A 54 - year - old woman with stage IV NSCLC was treated with carboplatin and paclitaxel without disease response . Molecular analysis of tumor tissue was unavailable at that time . However , her demographic profile ( Asian , minimal smoking history , non - small cell histology ) predicted her disease would harbor EGFR TKI sensitive cells [ 2 ] . Therefore , she then initiated standard daily dosing of erlotinib ( 150 mg ) and her disease responded . Twenty - eight months later , she acquired resistance to erlotinib with progression of disease systemically . Following further progression through an experimental angiogenesis inhibitor , she initiated pemetrexed and resumed standard dose erlotinib . After initial response , 11 months later , her disease again progressed . DNA was extracted from biopsy of a progressing lung lesion and examined using established techniques for analysis of EGFR mutations [ 5 ] . Direct sequencing of exons 18–21 encoding the kinase domain of EGFR revealed the L858R mutation associated with EGFR TKI sensitivity ( Fig.1 ) [ 2 ] . It also demonstrated the T790 M mutation associated with acquired EGFR TKI resistance ( Fig.1 ) [ 2 ] . She also developed headaches and there was a high clinical suspicion of CNS metastases despite negative imaging ( not shown ) . She refused a lumbar puncture . She initiated empiric temozolomide plus standard dose erlotinib ( 150 mg daily ) for presumed CNS disease , but after one cycle her headaches worsened , and she developed nausea and vomiting concerning for CNS metastases with associated raised intracranial pressure . Magnetic resonance imaging ( MRI ) of the brain now demonstrated LM ( Fig.2 ) confirmed by CSF cytology ( not shown ) . By direct sequencing , DNA from CSF cells harbored L858R predicting EGFR TKI sensitivity ( Fig.3 , left panel ) but not the T790 M resistance mutation ( data not shown ) . Because the result for T790 M was negative in this sample , we performed a more sensitive fluorescence detection PCR - based assay that takes advantage of a PCR restriction fragment length polymorphism generated by the specific missense mutation ( Fig.3 , right panel , arrow , positive control ) [ 6 ] . That result was also negative , as only the wild type peak was detected ( Fig.3 , right panel , bottom ) . Therefore , we hypothesized that the LM remained sensitive to an EGFR TKI if sufficiently high concentrations of drug could be achieved in the CSF . The erlotinib concentration required to inhibit growth of cell lines harboring L858R by 50 % ( IC50 ) is 100 nM ( nM ) [ 2 ] . Standard dose erlotinib ( 150 mg daily ) achieves 3000 nM in plasma [ 7 ] , but CSF concentrations of EGFR TKIs are as low as 1 % plasma levels below the IC50 [ 3 , 8 ] . Increasing the daily dose of gefitinib to enhance CSF penetration has been an effective strategy [ 3 ] , but gefitinib is no longer available in the United States following failure in phase III NSCLC trials . An analogous increase of the daily erlotinib dose above 150–200 mg daily induces unacceptable toxicity . However , weekly high - dose erlotinib up to 2000 mg is tolerable [ 4 ] . Pharmacokinetic analysis of CSF from another patient with NSCLC LM ( not shown ) treated with 1500 mg erlotinib weekly demonstrated a peak plasma concentration of 11,300 nM with a concurrent CSF concentration of 130 nM. Therefore , such high dose weekly administration of erlotinib achieved a CSF concentration exceeding the IC50 . Therefore , to increase CSF penetrance over standard daily erlotinib dosing in this patient , we initiated high - dose weekly erlotinib at 1000 mg then 1200 mg ; persistent nausea precluded higher doses . Pharmacokinetic analysis was not undertaken in this patient . After 1 month there was a partial radiographic response of LM on brain MRI ( Fig.2b ) and after 2 months in the cauda equina ( not shown ) . However , hydrocephalus and persistent symptoms referable to increased intracranial pressure led to a VP shunt and whole - brain radiation therapy , after which she resumed treatment with 1500 mg weekly erlotinib . One month later , progressive intra - thoracic disease led to initiation of cetixumab and erlotinib was continued but changed to low dose ( 100 mg ) daily . She survived 14 months following the diagnosis of CNS disease .


