A 75 – year – old female presented in the Emergency Department of Ilfov Clinical Hospital , Bucharest , Romania , with dyspnea , orthopnea , lower extremities swelling , palpitations . She had a 3 years history of atrial fibrillation diagnosed by her family doctor and one - year history of cardiac failure NYHA ( New York Heart Association ) class Ⅱ. Physical examination revealed an irregular pulse 80 beats / min , blood pressure of 100/60 mmHg , bi – basal crackles on chest auscultation , lower extremities swelling . Heart sounds examination revealed a IVth degree pansystolic murmur at the left border of the stern . The jugular veins were dilated . The patient complained of pain in the upper right abdominal region , enhanced by palpation . The liver margin was tender , round , of 6 cm below the costal rib , with a smooth liver surface . The spleen could not be felt . EKG : atrial fibrillation of 80 / min , right bundle branch block , infero - lateral ischemia . Transabdominal ultrasound showed a homogenous , enlarged liver . The suprahepatic veins were dilated , as well as the inferior vena cava ( 30 mm , without respiratory variations ) . Transthoracic echocardiography revealed a dilated right atrium of 74,2 mm ( Figure 1 ) , dilated left atrium of 55,2 mm , dilated left ventricle of 64/72,3 mm , dilated right ventricle of 44,4 mm . Atrial septal defect ostium secundum type , of 6 cm ( Figure 2 ) , with left – to – right shunt . Severe tricuspid insufficiency with maximum gradient of 55,4 mm Hg . 4th degree mitral insufficiency . Severe pulmonary hypertension of 75 mm Hg . The ejection fraction of 29 % . Atrial fibrillation . Interventricular sept with paradoxical motion . Flattening of the interventricular septum ( Figure 3 ) . The diagnosis was IVth degree chronic heart failure NYHA . Atrial septal defect ostium secundum type with left – to – right shunt . Severe tricuspid insufficiency . 4th degree mitral insufficiency . Severe pulmonary hypertension of 75 mm Hg . Chronic atrial fibrillation . Right bundle branch block .


An 81 - year - old female with hypertension and gout was admitted to Taichung Veterans General Hospital due to abdominal pain and hematemesis . She began to suffer from intermittent epigastralgia more than 10 years ago , and a 4 cm gastric tumor was found . The abdominal pain got worse 2 years before admission , and she went to a local hospital where abdominal CT scan revealed a gastric tumor about 6 cm in length with well - circumscribed calcification(figure 1 ) . Surgical intervention was suggested , but she declined . About 10 days before admission , tarry stool passage was noted , and bloody vomitus was found 1 day later . UGI scope revealed submucosal gastric tumor with central ulceration and she was then transferred to our hospital . Physical examination showed upper abdominal tenderness with mild muscle guarding . The plain radiography showed an irregular shape calcification over upper abdomen . UGI scope revealed deep gastric ulcer with foreign body . CT scan showed an irregularly shaped space - occupying lesion in front of the stomach with plate calcifications and localized free air ( figures 2 and 3 ) . Under the impression of perforated gastric tumor , emergent laparotomy was performed . An infiltrative mass between the stomach and transverse colon was noted during operation . A sharp , bone - like and thick calcified plate penetrating into the gastric mucosa and pericolic soft tissue was observed . A submucosal tumor about 2.3 cm in size adherent to the calcified plate was also noted ( figures 4 and 5 ) . Distal subtotal gastrectomy and partial colectomy were performed . The patient was discharged 13 days after operation uneventfully . Microscopically , spindle - shaped tumor cells with low mitotic frequency ( 4/50 HPF ) were found . Immunohistochemical staining of the tumor demonstrated diffusely strong positive reactivity for CD 117 , positive reactivity for CD34 , but negative reactivity for S100 protein and desmin . The diagnosis of the tumor was established as GIST . Due to the small size and the paucity of mitotic figures of the tumor located in the stomach , it was classified as very low risk[4 ] . Sporadic GIST was impressed due to no family history of GIST nor other GIST presented in this patient .


The 31 - year - old white primipara with twin pregnancy was admitted to hospital in the 38th week of gestation with elevated blood pressure ( 150/100 mmHg ) . After receiving antihypertensive treatment blood pressure was 120/80 . All laboratory variables , including plasma proteins , were within their respective reference intervals . Few hours after admission to the hospital the contractions started , and the caesarean section was performed because of vertex - transverse presentation of twins . Liveborn female and male were delivered . The postoperative course was initially inconspicuous . Four hours postpartum she experienced sudden epigastric pain . The blood pressure rose to 190/130 . Laboratory findings showed haemolysis , thrombocytopenia , and an increase in serum creatinine and aminotransferases ( Table I ) . Intravenous magnesium sulphate was administered . Abdominal ultrasound disclosed an empty uterine cavity without placenta residue . Five hours postpartum , the patient was transferred to the intensive care unit because of poor urine output , drowsiness , and suspicion of DIC . On examination she was sleepy and disoriented . The combination of haemolysis , thrombocytopenia , and elevated liver enzymes suggested a postpartum HELLP syndrome , complicated by DIC . The patient was rehydrated , and treatment was instituted with fresh frozen plasma , red cell transfusion , fresh platelets , and kybernin P ( antithrombin III ) . High serum urea , creatinine , and persistent anuria were compatible with acute renal failure . A high dose of furosemide failed to increase diuresis . Sixteen hours postpartum her blood pressure was 60/40 and oxygen saturation 70 % . Few minutes later the patient had acute cardiac arrest , and resuscitation started . Resuscitation was successful , and normal heart action was re - established ; blood pressure rose to 150/110 , and oxygen saturation was 90 % . Laboratory findings were deteriorated , and development of acute renal failure indicated the necessity of urgent dialysis . Following dialysis , the patient was stable , oxygen saturation 98 % . Twenty hours postpartum patient developed again cardiopulmonary arrest . Despite resuscitation attempts the outcome was lethal . Due to the fact that death occurred in the hospital a short time after a surgical intervention , a medico - legal autopsy was ordered . An autopsy revealed oedema of the brain and lungs as well as dilatation of right and left ventricles . Hydrothorax ( 900 mL ) , hydroperitoneum ( 2500 mL ) , and hydropericardium ( 200 mL ) were present . The field of operation of the caesarean section was unremarkable . Petechial and suffusional haemorrhages were observed under the pleura , endocardium , in the mucosae of the renal pelvis , and peritoneum of the small and large bowel . Histology revealed periportal hepatocellular necrosis , bloodless glomeruli with swollen and vacuolated intracapillary cells , as well as confluent haemorrhages in kidneys , liver , and spleen . Death was attributed to multiple organ failure due to DIC as a consequence of HELLP syndrome .


The patient is a 59 - year - old man diagnosed with PD at the age of 49 years . Fluctuations with recurring “ off ” states and peak dose dyskinesias had severely diminished the patient ’s quality of life . Thus , the patient was deemed a candidate for bilateral subthalamic DBS . Multidisciplinary evaluation with 75 % positive response in the standardized levodopa test , exclusion of cognitive decline or psychiatric comorbitity , and absence of structural brain damage potentially relevant to the lead placement led to the unanimous decision for DBS placement . When decision was made to proceed to surgery the medication consisted of 1112.5 mg of levodopa and 150 mg of piribedil . There was no history of orofacial or cervical dystonia . In the “ on ” state the patient was alert without any signs of psychiatric comorbidity . Neuropsychological testing was adequate . No cranial nerve deficits were found and swallowing was normal . Gait and postural stability was normal with minimal rigidity in the neck and right arm . Coordinative motor skills such as rapid pro- and supination were restricted in the left hand . Dyskinesias were evident with moderate impairment . In the “ off ” state after the medication was held for 12 h , the patient showed mild dysarthria and dysphonia , resting tremor of the right arm and leg , as well as slight action tremor in the right hand . Rigidity was severe in the neck , marked in the right , and mild on the left side . Motor skills of the hands were markedly impaired . Gait was slow but unaided and comprised of by intermittent freezing ; there was mild dystonic posturing of the right foot . There were no signs of laryngeal spasms , however . On the day before surgery , the last dose of dopaminergic medication was administered at 07:00 p.m. , the bedtime dose of levodopa was held to facilitate intraoperative testing . On the day of the operation , the patient underwent placement of the stereotactic frame under local anaesthesia around 09:00 a.m. After planning standard STN coordinates and trajectories , the patient was placed in a semi - sitting position on the O.R. table , with the frame attached to the table . At the patient ’s request , the head was slightly flexed anteriorly for comfort . The left electrode was placed uneventfully . When performing the bur hole on the right side , the patient complained of cramping in the neck and facial muscles as well as difficulties breathing although at that point , pulse oximetry showed good saturation readings at ≥95 % . He progressed to dystonic dysarthria [ 6 ] . Microelectrode recordings had already been done and macroelectrode test stimulation was about to begin , when the patient showed high - pitched inspiratory stridor . Pulse oximetry showed decreasing oxygen saturation at 02:15 p.m. and , shortly thereafter , narrow complex tachycardia was noted . Within a minute , the patient became unresponsive . Cardiac resuscitation was initiated and the patient was fiberoptically intubated after removal of the front bar of the stereotactic frame . During fiberoptic intubation laryngeal spasm was confirmed visually . A transthoracic echocardiogram obtained immediately after successful resuscitation showed no cardiac pathology or any air bubbles . Stimulation using the implanted lead to resolve the symptoms was not possible as at that time the lead was subcutaneously tunnelled with no impulse generator attached . The right permanent electrode was placed without further testing according to microelectrode recordings . 50 mg levodopa was administered over a nasogastric tube every two hours during the subsequent postoperative period . Postoperative head CT scan done immediately after the procedure was normal . The patient was transferred to the intensive care unit and was extubated at 02:00 p.m. the following day without any neurological deficit or signs of laryngeal spasms . By then , the nasogastric tube was discontinued and the preoperative medication was resumed . Cardiac workup was negative . The impulse generator was implanted 7 days later and the patient showed good symptom control of PD .


