Another gift of a question, the association of S.bovis endocarditis and colon cancer. By the way, it is funny that they give Chest Rx as a test to be performed..... are you telling me that a patient with fever and dyspnea will have an echocardiogram before a simple chest x-ray? And on the other hand... why don't those who write the MIR ask shorter questions without so much back and forth? If what they want is to ask the test to be performed on a patient with S. bovis endocarditis, they could ask the question directly without telling us about the patient's moles...

Another gift of a question, the association of S.bovis endocarditis and colon cancer. By the way, it is funny that they give Chest Rx as a test to be performed..... are you telling me that a patient with fever and dysphea will have an echocardiogram before a simple chest x-ray? And on the other hand... why don't those who write the MIR ask shorter questions without so much back and forth? If what they want is to ask the test to be performed on a patient with S. bovis endocarditis, they could ask the question directly without telling us about the patient's moles...

A 68-year-old man is evaluated for fever, weight loss and dyspnea on exertion. The EP reveals a new aortic diastolic murmur and stigmata of peripheral embolisms. Echocardiography showed a 1 cm vegetation on the aortic valve and two blood cultures isolated penicillin-sensitive Streptococcus bovis. After starting treatment for endocarditis, which of the following examinations could help us in the diagnosis?

[Infectious thyroiditis as initial manifestation of embolizing endocarditis of the aortic valve].

A 47-year-old patient was admitted to hospital with fever (39.2 degrees C), weight loss and sore throat. The right thyroid area was painful on palpation. The erythrocyte sedimentation rate was 56/86 mm, white blood cell count 10,600/l, with shift to the left and toxic granulations. Blood culture grew Streptococcus mitis; the echocardiogram showed vegetations on the aortic valve. Therefore aortic valve endocatidits was suspected. Ultrasound examination of the thyroid gland showed an echo poor area with an enlarged thyroid artery; thyroid cytodiagnosis was unremarkable. The fever quickly subsided on administration of penicillin G (7.5 mill I.U. three times daily) and tobramycin (80 mg three times daily) for two weeks, followed by penicillin G in the same dosage for four more weeks. Vancomycin was then given for two weeks (1 g twice daily intravenously). The aortic valve vegetations were no longer seen three weeks after onset of treatment. Two months after discharge the thyroid and heart were normal on ultrasound examination. Bacterial thyroiditis was caused by embolisation to the thyroid artery from vegetations on the aortic valve in aortic valve endocarditis, probably due to carious teeth.

Human disease caused by Streptococcus alactolyticus: a case report of native valve infective endocarditis and review of the literature.

Streptococcus alactolyticus, a member of the Streptococcus bovis/Streptoccus equinus complex, is primarily hosted in the gastrointestinal tract of animals and rarely of humans, with only scarce reports relating to human disease. We herein present a case of subacute infective endocarditis (IE) caused by S. alactolyticus in a 64-year old male with pre-existing mitral prolapse. Despite a 10-month history of low-grade fever and weight loss, the diagnosis of IE was triggered by left quadrant abdominal pain which revealed splenic infarcts on computed tomography. A definitive diagnosis of IE was subsequently established by four consecutive blood cultures positive for S.alactolyticus plus demonstration of a vegetation on the mitral valve by trans-esophageal ultrasound. Further workup revealed multiple embolic phenomena including brain and spine. A dental abscess was identified as the most probable origin of the bacteraemia, while colonoscopy revealed no evidence of cancer. The patient recovered uneventfully with antibiotic treatment and underwent successful cardiac surgery post-discharge. Although rare, IE caused by S. alactolyticus may be severe and of obscure origin; oral cavity should not be overlooked as a possible origin. Attention should be given in patients with preexisting risk factors.

[A case of infective endocarditis due to Streptococcus agalactiae].

A 60 year-old woman, who was pointed out as having hyperglycemia, was admitted to our hospital, with a two-week history of fever. Blood sugar on admission was 424 mg/dl and blood cultures yielded Streptococcus agalactiae. Systolic and diastolic heart murmurs were heard. Echocardiography showed aortic regurgitation and vegetation on the aortic valve. Penicillin-G (4 million units every 4 hr) iv and streptomycin (1 g every 12 hr) im were started. Chemotherapy was continued for 48 days. After chemotherapy, aortic valve replacement was done. We reported a very rare infective endocarditis case due to Streptococcus agalactiae.

[A case of infective aortic valve endocarditis with splenic abscess].

A 47-year-old woman was admitted to our hospital with high fever, exertional dyspnea and left flank pain. Echocardiography revealed vegetations attached to the aortic valve and moderate aortic regurgitation. Streptococcus anginosus was identified by blood culture examination. Abdominal CT scan showed a low density area in the spleen. The diagnosis of infective aortic valve endocarditis with splenic abscess was obtained. The splenectomy and the aortic valve replacement were performed simultaneously after the treatment with antibiotics. The postoperative clinical course was uneventful. In the case of infective endocarditis with splenic abscess, the splenectomy concomitant with valve surgery should be performed for removing all of the infected tissues.

Image of the Month: Concomitant Tricuspid and Mitral Native Valve Infective Endocarditis.

A 33-year-old immunocompetent man was admitted to the authors' hospital with a one-month duration of fevers, chills, and non-productive coughs, and suddenonset weakness and ischemic pain of both lower extremities. Physical examination revealed crepitating rales heard over bilateral lung fields. On auscultation, a grade 2~3/6 systolic murmur was heard over the leftlower sternal border and apical area. Transthoracic echocardiography revealed a mobile mass on the tricuspid valve compatible with vegetation, in addition to concomitant mitral valve vegetation (Video 1). Thoracic computed tomography (CT) with contrast revealed cavitary lesions of the left and right lung fields (Fig. 1A and B). Abdominal CT showed a splenic infarction (Fig. 2A), a renal infarction (Fig. 2B), and thromboembolic occlusion of the distal aorta and right common iliac artery (Fig. 3). The patient denied any history of intravenous drug abuse. Blood cultures grew Streptococcus agalactiae (penicillin G-sensitive with a minimal inhibitory concentration ≤0.06 μg/ml). Video 1: Transthoracic echocardiography showing mobile masses on tricuspid and mitral valves compatible with vegetation on the apical four-chamber view.

Peripheral arterial embolism and pyrexia in a young patient without comorbidities.

Peripheral arteries embolism can be located in various organs. It can be caused by many medical conditions, diagnosis and treatment of which allows to prevent further complications. 26-year-old male patient was admitted to the Department of Internal Medicine, Hypertension and Vascular Diseases due to lasting over two months fatigue, recurrent pyrexia, weight loss and abdominal pain. Prior to that, he presented to physician several times. First time because of left foot pain with oedema and fever. USG revealed embolus in anterior tibial artery. Outpatient antibiotic, antithrombotic and anti-inflammatory treatment was given. The symptoms subsided, but appeared in other limb. After a while patient presented with pyrexia, fatigue, abdominal and lumbar region pain and melaena. CT showed infarction of spleen and left kidney. Once again outpatient treatment with amoxicillin with clavulanate was administered. Eventually, at admission to the clinic, infective endocarditis (IE) with dental origin was suspected. Echocardiography showed vegetation on bicuspid aortic valve, causing regurgitation. Blood culture was taken and empiric antimicrobial therapy with ampicillin, gentamicin and cloxacillin was administered. Blood culture was positive for Streptococcus sanguinis. Carious teeth were extracted, then the aortic valve replacement surgery was performed. Ampicillin was replaced with vancomycin, and gentamicin was continued. After the surgery, patient's condition improved. He was discharged on demand without completing antibiotic treatment, so he had follow-up appointment and IE prophylaxis recommended. Despite peripheral embolism is common manifestation of IE, this disease is relatively rare and not suspected in young people. The symptoms can be non-specific, what makes diagnosis challenging, as described in this case.

Aortic and tricuspid endocarditis due to <i>Streptococcus gallolyticus</i> in an immunocompetent patient with a normal heart.

Endocarditis due to <iStreptococcus gallolyticus</i, an agent previously included in the <iStreptococcus bovis</i denomination is a serious disease, often associated with lesions of the colon mucosa. Aortic valve is more often affected and tricuspid involvement is quite rare. We present a case of a 56-year-old man who was admitted with a 2-month history of fever. Echocardiogram revealed vegetations on the aortic and tricuspid valve and blood cultures grew <iS. gallolyticus</i. Thoracic X-ray and computed tomography were consistent with septic pulmonary embolism. Despite optimal antibiotic therapy he developed an ischemic stroke and acute aortic regurgitation, which led to emergent surgery. Colonoscopy found a benign adenoma which was excised, and the patient had a full recovery.

Comparison of clinical and echocardiographic characteristics of Streptococcus bovis endocarditis with that caused by other pathogens.