A 53 - year - old man came to our hospital with signs and symptoms of acute heart failure after a 2 - week history of progressive breathlessness . He had a history of recurrent skin abscesses and atopic dermatitis and regularly visited a dermatologist in our hospital . On arriving at our hospital , his extremities were warm and dry . According to the New York Heart Association criteria , he had class III congestive heart failure ( CHF ) . An electrocardiogram revealed diffuse nonspecific T - wave changes , low voltage ( < 5 mm ) in the extremity leads and poor R - wave progression in the anterior chest leads . Multiple sporadic ventricular premature beats were seen ( Figure 1 ) . Chest x - ray film confirmed right pleural effusion , and mild cardiomegaly but no pulmonary congestion ( Figure 2 ) . Blood tests showed severely elevated B - type natriuretic peptide ( 901 pg / mL ) and markedly raised IgE ( 12 000 IU / mL ) without eosinophilia ( eosinophil count of 1.62×108 / L ) . Biochemical analysis revealed no significant findings : blood urea nitrogen of 14.3 mg / dL [ reference value ( RV ): 7.00–22.00 ] , creatinine of 0.90 mg / dL ( RV : 0.60–1.00 ) , C - reactive protein ( CRP ) of 0.2 mg / dL ( RV : 0.00–0.50 ) , serum amyloid A ( SAA ) of 7.0 μg / mL ( RV : 0–8.0 ) , and troponin T of 0.07 ng / mL ( RV : 0–0.1 ) . Immunology testing revealed negative perinuclear anti - neutrophil cytoplasmic antibodies and no elevation of myeloperoxidase antibodies . The distribution of albumin and globulin in the serum was normal . Serum protein immuno - electrophoresis did not reveal M - protein , and urinalysis revealed no Bence - Jones protein . Transthoracic echocardiography ( Figure 3 ) showed concentric mild left ventricular ( LV ) hypertrophy ( 12 mm ) without the characteristic granular sparkling appearance and pericardial effusion , preserved ejection fraction ( 60 % ) , and bi - atrial enlargement with normal ventricular chambers . Doppler - derived LV diastolic filling demonstrated a restrictive pattern with a trans - mitral early filling wave deceleration time of 160 ms and an elevated E / A ratio of 2.8 . A markedly elevation of E / e ’ ratio of 27.3 indicated elevated LV filling pressure . On day 1 of hospitalization , we prescribed an angiotensin - converting enzyme ( ACE ) inhibitor and low - dose diuretics . On day 3 of hospitalization , after initiating ACE inhibitor and diuretic therapy , the patient ’s symptoms resolved . The dermatologists performed a biopsy of a blue macula of the forehead skin . On day 4 , we introduced a low - dose β - blocker and performed an endomyocardial biopsy ( EMB ) , obtaining 3 fragments of the right ventricular septum because diagnostic confirmation of cardiac amyloidosis requires the demonstration of amyloid deposits . In addition , we performed right heart catheterization ( RHC ) , and coronary angiography to exclude obstructive coronary artery disease . The data obtained from the RHC indicated subset type IV according to the Forrester classification . The right ventricular pressure curve did not show a dip - and - plateau configuration . Skin biopsy revealed hyperkeratosis in the epidermis and mild inflammatory changes throughout the dermis with an infiltration of lymphocytes . The specimen exhibited apple - green birefringence with polarized light after Congo red staining ( Figure 4 ) . Histological examination of the myocardial specimen showed no signs suggesting myocarditis , eosinophilic granulomas , or cardiomyopathy with iron deposition , but Congo red staining revealed amyloid deposits ( Figure 5 ) . In addition , a strongly positive immunohistochemical reaction to immunoglobulin λ - chain in the myocardial interstitium led us to diagnose this patient ’s systemic amyloidosis as AL amyloidosis . The patient generally tolerated the low - dose β - blocker well and was discharged on day 10 with no complications . The patient is currently being followed - up at 6 - month intervals as an out - patient , with no exacerbation of the CHF thus far .


Our patient was a 7 - year - old Italian boy born after an uneventful gestation of normal duration . At the age of 16 months , he presented with a clinically evident enlarged abdomen and was referred for oncological examination . Initial tests revealed anemia , thrombocytopenia , and splenomegaly . A bone marrow biopsy revealed the presence of foam cells , which led to suspicion of lysosomal storage disease . Biochemical testing revealed elevated level of acid phosphatase ( 47.8 IU / L [ normal range 5–7 IU / L ] ) and chitotriosidase activity ( 508 nmol / mg protein [ normal range 5.9–41.0 nmol / mg protein ] ) , as well as reduced beta - glucosidase activity ( 2 nmol / mg / protein [ normal range 4.5–18.0 nmol / mg / protein ] ) . Molecular analysis showed homozygous L444P mutations in the GBA gene ( OMIM reference 606463 ) , confirming the diagnosis of chronic NGD . The patient began ERT at a dosage of 60 U / kg every 2 weeks at the age of 18 months . Thereafter , when the patient reached the age of 30 months , we decided to combine ERT with SRT with miglustat . This clinical decision was approved by our institution ’s ethics committee , and informed consent was obtained from the patient ’s parents before commencing combination therapy . The dose of miglustat was adjusted according to the patient ’s body surface area and was uptitrated during the first 4 weeks with the following scheme : one - third of target dose during weeks 1 and 2 , two - thirds of target dose during weeks 3 and 4 , and target dose ( 100 mg three times daily ) after 1 month . From 2 weeks before starting miglustat therapy , the patient also followed specific dietary modifications , avoiding high intake of carbohydrate - containing food in single meals , especially foods high in disaccharides , such as sucrose and maltose , to ensure acceptable gastrointestinal tolerability . He experienced mild episodes of diarrhea after commencing miglustat therapy , which decreased in frequency / severity over time . From the start of ERT / miglustat combination treatment , we observed a reduction in splenomegaly and a gradual normalization of hematological values and plasma angiotensin - converting enzyme activity ( Table 1 ) . Plasma chitotriosidase was evaluated at the time of diagnosis and then approximately every 6 months during follow - up . Values showed an initial reduction after the start of ERT , with a further , substantial , and sustained decrease after commencement of miglustat treatment ( Fig.1 ) . The patient has been followed according to recommended guidelines for GD , which specify a complete neurological examination , clinical evaluation of ocular movements , and psychological evaluations every 6–12 months [ 10 ] . After 5 years of combination therapy and follow - up , the patient did not show any signs of neurological impairment . As of February 2016 , he had not displayed any epileptic crises and had demonstrated clinical performance and cooperation . He showed good muscular tone and trophism , normal reflexes with a slight hyperreflexia in his legs , and a negative Romberg sign . His toe and heel deambulation was normal . In particular , ocular evaluations revealed no evidence of saccadic movement velocity reduction and normal visual evoked potentials . The patient ’s auditory brain responses were also normal . In addition , he has not demonstrated any cognitive impairment , and he has regularly attended school with good performance since the age of 5 years .