A 54 - year - old Asian man with IgA nephropathy underwent living - donor kidney transplantation 14 years previously . His medical condition had been almost stable for 14 years . He developed multifocal salmon - pink skin discoloration , and swelling and spontaneous pain in the left knee and leg . The symptoms had gradually expanded across the right forearm and outside of the right thigh . He was admitted to our hospital for the evaluation of fever ( 39 ° C ) and multifocal cellulitis ( Fig.1 ) . Two months before admission , he had developed chronic diarrhea . His serum creatinine level was stabilized at 1.7 mg / dL with maintenance immunosuppressive therapy comprising tacrolimus ( 3 mg / day ) , mycophenolate mofetil ( 1500 mg / day ) , and prednisone ( 4 mg every other day ) . The tacrolimus trough concentration was 6.3 ng / mL. The patient had been a dog breeder for 12 years . On admission , his white blood cell count was 12,400 / μL and his C - reactive protein level was 3.9 mg / dL. The patient was initially treated with ampicillin / sulbactam ( 9 g / day intravenously ) . Two days after the initiation of this therapy , he was afebrile . Four days later , an automated blood culture ( Bactec FX ® ; Becton – Dickinson and Company , Sparks , MD , USA ) showed positivity for gram - negative spiral bacilli . A colony obtained from the patient ’s blood culture was analyzed by MALDI - TOF MS ( Biotyper ver . 3.0 ® ; Bruker Corporation , Germany ) . The identification score was 2.064 ( > 2.0 ) , indicating accurate identification of H. cinaedi ( Fig.2 ) . Additional evaluation of the patient ’s blood specifically for H. cinaedi by means of gyrase subunit B ( gyrB)-targeted PCR assays ( using the forward primer AGGGATTCCACAAAGTGAGC and the reverse primer TCTTGTCCTGTGCGTTCATC to amplify the region of the gyrB gene ) yielded positive results . We performed gyrB - targeted PCR using a single colony isolated from a blood culture . We used distilled water ( DNA- and DNase - free water ) as a negative control to prevent contamination of gyrB - targeted PCR ( Fig.3 ) . In addition , we performed 16S rRNA gene sequencing of this strain , and the results were > 99 % consistent with the existing sequence ( Fig.4 ) . Given these results , we diagnosed the patient with H. cinaedi bacteremia with cellulitis . We examined the genomic heat shock protein ( HSP ) 60 sequence of the blood culture isolate , which resulted in identification of cluster B H. cinaedi . A blood culture obtained at 11 days was positive for H. cinaedi , but a culture obtained at 15 days was negative . The patient ’s cellulitis gradually resolved . The patient continued antibiotic treatment for a total of 6 weeks ( ampicillin - sulbactam in a drip for 2 weeks and oral levofloxacin for 4 weeks ) , and he had no recurrence 6 months after this therapy . His stool culture was negative , although it was taken after treatment . We did not apply enteric bacteria elimination in this case .


A 65 - year - old woman presented with a complaint of right upper quadrant pain . Three years prior , the patient was incidentally diagnosed with idiopathic BCS during health checkup ; Doppler ultrasound ( US ) examination showed obstruction of the middle and left hepatic veins , and investigations for underlying thrombophilia were unremarkable . She was treated with warfarin to maintain an international normalized ratio between 2 and 3 , but discontinued after at least 1 year due to non - compliance ; the patient did not consult with any doctors for 2 years . She has remained asymptomatic for the past 3 years until recently she started experiencing steadily worsening , intermittent pain in the right upper quadrant of her abdomen , with no associated or alleviating factors . Physical examination was only notable for mild right upper quadrant tenderness . Laboratory tests revealed mildly elevated bilirubin ( 2.2 mg / dL ) and albumin deficit ( 2.38 g / dL ) . Her Child - Pugh ( CP ) score was 8 , Model for End - Stage Liver Disease ( MELD ) score was 11 , Rotterdam score was 0.15 , and BCS - TIPS prognostic index ( BCS - TIPS PI ) score was 6.3 . A contrast - enhanced computed tomography ( CT ) scan showed non - visualized middle and left hepatic veins , hepatomegaly with hypertrophy of the caudate lobe , splenomegaly , hepatic venous collaterals , and a saccular aneurysm located at the extrahepatic portal vein main branch measuring 3.2 cm in height and 2.5 cm × 2.4 cm in diameter ( Figure 1A ) . The aneurysm was thought to be associated with BCS as there was no preceding history of trauma and it had not been present on Doppler US examination performed 3 years previously . Although the patient had no ascites or variceal bleeding , the decision was made to create a TIPS to relieve hepatic venous outflow obstruction because of increasing pain and concern for complications due to aneurysm size ; direct approach to the aneurysm was not considered due to risk of associated complications in the setting of portal hypertension , and stent - grafting was not considered due to concerns about patency in the settings of hepatic venous outflow obstruction and underlying thrombophilia . After informed consent was obtained , the patient was brought to the interventional radiology suite . The procedure was performed with the patient under conscious sedation . Portal vein access was obtained via the right hepatic vein under fluoroscopy , and portography showed a saccular aneurysm located at the main portal vein , extensive intrahepatic portal vein thrombosis , and small splenorenal varices ( Figure 2A ) . A 10 - mm diameter expanded polytetrafluoroethylene ( ePTFE ) covered stent - graft ( Fluency Plus ; Bard Peripheral Vascular , Tempe , Arizona , United States ) was deployed across the liver parenchymal tract ; deploying the stent - graft into the main portal vein trunk to cover the aneurysm neck was not considered because it would obstruct blood flow to the portal vein branches . Completion portography showed a widely patent shunt and markedly decreased aneurysm filling ( Figure 2B ) . The portosystemic pressure gradient ( PPG ) was decreased from 19 mmHg to 8 mmHg . The patient recovered uneventfully and had complete resolution of her abdominal pain in 2 d. She was discharged on long - term warfarin and remained asymptomatic after 1 year of follow - up . Most recent laboratory tests revealed normal liver function , and Doppler US examination performed at 1 , 3 , 6 , and 12 mo postprocedure confirmed a patent shunt . Her CP score was 5 , MELD score was 8 , Rotterdam score was 0.12 , and TIPS - BCS PI score was 6.1 . CT scans showed that the aneurysm had decreased in size to 2.4 cm in height and 2.0 cm × 1.9 cm in diameter at 3 mo after TIPS ( Figure 1B ) , and had further decreased to 1.9 cm in height and 1.6 cm × 1.5 cm in diameter at 1 year ( Figure 1C ) .


A 73 - year - old man who had been transferred to our emergency room due to sudden chest pain was diagnosed with ST - segment elevation myocardial infarction ( STEMI ) . He had no coronary risk factors except for a history of smoking for 50 years . Primary percutaneous coronary intervention was performed , and a long , string - shaped contrast defect was observed in the left anterior descending artery ( Fig.1A ) . Optical coherence tomography ( OCT ) imaging revealed an odd , smooth - surfaced 50 - mm long object ( Fig.1B ) . A long , white object which looked like a parasitic worm was retrieved via intracoronary aspiration and revascularization was successfully completed since neither plaque rupture or the presence of thrombus was detected by OCT ( Fig.1C ) . On the eleventh hospital day , transthoracic echocardiography revealed a new floating object in the left atrium . Contrast computed tomography revealed a huge 7×6 cm mass that was recognized at admission in the right upper pulmonary lobe with direct pulmonary vein invasion ( Fig.1D ) . Although the bronchoscopic findings were negative for a lung tumor , a histopathologic examination of the aspirated coronary object revealed pleomorphic lung carcinoma ( Fig.2 ) . The patient was diagnosed with STEMI due to coronary embolization associated with lung carcinoma . Brain MRI revealed that the patient had an asymptomatic cerebral infarction in the right frontal lobe and a small parietal lobe lesion was diagnosed to be metastasis . Given all these observations , he was diagnosed with right lung carcinoma , stage IV ( c - T2bN2M1b ) . He was treated according to the chemotherapy regimens ( carboplatin & paclitaxel ) known to be effective for the treatment of advanced non - small cell lung cancer . He responded to the treatment and showed a good clinical course afterwards ( Fig.3 ) . Chemotherapy with a total of 9 cycles of the same regimen was used and the carcinoma progression was suppressed . He has been doing well for more than two years of PCI and has been followed - up regularly .


CASE : A 28 - year - old previously healthy man presented with a 6 - week history of palpitations . The symptoms occurred during rest , 2–3 times per week , lasted up to 30 minutes at a time and were associated with dyspnea . Except for a grade 2/6 holosystolic tricuspid regurgitation murmur ( best heard at the left sternal border with inspiratory accentuation ) , physical examination yielded unremarkable findings . An electrocardiogram ( ECG ) revealed normal sinus rhythm and a Wolff – Parkinson – White pre - excitation pattern ( Fig.1 : Top ) , produced by a right - sided accessory pathway . Transthoracic echocardiography demonstrated the presence of Ebstein 's anomaly of the tricuspid valve , with apical displacement of the valve and formation of an “ atrialized ” right ventricle ( a functional unit between the right atrium and the inlet [ inflow ] portion of the right ventricle ) ( Fig.2 ) . The anterior tricuspid valve leaflet was elongated ( Fig.2C , arrow ) , whereas the septal leaflet was rudimentary ( Fig.2C , arrowhead ) . Contrast echocardiography using saline revealed a patent foramen ovale with right - to - left shunting and bubbles in the left atrium ( Fig.2D ) . The patient underwent an electrophysiologic study with mapping of the accessory pathway , followed by radiofrequency ablation ( interruption of the pathway using the heat generated by electromagnetic waves at the tip of an ablation catheter ) . His post - ablation ECG showed a prolonged PR interval and an odd “ second ” QRS complex in leads III , aVF and V2 – V4 ( Fig.1Bottom ) , a consequence of abnormal impulse conduction in the “ atrialized ” right ventricle . The patient reported no recurrence of palpitations at follow - up 6 months after the ablation .


A 50 - year - old male patient was admitted to our Department for a thyroid nodule on the right side of the neck , which was incidentally detected on carotid Doppler ultrasound scan . Fine - needle aspiration cytology ( FNAC ) showed a follicular lesion . At the time of our evaluation , the patient was in good health . The medical history revealed hypertension , vitiligo , and celiac disease . On physical examination , a small nodule ( 1 cm ) was palpable in the right thyroid lobe . No enlarged neck lymph nodes were palpable . Neck ultrasound showed a 1.3 cm hypoechoic nodule with irregular margins in the right thyroid lobe together with bilateral small thyroid nodules ( 4–5 mm ) and the absence of enlarged cervical bilateral lymph nodes . Thyroid function tests were normal with the absence of thyroid autoantibodies . Serum calcium was normal ( 9.7 mg / dl ; normal range , 8.4–10.4 mg / dL ) and PTH , routinely measured together with serum calcium in our Center in patients undergoing thyroid surgery , slightly elevated ( 68 pg / mL ( intact PTH , 2nd generation assay ; normal range , 10–65 pg / mL ) ) . The re - review of the original slides of FNAC confirmed a follicular lesion . In particular , the cytology of the nodule showed epithelial cells with hyperchromatic nuclei organized in small cohesive clusters resembling microfollicles typically observed in thyroid follicular lesions were evident ( Fig.1a ) . The patients underwent right lobectomy . During neck exploration , there were no macroscopic signs of local invasion . The intraoperative frozen - section pathological examination raised the suspicion of a PC . Definitive histology showed a markedly irregular infiltrative growth of the tumor with invasion of the thyroid tissue and cervical soft tissues ( Fig.1b , c ) . Immunostaining for thyroglobulin was negative , whereas staining for chromogranin A and PTH showed a strong reactivity ( Fig.1d – f ) . Based on the light microscopic findings and the immunohistochemical profile , the tumor was diagnosed as a PC . Postoperative serum calcium ( 8.7 mg / dl ) and phosphate ( 3 mg / dl ) levels were in the normal range . One month after surgery , serum calcium and plasma PTH were 9.6 mg / dL and 47 pg / mL , respectively . Neck ultrasound and total body computed tomography scan were negative for local and metastatic disease . Eight months later , serum calcium and plasma PTH levels were 9.1–9.2 mg / dl and 38–44 pg / ml ( 1–84 PTH 3rd generation assay , normal range , 8–40 pg / mL ) , respectively . Neck ultrasound did not show any pathological lesions . In order to exclude a familiar form of PHPT , in which PC may rarely occur as a nonfunctioning tumor [ 11 ] , the screening of serum calcium and neck ultrasound in the first - degree relatives was normal .


