnose different kinds of breast cancer. When compared with invasive ductal carcinoma, E-cadherin expression is markedly reduced or absent in the great majority of invasive lobular carcinomas when studied by immunohistochemistry. E-cadherin and N-cadherin temporal-spatial expression are tightly regulated during cranial suture fusion in craniofacial development. Interactions CDH1 (gene) has been shown to interact with CBLL1, CDC27, CDON, CDH3, C-Met, CTNND1, CTNNB1, CTNNA1 FOXM1, HDAC1, HDAC2, IQGAP1, FYN, NEDD9, Plakoglobin, Vinculin, PTPmu(PTPRM) PTPrho(PTPRT)

Epidemiologic and genetic follow-up study of 544 Minnesota breast cancer families: design and methods.

In 1944, a case-control family study was initiated at the Dight Institute for Human Genetics at the University of Minnesota to study the influences of childbearing breastfeeding, and hereditary susceptibility on the occurrence and age-of-onset of breast cancer. Index cases (probands) were women ascertained at the Tumor Clinic of the University of Minnesota Hospital. Medical history and life style information were obtained on probands and relatives, and all cancers were histologically verified. A total of 544 families were studied, with probands diagnosed between 1931 and 1952. All of the records and pathology slides have been maintained from the original study; for most probands this includes the original tissue blocks. We are conducting a historical cohort study of selected of selected first- and second-degree female relatives (sisters, daughters, nieces, granddaughters) of the probands and a group of control women identified as the spouses of all male first- and second-degree relatives (brothers, sons, grandsons, and nephews). The subsequent development of breast cancer is being determined to quantify the absolute risk associated with a positive family history. Current disease status is ascertained with mammography, and stromal density is measured using digital imaging. Segregation analysis will be applied to examine how non-genetic factors such as diet, exogenous hormone use, and body fat distribution influence risk in women at high risk because of family history. A subset of families are being selected for molecular analysis of the BRCA1 gene or for linkage analyses to identify putative susceptibility loci other than BRCA1. Documented cancer histories were known for at least three generations, and the current study extends the pedigrees up to four or five generations for every family, allowing a detailed description of familial risk. This cohort study of breast cancer families is likely to be important in both quantity and quality of data and will serve as a major genetic epidemiologic resource, being free of selection bias and having relevant non-genetic exposure determined in at least four generations.