A 69 - year - old male diabetic patient was admitted with acute left ventricular ( LV ) failure and was treated with intensive decongestive therapy . He had severe peripheral edema and bilateral basal crepitations . Initial workup revealed normal levels of troponine ( < 0.01 ng / ml ) and CPK - MB ( 4.6 ng / ml ) , thereby ruling out acute coronary syndrome . The level of BNP was 1230 pg / ml confirming the diagnosis of heart failure . Echocardiographic assessment revealed LVEF of 10 % with dilated cardiac chambers , and estimated pulmonary artery systolic pressure ( PASP ) was 70 mm of Hg with features of raised LV diastolic pressure . Angiography was performed after 3 days of decongestive therapy which revealed critical triple vessel disease with left main coronary artery disease ( Fig.1 ) . He was referred for CABG . The patient was put on frusemide infusion with oral ramipril and aldactone . He was taken up for elective OPCAB 1 week after angiography . Renal function was monitored regularly to adjust diuretic dose . There was no feature of end organ dysfunction . STS risk of mortality was 2.4 % . Repeat echocardiographic assessment revealed improvement of LVEF to 15 % and decrease in PASP to 30 mm Hg and decrease in LV filling pressure . OPCAB was performed through median sternotomy . Left ITA was used for grafting left anterior descending artery ( LAD ) . After revascularizing LAD , right ITA ( RITA ) and RA composite , graft was prepared . The distal end of RITA was used for revascularizing the diagonal artery . There was significant improvement in systolic blood pressure after this distal anastomosis . After these two grafts , heart was lifted for lateral and posterior wall vessels . We make a longer skin incision , open the sternum widely , and release pericardium on the right side to displace the heart gradually . This was supplemented with headlow and lateral tilt position . Liberal doses of inotropic support were used . RA was used for sequential grafting of obtuse marginal , posterior LV branch , and posterior descending artery . All these five distal anastamoses were performed uneventfully . The patient was electively ventilated for 2 days . Echocardiography on 1st POD revealed improvement in LVEF to 20 % . He was started on low dose beta blockers after inotropic supports were weaned off . He had slow and uneventful recovery . Echocardiography on 4th POD revealed improvement in LVEF to 30 % ( Table 1 ) . He had persistent pleural drainage requiring prolonged intensive care unit stay . After pleural drainage subsided and drains were removed , he was discharged on diuretics , low dose beta blocker , and ramipril .


Our 24 - year - old non - smoking male patient presented with repeated hemoptysis in May 2008 with 4 days of concomitant right thoracic pain which intensified while breathing . During holidays in his home country , this Cuban patient suffered from a cold with fever and a strong cough . The strong dry cough persisted after recovery from the cold . The patient did not report any loss of weight . The initial CT scan of the thorax showed a 12 × 4 cm solid mass paravertebral right in the lower thorax without any signs of metastases ( Figure 1 ) . The bronchoscopy ( Figure 2 ) with non - bleeding biopsy revealed a mass of the lower right bronchus which histologically and immunohistologically provided evidence of a granular cell or Abrikossoff tumor [ 1 ] . The bronchial lavage which followed was negative for malignant cells . The patient was discharged and surgical intervention was planned . Four days after discharge a spontaneous hemothorax developed . The patient needed to be readmitted and the hemothorax was drained . No malignant cells were detected in the cytological examination of the drained liquid . After an uneventful course and decreasing of the hematoma , the tumor was excised by performing a lower right lobectomy 6 months after the initial admission . The final histological examination confirmed a peribronchial and infiltrating S100 positive tumor supporting the Schwann cell origin theory with very low growth rate of 2 % and a size of 15 mm ( Figure 3 ) .


A 25 - year - old female patient had noticed left - sided visual loss and amenorrhea 2 years prior to being seen , with right hemiparesis developing 6 months beforehand . Aggravated symptoms ( drooping at corner of right lip and bilateral temporal hemianopia ) finally prompted hospitalization . At that time , a massive ( > 5 cm ) tumor of intra- and suprasellar location , excluding mesencephalon backward , was seen on computerized tomography ( CT ) of the head ( Fig.1a ) . Further testing revealed an exceedingly high - serum level of prolactin ( PRL ) ( 4408 ng / ml ) , whereas levels of all other pituitary hormones were within reference ranges ( growth hormone ( GH ) , 0.50 ng / ml ; luteinizing hormone ( LH ) , 2.60 mIU / ml ; follicle - stimulating hormone ( FSH ) , 4.57 mIU / ml ; adrenocorticotropic hormone ( ACTH ) , 37.4 pg / ml ; thyroid - stimulating hormone ( TSH ) , 2.68 μIU / ml ) . T1 - weighted magnetic resonance ( MR ) imaging with contrast ( gadolinium ) showed homogeneous tumor enhancement , but adjacent tissue was not edematous in T2 - weighted views . The mass did not regress , despite a 4 - week course of the dopamine analog , cabergoline ( 1 mg / week ) , and serum PRL level ( 2207 ng / ml ) remained elevated . Relative to status at admission , the right lateral ventricle also had enlarged somewhat , due to obstruction at foramen of Monro ( Fig.1b ) . In light of this intransigence , surgical debulking of tumor was elected first , through craniotomy and then via transsphenoidal approach . The hardened elastic quality of the tumor and its strong attachments to neighboring structures prevented complete removal , but related mass effect was significantly reduced and serum PRL level declined ( to 250 ng / ml ) in steps at each procedural stage . But the normalization of PRL level had not been achieved with the administration of cabergoline increased up to 0.5 mg / day . The residual tumor showed no evidence of regrowth or distant metastasis 1 year after surgery . Histopathologically , hematoxylin and eosin ( H&E)-stained sections of specimens from the first and second surgical procedures similarly were composed of polygonal and spindle cells with round , oval , or elongated nuclei and eosinophilic cytoplasm ( Fig.2a – c ) . The cells formed irregular nests or short fascicles , accompanied by frequent hyaline changes in vessel walls and vacuolation ( Fig.2d ) . Some nuclear pleomorphism was prominent ; on the other hand , neither a high mitotic rate nor necrosis was evident ( Fig.2b , c ) . Conspicuous fibrous change of tumor stroma was noted focally as well ( Fig.3a ) . The chromophobic nature of tumor cells was confirmed by Pearse ’s Periodic Acid Schiff ( PAS ) stain ( Fig.3b ) . Immunostains showed strong diffuse positivity for PRL ( Fig.3c ) , chromogranin - A , and synaptophysin . No other hormones ( GH , TSH , ACTH , LH , FSH ) were expressed by tumor cells , and the other markers , including S-100 protein ( Fig.3d ) , glial fibrillary acidic protein ( GFAP ) , epithelial membrane antigen ( EMA ) , cytokeratin AE1 / AE3 ( CK AE1 / AE3 ) , vimentin , p53 , and bcl-2 , were also negative by immunostaining . Ki-67 labeling index was approximately 2 % . A final diagnosis of PRL - producing pituitary adenoma was reached after considering the immunohistochemical profile , suprasellar location , and prolactin production of the tumor , as well as the absence of metastatic foci and invasion into surrounding tissue .