A 44 - year - old Chinese man with a 7 pack - year smoking history was referred to Shanghai Pulmonary Hospital in February 2013 for a left upper lobe lung mass with multiple bilateral intrapulmonary metastases , left pleural effusion , and 2R/4R/10L/11L lymphadenopathy . Pleural fluid cytology revealed adenocarcinoma and Scorpion Amplification Refractory Mutation system ( AmoyDx Co. , Xiamen , China ) . showed no detectable epidermal growth factor receptor mutation . He commenced chemotherapy with gemcitabine and cisplatin . However , after a single cycle , his symptoms worsened and imaging confirmed progressive disease . A second opinion was requested from the University of Colorado and a computed tomography – guided biopsy of the left upper lobe lesion was performed to permit additional molecular testing . In the interim , the patient commenced pemetrexed and nedaplatin . Unfortunately , after two cycles his shortness of breath worsened , with evidence of further progression on his scans ( Fig.1A ) . Molecular testing on his repeat biopsy specimen revealed no mutations by SNaPshot multiplex PCR testing ( Life Technologies , Carlsbad , CA ) . However , although technically negative , the ALK break - apart FISH test showed an atypical negative pattern . Specifically , 68 % of cells demonstrated single copies of the 5′ ALK signal and numerous cells with doublets of the 5′ ALK signal combined with one 3′ ALK signal ( Fig.2A ) . Subsequently , confirmatory diagnostic assays demonstrated ALK protein expression by IHC using the D5F3 antibody ( Cell Signaling Technology Inc. , Danvers , MA ; H score = 150 ; Fig.2B ) and the presence of an echinoderm microtubule - associated protein - like 4 ( EML4)-ALK transcript ( E13 ; A20 ) by RT - PCR ( Fig.2C ) . The patient then received crizotinib ( 250 mg twice daily ) as third - line therapy in May 2013 with an impressive symptomatic improvement and CT response after 1 month of therapy ( Fig.1B ) . He remains on treatment with crizotinib with no evidence of progression as of September 2013 .


The patient was a 48 - year - old man who had previously been hospitalized due to hemoptysis at 42 years of age . At that time , a chest radiograph and chest computed tomography ( CT ) revealed diffuse ground - glass opacity ( GGO ) in the bilateral lung fields ( Fig.1,2 ) , and a bronchoscopic examination revealed the accumulation of large amounts of blood in the trachea and bronchi ( Fig.3 ) . The patient 's bronchoalveolar lavage fluid ( BALF ) was bloody and contained numerous hemosiderin - laden macrophages . A culture test of the BALF revealed no findings . An electrocardiogram and transthoracic echocardiogram revealed no abnormalities . A questionnaire that was completed at that time did not reveal the patient 's hemorrhagic episode or a family history of bleeding disease , with the exception of his younger brother who had been diagnosed with hepatitis C. Furthermore , he had not received any drugs that had the potential to cause DAH . Following the above - mentioned examinations , DAH due to some sort of vasculitis was suspected . Thus , treatment with high - dose intravenous methylprednisolone ( 1,000 mg daily ) for 3 days followed by prednisolone ( 25 mg daily ) was initiated . This relieved his symptoms . Chest CT showed the resolution of the GGO . The patient 's prednisolone dose was tapered and eventually discontinued at two - and - a - half years after his discharge from our hospital . The patient was readmitted to our hospital with a recurrence of hemoptysis at 46 years of age . The above - described therapy was initiated and led to the improvement of his condition . The prednisolone dose was tapered from 60 mg daily to a maintenance dose of 5 mg daily . At 48 years of age , he was readmitted to our hospital with a further recurrence of hemoptysis . At this point , he had steroid - induced diabetes mellitus , which was treated with glimepiride ( 3 mg daily ) . At admission , his weight was 75 kg and height 167 cm ; his vital signs were as follows : blood pressure , 178/102 mmHg ; pulse rate , 109 beats / min , pulse oximetry , 97 % in room air ; and body temperature , 36.8 ° C . Chest auscultation revealed fine crackles in the right lung field . No skin rash , subcutaneous bleeding or joint swelling were present . A chest radiograph and CT showed the presence of diffuse GGO in the bilateral lung fields . Mild anemia was observed ( hemoglobin , 11.3 g / dL ) , although hemoglobin levels had been 14.6 g / dL prior to the hemoptysis episode . The activated partial thromboplastin time ( APTT ) was prolonged to 53.5 seconds ( normal range , 25.1 - 40.7 seconds ) . Laboratory tests showed that the patient 's blood glucose and hemoglobin A1c levels were 299 mg / dL and 8.2 % , respectively , due to the steroid - induced diabetes mellitus . Autoantibodies for various collagen diseases were negative ( Table ) . We diagnosed the condition as a recurrence of DAH and again administered high - dose intravenous methylprednisolone for 3 days , followed by prednisolone ( 60 mg daily ) . His condition improved , as had been observed during the previous episodes . A further detailed inquiry regarding the patient 's medical history revealed that , as an elementary school student , he had been hospitalized and had received blood transfusions twice following abnormally heavy bleeding after tooth extraction ; however , a specific congenital bleeding disorder had not been diagnosed at that time . It was also revealed that his younger brother had been diagnosed with hemophilia B during adolescence . Considering the possibility of hemophilia , his blood coagulation factors were examined , revealing that his factor IX activity was 3 % . The patient was subsequently diagnosed with moderate hemophilia B. By the time of this diagnosis , the patient 's DAH had already resolved with the corticosteroid therapy . We decided to continue treating the patient using prednisolone alone , without coagulation factor IX replacement therapy . No recurrence of DAH or hemorrhagic symptoms have been observed during 3 years since the tapering and discontinuation of prednisolone .


An 84 - year - old woman presented to a local clinic with dyspnea on exertion and left back pain persisting for a month . She was admitted to our hospital because of left pleural effusion on a chest X - ray . She suffered hypertension and dyslipidemia but had no history of pleural tuberculosis or chronic pyothorax , nor a smoking history or dust exposure . On examination , her vital signs and oxygen saturation were normal ( SpO2 : 96 % ambient air ) . A chest examination revealed a mass on the left side of her back with pain and decreased breathing sounds in the left lower - lung field . The rest of the examination findings were normal . Laboratory tests revealed elevated levels of C reactive protein , lactate dehydrogenase ( LDH ) , and soluble interleukin-2 receptor ( sIL-2R ) ( Table 1 ) . A chest X - ray ( Fig.1 ) showed left pleural effusion with mediastinal shift . On the first hospital day , an intercostal drainage tube was inserted , and after drainage , chest computed tomography ( CT ) ( Fig.2 ) revealed an irregular pleural mass invading her left chest wall with rib destruction and pleural effusion . The mass was adjacent to the posterior mediastinum , but the lateral side of the mass was thick and invading the chest wall , so we diagnosed this mass as a chest wall tumor . The pleural fluid was serous and not purulent . A fluid analysis showed it to be exudative , and 81 % of the white blood cells were lymphocytes . The fluid culture was negative , and cytology did not show any evidence of malignancy ( Table 1 ) . CT - guided needle biopsy was performed . The histopathology results supported a diagnosis of diffuse large B - cell lymphoma ( DLBCL ) that was positive for CD10 and CD20 but negative for CD3 and CD5 ( Fig.3 ) . 18 - fluorodeoxyglucose positron emission tomography / computed tomography ( FDG - PET / CT ) revealed high FDG uptake in the left chest wall mass without any other uptake ( Fig.4A and B ) , so we diagnosed her with primary malignant lymphoma originating from the chest wall . We reconfirmed her medical history , and she never had either tuberculous pleurisy or pyothorax . Her performance status ( PS ) was 3 because of her back pain and fatigue . Owing to her bad PS and age , it was difficult to perform an operation or administer combination chemotherapy with Rituximab , so low - dose oral etoposide ( 50 mg / day d1 - 14 , q28 ) was administered . Her pleural effusion disappeared within two weeks , her back pain disappeared , and her PS improved to 1 within a month . Chest CT performed four months later showed complete response ( Fig.4C and D ) . She continued oral chemotherapy and maintained a good PS for one year after the diagnosis .


The patient is a 57 - year - old woman who had noted a rapidly enlarging mass on the left side of her neck in 2010 . She underwent a total thyroidectomy and central neck dissection , which revealed a 3.8 - cm anaplastic thyroid cancer arising in a background of an oncocytic variant of poorly differentiated thyroid cancer ( Fig.1A , and Fig . S1 in Supplementary Appendix 1 , available with the full text of this article at NEJM.org ) . Resection margins were positive , and 3 of 12 lymph nodes were involved . At 3 weeks after surgery , the serum thyroglobulin level was 17.2 ng per milliliter , with undetectable thyroglobulin antibodies . The patient received concurrent radiation therapy and weekly carboplatin and paclitaxel chemotherapy . The serum thyroglobulin level at 4 weeks after the completion of chemotherapy and radiation therapy was 12.0 ng per milliliter . Restaging scans obtained 3 months later revealed a new , right - sided hilar mass ( Fig.1C ) , and the patient enrolled in a phase 2 clinical trial of everolimus , which was administered at a dose of 10 mg daily . Within 6 months , follow - up scans showed that the lesion had greatly diminished in size ( from 3.0 by 2.6 cm to 1.1 by 0.8 cm ) ( Fig.1D ) . After 18 months of a sustained response to everolimus , scans revealed progressive disease ( Fig.1E ) . The patient underwent a mediastinoscopy with removal of an enlarged lymph node , which contained metastatic anaplastic thyroid cancer ( Fig.1B , and Fig . S1 in Supplementary Appendix 1 ) . Whole - exome sequencing was performed on biopsy samples of the pretreatment and resistant tumors as well as on a blood sample .