The aim of our study was to compare the clinical, echographic, and prognostic features of Streptococcus bovis (S. bovis) endocarditis with those caused by other streptococci and pathogens in a large sample of patients with definite endocarditis by Duke criteria, using transesophageal echocardiography. Two hundred six patients (149 men, mean age 57 +/- 15 years) with a diagnosis of infective endocarditis formed the study population. All patients underwent multiplane transesophageal echocardiography and blood cultures. Cerebral, thoracoabdominal computed tomographic scan was performed in almost all patients (95%). All patients with S. bovis endocarditis underwent colonoscopy. Incidence of S. bovis endocarditis in our sample was 19%. Patients with S. bovis endocarditis were older than other groups. Multiple valve involvement, native valves, and large vegetations (>10 mm) were more frequent in patients with S. bovis. There was a significantly higher occurrence of embolism in the S. bovis group. Splenic embolism and multiple embolisms were significantly more frequent in patients with S. bovis. Gastrointestinal lesions, anemia, and spondylitis were observed more frequently with S. bovis endocarditis. In addition to the requirement for gastrointestinal examination for S. bovis endocarditis, our study underlines the need for systematic screening for vertebral and splenic localizations, and suggests the use of early surgery to prevent the high risk of embolism in these patients.

[A case of Streptococcus gallolyticus subsp. gallolyticus infective endocarditis with colon adenoma].

An 80-year-old Japanese man had a fall presented with a 3-week history of right lumbago exacerbated by body movement as well as a 1-week history of anomalous behavior and appetite loss. He visited our hospital complaining of difficulty in standing up. He had a history of mitral prolapse due to an unknown rupture of the chordae tendineae 3 years earlier, which resulted in moderate mitral valve regurgitation and atrial fibrillation. Upon visiting the hospital, he had petechial hemorrhage and jaundice of the conjunctiva, a systolic murmur (Levine II/VI) at the apex and 4th interspace of the left sternal border, and a positive right straight leg raising test result. Moderate bilirubinemia and disseminated intravascular coagulation which were considered to have been produced secondarily were observed. Infective endocarditis was suspected, and 3 sets of blood culture were extracted. The patient was admitted on the same day. Blood cultures were positive for Streptococcus gallolyticus subsp. gallolyticus (6/6) on the following day. Transesophagela echocardiography was carried out on the same day, and vegetation with a diameter of 4mm was observed in the anterior mitral leaflet; the patient was subsequently diagnosed as having infective endocarditis. Colonic endoscopy was performed after hospitalization. Twelve colonic adenomata were found, and endoscopic mucosal resection was performed on one polyp. The bacterium found in the culture was classified as Streptococcus bovis type I, which causes infective endocarditis and bacteremia. Furthermore, this bacteria is a relatively rare causative organism of infective endocarditis. Tolerance to macrolide and tetracycline are reported in the literature. Moreover, the cell wall of this bacterium may have low pathogenicity as well as cause chronic inflammation in the large intestine mucous membrane, colonic polyps, and colorectal cancer. Several colonic adenomata and a partial shift to a malignant pathology were observed in this case. When this bacterium is detected, searching for a pathological change in the large intestine is believed to be indispensable.

[A case of brucellosis complicated with endocarditis, pyelonephritis, sacroileitis and thyroiditis].

Brucellosis which is a endemic in Turkey, is a systemic infection which can affect any organ or system in the body. Since signs and symptoms of brucellosis resemble many other diseases, misdiagnosis and related increase in morbidity rate, are common. In this report, a case of brucellosis complicated with endocarditis, pyelonephritis, sacroileitis and thyroiditis, was presented. The case was a 32-years-old female patient in whom the diagnosis of brucellosis was delayed by 12 months since it was not taken into consideration during the clinical follow-up of the patient in various clinical centers. The patient was admitted to our center with the complaints of fever, headache, back pain, night sweats, fatigue, loss of appetite, weight loss, dysuria and polyuria. The patient had a history of consumption of raw milk and dairy products. Positive Brucella tube agglutination test (1/1280) and isolation of Brucella spp. in blood cultures led to the diagnosis of brucellosis. Sacroileitis was diagnosed upon pain on right hip joint movements, pain and restriction at the same joint in FABER test. The detection of vegetation during echocardiography, cardiac murmur during physical examination and the determination of increased ESR and CRP levels led to the diagnosis of endocarditis. Abdominal ultrasonography and urinalysis results (hematuria, proteinuria and pyuria) revealed pyelonephritis and increased free T3 and T4, decreased TSH and positive anti-thyroid autoantibodies (anti-TG, anti-TPO) revealed thyroiditis. Treatment was started with combination of rifampisin (1 x 600 mg/day) and doxycycline (2 x 100 mg/day). After the diagnosis of endocarditis, trimethoprim-sulfamethoxazole (3 x 960 mg/day) and streptomycin (1 x 1 g/day) were added to the treatment. Valve replacement surgery was planned, however, the patient didn't accept surgical intervention and antimicrobial treatment continued with streptomycin for 21 days and other antibiotics for six months. The patient exhibited significant improvement after the medical treatment. Although sacroileitis is a frequent complication of brucellosis, endocarditis, thyroiditis and pyelonephritis are among the rare complications. In cases of brucellosis with multiorgan involvement including endocarditis, successful results may be achieved by aggressive antimicrobial treatment. In endemic areas, brucellosis should always be taken into consideration in patients with fever of unknown origin and multisystem involvement.

Streptococcus bovis endocarditis associated with colonic adenocarcinoma: report of a case.

Streptococcus bovis (S. bovis) endocarditis has been increasing over recent decades, especially among the senile population. A 74-year-old man presented with intermittent fever for two months. He had a past history of aortic dissection and underwent a Bentall operation one year before admission. A Janeway lesion was noted on his right hand and six blood cultures grew S. bovis. He was treated with penicillin-G, 3 microU intravenously, every six hours, and became afebrile three days later. A colonofiberoscopy was carried out despite the absence of any gastrointestinal symptoms, and a 2 x 2 cm mass was found at the cecum, with pathologic proof of adenocarcinoma. The patient died from a massive intracranial hemorrhage on the 23rd hospital day. Review of the literature revealed an intimate association between S. bovis bacteremia (or endocarditis) and underlying colonic neoplasia. Failure to be aware of the possible consequences of this combination may lead to detrimental patient prognosis. We strongly advise that every patient presenting with bacteremia or endocarditis due to this organism, even if they are free from gastrointestinal symptoms, should undergo a thorough lower gastrointestinal investigation to rule out colonic neoplasia.

Septic Emboli -- History and Physical -- Right-sided endocarditis vegetations embolize to the lungs causing septic pulmonary emboli present with fever, dyspnea, pleuritic chest pain, cough, and occasionally hemoptysis. Left-sided endocarditis may result in systemic emboli in different organs with different clinical presentations :

Also, there is a case outlining infective endocarditis caused by Streptococcus bovis with complications including systemic septic emboli and superior mesenteric artery mycotic aneurysm in a patient with colon diverticulitis who received successful treatment with surgical resection of the mycotic aneurysm, removal of the mycotic thrombi, and mitral valve replacement. [24]

Heyde's syndrome

Heyde's syndrome is now known to be gastrointestinal bleeding from angiodysplasic lesions due to acquired vWD-2A deficiency secondary to aortic stenosis, and the diagnosis is made by confirming the presence of those three things. Gastrointestinal bleeding may present as bloody vomit, dark, tarry stool from metabolized blood, or fresh blood in the stool. In a person presenting with these symptoms, endoscopy, gastroscopy, and/or colonoscopy should be performed to confirm the presence of angiodysplasia. Aortic stenosis can be diagnosed by auscultation for characteristic heart sounds, particularly a crescendo-decrescendo (i.e., 'ejection') murmur, followed by echocardiography to measure aortic valve area (see diagnosis of aortic stenosis). While Heyde's syndrome may exist alone with no other symptoms of aortic stenosis, the person could also present with evidence of heart failure, fainting, or chest pain. Finally, Heyde's syndrome can be confirmed using blood tests for vWD-2A, although

Endocarditis due to a penicillin-tolerant streptococcus bovis: microbiological findings and echocardiographic follow-up.

We are presenting a case of endocarditis due to a penicillin-tolerant Streptococcus bovis in a 65-year-old patient. The minimal bactericidal concentration of penicillin (40 mg/l) was more than 100-fold the minimal inhibitory concentration (0.08 mg/l). The MBC of penicillin was 0.31 mg/l in the presence of 1.25 mg/l gentamicin. Cross-sectional echocardiography revealed endocarditis of the anterior leaflet of the tricuspid valve and a vegetation on the aortic valve which appeared to be pedunculated and which prolapsed into the left ventricular outflow tract during diastole. During therapy, the pedunculated part of the vegetation disappeared without signs of embolization. After initial clinical improvement, the patient died of cerebral bleeding caused by a mycotic aneurysm of the left median cerebral artery. The patient's final outcome suggested an asymptomatic embolus. Cross-sectional echocardiography was distinctly superior to M-mode echocardiography in estimating changes in the size and shape of the valve vegetation. The results of the post-mortem examination of the aortic and tricuspid valves corresponded to the echocardiographic findings.

Thirteen square centimetre mass causing syncope in a patient with device related infective endocarditis.