A 70 – year – old female presented to the Emergency Department with palpitations , dyspnea and anterior epistaxis . She had a 3 years history of atrial fibrillation and chronic heart failure NYHA class III . She was treated with aspirin 100 mg / day . Physical examination revealed an irregular pulse of 148 beats / min , blood pressure of 130/100 mmHg , pansystolic mitral murmur of 2/6 grade , murmur of tricuspid regurgitation of 3/6 grade , lower extremities swelling . The oto - rhino - laryngology exam conclusion was of anterior epistaxis . The 12 – lead electrocardiogram revealed atrial fibrillation , inferior ischemia . Her International Normalized Ratio ( INR ) was of 1,24 . The two – dimensional transthoracic echocardiography showed the thickening of the mitral valves with a moderate mitral insufficiency and a mobile round mass in the left atrium , heterogeneous , inhomogeneous , of 18 mm in size , attached with a narrow stalk to the interatrial septum . It showed a tumor – like movement with a cardiac cycle , reaching the mitral annular plane ( Figure 1,Figure 2 ) . Also , echocardiography showed tricuspid insufficiency with a maximum gradient of 30 mmHg , intact interatrial septum , akinesia of two thirds of basal inferior wall , ejection fraction of 42 % . There was no mass in the left atrial appendage . The two – dimensional transesophageal echocardiography confirmed the presence of the intraatrial mass . Epistaxis was considered to be due to heart failure and the increased venous pressure . The patient was referred to the cardiovascular surgery clinic , but she refused surgery . Anticoagulation with fraxiparine of 0,6 ml / day was started and continued for 3 weeks , after cessation of epistaxis by nasal tamponament . After 3 weeks the echocardiography was repeated , with no remnant mass in the left atrium . The conclusion was that the mass must have been a thrombus that has melted away . In this particular case , the left intraatrial thrombus may have been due to the presence of atrial fibrillation .


A 78 - year - old previously healthy male heavy smoker presented at the Emergency Department with generalized jaundice ( sclera and skin ) , ascites , and hepatic coma . The relatives declared that he was known to have a urinary bladder carcinoma that was diagnosed at a routine control performed 3 months before but no medical papers to prove this diagnosis were shown . They also mentioned a 2 - month history of progressive jaundice , somnolence , and temporary loss of consciousness . No weight loss or other clinical signs were mentioned . No previously viral hepatitis or drug excess was reported . No family history of cancer was declared . At the present admission , the abdominal CT scan showed marked hepatomegaly with multiple small nodules ( 2–10 mm in diameter ) that was supposed to be hepatic metastases from the bladder carcinoma . The thoracic x - ray showed a bilateral bronchopneumonia without abnormal opacities . The patient died with hepatic encephalopathy at 7 hours after admission . Prior to the autopsy , signed informed consent of the relatives was obtained for the case publication . Being about a case report , no Ethical Committee approval was necessary . At autopsy , the macroscopic examination showed a huge liver ( 6.5 kg ) with widely distributed white nodules of varying sizes ( Fig.1 ) . The urinary bladder was not modified , but a 30 × 30 × 50 mm prostate nodule with infiltrative aspect was observed ( Fig.2 ) . The bilateral bronchopneumonia was confirmed , without any central tumor mass . A 10 - mm white nodule was identified encasing a small bronchus from the middle lobe of the right lung , without peripheral nodules ( Fig.3 ) . Except for moderate edema , no other brain lesions were identified . The other organs did not show modifications . The tissues were fixed in 10 % neutral formalin and embedded in paraffin together with iliac crest bone grafting . Microscopic examination of the prostate showed a 3 + 3 Gleason 's grade 2 occult adenocarcinoma ( Fig.2 ) . Clusters and sheets of small round cells were seen in the liver parenchyma ( Fig.1 ) and the lymph nodes from the hepatic hilum . Examination of the lung parenchyma showed a peribronchial SCLC with multiple tumor emboli in both veins and lymphatic vessels and multiple “ coin - shaped ” tumor nodules of 1 to 2 mm in diameter below the pleura ( Fig.3 ) . The small round tumor cells were also seen in bone marrow from the iliac crest bone ( Fig.3 ) . No brain metastases have been detected . Based on the macro- and microscopic features and clinical picture , the final diagnosis was “ peribronchial and coin - like peripheral SCLC with massive angiolymphatic invasion and metastases in the lymph nodes , liver and bone , associated with encephalopathy and synchronous occult adenocarcinoma of the prostate . ”