An 18 - year - old college student was referred from the University Clinic for having low hemoglobin ( Hg 4.7 g / dl ) . He was completely well till one month back when he presented with easy fatigability , postural dizziness , palpitation and dyspnea . He gave history of 30 kg weight loss over the past 6 months . On physical examination , he looked pale , not jaundiced or cyanosed . His vital signs were all within normal limits , except for an elevated heart rate ( 98 / min ) . Cardiovascular , respiratory and abdominal examinations were unremarkable . Primary investigations in our hospital revealed low hemoglobin level ( 5.1 g / dl ) , low iron ( < 10 ug / dl ) , and a positive occult blood test . A provisional diagnosis of microcytic hypochromic anemia for further workup was made . Bone marrow aspirate and trephine biopsy revealed normocellular marrow , depicting normal trilineage hematopoiesis . Upper GI endoscopy showed erosive antral gastritis with patchy ulcerative inflammation . Abdominal ultrasound showed a slightly enlarged liver with a rounded echogenic lesion in the anterior wall of the right lobe suggestive of hemangioma . The spleen was slightly enlarged and normal in echogenicity with no focal lesions . Computed Tomography ( CT ) scan of the abdomen and pelvis showed a fairly large well defined soft tissue mass located in the anterior upper pelvis and engulfing jejunal loops causing bowel wall thickening . The patient underwent an exploratory laparotomy and excision of the jejunal mass . Macroscopic examination revealed an 11 × 8 × 2 cm annular mass located within the jejunal wall ulcerating through the mucosa and extending to the serosal surface . Microscopic examination revealed a tumor situated in the muscularis propria and extending to the mucosa and the serosa . The neoplastic cells were arranged in predominantly pseudoalveolar pattern ( Fig.1a , b ) . They were polygonal in shape with variable amount of eosinophilic to clear cytoplasm ( Fig.1c ) . The nuclei were oval with vesicular chromatin and inconspicuous nucleoli . Scattered osteoclast - like multinucleated giant cells were also identified ( Fig.1b , c ) . Frequent mitotic figures and necrosis were noted . All lymph nodes were not involved by tumor . Immunohistochemically , the neoplastic cells were strongly and diffusely positive for S-100 protein ( Fig.1d ) . They were also positive for vimentin . Melanocytic markers ( HMB45 and Melan A ) , neuroendocrine markers ( chromogranin A , synaptophysin and CD56 ) , smooth muscle actin , desmin , CD34 , CD117 , cytokeratin and LCA were all negative in the neoplastic cells . Fluorescein in situ hybridization ( FISH ) analysis for EWSR1 break apart probe on paraffin - embedded tumor showed evidence of a 22q12 rearrangement in 197 out of 205 ( 96 % ) of interphase nuclei scored . The native state of EWSR1 break apart probe will be seen as two adjacent or fused ( overlapping ) red / green ( yellow ) signals . However , EWSR1 gene rearrangement presented as one red and one green separated signal ( Fig.1e ) . The patient did not receive chemotherapy or radiotherapy . During the clinical follow up , the patient remained disease free for 3 years until he presented with local recurrence . The treatment plan was surgical resection but the patient sought medical advice in a different institution where he died of the disease a year later .


The proband ( II-2 in Fig.2 ) is a 45 - year old woman , who first presented to our university hospital at the age of 35 and was referred to us because of her pregnancy . She has congenital deafness , first experienced syncope at the age of 3 , and was diagnosed with epilepsy . She was treated with anti - epilepsy medications ; however , she subsequently experienced several instances of syncope . At the age of 13 , she had a syncope event , and was suspected of having JLNS because of her congenital deafness and prolonged QT interval . Her syncope was diagnosed as an arrhythmic episode when she was aware of tachycardia and as epilepsy when she was not . She also had a subarachnoid hemorrhage at the age of 29 . When she first presented at our hospital , she was not taking beta - blockers , because of a history of asthma , but was taking mexiletine in addition to phenytoin . Her QTc was found to be prolonged ( 584 ms ) at presentation and administration of atenolol was initiated . She delivered her baby ( III-1 in Fig.2 ) through Caesarean operation at our hospital at the age of 35 . At 37 , she delivered her second baby ( III-2 in Fig.2 ) through Caesarean operation at our hospital . Despite administration of beta - blockers , her QTc remained prolonged ( 600 msec at the age of 37 , 780 msec at 44 ) ( Figs.2 and 3a ) , which is not unexpected because treatment with beta - blockers in LQTS1 is not expected to overtly reduce QTc [ 18 ] . However , she continued to experience occasional syncope and finally underwent an implantable cardioverter defibrillator ( ICD ) operation at 38 years of age . Subsequently , she is in a stable clinical condition . Because the proband was suspected of JLNS and both infants had a measured QTc of 500 ms or greater within 1 month after birth , beta blockers were initiated and both children remain in stable condition at ages 10 and 8 ( Figs.2 and 3b , c ) . QTc of the son ( III-1 in Fig.2 ) was measured as 500 ms one month after birth , while the QTc of his sister ( III-2 ) was 530 ms at birth . The father ( I-1 ) and mother ( I-2 ) of the proband were first cousins . There is no history of sudden unexplained syncope or death of children or adults in the immediate family members , despite the prolonged QTc of the children . Clinical evaluation and consultation of the proband and her family members were performed at Chiba University Hospital . Clinical phenotypes were deduced from the clinical history , physical examinations , and ECG . Blood samples were collected from the proband and her family members following genetic counseling , and written informed consent was obtained prior to sample collection . Genomic DNA was isolated from peripheral blood lymphocytes according to established protocols at our laboratory [ 19 ] . Entire coding exons , including the intronic boundaries of the genes , of KCNQ1 ( NCBI ref : NM_000218 ) and other LQT causative genes ( KCNH2 , SCN5A , KCNE1 , KCNE2 , KCNJ2 , SCN4B , KCNJ5 ) were amplified by polymerase chain reaction ( PCR ) , according to established protocols in our laboratory . Briefly , 30–100 ng of genomic DNA was subjected to PCR amplification with DNA polymerase ( PrimeSTAR GXL DNA Polymerase ; Takara Bio Inc. , Kusatsu , Japan ) and primer sets . The amplicons were subjected to conventional sequencing with Sanger sequencers ( Applied Biosystems 3730/3130 DNA analyzers ; Thermo Fisher Scientific , Waltham , MA , USA ) . The sequence data were processed with Gene Codes Sequencher Software ( Takara Bio Inc. ) and mapped to the human genome sequence ( build GRCh37 / hg19 ) . Genetic analysis was performed to screen all coding exons and the exon – intron boundaries of the KCNQ1 gene ( NCBI ref : NM_000218.2 , NP_000209.2 ) with concurrent screening of other LQT causative genes ( KCNH2 , SCN5A , KCNE1 , KCNE2 , KCNJ2 , SCN4B , KCNJ5 ) . We detected a novel homozygous nonsense variant , NM_000218.2 : c.115 G > T ( p. Glu39X , in exon 1a ) , in the KCNQ1 gene of the proband , as well as a homozygous common variant ( NM_000218.2 : c.1343C > G , p. Pro448Arg ) ( Additional file 1 : Table S1 ) . Genetic screening of her mother ( I-2 ) and children ( III-1 and III-2 ) revealed that they were heterozygous for the nonsense variant ( Fig.2 ) . Her husband ( II-3 ) was also screened and found to be heterozygous for the common variant ( NM_000218.2 : c.1343C > G , p. Pro448Arg ) . The proband is a child from a first - cousin marriage , and we have concluded the homozygous nonsense variant in the proband is the cause of her JLNS1 . The proband was negative for pathogenic variants in other LQT causative genes , including the KCNE1 gene ( Additional file 1 : Table S1 ) .


An 8 - year - old boy with S549R/1717 - 1 G > A genotype was started on ivacaftor ( 150 mg b.i.d . ) on compassionate use . At the age of 9 months he was diagnosed with CF due to failure to thrive . His previous history was remarkable for recurring nasal polyposis requiring endoscopic surgery and exocrine pancreatic insufficiency necessitating enzyme replacement therapy . He grew with body weight and height along the 10th percentile . He suffered from rather mild respiratory symptoms , primarily intermittent productive cough , and had close to normal lung function parameters in previous years as measured by body plethysmography and spirometry ( minimal z - score of FEV1 : −1.2 ) . Sputum cultures grew Haemophilus influenzae and Staphylococcus aureus on several occasions . After 6 weeks of ivacaftor treatment , the patient reported clinical improvements in cough frequency , sputum production , physical performance , and less salt cravings . He gained 1.4 kg in body weight without changing the dose of his pancreatic enzyme replacement therapy . His sweat chloride level ( Macroduct ® ) decreased from 115 mmol / l before ivacaftor to 40 mmol / l after 6 weeks and 52 mmol / l after 41 weeks ( normal < 30 mmol / l [ 11 ] ) of treatment . His FEV1 increased from 1.25 L ( −1.2 z - score ) to 1.65 L ( +0.5 z - score ) after 41 weeks of ivacaftor therapy . The LCI ( normal < 8) measured by N2 - MBW decreased from 14.5 to 8.3 after 6 weeks and 7.8 after 41 weeks of ivacaftor treatment ( Table 1 and Fig.1 ) .


A 36- year- old white woman at 40 week of gestation was admitted to a local obstetric clinic for elective repeated cesarean delivery due to slanting position of the fetus . Both her previous and current pregnancy were uncomplicated . Her past medical history was unremarkable and no family history of cardiac disease was reported . The caesarean delivery was performed following the administration of standard spinal anesthesia . During surgery the patient became hypotensive and ephedrine was injected to maintain her blood pressure in the normal range . Three hours after delivery of healthy male infant , the patient complained of nausea , increasing dyspnoea and palpitations . On physical examination tachycardia with ventricular extra systoles and pulmonary rales were detected . Her blood pressure was 80/40 mmHg and demanded the administration of inotropic agents ( initially continuous infusion of norepinephrine 0.5 mg / h followed by dobutamine 7 μg / kg / min ) . Owing to worsening of oxygen saturation up to 70 % and gradual deterioration of consciousness , mechanical ventilation was applied and the patient was transferred to intensive care unit . Chest X ray indicated pulmonary congestion . Emergency computer tomography excluded pulmonary thromboembolism ( PE ) and confirmed severe pulmonary oedema ( Fig.1 ) . The patient received loop diuretic , furosemide , at initial daily dose 80 mg , which was progressively reduced . The diuretic was discontinued after 12 days of treatment . The electrocardiogram disclosed sinus tachycardia with ST- segment elevation of 1,5 mm with negative T waves in aVL and ST- segment depression of 1 mm in II , III , aVF , V5 - V6 ( Fig.2 ) . Laboratory tests showed elevated troponin up to 908 pg / ml ( normal value < 14 pg / ml ) , NT- pro BNP 6236 pg / ml ( normal value < 125 pg / ml ) . The bedside transthoracic echocardiography ( TTE ) revealed severe left ventricular ( LV ) systolic dysfunction . Therefore the patient was transferred to Intensive Cardiac Therapy Clinic . Repeated TTE showed LV ejection fraction 30 % with hypokinesis of the mid and basal segments of posterior , anterior and lateral wall with preserved contractility of the apical segments . Urgent coronary angiography presented normal coronary arteries . The diagnosis of inverted stress- induced cardiomyopathy was set upon the overall clinical data . After 3 days the patient was weaned from respirator and extubated . Following hemodynamic improvement , inotropic agents were tapered gradually . Both TTE and magnetic resonance imaging ( Figs.3 and 4 ) performed on the fifth day showed complete recovery of myocardial function . The patient was discharged after 15 days in good overall condition . At 12- month follow- up she remained asymptomatic with no echocardiographic abnormalities .


An 82 - year - old male was admitted in our outside hospital ’s emergency room due to abdominal pain and faint . He had a previous history of auricular fibrillation in treatment with a dicumarinic anticoagulant and a previous episode of abdominal pain which was diagnosed as spontaneous mesenchimal haematoma and treated non operatively . He denied any kind of trauma , and had no hematemesis or melena . At physical examination the patient was stable and suffered from intense pain at the right lower abdomen with no defense . Blood tests showed a haemoglobin level of 10 g / dl . Coagulation was altered as expected . CT scan showed massive hemoperitoneum ( Figure 1 ) and the already known mesenteric hematoma ( Figure 2 ) . Assuming the diagnosis of expansive mesenteric hematoma plus ongoing bleeding a laparotomy was performed . During first exploration , 3 liters of fresh and old blood clots were found . At 90 cm from the ileocecal valve a torsionated and perforated meckel diverticulum with intradiverticular bleeding was found ( Figure 3 ) and a diverticular resection was performed . The postoperatory was uneventful and the patient was discharged home at the 9th postoperative day .