A 68-year-old man presented with anorexia, weight loss and severe asthenia starting 2 months before and fever lasting over 2 weeks. Analytical study revealed increased C reactive protein and sedimentation velocity. While thoracic x-ray and urinalysis were unremarkable, blood cultures were consistently positive for Enterococcus faecalis. A thoracic echocardiogram revealed a very large vegetation adherent to the ventricular electrocatheter of the patient's pacemaker, so parenteral antibiotics were started. During his stay at the internal medicine ward, patient suffered three syncopal episodes and maintained intermittent fever. A transesophageal ECG performed at a tertiary centre on the 14th day unmasked a 9-12 cm(2) organised mass, ovoid and with regular borders, adherent to the ventricular electrocatheter at right atrium level and protruding to the ventricle at systole. Patient was referred for cardiothoracic surgery and a 13 cm(2) mass was removed alongside the ventricular electrocatheter. Two weeks following surgery, patient remains stable and asymptomatic.

[Endocarditis caused by Cardiobacterium hominis].

The incidence of endocarditis due to Cardiobacterium hominis is probably underestimated because clinical presentations vary greatly and culture of this Gram negative germ is difficult. A 48-year-old man with a past history of post-streptococcic aortic regurgitation was hospitalized twice within 1 week for fever (38 degrees C) and junctional tachycardia which responded to amiodarone. Subsequently, infero-apical necrosis was documented. Based on the result of the laboratory tests, coronary embolism was suspected although 12 blood cultures were negative. The patient recovered well with a standard antibiotic treatment. Fifteen days later, the blood cultures revealed Cardiobacterium hominis. Antibiotic therapy was adapted and aortic valve replacement was programmed. Two months later the patient died from uncontrollable left heart failure. A 63-year-old man who had had mitral valve replacement 10 years earlier for Streptococcus mitis endocarditis was hospitalized for fever (38 degrees C) and a painful left calf. Phlebocavography eliminated deep vein thrombosis and a complete cardiac work-up was inconclusive. Endocarditis was suspected although blood cultures were negative. The patient was given oral penicillin and discharged after one week. Three months later, the patient was again febrile (38 degrees C) and suffered a cerebral vascular event. Fourteen days after blood sampling, cultures revealed Cardiobacterium hominis. The patient's haemodynamic status worsened and valve replacement with atrioplasty was performed. Outcome after 4 years follow-up has been favourable. Endocarditis due to Cardiobacterium hominis, a saprophitic germ of the upper airway and the female genital tract, has been reported in 64 cases in the literature. The clinical picture is often limited to fever and a heart murmur and laboratory tests show an accelerated erythrocyte sedimentation rate and hyperleukocytosis. Inflammatory type anaemia is often found due to the latency of the endocarditis. Complications are frequent and can be fatal due to massive pulmonary emboli, cerebral vascular events or irreversible heart failure. C. hominis is sensitive to amoxycillin and netilmicin. Surgical treatment of the valvulopathy is indicated.

[A 34-year-old male presented with fatigue, weight loss, double vision and extra heart sounds].

The diagnosis of culture-negative endocarditis, defined as an active infection of the endocardium in the absence of positive blood cultures, is challenging. A 34-year-old male presented with persistent fever and negative blood cultures. The echocardiogram showed a bicuspid aortic valve, severe aortic regurgitation, an abscess cavity in the aortic root, and a mass on the anterior leaflet of the mitral valve. The abscess cavity could be visualised only with transoesophageal echocardiography. The diagnosis of infective endocarditis could be established clinically with the Duke criteria. The echocardiographic findings were confirmed at surgery. Cultures of the excised tissue were negative, but histology showed strong evidence of infection. The Duke criteria can be useful in the assessment of a clinical diagnosis in subjects with endocarditis and negative blood cultures. Transoesophageal echocardiography is especially important in this setting.

Pylephlebitis: portal vein thrombosis due to intrabdominal infection such as ascending cholangitis or diverticulitis usually presents with non-specific symptomatology of fever and abdominal pain and diagnosed with CT abdomen with contrast and abdominal ultrasound, and the etiology is often polymicrobial. Pyogenic liver abscesses could experience complications with metastatic infections, including septic embolism. [25]

Tricuspid Valve Endocarditis -- History and Physical

History and physical exam are essential towards making an adequate diagnosis in cases of TVIE. Establishing diagnosis can be more difficult in these cases because presentation can often be subacute or present with absence of typical IE features. Peripheral phenomenon such as splinter hemorrhages is less common, as is a cardiac murmur. However, clinicians must always be aware of potential complications of this disease process that are manifested by the various embolic phenomenon. Characteristics, which should lead clinicians to consider TVIE, include: Fever Chills Anorexia Weight loss Fatigue Malaise Arthralgia Dyspnea on exertion A cough Pleuritic pain Abdominal Pain

Urgent splenectomy in the course of prosthetic valve endocarditis.

We present a case of a 51-year-old male patient hospitalized due to acute coronary syndrome requiring stent implantation to the left main stem. Double antiplatelet therapy was commenced. After 2-3 days, the patient presented with high fever, dyspnea on exertion, pain in the chest, myalgia, and general weakness. Transthoracic (TTE) and transesophageal (TEE) echocardiography revealed abnormal, turbulent flow across the aortic prosthesis, which was probably caused by the presence of a pathological smooth and mobile structure (10 × 9 × 5 mm) in front of the aortic annulus. Blood cultures were positive and staphylococcal prosthetic valve endocarditis (PVE) was diagnosed. Despite antibiotic treatment, the patient's condition deteriorated, and he was referred for prosthesis reimplantation. After being transferred to the Cardiac Surgery Clinic, he presented with nausea, vomiting, and abdominal pain. The results of imaging examinations suggested spleen hematoma. The patient underwent an urgent splenectomy. Histopathological examination revealed a spleen infarction consequent to an embolic event and subscapular hematoma. On the 10(th) day after the laparotomy, cardiac surgery was performed. No large vegetations were found on the aortic prosthesis. The mechanical valve, implanted 20 years earlier, was functioning properly; it was intact and well healed. Several fragments of a thrombus and fibrous tissue, resembling a pannus and covered with minor calcifications, were removed from the ventricular surface of the discs. A decision was reached to leave the aortic prosthesis in situ. The valvular material culture revealed the presence of Streptococcus anginosus, and the antibiotic scheme was modified. The postoperative period was uneventful.

Echocardiographic demonstration of Escherichia coli endocarditis restricted to the pulmonary valve.

A 25 year old man with no history of heart disease presented with sweats and rigors. Echocardiography showed a large vegetation on the pulmonary valve and blood cultures grew Escherichia coli. Because of recurrent pulmonary emboli a large vegetation on the anterior leaflet of the pulmonary valve was excised. He recovered after a full course of antibiotics.

[Case report: infective endocarditis caused by Streptococcus agalactiae].

A 42-year-old male was admitted to our hospital because of high grade fever on October 6, 1992. He had no history of cardiac and underlying disease. For the past 10 days, he had complained of high grade fever and noticed arthralgia on his left shoulder. Physical examination on admission revealed that there was a body temperature of 39.0 degrees C and tenderness in the left shoulder. There were no abnormal findings for the chest or abdomen. On the second hospital day, he developed a diastolic murmur which had not been present on admission. And blood culture was positive for Streptococcus agalactiae. Ultrasonic-cardiogram indicated the presence of vegetation. He was diagnosed as infective endocarditis and treated with PCG 20 million units/day, IPM/CS 2 g/day and ISP 400 mg/day. But he was not responding to the chemotherapy. Aortic valve replacement was done on 22nd, October. Valve surgery succeeded and he became well after that time. Endocarditis caused by S. agalactiae is extremely rare, and is an important condition which carries a high mortality. Only seven cases of S. agalactiae endocarditis have been reported in Japan. It is difficult to treat these cases with antibiotic therapy alone. Therefore, we suggest that early surgery should be considered in infective endocarditis caused by S. agalactiae.

Iatrogenic aortic insufficiency following mitral valve replacement: case report and review of the literature.

We report a 28-year-old white female who suffered significant aortic insufficiency (AI) following mitral valve (MV) replacement for endocarditis. The patient had history of rheumatoid arthritis and presented to our emergency department with a 3-month history of dyspnea, orthopnea, fevers and weight loss, worsening over 2 weeks, for which she took intermittent acetaminophen. On admission, vital signs revealed blood pressure of 99/70 mm Hg, heart rate of 120 beats/minute, and temperature of 98.8 °F; her weight was 100 lbs. Physical exam revealed a thin and pale female. Cardiac auscultation revealed regular tachycardic rhythm with a third heart sound, and a short early systolic murmur at the left lower sternal border without radiation. Lungs revealed right lower lobe rhonchi. Initial pertinent laboratory evaluation revealed hemoglobin 9.6 g/dL and white blood cell count 17,500/μL. Renal function was normal, and hepatic enzymes were mildly elevated. Chest radiogram revealed right lower lobe infiltrate. Blood cultures revealed Enterococcus faecalis. Two-dimensional echocardiogram revealed large multilobed vegetation attached to the anterior MV leaflet with severe mitral regurgitation (MR), otherwise normal left ventricular systolic function. She was started on appropriate antibiotics and underwent MV replacement with 25-mm On-X prosthesis. She was noted post-operatively to have prominent systolic and diastolic murmurs. Repeat echocardiogram revealed normal mitral prosthesis function, with new moderately severe AI. Transesophageal echocardiogram revealed AI originating from a tethered non-coronary cusp, due to a suture preventing proper cusp mobility. The patient declined further surgery. She recovered slowly and was discharged to inpatient rehabilitation 4 weeks later. This case highlights the importance of vigilance to this potential serious complication of valve surgery with regard to diagnosis and treatment to prevent long-term adverse consequences.