A 42 year - old man with chronic lymphocytic leukemia underwent allogeneic bone marrow transplant in September 2013 . The graft was mismatched at a single human leukocyte antigen allele ( DQB1 ) , and was T - cell depleted using in vivo alemtuzumab . He engrafted on day 12 after transplant . Aside from persistent lymphopenia and diarrhea from norovirus infection , his posttransplant course was unremarkable until mid - October when he developed tinnitus and rapidly progressive sensorineural deafness , resulting in subtotal hearing loss bilaterally ( > 95 dB ) over 2–3 weeks . Brain magnetic resonance imaging ( MRI ) was unremarkable , as was cerebrospinal fluid ( CSF ) analysis ( 4 leukocytes/µL with 50 % neutrophils and 50 % lymphocytes , 6 red blood cells/µL , glucose 2.4 mmol / L [ normal range , 2.2–4.7 mmol / L ] , protein 61 mg / dL [ normal range , 15–45 mg / L ] , absence of oligoclonal bands ) . Viral polymerase chain reaction ( PCR ) testing of CSF was negative for enterovirus and herpesvirus infection . The patient was treated empirically with high - dose valacyclovir , broad - spectrum antibiotics , and 2 g / kg intravenous immunoglobulin ( IVIG ) . Despite these interventions , he developed new symptoms of central dyspnea , postural hypotension , nausea , and gradually worsening balance . Repeat neurological assessment confirmed persistent vestibulocochlear dysfunction 6 weeks after symptom onset . By mid - December , the patient had become increasingly withdrawn , irritable , and intermittently agitated . He remained lymphopenic ( lymphocytes 0.54 × 106 / μL [ normal range , 1.2–3.6 × 106 / μL ] ) . MRI scans of the brain were unremarkable , as was serum testing for antineuronal antibodies ; an electroencephalogram revealed only diffuse encephalopathy . Given continued suspicion for a viral etiology , the patient was treated with high - dose glucocorticoids and again with IVIG . He began refusing fluids , food , and medication , and was detained under the UK Mental Health Act . Repeat MRI scanning showed interval development of new , nonenhancing signal abnormalities in both thalami and midbrain with cranial nerve involvement but no meningeal enhancement ( Figure 1A ) . Near the end of December , a frontal lobe biopsy was performed . Histology revealed reactive gliosis and diffuse infiltration with CD3+/8 + lymphocytes ( Figure 1B ) . Extensive microbiological testing of the biopsy tissue for an infectious etiology was negative ( Supplementary Table 1 ) . Given the absence of a diagnosis and the patient 's progressive neurological deterioration , CSF and brain biopsy tissue were analyzed in January 2014 by metagenomic next - generation sequencing ( NGS ) [ 2 ] . NGS analysis of the brain biopsy , genome assembly , and in situ hybridization revealed findings of neuroinvasive astrovirus ( AstV ) infection . Despite lack of approved therapies , the patient was treated with ribavirin and IVIG . However , he did not respond to these interventions , and remained in a minimally conscious state following withdrawal of sedation in March 2014 . He eventually died at the end of May , 4 months after the NGS diagnosis and approximately 7.5 months after onset of symptoms .


A 64 - year - old man was admitted to the Department of Gastroenterology of the Affiliated Hospital of Qingdao University Medical College ( Qingdao , China ) due to epigastric pains . Physical examination revealed no palpable mass , lymphadenopathy , or organomegaly . On endoscopy , several submucosal lesions were identified in the gastric antrum and the duodenal bulb ( Fig.1 ) . Endoscopic ultrasonography ( EUS ) ( OLYMPUS EUS EU - ME2 , Miniprobe sonography ) demonstrated that the lesions were almost 0.5 - cm homogeneously hypoechoic neoplasms originating from the submucous layer ( Fig.2 ) and the initial diagnosis was digestive neuroendocrine tumors . Computed tomography revealed enlarged lymph nodes in multiple regions ( mediastinal , retroperitoneal , mesenteric , and inguinal ) and intracavitary nodules in the duodenum . To reach a definitive diagnosis , the patient underwent repeat EUS and biopsy was performed . On endoscopy , a 2 × 1 - cm columnar uplift in the terminal ileum and multiple submucosal lesions in the rectum were identified ( Fig.3 ) . EUS revealed that the lesions in the terminal ileum were sized 1.6 × 1.2 cm and the lesions in the rectum were sized almost 0.6 × 1.0 cm , they were all homogeneously hypoechoic and originated from the muscularis mucosa layer . Pathological examination of the biopsied specimens from the lesions of the rectum showed diffuse lymphomatous proliferation and dense infiltration by monomorphic , small cleaved cells with irregularly shaped nuclei ( Fig.4 ) . On immunohistochemical analysis , the cells were positive for cyclin D1 , CD20 , CD21 , SOX-11 , and Bcl-2 , but negative for CD3 and CD10 , which was compatible with the diagnosis of MCL . Ki-67 staining revealed a proliferative index of 30 % . Based on these findings , the diagnosis of Ann Arbor stage IV MCL was confirmed . The patient was referred for combination chemotherapy with rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisone ( R - CHOP regimen ) . The patient has been in remission clinically .