A 26 - year - old man of Portuguese descent with no significant past medical history presents with subacute onset of right - sided hemiparesis and aphasia , with marked expressive aphasia , word - finding difficulty , and rare paraphrasic errors . Examination demonstrated right central facial weakness , 2–3/5 strength in the right arm and leg , and dysmetria in the right upper and lower extremities . Reflexes were hyperactive on the right with a right - sided Babinski response . MRI of the brain showed multiple bilateral concentric ring - like structures in the centrum semiovale and the corona radiata on T2 imaging ( figure , A ) , consistent with the pattern of Balo concentric sclerosis . There was associated restricted diffusion in 3 lesions and incomplete ring enhancement in 1 lesion . CSF analysis showed 30 leukocytes ( 79 % lymphocytes , 4 % monocytes ) , erythrocyte count was 850 , and oligoclonal bands were absent . He was treated with 1 g of IV methylprednisolone daily for 5 days , with little improvement . He then underwent 5 plasmapheresis exchanges , with significant improvement of motor , sensory , speech deficits , and gait . Forty - five days after discharge , his examination showed 4+/5 strength in the right intrinsic muscles of the hand and a right - sided positional tremor . Gait and tandem gait were normal . He was placed on β - interferon-1a 44 μg subcutaneously 3 times a week , for treatment of presumed clinically isolated syndrome , with good response . One year later , his neurologic examination was essentially normal . There was no family history of demyelinating or autoimmune disorders . His mother has a significant history of headaches and early - onset strokes , and was found to be a carrier of the Notch3 mutation consistent with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( CADASIL ) . His sister had a stroke in her 30s , and a history of migraine headaches , but has not undergone medical evaluation . Testing for CADASIL in the patient showed the Notch3 mutation associated with CADASIL ( transition C > T , nucleotide position 1750 , codon 558 ) . Skin biopsy showed electron - dense extracellular material in close apposition to the smooth muscle of the vascular media1 ( figure , B ) .


A 49 - year - old man , with no history of cardiac disease , presented with progressive dyspnea of one month 's duration . Medical History . His medical history included blunt chest trauma , the result of an accidental fall from scaffolding 15 months earlier . He had fallen approximately 8 feet and had landed on the right side of his back and on his right shoulder . The patient had sustained bilateral pneumothorax , right iliopsoas muscle hematoma , multiple right costal fractures , fracture of the L3 vertebral body and the transverse process , and displaced fractures of the right clavicle . That hospitalization had lasted 40 days , during which time the clinicians had not detected any murmur or requested a cardiac evaluation . The patient returned to normal activities 4 weeks after discharge from the hospital and remained asymptomatic for one year . Upon his arrival at our department , auscultation revealed bibasilar rales and a pansystolic murmur . Chest radiography showed mild lung congestion ; and transthoracic echocardiography , limited by suboptimal acoustic windows , revealed severe , eccentric mitral regurgitation . The valvular and subvalvular apparatus appeared to be structurally normal , and the left atrium was only mildly dilated . The patient was treated with intravenous diuretics until the signs and symptoms of congestion were relieved . Coronary angiography revealed an absence of substantial coronary disease . We therefore planned an elective surgical procedure for mitral valve repair . Surgical Procedure . During intraoperative transesophageal echocardiography ( TEE ) , we observed both a trivial central mitral regurgitant jet and a severe perivalvular regurgitant jet , this last originating from a ventriculoatrial fistulous communication behind the P1 scallop ( Fig.1 ) . Further examination confirmed the absence of structural disease involving the mitral leaflets or subvalvular apparatus . After surgical exposure of the mitral valve , a small tear ( length , 6–7 mm ) could be seen behind the posterior leaflet , in a lateral position , involving also the annulus and the left atrial wall . The absence of leaflet abnormalities or vegetations suggested the posttraumatic origin of the perivalvular leak . Valvular repair was successfully achieved by direct suture of the tear with three 5 - 0 Prolene stitches and by the subsequent insertion of a 30 - mm mitral annuloplasty ring . The patient was extubated the next day and his postsurgical course was uncomplicated . One year later , he was asymptomatic , and his one - year follow - up transthoracic echocardiogram confirmed the excellent result of his surgical treatment .


A 33 - year - old man presented with left flank dull ache . On the abdominal computed tomography , a solid renal mass in the upper portion of the left kidney was identified . The mass was measured 2.8 cm × 2.8 cm × 2.5 cm in size , was well - defined . The patient had no other abnormal findings , such as suspected distant metastasis or lymph node metastasis . Radical nephrectomy was performed on 14/9/2005 . On gross examination , the nephrectomy specimen measured 11.5 cm × 6.5 cm × 4.5 cm and the tumor was a solid , grayish - brown mass measured 3.5 cm × 2.5 cm × 2.2 cm in size . Histologic examination demonstrated trabecular and ribbonlike patterns with minimal fibrotic stroma . The cytoplasm was granular and eosinophilic with uniform round to oval nuclei with finely stippled chromatin and inconspicuous nucleoli . Mitoses were not found ( 0 per 10 high - power fields ) on H&E stain . The final pathologic examination revealed a well - differentiated neuroendocrine ( carcinoid ) tumor confined to the kidney ( Fig.1 ) . Immunohistochemical stains demonstrated labeling with chromogranin , neuron - specific enolase and synaptophysin ( Fig.2 ) , and the proliferation index was less than 2 % as measured by immunohistochemistry for Ki-67 . Further radiation and chemotherapy were not received . Nine years after radical nephrectomy , computed tomography of the abdomen demonstrated a 2 cm × 1.8 cm cyst mass in the right liver and multiple high density shadow in gallbladder . No enlarged lymph nodes were found in the abdominal cavity . Cholecystectomy and extirpation for hepatic cyst were performed by laparoscopy surgery . Histologic examination demonstrated trabecular and glandlike growth ( Fig.3 ) , moderate and uniform nuclei and mitoses were n't found ( 0 per 10 high - power fields ) . Advanced immunohistochemistry revealed that the lesion was positive for synaptophysin ( Fig.4 ) and CD56 , but negative for chromogranin and neuron - specific enolase . These features are supported in a neuroendocrine tumor . Due to the similar pathologic characteristics between the primary renal carcinoid tumor and liver tumor . The final pathology report indicated a carcinoid tumor of the left kidney with liver metastasis .


A 62 - year - old male presented with a 15 - day history of dyspnea on exertion , associated with both lower extremity edema . Before this admission , he also had suffered from abdominal bloating and tasteless for a year with noticeable body weight loss at the same time ( up to 20 kg ) . Over the past 6 months , he developed a multiple system disorder , which included painless paresthesias in the lower limbs , erectile dysfunction , and chronic diarrhea . He had an average stool frequency of up to ten times per day , with no obvious blood or mucus and no abdominal pain or tenesmus . Unfortunately , previous stomach and rectum biopsy did not examine for accumulations of amyloid fibril protein . His family history was unremarkable . On physical examination , his blood pressure was 82/56 mmHg and heart rate was 52 bpm . Significant jugular venous distention , moderate hepatomegaly , and lower extremity edema were noted . A neurological examination revealed weakness and muscular atrophy in the bilateral tibialis anterior and gastrocnemius . Hyporeflexia was noted on both knees and ankles . Sensory examination revealed diminished tactile and pain sensation in a stocking and glove pattern and vibratory sensation was distally reduced in the lower limbs . The motor and sensory functions of upper extremities were relatively spared . Initial laboratory data that included full blood count , transaminase , creatinine , electrolytes , cardiac troponin , and thyroid function were normal or negative . N - terminal fragment of pro - brain natriuretic peptide ( NT - proBNP ) was 3,996 pg / mL. Nerve conduction studies confirmed bilateral sensory - motor neuropathy ( Table 1 ) . An electromyography study demonstrated active denervation and chronic reinnervation changes in the tibialis anterior and gastrocnemius . Electrocardiogram ( ECG ) revealed sinus rhythm , low voltages in limb leads , QS waves in precordial and inferior leads , first - degree atrioventricular block , and prolonged QTc ( Figure 1 ) . Two - dimensional echocardiography revealed marked concentrically thickened and speckled appearance of ventricular walls , biatrial dilatation , and left ventricular ejection fraction of 70 % ( Figure 2 ) . Doppler revealed a severe restrictive mitral filling pattern with E / A ratio 2.1 . Coronary angiography findings were normal . The combined occurrence of low QRS voltage in the ECG , ventricular thickening , and signs of diastolic dysfunction is strongly suggestive of cardiac amyloidosis . The following serum λ light - chain concentration was 1,763 ( normal range : 598–1,329 mg / dL , and κ light - chain concentration was normal . Rectum biopsy confirmed amyloid infiltrate ( Figure 3 ) . So , the diagnosis of AL amyloidosis was established . Despite chemotherapy administration of melphalan , dexamethasone , immunomodulator lenalidomide , and supportive therapy including montmorillonite to decrease diarrhea and low - dose furosemide to alleviate fluid retention , the patient continued to deteriorate and died at home after 3 months after the initial diagnosis .


A 73 - year - old man who had been diagnosed with type 2 diabetes mellitus at 35 year of age , who had severe diabetic neuropathy and diabetic - ESRD complained of respiratory distress and sudden chest pain . On the first day of treatment , he visited the emergency room . A physical examination revealed that his body temperature was 35.4 ° C , his heart rate was 90 beats / min with a regular rhythm ; and his blood pressure was 130/77 mmHg . A physical examination revealed coarse crackles on bilateral lung auscultation . The laboratory data showed a WBC count of 8,800 / μL with a shift to the left ( neutrophils 82 % ) , Hb 10.2 g / dL , blood urea nitrogen ( BUN ) 82.2 mg / dL , creatinine ( Cre ) 6.50 mg / dL , HbA1c 5.9 % , creatine kinase ( CK ) 189 IU / L , C - reactive protein ( CRP ) 8.51 mg / dL , brain - type natriuretic peptide ( BNP ) 127.4 pg / mL. A chest radiograph revealed perihilar consolidations and air bronchograms ( Fig.1 ) . An electrocardiogram revealed ST - segment elevation and poor R - wave progression in leads V1 - V3 , and echocardiography revealed apical and ventricular asynergy . The patient was therefore diagnosed with acute myocardial infarction and congestive heart failure . Coronary angiography was performed , revealing severe angiostenosis in the septal branch . PCI was therefore performed . The patient required continuous maintenance dialysis . On the following day , the patient went into cardiorespiratory arrest and cardiopulmonary resuscitation was performed , followed by mechanical ventilation . On day 8 , ventilator assistance was discontinued . However , the patient produced an increasing volume of sputum , which began to appear purulent . Pseudomonas aeruginosa was identified from a sputum culture , and tazobactam / piperacillin ( TAZ / PIPC ) ( 4.5 g q12h ) was administered . Despite this therapy , the patient 's respiratory condition worsened and a chest computed tomography ( CT ) scan on day 15 revealed bilateral perihilar opacities , pleural effusion , and atelectasis.(Fig.2 ) . We suspected the development of complications such as microbial substitution , pneumomycosis and thus performed sputum culturing and serum fungal antigen tests . The administration of TAZ / PIPC was changed to meropenem ( 0.5 g / day ) . On day 16 , the patient 's serum tested positive for Cryptococcus antigen . On day 21 , cryptococcal bodies were identified in two sets of blood cultures and liposomal amphotericin B ( L - AMB ) ( 3 mg / kg / day ) was administered . On day 23 , cryptococcal bodies were identified in the sputum , cerebrospinal fluid , and bilateral pleural effusion ( Fig.3 ) . The patient was therefore diagnosed with disseminated cryptococcosis . On day 25 , brain CT revealed the absence of intracranial hypertension and a brain abscess . The patient was not infected with human immunodeficiency virus ( HIV ) . The administration of L - AMB ( 3 mg / kg / day ) was continued . On day 31 , chest CT revealed a solitary nodule in the left lingular segment for the first time , which was suspected to be a pulmonary cryptococcus lesion ( Fig.4a ) . After several days , all of the sputum , blood , bilateral pleural effusion , and cerebrospinal fluid cultures tested negative . On day 52 , chest CT revealed another lung nodule in the right pulmonary apical region . These nodules gradually decreased in size until day 79 ( Fig.4b and c ) . Although L - AMB was considered effective , the C - reactive protein level remained elevated and the bilateral pleural effusion continuously increased . The patient lost consciousness because of decreased vital capacity with increasing bilateral pleural effusion and was diagnosed with CO2 narcosis . The patient 's general condition deteriorated . On day 87 , ventricular fibrillation occurred and the patient died . Autopsy was not performed . At a later date , the Cryptococcus isolate was identified and classified as Cryptococcus neoformans var . grubii ( serotype A ) by a genetic analysis .