Pulmonary embolism and fever: an indication for urgent echocardiography not reported in clinical guidelines?

We report the case of a 39-year-old woman who developed worsening dyspnea and abdominal pain 4 days after subtotal gastroresection. She underwent thoracic computed tomography scan and lung scintigraphy and was diagnosed with pulmonary embolism. Despite the fact that she was feverish, she was treated by the insertion of a vena cava filter and transferred to our Emergency Department. Twelve hours later, a beta-haemolytic Streptococcus agalactiae was reported to be growing in both bottles of blood cultures that had been taken. The patient underwent transthoracic two- and three-dimensional echocardiography, which showed a large pulmonary valve vegetation prolapsing into the main and right pulmonary artery during systole.

Native triple-valve endocarditis caused by penicillin-resistant Streptococcus sanguis.

A 26-year-old man with known but untreated ventricular septal defect was admitted to the emergency ward with abdominal pain, fever and weight loss. Transthoracic echocardiography showed multiple vegetations on the anterior mitral leaflet, a mobile vegetation on the surface of the aortic noncoronary cusp and another on the tricuspid valve. His blood cultures grew Streptococcus sanguis with a penicillin minimum inhibitory concentration of 3 microg/ml. Physical examination, echocardiography, blood cultures, minimal inhibitory concentration detection. Multivalvular infective endocarditis caused by S. sanguis with a high penicillin resistance. A combination of intravenous vancomycin and gentamicin, followed by early surgery.

[Multivalvular infective endocarditis with Enterococcus faecalis].

Infective endocarditis (IE) is a relatively rare disease that can take part of sepsis and may be a diagnostic and therapeutic challenge. Polyvalvular location of El is rare. We present a patient of 60 years diagnosed with plurivalvular infective endocarditis by Enterococcus faecalis with septic complications, visceral, dragged, hospitalized for a psychiatric pathology, who raised the problems of diagnosis and treatment, without being able to make assessments on the entrance gate. For help in diagnosing this case proved that cardiac ultrasound studies recommended that a screening method for patients with bacteremia, but the presence of vegetation is the major criterion for diagnosis of EI. Blood cultures and echocardiography led to the diagnosis of infectious endocarditis. Also abdominal ultrasound confirmed the clinical suggestion of gravity, the septic multiviscerale release by splenic abscess image objectivity. Under vigorous antibiotic treatment and symptomatic treatment in combination evolution was to worse, death occurring after 15 days of hospitalization, toxic-septic shock being irreversible. Our case is particular by locating polyvalvular vegetation, the germ involved, the court altered the immunological and disseminator septic complications that have limited therapeutic options and made predictable fatal diagnosis.

HACEK-induced endocarditis.

A 61-year-old patient with diabetes had a bio-prosthetic aortic valve replacement 3 years before admission. He complained of lethargy, night sweats, decreased appetite and erratic blood glucose with no weight loss. He had splinter haemorrhage and a systolic ejection murmur at the aortic area. Chest and abdominal examination revealed no abnormality. The erythrocyte sedimentation rate and C reactive protein were raised. He had several sets of blood cultures and he was started on empirical vancomycin, rifampicin and gentamicin. Transthoracic echocardiography showed vegetation on the base of the anterior mitral leaflet, which was confirmed by a trans-oesophageal echocardiography. Blood culture was positive for Haemophilus aphrophilus, and he was started on ceftriaxone for 6 weeks instead of vancomycin and rifampicin and continued gentamicin for 2 weeks. Follow-up echocardiography showed no evidence of vegetations. The patient recovered completely and he was discharged home.

[Value of echocardiography in detection of vegetation and their clinical significance].

The aim of the study was to assess usefulness of echocardiography in bacterial vegetations detection as well as their clinical value as the indicator for surgical treatment. 44 patients aged 16-65 (mean 37.6) with infective mitral and aortic valve endocarditis underwent the study. Authors assessed clinical state taking into consideration blood culture tests as well as M-mode and parasternal and apical projections two-dimensional echocardiographic examinations. Data were compared with intraoperative or pathomorphological findings to estimate specificity and sensitivity of echocardiography in bacterial vegetation detection. Vegetations were pathomorphologically or intraoperatively stated in 21 patients (48%). M-mode echocardiography revealed changes in 16 patients, and two-dimensional one in the next 3. In the group of 23 patients without vegetations, concordance between intraoperative findings and echocardiographic results was stated in 19 subjects. Therefore, sensitivity and specificity of two-dimensional echocardiography were respectively 91% and 83%. Vegetations stated in two-dimensional echocardiographic examination had an unfavourable prognosis. Embolic complications were observed in 14, and myocardial infarction in 7 of 21 patients with bacterial vegetations. Authors thought it advisable to early operate on such patients. Whereas in patients without vegetations embolic complications were stated only in 3, and myocardial infarction in 1 patient. Therefore two-dimensional echocardiography making bacterial vegetations detection possible in patients with infective valve endocarditis allows to identify patients with higher risk of thromboembolic complication or death.

Infective endocarditis caused by Streptococcus acidominimus.

A case of infective endocarditis caused by Streptococcus acidominimus is reported. An 81-year-old Caucasian man underwent an elective transcatheter aortic valve implantation due to his severe aortic valve stenosis. He presented to the hospital 3 weeks later with a 1-week history of fever (39ºC) that did not resolve following a 3-day course of azithromycin and a 5-day course of ciprofloxacin. Three sets of blood sample cultures were taken. Empirical antimicrobial treatment was initiated to target gram-positive and gram-negative microorganisms and consisted of vancomycin 1 g intravenous (i.v.) every 12 hours and imipenem-cilastatin 500 mg i.v. every 6 hours. After 48 hours, the blood culture was positive for S. acidominimus. The strain was sensitive to ampicillin, cephalosporins, tetracycline, and vancomycin. It was resistant to penicillin, macrolides, trimethoprim-sulfamethoxazole, and fosfomycin. Transesophageal echocardiography showed a small mobile vegetation attached to the anterior mitral valve leaflet, along with mild mitral regurgitation. The patient was diagnosed with native mitral valve infective endocarditis, and imipenem-cilastatin was discontinued. The patient showed clinical and laboratory improvement during his 2-week hospitalization. A peripherally inserted central catheter was put in place, and the patient was discharged on i.v. vancomycin to complete a total of 6 weeks treatment, after which the infection resolved. An 81-year-old man diagnosed with mitral valve endocarditis caused by S. acidominimus was successfully treated with vancomycin.

[A case of isolated pulmonary valve infective endocarditis in a 78-year-old woman].

A 78-year-old woman was admitted to our hospital with lumbago. Her activities of daily living had previously been completely independent. However, she developed temporary chills in January 2009, that improved without treatment, but recurred on February 7, 2009 in association with left lumbago and loss of appetite. She was then referred to our hospital with a disturbance of consciousness and high fever on February 14. A blood test performed on admission revealed an elevated inflammatory response, coagulation disorder and low platelet count, and abdominal computed tomography demonstrated findings suggestive of pyogenic spondylitis. The patient was therefore admitted and treated with antibiotic therapy; however, she died on day 8 due to complications of disseminated intravascular coagulation. An autopsy showed isolated pulmonary valve endocarditis. The patient's history was later found to include regular dental treatment, and the same Streptococcus group G was detected in cultures of the sputum, blood and vegetation. It is important to interview patients regarding their history of dental treatment, particularly elderly individuals with fever of unknown origin.

Prosthetic valve endocarditis caused by Staphylococcus capitis: report of 4 cases.

Although Staphylococcus capitis is considered to be a rare causative organism for prosthetic valve endocarditis, we report 4 such cases that were encountered at our hospital over the past 2 years. Case 1 was a 79-year-old woman who underwent aortic valve replacement with a bioprosthetic valve and presented with fever 24 days later. Transesophageal echocardiography revealed an annular abscess in the aorto-mitral continuity and mild perivalvular regurgitation. We performed emergency surgery 5 days after the diagnosis of prosthetic valve endocarditis was made. Case 2 was a 79-year-old woman presenting with fever 40 days after aortic valve replacement with a bioprosthesis. Transesophageal echocardiography showed vegetation on the valve, and she underwent urgent surgery 2 days after prosthetic valve endocarditis was diagnosed. In case 3, a 76-year-old man presented with fever 53 days after aortic valve replacement with a bioprosthesis. Vegetation on the prosthetic leaflet could be seen by transesophageal echocardiography. He underwent emergency surgery 2 days after the diagnosis of prosthetic valve endocarditis was made. Case 4 was a 68-year-old woman who collapsed at her home 106 days after aortic and mitral valve replacement with bioprosthetic valves. Percutaneous cardiopulmonary support was started immediately after massive mitral regurgitation due to prosthetic valve detachment was revealed by transesophageal echocardiography. She was transferred to our hospital by helicopter and received surgery immediately on arrival. In all cases, we re-implanted another bioprosthesis after removal of the infected valve and annular debridement. All patients recovered without severe complications after 2 months of antibiotic treatment, and none experienced re-infection during 163 to 630 days of observation. Since the time interval between diagnosis of prosthetic valve endocarditis and valve re-replacement ranged from 0 to 5 days, early surgical removal of the infected prosthesis and an appropriate course of antibiotics were attributed to good clinical outcomes in our cases.