In 2013 , a 50 - year - old man patient visited hospital complaining of local bone pain in the left leg . On August 14 , 2013 , the patient underwent a left distal femoral tumor en bloc resection and reconstruction with a modular femoral prosthetic system . Pathology diagnosis confirmed osteoblastic osteosarcoma ( Fig.2 ) . One cycle of neoadjuvant chemotherapy and 4 cycles of adjuvant chemotherapy with MAP regimen ( high - dose methotrexate , cisplatin , and doxorubicin ) were administered . In January 2015 , a mass was found on the left upper crus area . Tumor recurrence was confirmed by biopsy on January 23 , 2015 . However , only an upper femur amputation was carried out , as the patient refused hip joint replacement . After wound healing , the patient went back to his normal life in the help of artificial limb , but refused to receive further chemotherapy due to concerns regarding the chemotherapy toxicities such as nausea , vomiting , leucopenia , deadlimb , and headache . About half a year after the amputation , the patient got occasional cough and chest tightness . Then a thin chest computed tomography ( CT ) was performed on July 15 , 2015 . The CT results revealed multiple pulmonary nodules ( Table 1 ) , considering the possibility of metastases . The patient still rejected further chemotherapy . Immunophenotype was suggestive of CD31 + and CD34 + tumor cells ( Fig.3 ) . Furthermore , most cells showed strong positive staining for VEGFR-2 ( Fig.3 ) . Apatinib was administered at a dose of 500 mg daily . Half a month later , the symptoms disappeared , but a progressive wound necrosis appeared . A debridement surgery was finally conducted and an enlarged lymph node near iliac vessels was resected on February 24 , 2016 ( Fig.(Fig.4).4 ) . The result of pathological examination revealed an inflammatory hyperplasia lymph node . Apatinib administration was stopped during the 3 weeks of wound healing period . The thin chest CT was performed 7 and 11 months following apatinib administration . At the 7 - month follow - up time point , 2 out of 5 measurable and 9 out of 17 non - measurable lesions disappeared , but 1 new measurable nodule and 6 new non - measurable lesions were observed ( Table 1 , Fig.5 ) , which considered PD according to the Response Evaluation Criteria in Solid Tumors ( RECIST ) 1.1 standard . However , at the 11 - month follow - up time point , a total of 9 lesions disappeared , including 1 measurable nodule and 2 non - measurable lesions presented before apatinib treatment as well as 6 non - measureable lesions presented 7 months after apatinib treatment . No new lesion was raised . After target lesion measurement according to the RECIST 1.1 standard , it was narrowly considered PR . The toxicities the patient experienced included mild hand - foot syndrome and slight high blood pressure . Both were well controlled after appropriate treatment . No severe toxicities and other treatment - related adverse events were observed . The patient continued to use apatinib as maintenance therapy without major toxic effects , and went back to normal life , even driving an automatic car .


A 29 - year - old primipara presented with complaints of persistent , severe right -sided upper abdominal pain during deep inspiration , physical exercise and on local pressure . These complaints had developed gradually after giving birth one year earlier . This pregnancy had been complicated by HELLP syndrome with a subcapsular liver hematoma sized 20 cm × 5 cm , which had resolved spontaneously . At current presentation , liver function tests were normal . She assured having never experienced signs suggestive of sexually transmitted diseases or pelvic inflammatory disease ( PID ) . She had never undergone intra - abdominal interventions . An upper - abdominal magnetic resonance imaging revealed a density between liver and diaphragm at the site of the former subcapsular hematoma , suspect of perihepatic adhesions ( Figure 1 ) . She was referred to the hepatobiliary surgeon , who performed a laparoscopy and confirmed the presence of a thick adhesion between liver segment V / VIII and the diaphragm ( Figure 2 ) . Adhesiolysis was performed in the same session by monopolar diathermia and sharp dissection , followed by the instillation of 1.5 L Adept ( 4 % icodextrin solution ) into the peritoneal cavity to prevent the formation of new adhesions . On follow - up until three years post - surgery , she was free of symptoms .