A 46 - year - old Caucasian woman with type 2 diabetes mellitus and bipolar disorder presented to our emergency department with vague abdominal symptoms and vomiting . Her pertinent history includes left below knee amputation and right toes amputation for complications secondary to diabetic neuropathy . At the time of admission , she was undergoing care for an infected diabetic ulcer of her right foot . Of note , she did not have a history of CAPD or a history of renal disease : creatinine 1.23 mg / dL , blood urea nitrogen ( BUN ) 16 mg / dL. Her blood glucose levels were poorly controlled via subcutaneous insulin injection ; she reported a range of 400 to 500 mg / dL at home ( due to poor drug compliance ) . Her blood glucose levels were decreased to a range of 175 to 378 mg / dL after implementation of a stricter insulin regimen upon admission . A non - contrast CT scan showed confluent , bilobar geographic regions of hypoattenuation in a subcapsular distribution throughout her liver ( Fig.1 ) . A MRI liver protocol was performed for further evaluation of these indeterminate findings to assess for possible vascular etiology as areas of infarction could also be possible in this patient . In - phase gradient echo images demonstrated hyperintense foci in her liver in a distribution corresponding to the hypoattenuating regions seen on CT . On the opposed - phase sequence , there was loss in signal within these areas indicating the presence of intracellular fat and water ( Fig.2 ) . In addition , these areas were hypointense to the remaining hepatic parenchyma on the fat suppression MR sequences , confirming presence of fat and thus establishing a diagnosis of SHS . Furthermore , a follow - up CT of her abdomen and pelvis was performed 3 months later , which showed near complete resolution of these findings ( Fig.3 ) . Of note , stricter glucose control had decreased her average blood glucose level to below 200 mg / dL.


A 47 - year - old woman presented to the hospital with a 1 - month history of abdominal distention . Physical examination revealed a huge mass in the lower abdomen . The peripheral blood test showed elevated levels of carcinoembryonic antigen ( CEA , 335.2 ng / mL [ normal , < 5 ng / mL ] ) and carbohydrate antigen ( CA ) 125 ( 219 U / mL [ normal , < 45 U / mL ] ) but a normal level of CA19 - 9 ( 9 U / mL [ normal , < 37 U / mL ] ) . Computed tomography ( CT ) demonstrated a large , round mass with a maximum diameter of 15 cm in the pelvic cavity without the presence of ascites or pleural effusion ( Fig.1a , b ) . Colonoscopy identified an elevated lesion with severe stenosis in the sigmoid colon , and histopathological examination of biopsy specimens from the tumor showed moderately differentiated adenocarcinoma . Although we scheduled an early operation , the patient developed acute dyspnea and general edema 2 weeks after the first CT scan . The second CT scan examination demonstrated massive bilateral pleural effusion with atelectasis and ascites ( Fig.2a , b ) . Thoracic drainage and laparotomy were emergently performed . Macroscopically , the tumor in the sigmoid colon had invaded the serosa , and the huge pelvic mass was found to contain a right ovarian tumor . Several small nodules of peritoneal dissemination were distributed over the greater omentum . Perioperatively , 3800 mL of serous ascitic fluid was drained . Cytodiagnosis of the fluid drained from the ascites and pleural effusion revealed no tumor cells . Bilateral oophorectomy , total hysterectomy , omentectomy , and sigmoidectomy with regional node dissection were performed ( Fig.3a ) . Histopathological examination of the resected specimens showed moderately differentiated adenocarcinoma in the tumors of both the ovaries and the sigmoid colon ( Fig.3b ) . The dissected paracolic nodes showed malignant cells . Immunohistochemically , tumor cells from the ovaries and the colon both showed positive expression of cytokeratin 20 ( CK20 ) but no expression of cytokeratin 7 ( CK7 ) , confirming that the ovarian tumors were metastases from primary colon cancer ( Fig.4a , b ) . The postoperative course was uneventful , and both pleural effusion and ascites rapidly resolved . Postoperatively , a regimen of 5 - fluorouracil ( 5 - FU ) , leucovorin , and oxaliplatin ( FOLFOX ) was administered every 2 weeks for 5 months . At 29 months after the first operation , the patient required curative hepatic resection for liver metastases . At 78 months after the first operation , the patient remains alive with no evidence of a disease .


An 82 - year - old woman was transferred to our hospital because of dyspnea and massive hemoptysis . The patient had a history of bronchial asthma that was well - controlled with bronchodilator medications . She had no history of tuberculosis , nontuberculous mycobacterial infection , or smoking . The physical examination revealed diffuse bilateral crackles . She suffered from severe hypoxemia ( pH 7.362 , PCO2 35.1 mmHg , PO2 61.0 mmHg , HCO3- 20.1 mmHg , BE -5.5 mmHg , SpO2 90.5 % , under 10 L O2 / min , reservoir mask ) . After the tracheal intubation , 100 mL of bright - red blood was aspirated . A chest radiograph showed bilateral infiltrates ( Fig.1 ) . A chest CT further demonstrated multiple consolidations and ground glass opacity and focal bronchiectasis in right segment 4 ( S4 ) ( Fig.2 ) . There were no space - occupying lesions . Four days after admission , her respiratory condition was improved . Since there was no active hemorrhaging from the tracheal tube , she was then extubated . After that , only a small amount of bloody sputum was coughed up . To determine the origin of bleeding , she underwent contrast - enhanced CT , which showed bronchiectasis in right S4 and regression of the infiltration . CTA revealed an abnormal vascular anastomosis between the right inferior phrenic artery and right pulmonary artery beside the focal bronchiectasis at the right middle lobe ( Fig.3 ) , which led us to suspect it as the possible source of the massive hemoptysis . We therefore performed embolization by superselecting the right inferior phrenic artery with a 2.2 - Fr . microcatheter ( Fig.4 ) . An angiogram of the right bronchial artery showed no obvious active bleeding . Three weeks after the embolization , she was successfully discharged and has been free from recurrent hemoptysis for three years .


In February 2010 , a 77 - year - old man with a history of stroke and peripheral vascular disease presented at our emergency department in florid pulmonary edema . He had a 6 - month history of worsening dyspnea on exertion , paroxysmal nocturnal dyspnea , and leg edema . Upon physical examination , he had diffuse rales and a murmur of aortic stenosis . A 2 - dimensional Doppler transthoracic echocardiogram revealed severe aortic valve stenosis with a peak gradient of 70 mmHg and a mean gradient of 45 mmHg , a calculated aortic valve area of 0.7 cm2 , severe mitral regurgitation , and a severely dilated left ventricle ( LV ) with an ejection fraction of 0.20 . After the pulmonary edema had resolved , cardiac catheterization confirmed the echocardiographic findings and showed nonobstructive coronary artery disease . Given these findings and the patient 's comorbidities , we decided on a minimally invasive surgical approach . The patient was placed in the supine position and underwent anesthetic induction and intubation with a single - lumen endotracheal tube and a bronchial blocker . Intraoperative transesophageal echocardiography ( TEE ) confirmed the previous findings , also showing that the mitral valve leaflets were free of significant disease and that the mitral regurgitation originated in the A2 – P2 portion of the mitral valve ( Fig.1 ) . The mitral regurgitation was thought to be functional , caused by mitral annular dilation and tethering of the papillary muscles by the severely dilated LV . We decided to perform edge - to - edge repair of the mitral valve from a transaortic approach . A femoral platform was used to establish cardiopulmonary bypass . A 2- to 3 - cm incision was made in the left inguinal crease . A 5–0 Prolene purse - string suture ( Ethicon Inc. , a Johnson & Johnson company ; Somerville , NJ ) was placed in the femoral artery and vein . The left femoral artery was cannulated with a 16F–18F arterial cannula . The left femoral vein was cannulated with a 25F Bio - Medicus ® femoral venous cannula ( Medtronic , Inc. ; Minneapolis , Minn ) , which was placed in the superior vena cava with the aid of TEE . We then made a 4- to 5 - cm transverse parasternal incision over the 3rd intercostal space and transected the 4th costochondral cartilage to enable adequate exposure of the aorta . This interspace was chosen in the event that the left atrium needed to be entered . The pericardium was opened above the phrenic nerve and over the aorta to facilitate exposure . A retrograde coronary sinus catheter was inserted directly through the incision , and a purse - string suture was placed in the right atrium . A LV vent was inserted via a purse - string suture in the right superior pulmonary vein . A transverse aortotomy was performed to expose the aortic valve , which was removed under direct vision . The A2 and P2 segments of the mitral valve were identified , and an edge - to - edge repair was carried out with a 5–0 Prolene mattress suture that was reinforced with pericardial pledgets on the ventricular side of the mitral valve ( Fig.2 ) . Next , a 27 - mm Hancock ® II bioprosthetic aortic valve ( Medtronic ) was implanted by use of standard techniques . The aortotomy was closed in 2 - layer fashion , and the patient was weaned from cardiopulmonary bypass . The transected rib was reattached to the sternum with a 1 - cm metal plate ( Synthes , Inc. ; West Chester , Pa ) , and a fiber wire was placed in figure-8 fashion . A single chest tube was left in the pleural space . The thoracotomy was closed in routine fashion . Postoperative TEE showed no mitral regurgitation ( Fig.3 ) ; “ elbowing ” of the anterior leaflet during mid - diastole due to tethering of the anterior leaflet to the posterior leaflet ( Fig.4 ) ; and the double - orifice mitral valve that resulted from the edge - to - edge repair ( Fig.5 ) . After surgery , the patient did well . His shortness of breath resolved , and he was discharged from the hospital on postoperative day 6 . Upon follow - up evaluation in March 2011 , he was asymptomatic , and echocardiography showed grade 1 + mitral regurgitation .