[Infective endocarditis--a review of 21 cases in last 10 years].

Twenty one cases of infective endocarditis in last 10 years were re-evaluated by Duke's criteria. Fourteen strains of Streptococcus viridans, 4 of Enterococcus faecalis, 1 of Haemophilus parainfluenzae were isolated from blood culture. As to the minimum inhibitory concentration (MIC) of 8 strains of Streptococci, imipenem revealed the lowest MIC value, following penicillin G, ceftriaxon not equal to ampicillin, vancomycin and gentamicin. One strain of them was penicillin-resistant (0.8 micrograms/ml). Serum inhibitory test (SIT) and serum bactericidal test (SBT) were undergone for 6 cases. The assay was efficient to determine penicillin-tolerance of causative bacterium. Vegetations were observed in 18 cases of 21 by the echo-cardiography, especially transesophageal echocardiography had better diagnostic sensitivity compared to transthoracic echocardiography. However, it took 12 weeks from the first febrile episode to achieve definite diagnosis. One of reasons to take such a long time to reach diagnosis was that major causative organism was S. sanguis, whose inflammatory reaction to the host was said to be strikingly weak.


Very nice clinical question from MEN. Pancreatic neuroendocrine tumor + pituitary adenoma (prolactinoma) + hyperparathyroidism (renoureteral colic in young people): MEN 1. Medium difficulty because you have to know the MEN triad and recognize the different tumors.

Very nice clinical question from MEN. Pancreatic neuroendocrine tumor + pituitary adenoma (prolactinoma) + hyperparathyroidism (renoureteral colic in young people): [HIDDEN]. Medium difficulty because you have to know the MEN triad and recognize the different tumors.

A 45-year-old woman comes to the clinic referred from surgery with the diagnosis of a neuroendocrine tumor diagnosed after partial pancreatectomy for a 2-cm tumor in the tail of the pancreas. The tumor had been detected by chance in an abdominal CT scan requested to complete the study of a simple hepatic cyst. On questioning the patient, the history of irregular menstruation, amenorrhea for the last 6 months, and repeated renal colic since she was 20 years old, for which she has required lithotripsy on several occasions, stand out. She also has a family history of renoureteral colic. What is her suspected diagnosis?

Multiple endocrine neoplasia type 1 or Wermer's syndrome.

Multiple endocrine neoplasia type 2 A or Sipple's syndrome.

A primary hepatic gastrinoma accompanied by hyperplasia of multi-nodular Brunner's glands.

Primary hepatic gastrinoma causing severe ulcerogenic syndrome is extremely rare. Herein, we report a case of primary hepatic gastrinoma accompanied by hyperplasia of multi-nodular Brunner's glands in a patient who instead, preoperatively, was suspected of having multiple duodenal gastrinomas and hepatic metastasis. A 57-year-old woman consulted a clinic complaining of melena, intermittent abdominal pain, diarrhea, and vomiting which had persisted for about 3 years. Six months before her presentation, she underwent segmental resection of the jejunum for acute peritonitis due to the spontaneous jejunal perforation. A blood test revealed that her serum immunoreactive gastrin (IRG) level was 12,037 pg/mL. Subsequently, she was transferred to our hospital. On computed tomography (CT), a hypervascular tumor of 23 mm in the segment 5 (S5) region of the liver was visualized. A selective arterial secretagogue injection test (SASI test) was performed twice. The first SASI test revealed that the hepatic tumor was a gastrinoma, and there was no gastrinoma in the duodeno-pancreatic region. Additionally, somatostatin receptor scintigraphy only visualized the tumor in the liver. However, the second SASI test, which was performed during the administration of a proton pump inhibitor and a somatostatin analog (octreotide acetate), revealed that there may have been gastrinomas existing not only in the liver but also in the upper part of the duodenum or the head of the pancreas. Duodenal endoscopy revealed multiple submucosal tumors in the first and the second portion of the duodenum, although a pathological examination of biopsied specimens obtained from the duodenal lesions was negative for malignant cells. Multiple endocrine neoplasia type 1 (MEN1) was excluded from her family history, and serum levels of both intact parathyroid hormone (iPTH) and calcium were within normal ranges. An anterior segmentectomy of the liver and pancreas-preserving total duodenectomy were performed on September 9, 2013. Postoperatively, her serum immunoreactive gastrin level decreased to less than 50 pg/mL. Pathological study of the resected specimens revealed a gastrinoma in the liver, but no gastrinoma in the duodenum. Interestingly, the duodenal submucosal tumor-like lesions were hyperplastic Brunner's glands. Postoperatively, she has been well without recurrence of hypergastrinemia for 4 years. We report a case of primary hepatic gastrinoma in a patient who has been cured for 4 years postoperatively. The diagnosis was somewhat difficult due to the coexisting, multiple hyperplastic Brunner's glands of the duodenum mimicking the submucosal neuroendocrine tumors, which might have developed due to long-term hypergastrinemia.

[Multiple Endocrine Neoplasia I (Wermers Syndrome), Forms of Clinical Manifestation, 5 Case Studies].

Multiple Endocrine Neoplasia (MEN) is a condition in which several endocrine organs of an individual are affected by adenoma, hyperplasia and less often carcinoma, either simultaneously or at different stages of life. Two existing syndromes, MEN1 and MEN2 (2A, 2B), in literature is also mentioned MEN4, are associated also with other non-endocrine disorders. MEN1 (Wermer syndrome) affects the pituitary, parathyroid, and pancreatic area. 95 % of patients show very early manifestation of hyperparathyroidism, often before 40 years of age. Multiple adenomas gradually involve all four parathyroid glands. The first clinical sign of MEN1 includes recurrent nephrolithiasis. The second most frequent manifestation of MEN1 is pancreatic area (pancreas, stomach and duodenum), again multiple malignancies of varying degree which can metastasize. Most often gastrinomas and insulinomas are involved. Pituitary adenomas occur in about one third of MEN1 patients and tend to be larger and less responsive to treatment. Tumors appearing most often are prolactinomas, tumors producing growth hormone, or afunctional adenomas. The other endocrine tumors include carcinoids and adrenal lesions. In the last year we have registered four MEN1 syndrome patients in our center and one patient has been already followed since 2008. In four out of five patients, nephrolithiasis after 30 years of age was the first clinical symptom, but only one of theses cases resulted in MEN1 diagnosis. In all patients, the clinical symptoms intensified and the diagnosis was established between 36 and 40 years of age. A crutial factor is a cooperation with the urology examination of kidney stones formation in young individuals with nephrolithiasis in order to reveal the potential cases of MEN1 syndrome very early on. Consider the MEN1 genetic diagnostics if recurrent primary hyperparathyroidism or recurrent gastroduodenal ulcer disease appear in patients under 40 years of age.Key words: carcinoid - gastrinoma - hyperparathyroidism - insulinoma - MEN1 - multiple endocrine neoplasia - nefrolithiasis - neuroendocrine tumor - pancreatic area - pituitary gland.

[Diagnosis of pancreatic neuroendocrine tumor led to diagnosis of multiple endocrine neoplasia type 1:a report of two cases].

Two cases of multiple endocrine neoplasia type 1 are reported. In both cases, computed tomography (CT) showed hypervascular lesions of the pancreas. Endoscopic ultrasound showed multiple lesions in the pancreas, and each case was diagnosed as pancreatic neuroendocrine tumor by EUS-FNA. In addition to a pancreatic neuroendocrine tumor, case 1 had hyperparathyroidism and case 2 had a history of parathyroid tumor. Furthermore, case 1 had a family history of pancreatic tumor and case 2 had a family history of pancreatic tumor and parathyroid resection. From these indications, multiple endocrine neoplasia type 1 was diagnosed by genetic testing. As demonstrated in these two cases, it is important to consider multiple endocrine neoplasia type 1 when diagnosing pancreatic neuroendocrine tumor.

[Multiple Endocrine Neoplasia Type 1(MEN1)Presenting with Hypoglycemic Attacks - A Case Report].