A 34 - year - old Japanese woman had a diagnosis of MCTD with the presence of Raynaud 's phenomenon , pancytopenia , elevated plasma creatinine kinase , and antibodies against U1 - ribonucleoprotein in 2005 and received 10 mg of prednisolone daily . Pulmonary arterial systolic pressure estimated by echocardiography was slightly elevated ( 48 mmHg ) in 2006 . She felt progressive shortness of breath on physical effort in 2011 . Pulmonary arterial hypertension was diagnosed with 74 mmHg of mean pulmonary arterial pressure ( mPAP ) evaluated by right heart catheterization ( RHC ) in 2012 . Cyclophosphamide - based immunosuppressive therapy was proposed but refused because of possible early menopausal symptoms . Treatment with 250 mg / day of bosentan and 120 μg / day of beraprost was initiated . However , in January 2014 , her dyspnea deteriorated ( WHO functional class IV ) , and she was admitted to our hospital . A physical examination showed low systemic blood pressure ( 89/61 mmHg ) , tachycardia ( 104 / min ) , low blood oxygen level ( percutaneous oxygen saturation ( SpO2 ) 95 % ) , jugular venous distension , and severe systemic edema . Coarse crackles and loud pulmonic valve closure sounds were detected . She was unable to undergo the 6 - minute walk test due to severe dyspnea . Laboratory examinations showed elevated plasma brain natriuretic peptide ( BNP ) level ( 929.4 pg / mL ) , hypoxemia ( PaO2 62.5 mmHg , PaCO2 27.1 mmHg ) , and the presence of antibodies against U1 - ribonucleoprotein ( 97.9 U / mL ) as well as antinuclear antibodies ( 1:640 , speckled pattern ) . A chest X - ray showed enlarged pulmonary arteries and cardiomegaly ( Figure ) . Electrocardiogram showed P wave elevation in the V1 - V2 leads . RHC demonstrated elevated mPAP ( 65 mmHg ) with normal pulmonary arterial wedge pressure ( 12 mmHg ) , high pulmonary vascular resistance ( 1,547 dyne・sec・cm-5 ) , and decreased cardiac output ( cardiac index 1.69 L / min / m2 ) . A ventilation / perfusion scan showed no signs of pulmonary thromboembolism . No signs of chronic obstructive pulmonary disease or interstitial lung diseases were found with computed tomography . Her dyspnea was therefore considered to be due to MCTD - associated PAH which was refractory to bosentan and beraprost therapy . In addition to supportive therapy with oxygen supplementation and diuretics ( 40 mg / day of furosemide ) , initiation of 60 mg / day of sildenafil as well as gradual increment in the dose of beraprost was chosen as an additional treatment . However , her dyspnea remained unchanged , and her plasma BNP level increased . IVCY ( 750 mg / m2 , every 4 weeks ) was initiated , and the dose of prednisolone was increased to 60 mg daily . Her dyspnea then ameliorated , and she became able to undergo the 6 - minute walk test ( 260 m , minimum SpO2 95 % ) . Her plasma BNP level also decreased after the initiation of IVCY ( Figure ) . Six months after the admission , a follow - up RHC revealed improved mPAP ( 65 to 53 mmHg ) , pulmonary vascular resistance ( 1,547 to 1,116 dyne・sec・cm-5 ) , and cardiac index ( 1.69 to 1.83 L / min / m2 ) ( Table ) . Since she remained stable but did not obtain further improvements 18 months after the admission ( Table ) , we consider parenteral prostanoids or lung transplantation as a subsequent treatment .


A 61 - year - old Chinese woman complained of dizziness for 3 weeks and was admitted to our hospital after a bifrontal mass was found radiologically . Other than dizziness , the patient presented no signs or symptoms that are commonly associated with neurological disease , such as headache , vomiting , sensory disturbances , altered consciousness , or seizures . Except for a 20 - year history of hypertension , which was properly controlled with angiotensin - converting enzyme inhibitors , the patient was otherwise healthy . No special circumstances were identified regarding her personal or family history , and the patient was found to be normal upon neurological examination . Plain and contrast - enhanced magnetic resonance imaging ( MRI ) of the head showed a space - occupying lesion in the bifrontal lobe , mainly on the right side , clinging to the sagittal sinus and the cerebral falx . The 5.7 × 5.0 × 5.0 cm dural - based mass growing across the sagittal midline revealed isointensity on the T1 - weighted image and a slight hyperintensity on the T2 - weighted image and was homogenously enhanced with a characteristic “ dural - tail ” sign ( Fig.1 ) . Diagnosis of a parasagittal - parafalcine meningioma was made , and a craniotomic meningioma resection was chosen as treatment . The blood cell examination ; coagulation function , liver and renal function tests ; urinalysis ; chest x - rays and electrocardiogram were normal . The albumin was 36 g / L , the total bilirubin ( TBil ) was 12.2 μmol / L , and the direct bilirubin ( DBil ) was 4.1 μmol / L. Alanine transaminase ( ALT ) was 17 U / L , and the international normalized ratio ( INR ) for coagulation values was 1.02 . Because of the patient 's advanced age and history of hypertension , we performed an echocardiograph and a blood gas analysis and tested her creatine kinase levels and pulmonary functions . The results revealed no surgical contraindications . Written consent was obtained from the patient . Five hundred milligrams of VPA twice per day was initiated 3 days before the operation . The patient tolerated the administration well . A craniotomy was then performed with a radical tumor resection ( Simpson II ) . The tumor was pink and solid and had a moderate blood supply , and its texture was medium . Thirty minutes before the end of surgery , 800 mg of VPA was administered by intravenous infusion . After the operation , the patient regained consciousness within 30 minutes and scored 15 on the Glasgow coma scale ( GCS ) . Two hours later as she was being transported back to her ward , the patient underwent UGH . The vomitus ( approximately 50 mL ) was composed of coffee - colored blood . Excluding the possible etiology of endotracheal intubation damage , we diagnosed the patient as experiencing acute erosive - hemorrhagic gastritis , a reaction to the craniotomy injury . The patient was given omeprazole to inhibit gastric acid secretion , and the hematemesis ceased . The patient was administered VPA ( 1200 mg , intravenously ) during the first 2 postoperative days . Because of her stomach and intestine functional recovery , the VPA dosage was changed to 500 mg via oral administration twice a day . A brain MRI was performed on postoperative day 3 , and it revealed that the tumor was radically removed and the operative field was clean ( Fig.2A and B ) . A subsequent paraffin histological examination confirmed the diagnosis of meningioma . At 3 am on postoperative day 4 , the patient was suddenly found in a deep coma . Her pupils were dilated to 3.0 mm and round , and the light reflex was sensitive . The neurological examination was unremarkable , and her vital signs were stable ; however , her mental state gradually changed to a deep coma ( GCS = 8) , which we believed was caused by intracranial lesions . A computerized tomography ( CT ) scan of the brain was immediately performed ; however , it failed to reveal any abnormalities , such as severe brain swelling , intracranial hemorrhage , or cerebral infarction ( Fig.2C ) . Because a possible cerebral infarction could not be excluded within 24 hours , glucocorticoid , mannitol , and a vasodilator were used . The patient 's routine laboratory results for blood cell , liver , and renal functions were in relatively normal ranges . The albumin was 33 g / L , the TBil was 13.3 μmol / L , and the DBil was 4.5 μmol / L. ALT was 12 U / L , and the INR for coagulation values was 1.01 . Because of her history of UGH , we checked her blood ammonia levels and performed a fecal occult blood test and blood gas analysis . Her blood ammonia was elevated ( 181.6 μmol / L ; normal range is 11–32 μmol / L ) , whereas the fecal occult blood test was positive . Thus , considering her history and elevated blood ammonia , she was diagnosed with UGH - induced hepatic encephalopathy , and the oral administration of VPA was changed to intravenous administration to prevent seizures . Lactulose , vitamin B , and L - arginine were administered , clysis with vinegar was performed , and the patient was fasted . The patient 's blood ammonia level fluctuated ( 144.8–207.7 μmol / L ) , and she remained unconscious during the following 3 days . Because of the unremarkable progress in the patient 's mental state and blood ammonia level , we held a multidisciplinary conference to discuss diagnosis and treatment , initially considering hemodialysis or peritoneal dialysis . After the multidisciplinary discussion , a suspected diagnosis of VHE was finally made , even though the blood VPA level was within the normal range . We decided to stop VPA administration before performing any dialysis and administered levetiracetam instead of VPA . The patient 's blood VPA and ammonia levels were then routinely monitored . The patient 's mental state began to improve from the first 24 hours of VPA discontinuation , and she achieved complete consciousness within 48 hours ( GCS = 15 ) . The ammonia levels in her blood decreased dramatically and returned to normal within 4 days ( Fig.3 ) . On postoperative day 15 ( 8 days after the discontinuation of VPA ) , the patient was discharged with no complications . The follow - up interviews in postoperative month 5 witnessed her full consciousness and non - recurrence of the primary tumor ( Fig.2D ) . The patient 's GCS score was 15 , and she reported enjoying a satisfying quality of postoperative life .