n March 2015 , a 62 - year - old woman was admitted to our hospital . She complained of progressive visual disturbance , which began about 4 years ago and was treated as cataract in local hospital , but no relief was seen . On the contrary , the symptoms aggravated half a year ago , together with headache , left eye pain , tearing and increased secretions , and the computed tomography ( CT ) scan of the brain in local hospital showed a sellar region lesion . Besides , 2 years earlier , the patient underwent resection of melanoma in the left heel ( T2N0M0 , ki67 3–5 % , Stage II ) , followed by resection of the recurred melanoma nearby the primary site 15 months later ( T3N3M0 , Stage III ) , without lymphadenectomy . She had no family history of melanoma . On physical examination , the patient had bilateral temporal hemianopsia , the right finger counting was 1 m , and the left finger counting was no more than 0.5 m. Enlarged lymph nodes were palpable in the right groin . On ophthalmologic examination , the patient had right vision of 0.4 and left vision of 0.08 , with the same intraocular pressure 15 mm Hg bilaterally . The optometry found the right eye of +6.00DS/+0.25DC∗65 ° and the left eye of +6.25DS/+0.50DC∗20 ° . The patient had maculopathy of both eyes and optic atrophy of the left eye . Light reflex and eye movement of both eyes were normal . CT scans of the brain parenchyma , orbital , and chest were unremarkable . CT scan and ultrasound examination of the abdomen showed hepatic portal and retroperitoneal lymphadenectasis and enlarged left lobe of the liver with substantial placeholder lesions . Ultrasound examination of bilateral inguinal lymph nodes discovered multiple low echo light groups , the largest of which was 31 mm in diameter , with hilus of the echo and asymmetrical thickening of the skin . CT scan of sellar region revealed a crumby mass , protruding out of the sphenoid sinus , with obscure boundary and bone destruction . And the average CT value of the mass was 46 HU . Sellar region magnetic resonance imaging ( MRI ) revealed a round mass of 30 mm in diameter in the enlarged sellae ( Fig.1A , B ) . The mass showed isointense in T1 - weighted images ( T1 - WI ) and T2 - weighted images ( T2 - WI ) , with homogeneous enhancement after Gadolinium - DTPA injection , and dural tail sign was seen . Small foci inside the tumor showed hyperintense signals in T1 - WI and hypointense signals in T2 - WI , without enhancement . And it was seen that the mass penetrated meninges , surrounded the left internal carotid artery , and was blurred with the left optic nerve . Pituitary stalk became shorter with a right displacement . Laboratory findings revealed increased levels of prolactin ( 119.08 μg / L , normal range 5.99–30.04 μg / L ) and cortisol ( 677.10 nmol / L , normal range 118.60–618.00 nmol / L ) and decreased levels of free thyroxine ( FT4 ) ( 6.04 pmol / L , normal range 12.00–22.00 pmol / L ) and free triiodothyronine ( FT3 ) ( 2.09 pmol / L , normal range 3.50–6.50 pmol / L ) . The patient was diagnosed with a giant prolactinoma . The patient underwent transnasal transsphenoidal surgery to remove the tumor and relieve the compression of the optic nerve . Intraoperatively , it was seen that the tumor invaded and filled the left interval of the sphenoid sinus , and part of bone in sellar floor and left side parasellar was destroyed and absorbed . A little normal pituitary tissue was seen in the top right of tumor in the sellar turcica . The tumor was reddish black with extremely rich blood supply and had close adhesion to the surrounding structure . The texture in the center of the tumor was soft and much tougher over the rim . Intraoperative frozen - section examination found melanin granules , and it was considered to be malignant melanoma or meningioma . The tumor cells were composed of eosinophilic staining epithelial cells . Most of cell nuclei were round , a few were reniform and hippocrepiform with evident nucleoli , and nuclear fission was seen . The tumor showed no evidence of necrosis ( Fig.2 ) . The tumor was immunopositive focally for melanoma - specific markers such as S-100 , HMB45 , and Vimentin , and immunopositive for neuroendocrine tumor markers such as CgA and Syn ( Fig.3 ) . The Ki67 index was 3 % to 5 % ; it was higher in metastatic melanoma than in the adenomatous component . Taken the melanoma history and suspected lymph node and hepatic metastasis into consideration , the patient was diagnosised with MMPA . After surgery , significant relief was seen in visual field and headache , and the level of prolactin , cortisol , and FT4 returned to normal with hormone replacement therapy . Because the focal liver lesions and lymphadenectasis did not cause much discomfort , the patient refused any further surgical intervention or other treatment . She was discharged from the hospital immediately and was disease free until 2 months after the third surgery . The patient successively found new melanoma metastatic sites in the skin of lower left leg , knees , the upper left leg , the left groin and the right groin , and the right leg . At the follow - up in late January 2016 , the patient could not walk and live by herself and was depressed . At the latest follow - up , in late January , 2017 , the patient was alive with worse symptoms , she had sensory deficits of both legs , which could not move , hyperalgesia of hands and mouth , impaired intelligence , but she lived well with the disease by careful nursing of her daughter .


This 16 - year - old boy was the first child to non - consanguineous parents . His parents and two younger siblings were healthy . He was well until starting school at 7 years of age when he was found to be short in height , slightly myopic , astigmatic and to have subnormal visual acuity . Endocrinological investigations were performed that initially revealed borderline values for growth hormone ( GH ) deficiency and he was therefore treated for a period with GH without any beneficiary effect on his growth . At age 16 years , height and weight was −3 SD below the mean compared with a standardized Swedish growth chart . Ophthalmological investigations at 10 years of age showed pigmentary retinopathy and optic atrophy . An electroretinogram was performed and showed a severe rod cone dystrophy . He had decreased visual acuity , visual fields , color vision , and dark adaption . Nystagmus has been noted since 14 years of age . A year later , photophobia and bilateral cataracts were developed . The cataracts were operated on at 16 years of age . He is now blind . At 14 years of age , he was referred for neurological investigations . A clinical examination showed mild ataxia with tremor , dysmetria and gait instability together with mild to moderate muscle weakness , weak to absent tendon reflexes in the lower extremities , and exercise intolerance . Audiometric investigations revealed a mild bilateral sensorineural hearing impairment . At 15 years of age , he had an unprovoked epileptic seizure and he has since then been treated with levetiracetam . Decreased renal function was identified at 15 years of age , with increased serum creatinine to 145 μmol / l ( reference interval 30–90 μmol / l ) , proteinuria with urine albumine at 244–538 mg / l ( reference interval<20 mg / l ) , and urine albumine / creatinine ratio at 44–59 g / mol ( reference interval <3 g / mol ) . A renal scintigraphy demonstrated reduced kidney size . Cr51 - EDTA clearance showed a decreased glomerular filtration rate of 42 % of normal . The filtration rate decreased over time to 29 % of normal at 16 years of age . Since 14 years of age , cardiac investigations have demonstrated hypertrophy of the walls of the left ventricle ( +3 SD compared with normal ) with normal systolic and diastolic function and without obstruction of the outflow . Mitochondrial investigations were performed at 14 years of age . Blood levels of lactate and pyruvate were 1.6 and 0.096 mmol / l , respectively , leading to a ratio of 33 ( reference interval < 20 ) , while cerebrospinal fluid ( CSF ) levels of lactate and pyruvate were 3.6 and 0.137 mmol / l , respectively , leading to a lactate to pyruvate ratio of 26 . The urinary lactate excretion was normal . The CSF albumin was increased to 258 mg / l ( reference level < 225 mg / l ) and he also had an increased CSF / plasma albumin ratio of 7.4 ( reference level < 5 ) . The serum acyl carnitine profile and muscle carnitine levels were normal . The serum creatine kinase activity was mildly increased to 5.4 μkat / l ( reference interval < 3.5 μkat / l ) .


A 65 - year - old man with a 45 - year history of cigarette smoking visited our hospital for the diagnosis of an abnormal chest shadow on X - ray . He did not have any remarkable medical history and had not been prescribed anticoagulants or antiplatelet agents . A computed tomography ( CT ) scan revealed a huge mass in the left upper lobe ( maximum size : 11.0 cm in diameter ) that subsequently expanded to the left hilum and mediastinum , as well as an intrapulmonary metastasis located in the left lower lobe , pleural effusion on the left side , and multiple liver tumors ranging from 0.5 to 4.7 cm in diameter ( Fig.1 ) . Of note , some of the liver metastases were located subcapsularly , and the liver surface was irregularly distorted . The laboratory findings were as follows : white blood cell count 11,900 / mm3 , hemoglobin 14.8 g / dL , platelet count 214,000 / mm3 , aspartate transaminase 31 IU / L , alanine transaminase 19 IU / L , and lactate dehydrogenase ( LDH ) 749 IU / L. No coagulation abnormalities were found . A subsequent histological examination of a tumor specimen obtained by bronchoscopy confirmed the diagnosis of small cell carcinoma . On considering the clinical diagnosis , performance status , and age of the patient , we decided on a regimen of antitumor chemotherapy consisting of cisplatin ( 60 mg / m2 body surface area on Day 1 ) and etoposide ( 100 mg / m2 body surface area on Days 1 - 3 ) . On a day after 2 weeks from the initial CT scan , he started his first chemotherapy session . On Day 3 after initiating chemotherapy , he complained of abdominal discomfort , and his vital signs showed tachycardia ( 120 beats per minute ) and hypotension ( 85/55 mmHg ) . A hematological examination showed severe anemia ( hemoglobin 6.7 g / dL ) that had dramatically dropped from 14.8 g / dL over 10 days . We attempted to identify the bleeding site on gastrointestinal endoscopy , to no avail , but a CT scan revealed the rapid enlargement of a liver tumor in the left lobe , which contained partial high - density areas on the plain scan , and also a novel finding of ascites showing higher density than usual , all suggesting a ruptured liver metastasis and associated hemorrhagic ascites ( Fig.2 ) . A subsequent contrast - enhanced CT image was negative for extravasation . He underwent angiography for the left and right hepatic arteries , but we only observed obscure tumor vessels in the left hepatic lobe without extravasation ( Fig.3A ) . We suspected this might be due to the hypovascularity of the metastatic tumors and inactive bleeding at the time . Although the benefit of therapeutic embolization of the hepatic artery was uncertain based on the findings on angiography , we performed transcatheter arterial embolization ( TAE ) of the left main hepatic artery using gelform particles to prevent future re - bleeding . Post - embolization angiography revealed a slowed blood flow in the left hepatic artery , and the peripheral vessels were weakly visualized ( Fig.3B ) . After the embolization concomitant with supportive therapies , including RBC transfusions of 6 U in total , the clinical course of the patient stabilized . His blood pressure remained around 120/70 mmHg , tachycardia disappeared , and the anemia was improved after transfusion and did not progress again . Liver dysfunction did not appear . A month after the embolization , he was in relatively good health and re - started his antitumor chemotherapy , which he continued ( first - line regimen ) for six courses . A good partial response was gained after chemotherapy for both the lung and liver lesions .