A woman in her 60s visited our hospital because of frequent hypoglycemia and episodes of unconsciousness over the last 6 years. A 4 cm tumor was detected on the pancreatic tail using abdominal computed tomography and ultrasonography. An insulinoma was strongly suspected from the results of the fasting test and glucagon load test, and a distal pancreatectomy with splenectomy was performed. Pathological examination indicated an insulinoma and neuroendocrine tumor(NET)G2 based on the WHO 2010 classification. The patient's blood sugar and insulin levels returned to normal, and hypoglycemic attacks disappeared postoperatively. Six months later, a total parathyroidectomy was performed because of primary hyperparathyroidism with hypertrophy of the parathyroid glands. Furthermore, pituitary swellingwas also detected usinghead MRI. However, the patient has been under observation because the tumor was non-functional without any associated symptoms. Thus, we diagnosed the patient with multiple endocrine neoplasia type 1(MEN1). In patients with pancreatic NET, it is necessary to consider the possibility of MEN1.

Multiple endocrine neoplasia type 2

Multiple endocrine neoplasia type 2 (also known as "Pheochromocytoma and amyloid producing medullary thyroid carcinoma", "PTC syndrome," and "Sipple syndrome") is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant (cancer). They generally occur in endocrine organs (e.g. thyroid, parathyroid, and adrenals), but may also occur in endocrine tissues of organs not classically thought of as endocrine. MEN2 is a sub-type of MEN (multiple endocrine neoplasia) and itself has sub-types, as discussed below. Signs and symptoms MEN2 can present with a sign or symptom related to a tumor or, in the case of multiple endocrine neoplasia type 2b, with characteristic musculoskeletal and/or lip and/or gastrointestinal findings. Medullary thyroid carcinoma (MTC) represents the most frequent initial diagnosis. Occasionally pheochromocytoma or primary hyperparathyroidism may be the initial diagnosis.

[Pancreatic endocrine tumors].

Incidence of the endocrine tumors of the pancreas is about 4 to 10/1.000.000 peoples. We present 10 cases of endocrine pancreatic tumors which were operated in the First Surgical Clinic Iaşi in the last 20 years (1984-2003); these cases represent about 2.21% from all the pancreatic tumors (454 cases). It was 4 insulinoma, 2 gastrinoma, 2 gastrinoma associated with other endocrine neoplasia (Wermer syndrome) and 2 non-functioning endocrine pancreatic tumors. Female/men ratio was 9/1 and median age was about 41.9 yo (27-67 yo). In the four cases of insulinoma (all females) the diagnosis was delayed by two to five years due to misinterpretation of neurological symptoms generated by hypoglycemia. The diagnosis of insulinoma was based on Whipple triad, high plasma insulin levels associated with low plasma glucose levels, as well as the symptomatic relief after intravenous glucose injection. The surgical option was based on biological data, ultrasonography, computed tomography and arteriography. In two cases the localization of the insulinoma was established only by intraoperative ultrasonography. All tumors were localized in the tail of pancreas. In three cases we decided for a distal pancreatic resection with splenectomy and in one case for spleen preserving left pancreatectomy. Postoperative course was uneventful and all the symptoms disappeared. The diagnosis was confirmed on pathological examination in all cases. We also present two cases of gastrinoma with multiple ulcers and multiple surgical interventions for haemorrhage and perforation with peritonitis. Both patients died and diagnosis of pancreatic endocrine tumors was post-mortem. The two patients with Wermer syndrome also had ulcers complicated with haemorrhage and peritonitis and parathyroid adenoma. One case also had ante-hypophyseal and pituitary adenoma and the other had thyroid colloid hypertrophy. We performed left pancreatectomy with spleen preservation in one case and enucleation associated with total gastrectomy in the second case. The two cases of non-functioning pancreatic endocrine tumors had a non-specific symptoms. Diagnostic was established by abdominal ultrasound exam. We performed spleno-pancreatectomy in one case and pancreatectomy with spleen preservation in the other patient. Postoperative course was un-eventful.

[An unusual case of multiple endocrine neoplasia].

The patient A.M., woman, presented Multiple Endocrine Neoplasia, associating hyperparathyroidism, an adrenal tumor and pancreatic tumor; one can observe that the disease had features of Multiple Endocrine Neoplasia type-1 (pancreatic tumor), as well as Multiple Endocrine Neoplasia type-2 (MEN-2, pheochromocytoma), while the hyperparathyroidism is common for both two types of the syndrome. The development of the disease is extended over approximate forty years of life and finally led to death. The first symptoms appeared during pregnancy, at age 26, when the severe hyperparathyroidism determined bone mass acute loose, with decrease in height by affecting columnary vertebrae, severe bone pain due to bone resorption and soon after symptoms of renal stone disease. The patient suffered two surgical interventions for renal lithiasis. The biliary symptoms required also the surgical removal of the gall bladder, putting the diagnosis of active metabolic stone disease. At age 56, was established the diagnosis of carcinoma of the adrenal cortex, which was solved with surgical therapy. At age 66, digestive symptoms suggested the presence of a carcinoid tumor. Abdominal ultrasonography revealed a well-lined pancreatic tumor of 2-3 centimeters in diameter, probably adenoma. The malignant evolution of this tumor was rapid, leading to death in less than two years. The constant refuse of other investigations, by the patient, made us incapable to determine the type of secretion of the pancreatic tumor; we rather suspected a VIPoma, because of the watery diarrhea and severe weight loss. The most difficult to treat was anyway the hyperparathyroidism and its complications.

Insulinoma

Prognosis Most patients with benign insulinomas can be cured with surgery. Persistent or recurrent hypoglycemia after surgery tends to occur in patients with multiple tumors. About 2% of patients develop diabetes mellitus after their surgery. Incidence Insulinomas are rare neuroendocrine tumors with an incidence estimated at one to four new cases per million persons per year. Insulinoma is one of the most common types of tumors arising from the islets of Langerhans cells (pancreatic endocrine tumors). Estimates of malignancy (metastases) range from 5 to 30%. Over 99% of insulinomas originate in the pancreas, with rare cases from ectopic pancreatic tissue. About 5% of cases are associated with tumors of the parathyroid glands and the pituitary (multiple endocrine neoplasia type 1) and are more likely to be multiple and malignant. Most insulinomas are small, less than 2 cm.

[A Case of Von Hippel-Lindau Disease with Nonfunctioning Pancreatic Neuroendocrine Tumors Treated by Duodenum-Preserving Resection of the Head of the Pancreas and Spleen-Preserving Resection of the Tail of the Pancreas].

A 26-year-old woman presented to our department with a diagnosis of multiple nonfunctioning pancreatic neuroendocrine tumors. She had a family history of pheochromocytoma and a medical history of bilateral adrenalectomy for pheochromocytoma at the age of 25 years. During follow-up treatment for adrenal insufficiency after the surgery, highly enhanced tumors in the pancreas were detected on contrast-enhanced CT. Other examinations found that the patient did not satisfy the clinical criteria for von Hippel-Lindau (VHL) disease. Considering her age and risk of developing multiple heterotopic and heterochronous tumors, we performed a duodenum-preserving resection of the head of the pancreas and spleen-preserving resection of the tail of the pancreas with informed consent. The histopathological findings revealed that all of the tumors were NET G1. She underwent genetic testing postoperatively and was diagnosed with VHL disease. This diagnosis meant that we were able to create an optimal treatment plan for the patient. If a tumor predisposition syndrome is suspected, VHL disease should be borne in mind and genetic testing after genetic counseling should be duly considered.

Multiple endocrine neoplasia type 1

The two major forms of multiple endocrine neoplasia are called type 1 and type 2. These two types are often confused because of their similar names. However, type 1 and type 2 are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms. These disorders greatly increase the risk of developing multiple cancerous and noncancerous tumors in glands such as the parathyroid, pituitary, and pancreas. Multiple endocrine neoplasia occurs when tumors are found in at least two of the three main endocrine glands (parathyroid, pituitary, and pancreatico-duodenum). Tumors can also develop in organs and tissues other than endocrine glands. If the tumors become cancerous, some cases can be life-threatening. The disorder affects 1 in 30,000 people.

Late recurrence after surgical resection of a pancreatic tumor in von Hippel-Lindau disease.

Patients with von Hippel-Lindau syndrome, a dominantly inherited familial cancer syndrome, develop a variety of tumors in different organ systems which make the clinical management of these patients complex. The long clinical history of a 45-year-old woman started at 22 years of age when she had surgery for a right adrenal pheochromocytoma. Two years later, a pancreaticoduodenectomy was performed to remove a pancreatic mass which turned out to be a pancreatic neuroendocrine tumor. After a long period of relative wellness, 21 years after the surgical resection of her primary pancreatic neuroendocrine tumor, abdominal lymph node metastases of pancreatic neuroendocrine origin occurred. In fact, three abdominal nodules were removed by laparoscopic surgery, and the histological examination showed well-differentiated neuroendocrine tumors with similar immunohistochemical characteristics and Ki67 below 1%. Considering the patient's clinical history, an inherited cause was postulated and multiple endocrine neoplasia type 1 was first investigated, but the result was negative. Then, a missense mutation in exon 3 of the VHL gene (ACT>ATT; Thr157Ile) was found. Although no local and/or distant tumor recurrences are usually reported in radically operated on von Hippel-Lindau pancreatic neuroendocrine tumor patients after a median time of five years of follow-up, the present patient had a recurrence after a very long period of time, suggesting that a pancreatic neuroendocrine tumor associated with von Hippel-Lindau syndrome may behave more aggressively than that has previously been described, thus requiring a life-long follow-up.