The institutional review board ( Chengdu Military General Hospital ) approved this work and waived the need for informed consent . In 2013 , a 66 - year - old farmer with a history of ventricular tachycardia ( VT ) and hypertension presented to the Emergency Department with continuous palpitation , chest tightness , profuse sweating and nausea with no obvious predisposing causes . The patient experienced a sudden drop in blood pressure and acute confusion . After an immediate electrical conversion , his consciousness was gradually restored , and symptoms relieved . Then , this patient was transferred to the Department of Cardiology for further evaluations and treatments . The patient 's blood pressure was 105/75 mm Hg upon admission , with a heart rate of 75 beats / min , body temperature of 36.6 ° C and respiration rate of 18 times / min . The heart border extended to the left , with the apical impulse located in the left 5th intercostal space , 1.0 cm lateral to the midclavicular line . The patient had a history of hypertension over 30 years without regular antihypertensive medication . The highest blood pressure was 170/110 mm Hg . There was no family history of early coronary artery disease or sudden cardiac death . He did not smoke cigarettes or use illicit drugs , and rarely consumed alcohol . He also reported no known contacts with sick persons and no recent travel . Twelve - lead surface electrocardiogram ( ECG ) of VT indicated that the origin of VT was at the boundary between right ventricular outflow tract ( RVOT ) and tricuspid valve . When VT increased to 150 beats / min or higher , no epsilon waves were found in the precordial leads ( Figure1A and B ) . In contrast , when VT decreased to 120 beats / min or lower , epsilon waves appeared in leads V1 – V2 ( Figure1C ) . Notably , the epsilon waves preceded QRS waves in leads V1 – V2 , while endocardiac tracing confirmed that the corresponding local potential originating from RVOT appeared prior to the ventricular rhythm ( Figure (Figure1D).1D ) . Sinus ECG in the year of 2013 suggested a slight left deviation of electric axis , with a heart rate of 87 beats / min and flat T waves in lead II . T wave inversions were found in leads III , avF and V1 – V3 , meanwhile epsilon waves were found following QRS complex in leads V1 – V3 ( Figure (Figure2B).2B ) . When the lead avR was amplified , epsilon waves were also found behind QRS waves ( Figure 2C ) . Atrial premature beats appeared occasionally . Moreover , ventricular premature beats were also found to originate from the right ventricular apex , with epsilon waves appearing behind QRS waves ( Figure (Figure2B).2B ) . In contrast , sinus ECG obtained in the year of 1999 revealed similar left deviation of electric axis , flat T waves and T wave inversions , but absence of epsilon waves ( Figure (Figure2A).2A ) . Data from biochemical assays were as follows : cardiac troponin I level was 0.714 μg / L ( normal range , 0–0.06 μg / L ) , serum B - type natriuretic peptide level was 466.530 pg / mL ( normal range , 0–100 pg / mL ) , serum d - dimer level was 8.14 mg / L ( normal range , 0–0.55 mg / L ) , blood urea level was 11.69 mmol / L ( normal range , 2.90–7.20 mmol / L ) , serum creatinine level was 144.00 μmol / L ( normal range , 44–133 μmol / L ) , serum uric acid level was 611.40 μmol / L ( normal range , 100–432 μmol / L ) , and endogenous creatinine clearing value was 57.90 mL / min ( normal range , > 80 mL / min ) . Echo data revealed remarkably enlarged right atrium and right ventricle , and widened ROVT . Uncoordinated motions of the left and right ventricular walls were also detected . Moreover , we also found aortic valve degradation with slight regurgitation , slight mitral regurgitation , and moderate to severe tricuspid regurgitation . The left ventricular diastolic function was reduced to 55 % ( Figure 3A and B ) . The coronary angiogram revealed no vascular stenosis ( Figure 3C – E ) . Based on the above - mentioned examinations , this patient met at least 2 major criteria , the bilateral ventricular dilation and the existence of epsilon waves , providing diagnostic support for ARVC . A diet with low salt and low fat was suggested . The patient was also treated with metoprolol succinate sustained - release tablets ( 23.75 mg daily , p.o . ) , amiodarone ( 200 mg daily , p.o . ) , furosemide ( 20 mg daily , i.v . ) , and compound α - ketoacid tablets ( 2.52 g daily , p.o . ) . Moreover , VTs with different morphologies and cycle lengths were found during radiofrequency ablation ( Figure 4 ) . The substrate voltage mapping revealed that the anterior wall of RVOT was wrapped by circular scar ( Figure 5A ) . Considering the association of VT with scar areas , substrate ablation was chosen for this patient . The residual potentials in the scar areas were searched , and then linear and focal ablations were performed ( Figure 5B ) . Neither programmed stimulation nor induced stimulation could induce VT after the procedure was completed , indicating the success of operation . The ECG after radiofrequency ablation showed sinus rhythm , with a heart rate of 61 beats / min , T wave inversions in leads III and avF , and epsilon waves and T wave inversions in leads V1 – V3 ( Figure 2D ) . This patient was discharged from hospital on day 9 with a regimen of metoprolol succinate sustained - release tablets ( 23.75 mg daily , p.o . ) , amiodarone hydrochloride tablets ( 200 mg daily , p.o . ) , spironolactone tablets ( 40 mg daily , p.o . ) , and fosinopril sodium tablets ( 10 mg daily , p.o . ) . The patient was followed up 3 months after discharge . He had no recurrent palpitation , chest tightness , profuse sweating or nausea . Although ARVC was the main diagnosis at the time of this patient 's initial presentation , it is essential in such cases to perform a reassessment for the presence of structural heart disease , which can evolve over time .


A 65 - year - old man was admitted to the China - Japan Friendship hospital with a chief complaint of progressive dysphagia for 3 mo . He also complained of a drastic weight loss of 8 kg in the past 2 mo . He denied a history of smoking , alcohol intake and substance abuse , but had a chronic atrophic gastritis for nearly 10 years . Also , there was no family history of genetic defect or malignancy . Physical examination showed no palpable findings . Admission blood test showed a slight decrease in hemoglobin ( 106 g / L ) . Upper gastrointestinal ( GI ) examination using barium contrasts showed a large tumor blocking the esophago - gastric junction ( Figure 1 ) . Computed tomography ( CT ) scan revealed a soft mass in the esophago - gastric junction with lymph node metastasis in the lesser curvature of the stomach ( Figure 2 ) . Endoscopic examination showed a black spot in the lower esophagus and a bulky black mass blocking the esophago - gastric junction , as well as two black crater - like ulcers in the fundus of the stomach ( Figure 3 ) . Biopsy specimens taken from the tumor were identified as poorly differentiated adenocarcinoma . Preoperative nutrition status of this case was scored 2 based on the Nutrition Risk Screening 2002 ( NRS 2002)[6 ] . Because of the obstructive symptom caused by the tumor , a debulking surgery of distal esophagectomy and proximal gastrectomy was performed . Esophagogastric anastomosis and reconstruction was then completed with stapling device . Intraoperatively , the tumor was found located at the esophago - gastric junction and the tumor infiltrated the whole layer with lymph node metastasis at station four . No ascites or dissemination of the tumor was observed in the peritoneal cavity . The tumor measured 3 cm × 6 cm in size with black pigmentation ( Figure 4 ) . There were several pigmented satellite nodules beside the main tumor lesion , the largest one being 1 cm × 1 cm in diameter . Moreover , two ulceration lesions were found at the fundus of the stomach . Microscopically , the excised tumor tissue was composed of non - organized and pleomorphic cells exhibiting atypical nuclei , and abundant melanin granules ( Figure 5 ) . Pathological examination identified this case at a stage of IVA ( T4aN1M0 ) . Immunohistochemical staining showed that the tumor was positive for S-100 , HMB-45 , mclean - A and Vimentin , but negative for cytokeratin 7 and cytokeratin 20 ( Figure 6 ) . Based on these results , a diagnosis of primary advanced esophago - gastric melanoma was established . The postoperative course was smooth and without complications . The patient gradually recovered and was discharged 14 d after surgery . As the patient denied a postoperative adjuvant therapy , abdominal recurrence and hepatic metastases were found within one month by a postoperative follow - up CT . No other effective treatment was administered afterwards . The patient died of diffuse metastatic disease 2 mo later .


A 65 - year - old woman reported persistent back pain for almost 3 months . The symptoms would be severe after walking or changing positions and would be slightly relieve after taking painkillers . The patient described no pain or numbness in her legs . She also described no bowel or bladder voiding difficulties . The patient reported past medical history of hypertension , coronary heart disease , cerebral infarction , and asthma , all of which were well controlled . Physical exam demonstrated kyphosis of the thoracic spine in standing position and lumbar vertebra bend forward and backward straight activities were limited . There is obvious rap pain in back about T12 level . The patient 's general medical examination was unremarkable in upper and lower extremity motor , stretch reflex , and sensory examinations . X - ray , computed tomography ( CT ) , and magnetic resonance imaging ( MRI ) exams were performed after the patient in hospital ( Fig.1 ) . The lateral X - ray showed T12 fracture with 40 ° kyphotic cobb angle . CT showed an intravertebral vacuum sign . Sagittal T1 - weighted MRI showed a decreased signal intravertebral vacuum cleft and posterior cortex breakage with cord compression in T12 . Sagittal T2 - weighted MRI showed an increased signal in the intravertebral vacuum cleft . The patient was diagnosed with Kümmell disease ( Stage III).[9 ] The operation was performed under general anesthesia and prone position . A standard posterior exposure of the spine was given , pedicle screws were inserted in target vertebrae T10 , T11 , L1 , and L2 under C - arm guidance.[10 ] The screws were connected on the left side with a temporary stabilizing rod . Laminectomy was performed to decompress and fully visualize the spinal cord.[10 ] Careful subperiosteal dissection was carried out on the right side to exposure the lateral wall of the T12 vertebral body until the anterior aspect was reached . The right side pedicle and articular process of the T12 vertebral body were removed . T11 / T12 and T12 / L1 intervertebral disks were also removed . Then , the temporary stabilizing rod was replaced by rod bended to the desired contour . Autologous bone graft and titanium mesh were placed in the intervertebral space . Another rod with the desired contour was connected on the right side . Adequate hemostasis was ensured and wound was thoroughly irrigated with saline . Drainage tube was inserted and the surgical wound was closed layer - by - layer.[10 ] Time from skin incision to completion of wound closure lasted 150 minutes , and estimated blood loss totaled 600 mL. Postoperatively , the patient was given preventive antibiotic treatment for 1 day , pain treatment for 3 days , and anticoagulant therapy for 1 week . The drainage tube was removed at 3 days postoperative when volume of drainage was less than 50 mL per 24 hours . Patient was allowed out of bed with a custom - made plastic orthosis at 1 week after operation . The plastic orthosis was kept for at least 3 months . The patient was allowed out of hospital at 12 days after operation when surgical suture had been removed . Pain assessments were conducted using the visual analogue scale ( VAS ) . VAS for preoperative , 1 week after operation , and 1 year after operation were 9 score , 3 score , and 2 score , respectively , which demonstrated significant improvement . The patient resumed normal activities and returned to work at 3 months after operation . Kyphotic Cobb angle for preoperative , 1 week after operation , and 1 year after operation were 40 ° , 8 ° , and 17 ° , respectively , which demonstrated significant improvement ( Fig.2 ) .