Multiple endocrine neoplasia type 1

Treatment The treatment of choice of parathyroid tumors is open bilateral exploration with subtotal (3/4) or total parathyroidectomy. Autoimplantation may be considered in case of a total parathyroidectomy. Optimal timing for this operation has not yet been established but it should be performed by an experienced endocrine surgeon. Endocrine pancreatic tumor are treated with surgery and cytotoxic drugs in case of malignant disease. Pituitary tumors are treated with surgery (acromegaly and Mb. Cushing) or medicins (prolactinomas). Culture and society In the video game Trauma Team, Gabriel Cunningham's son, Joshua Cunningham, is diagnosed with Wermer's syndrome. It is also mentioned in the South Korean drama "Medical Top Team", as Dr. Choi Ah Jin (Oh Yeon-seo) is diagnosed with MEN-1. See also Acromegaly Multiple endocrine neoplasia Multiple endocrine neoplasia type 2a Multiple endocrine neoplasia type 2b Prolactinoma References

Gastrinoma in multiple endocrine neoplasia type 1 after total pancreatectomy: A case report.

Surgery for patients with multiple endocrine neoplasia type 1(MEN-1) related gastrinoma remains controversial and total pancreatectomy (TP) has rarely been performed. We reported a case of patient with MEN-1 related gastrinoma treated by TP. A 46-year-old female was admitted to our hospital due to abdominal distension and diarrhea for 2 years. The patient underwent pituitary tumor resection and kidney stone lithotripsy 10 years ago. Abdominal computed tomography showed single lesion in the duodenum and multiple lesions throughout the pancreas. The patient's gastrin level was significantly increased (1080 pg/ml). These findings in combination with the pituitary tumor history suggested the presence of gastrinoma associated with MEN-1 syndrome. An exploratory laparotomy was performed. Intraoperative ultrasound confirmed the numerous tumors diffusely distributed throughout the pancreas and the patient eventually underwent TP. Twelve months later, the patient was hospitalized again for anastomotic fistula and underwent a partial gastrectomy, small bowel resection and drainage of the abscess. One month later, she received gastrostomy and jejunostomy due to digestive tract fistula, and died a month later (14 months after TP). There still might be the possibility of recurrence even after radical surgical resection of gastrinomas, and we suggest the need to measure the basal acid output and maintain regular anti-acid therapy in the long-term follow-up of patients with MEN-1 related gastrinoma.

Endocrine oncology

Endocrine tumors There are many different kinds of endocrine tumors, some of which are listed below: Gastrointestinal ECLoma Midgut carcinoid Appendix carcinoid Hindgut carcinoid sometimes also referred to as Rectal carcinoid Pulmonary Typical bronchial carcinoid Atypical bronchial carcinoid Large cell neuroendocrine carcinoma Small cell lung cancer Endocrine pancreatic tumors Non-functioning endocrine pancreatic tumors Insulinoma Gastrinoma Glucagonoma VIPoma Adrenals Adrenocortical carcinoma Pheochromocytoma Endocrine tumor syndromes Multiple Endocrine Neoplasia I, MEN1 Multiple Endocrine Neoplasia II, MEN2 von Hippel Lindau syndrome References Endocrine neoplasia Rare cancers Oncology Oncology

Neuroendocrine tumor

Other In addition to the two main categories of GEP-NET, there are rarer forms of neuroendocrine tumors that arise anywhere in the body, including within the lung, thymus and parathyroid. Bronchial carcinoid can cause airway obstruction, pneumonia, pleurisy, difficulty with breathing, cough, and hemoptysis, or may be associated with weakness, nausea, weight loss, night sweats, neuralgia, and Cushing's syndrome. Some are asymptomatic.Animal neuroendocrine tumors include neuroendocrine cancer of the liver in dogs, and devil facial tumor disease in Tasmanian devils. Familial syndromes Most pancreatic NETs are sporadic. However, neuroendocrine tumors can be seen in several inherited familial syndromes, including: multiple endocrine neoplasia type 1 (MEN1) multiple endocrine neoplasia type 2 (MEN2) von Hippel-Lindau (VHL) disease neurofibromatosis type 1 tuberous sclerosis Carney complex

List of MeSH codes (C04)

– endocrine gland neoplasms – adrenal gland neoplasms – adrenal cortex neoplasms – adrenocortical adenoma – adrenocortical carcinoma – multiple endocrine neoplasia – multiple endocrine neoplasia type 1 – multiple endocrine neoplasia type 2a – multiple endocrine neoplasia type 2b – pancreatic neoplasms – adenoma, islet cell – insulinoma – carcinoma, islet cell – gastrinoma – glucagonoma – somatostatinoma – vipoma – carcinoma, pancreatic ductal – ovarian neoplasms – granulosa cell tumor – luteoma – meigs syndrome – sertoli-leydig cell tumor – thecoma – paraneoplastic endocrine syndromes – parathyroid neoplasms – pituitary neoplasms – acth-secreting pituitary adenoma – nelson syndrome – growth hormone-secreting pituitary adenoma – prolactinoma – testicular neoplasms – sertoli-leydig cell tumor – thyroid neoplasms – thyroid nodule

Multiple endocrine neoplasia type 1

Diagnosis In a diagnostic workup individuals with a combination of endocrine neoplasias suggestive of the MEN1 syndrome are recommended to have a mutational analysis of the MEN1 gene if additional diagnostic criteria are sufficiently met, mainly including: age <40 years positive family history multifocal or recurrent neoplasia two or more organ systems affected Types Multiple endocrine neoplasia or MEN is part of a group of disorders that affect the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia involves tumors in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, some cases can be life-threatening.

List of MeSH codes (C19)

– multiple endocrine neoplasia – multiple endocrine neoplasia type 1 – multiple endocrine neoplasia type 2a – multiple endocrine neoplasia type 2b – ovarian neoplasms – granulosa cell tumor – luteoma – meigs syndrome – sertoli-leydig cell tumor – thecoma – pancreatic neoplasms – adenoma, islet cell – insulinoma – carcinoma, islet cell – gastrinoma – glucagonoma – somatostatinoma – vipoma – carcinoma, pancreatic ductal – paraneoplastic endocrine syndromes – parathyroid neoplasms – pituitary neoplasms – acth-secreting pituitary adenoma – nelson syndrome – growth hormone-secreting pituitary adenoma – prolactinoma – testicular neoplasms – sertoli-leydig cell tumor – thyroid neoplasms – thyroid nodule – gonadal disorders – hypogonadism – eunuchism – kallmann syndrome – klinefelter syndrome – sexual infantilism

Multiple endocrine neoplasia type 2

Inheritance When inherited, multiple endocrine neoplasia type 2 is transmitted in an autosomal dominant pattern, which means affected people have one affected parent, and possibly affected siblings and children. Some cases, however, result from spontaneous new mutations in the RET gene. These cases occur in people with no family history of the disorder. In MEN2B, for example, about half of all cases arise as spontaneous new mutations. Diagnosis Diagnosis is suspected when a patient with family history of two of the three classical tumors (medullary thyroid cancer, pheochromocytoma, parathyroid adenoma) or MEN2 presents with one of the classical tumors. It is confirmed by genetic testing for mutation in RET gene. Differences in presentation As noted, all types of MEN2 include pheochromocytoma and medullary thyroid carcinoma. MEN2A is additionally characterized by the presence of parathyroid hyperplasia.

Gastrinoma and neurofibromatosis type 2: the first case report and review of the literature.

Gastroenteropancreatic neuroendocrine tumors have occasionally been described in association with neurofibromatosis type 1, whereas an association with neurofibromatosis type 2 has never been reported. This report refers to an Italian 69 year old woman with neurofibromatosis type 2 and a pancreatic gastrinoma. In the past she had encephalic meningiomas, a tongue schwannoma and bilateral acoustic neurinomas. She presented with weight loss and a long-term history of diarrhea, responsive to proton pump inhibitors. Upper gastrointestinal endoscopy revealed peptic ulcer of the duodenal bulb. Blood tests were normal, except for the elevation of plasma gastrin (1031 pg/ml; reference value <108) and chromogranin A (337 U/L; reference value <36). After secretin stimulation testing, the plasma gastrin level rose to 3789 pg/ml. The abdomen magnetic resonance imaging and gallium68-DOTATOC positron emission tomography scan demonstrated the presence of a 1.2 x 2 cm lesion in the pancreatic head and a liver metastatis. Pancreatic endoscopic ultrasound with fine needle aspiration revealed cytomorphologic features suggestive of pancreatic gastrinoma. Brain magnetic resonance showed a pituitary microadenoma. There was no evidence of hyperparathyroidism. The genetic test for multiple endocrine neoplasia type 1 syndrome mutation was negative. This report focuses on the first case of coexistence of gastrinoma with neurofibromatosis type 2. Although the clinical relevance of this association remains to be determined, our case report will surely give cause for due consideration.

Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1.

Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and localization of multiple endocrine neoplasia type 1 related tumors are crucial for determining the best surgical strategies in each individual case with pancreatic endocrine tumors.

Gastrinoma

Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger-Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region (gastrinoma triangle). Most gastrinomas are sporadic (75%–80%), whereas approximately 20% to 25% are associated with multiple endocrine neoplasia type 1(MEN-1). Over 50% of gastrinomas are malignant and can metastasize to regional lymph nodes and liver. One fourth of gastrinomas are related to multiple endocrine neoplasia type 1, Zollinger–Ellison syndrome, peptic ulcer disease.

InternalMed_Harrison

Insulinomas are uncommon, with an estimated yearly incidence of 1 in 250, 000. Because more than 90% of insulinomas are benign, they are a treatable cause of potentially fatal hypoglycemia. The median age at presentation is 50 years in sporadic cases, but the tumor usually presents in the third decade when it is a component of multiple endocrine neoplasia type 1 (Chap. 408). More than 99% of insulinomas are within the substance of the pancreas, and the tumors are usually small (<2.0 cm in diameter in 90% of cases). Therefore, they come to clinical attention because of hypoglycemia rather than mass effects. CT or MRI detects ∼70–80% of insulinomas. These methods detect metastases in the roughly 10% of patients with a malignant insulinoma. Transabdominal ultrasound often identifies insulinomas, and endoscopic ultrasound has a sensitivity of ∼90%. Somatostatin receptor scintigraphy is thought to detect insulinomas in about half of patients. Selective pancreatic arterial calcium

Multiple endocrine neoplasia

Recommended cancer surveillance A recommend surveillance program for Multiple Endocrine Neoplasia Type 1 has been suggested by the International Guidelines for Diagnosis and Therapy of MEN syndromes group. History In 1903 Erdheim described the case of an acromegalic patient with a pituitary adenoma and three enlarged parathyroid glands. In 1953 Underdahl et al. reported a case series of 8 patients with a syndrome of pituitary, parathyroid, and pancreatic islet adenomas. In 1954 Wermer noted that this syndrome was transmitted as a dominant trait. In 1959 Hazard et al. described medullary (solid) thyroid carcinoma. In 1961 Sipple described a combination of a pheochromocytoma, medullary thyroid carcinoma and parathyroid adenoma. In 1966 Williams et al. described the combination of mucosal neuromas, pheochromocytoma and medullary thyroid carcinoma.

Biochemically curative surgery for gastrinoma in multiple endocrine neoplasia type 1 patients.

To search for the optimal surgery for gastrinoma and duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Sixteen patients with genetically confirmed multiple endocrine neoplasia type 1 (MEN 1) and Zollinger-Ellison syndrome (ZES) underwent resection of both gastrinomas and duodenopancreatic neuroendocrine tumors (NETs) between 1991 and 2009. For localization of gastrinoma, selective arterial secretagogue injection test (SASI test) with secretin or calcium solution was performed as well as somatostatin receptor scintigraphy (SRS) and other imaging methods such as computed tomography (CT) or magnetic resonance imaging (MRI). The modus of surgery for gastrinoma has been changed over time, searching for the optimal surgery: pancreaticoduodenectomy (PD) was first performed guided by localization with the SAST test, then local resection of duodenal gastrinomas with dissection of regional lymph nodes (LR), and recently pancreas-preserving total duodenectomy (PPTD) has been performed for multiple duodenal gastrinomas. Among various types of preoperative localizing methods for gastrinoma, the SASI test was the most useful method. Imaging methods such as SRS or CT made it essentially impossible to differentiate functioning gastrinoma among various kinds of NETs. However, recent imaging methods including SRS or CT were useful for detecting both distant metastases and ectopic NETs; therefore they are indispensable for staging of NETs. Biochemical cure of gastrinoma was achieved in 14 of 16 patients (87.5%); that is, 100% in 3 patients who underwent PD, 100% in 6 patients who underwent LR (although in 2 patients (33.3%) second LR was performed for recurrence of duodenal gastrinoma), and 71.4% in 7 patients who underwent PPTD. Pancreatic NETs more than 1 cm in diameter were resected either by distal pancreatectomy or enucleations, and no hepatic metastases have developed postoperatively. Pathological study of the resected specimens revealed co-existence of pancreatic gastrinoma with duodenal gastrinoma in 2 of 16 patients (13%), and G cell hyperplasia and/or microgastrinoma in the duodenal Brunner's gland was revealed in all of 7 duodenal specimens after PPTD. Aggressive resection surgery based on accurate localization with the SASI test was useful for biochemical cure of gastrinoma in patients with MEN 1.

Multiple endocrine neoplasia

In 1993 mutations in the RET oncogene were shown to be the cause of MEN 2A by Lois Mulligan, working in the laboratory of Bruce Ponder in Cambridge. In 1998 the MEN1 gene was cloned. Terminology The older names, "multiple endocrine adenomas" and "multiple endocrine adenomatosis" (MEA), have been replaced by the current terminology. The term multiple endocrine neoplasias are used when two or more endocrine tumor types, known to occur as a part of one of the defined MEN syndromes, occurs in a single patient and there is evidence for either a causative mutation or hereditary transmission. The presence of two or more tumor types in a single patient does not automatically designate that individual as having MEN because there is a small statistical chance that the development of two "sporadic" tumors that occur in one of the MEN syndromes could occur by chance. The term "multiple endocrine neoplasia" was introduced in 1968, but descriptions of the condition date back to 1903.

Multiple endocrine neoplasia type 2

Prognosis Prognosis of MEN2 is mainly related to the stage-dependant prognosis of MTC indicating the necessity of a complete thyroid surgery for index cases with MTC and the early thyroidectomy for screened at risk subjects. See also Multiple endocrine neoplasia Multiple endocrine neoplasia type 1 Multiple endocrine neoplasia type 2b Multiple mucosal neuromata References External links MEN2 (RET) gene variant database GeneReview/NIH/UW entry on Multiple Endocrine Neoplasia Type 2 Endocrine system Autosomal dominant disorders Endocrine-related cutaneous conditions Syndromes affecting the endocrine system

Zollinger–Ellison syndrome

Gastrinomas may occur as single tumors or as multiple small tumors. About one-half to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liver and to lymph nodes near the pancreas and small bowel. Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called multiple endocrine neoplasia type 1 (MEN 1). MEN I patients have tumors in their pituitary gland and parathyroid glands, in addition to tumors of the pancreas.

Zollinger–Ellison syndrome

Zollinger–Ellison syndrome (Z-E syndrome) is a disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea. The syndrome is caused by a gastrinoma, a neuroendocrine tumor that secretes a hormone called gastrin. Too much gastrin in the blood (hypergastrinemia) results in the overproduction of gastric acid by parietal cells in the stomach. Gastrinomas most commonly arise in the duodenum, pancreas or stomach. In 75% of cases Zollinger–Ellison syndrome occurs sporadically, while in 25% of cases it occurs as part of an autosomal dominant syndrome called multiple endocrine neoplasia type 1 (MEN 1).

Multiple endocrine neoplasia

Multiple endocrine neoplasia (abbreviated MEN) is a condition which encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign. Benign or malignant tumors of nonendocrine tissues occur as components of some of these tumor syndromes. MEN syndromes are inherited as autosomal dominant disorders. Presentation Related conditions Although not officially categorized as multiple endocrine neoplasia syndromes, Von Hippel-Lindau disease and Carney complex are two other autosomal dominant endocrine tumor syndromes with features that overlap the clinical features of the MEN syndromes. Although not transmitted in the germline, McCune-Albright syndrome is a genetic disorder characterized by endocrine neoplastic features involving endocrine glands that overlap with those involved in MEN1 or MEN2.

VIPoma

Prognosis Surgery can usually cure VIPomas. However, in one-third to one-half of patients, the tumor has spread by the time of diagnosis and cannot be cured. References Jensen RT, Norton JA. Endocrine tumors of the pancreas and gastrointestinal tract. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease . 9th ed. Philadelphia, Pa: Saunders Elsevier; 2010:chap 32. National Cancer Institute. Islet cell tumors (pancreatic) treatment PDQ. Updated October 31, 2008. External links Endocrine neoplasia Rare cancers Syndromes

List of skin conditions

Hyperparathyroidism Hyperprolactinemic SAHA syndrome Hyperthyroidism Hypoparathyroidism Hypothyroidism Leydig cell tumor Multiple endocrine neoplasia type 1 (Wermer syndrome) Multiple endocrine neoplasia type 2 (multiple endocrine neoplasia type 2A, pheochromocytoma and amyloid-producing medullary thyroid carcinoma, PTC syndrome, Sipple syndrome) Multiple endocrine neoplasia type 3 (mucosal neuromata with endocrine tumors, multiple endocrine neoplasia type 2B, multiple mucosal neuroma syndrome, Wagenmann–Froboese syndrome) Myxedema Panhypopituitarism Persistent adrenarche syndrome (adrenal SAHA syndrome) Polycystic ovarian syndrome Seborrhoea–acne–hirsutism–alopecia (SAHA syndrome) Thyroid acropachy