A 58 - year - old white American male presented to the emergency department ( ED ) with acute onset of confusion , disorientation , inability to walk steadily , and dehydration with associated generalized weakness , polyuria , and polydipsia over the previous week . He had been diagnosed with CML six years earlier , with no hematological response to multiple chemotherapy regimens ; he was at that time on treatment with allopurinol and awaiting allogenic bone marrow transplant . Vital signs on admission to the ED included heart rate of 104 bpm , blood pressure of 122/68 mm Hg and temperature of 99.7 ° F ( 37.6 ° C ) . There were no remarkable findings on physical examination except for altered mental status and dehydration . Laboratory evaluations were : hemoglobin 13.3 g / dL , white blood cell count 18.3×109 / L ( neutrophils 79.6 % , lymphocytes 7.2 % , and monocytes 8.3 % ) , and platelet count 910×109 / L. Serum levels were : calcium 18.6 mg / dL , phosphate 4.6 mg / dL , sodium 135 mEq / L , potassium 2.7 mg / dL , albumin 4.0 g / dL , creatinine 2.2 mg / dL , total bilirubin 0.9 mg / dL , alkaline phosphatase 125 IU / L , aspartate aminotransferase 41 IU / L , and alanine aminotransferase 71 IU / L. SPEP was negative for an M spike . Hormones and vitamins levels were : PTH 8.5 pg / L ( 15–65 pg / L ) , PHTrP 1.4 pg / L ( < 2 pg / L ) , 25 - OH vitamin D 30.4 ng / mL ( 20–50 ng / mL ) and 1,25 OH vitamin D3 33.7 ng / mL ( 18–64 ) ng / mL. Chest CT scan showed diffuse lytic lesions and bone destruction throughout the visualized thoracic skeleton , concerning for diffuse bone marrow involvement . The clinical history and biochemical findings led to a diagnosis of CML - associated hypercalcemia in the context of a blast phase . Treatment with aggressive hydration with 0.9 % saline and calcitonin 400 units subcutaneous was administered . Additionally , zoledronic acid 3.3 mg intravenous , adjusted for renal insufficiency , was given . After five days of treatment , normalization of symptoms and serum calcium levels were achieved . After discharge from the hospital , the patient continued with palliative treatment with ponatinib and radiotherapy . Acceptable serum calcium levels were maintained with zoledronic acid 4 mg every eight weeks . Despite these therapies , his cancer progressed and he passed away approximately eight months after the initial admission for hypercalcemia .


A 76 - year - old woman presented to our hospital with complaints of epigastralgia since a day prior to admission . Laboratory data on admission revealed an elevation of aminotransferase , alanine aminotransferase , ɤ - guanosine triphosphate , and alkaline phosphatase . Serum total bilirubin and tumor markers , carcinoembryonic antigen ( CEA ) , carbohydrate antigen 19 - 9 ( CA19 - 9 ) , SPan-1 , and neuron - specific enolase ( NSE ) , were all within normal ranges . Abdominal computed tomography ( CT ) and magnetic resonance cholangiopancreatography ( MRCP ) showed a mass in an enlarged gallbladder and bulky hepatic lymph nodes surrounding the hepatic hilum ( Fig.1a , b ) . There were also no apparent lesions in upper and lower gastrointestinal endoscopy . Endoscopic ultrasound - guided fine - needle aspiration ( EUS - FNA ) was performed to obtain tissue from the hilar lymph node . Immunohistochemical staining of the specimen identified diffuse positivity for keratin , CD56 , and synaptophysin in the tumor cells , which is consistent with NEC . An endoscopic naso - gallbladder drainage ( ENGBD ) catheter was placed , and the bile cytology revealed class V malignant cells . Therefore , positron emission tomography / computed tomography ( PET / CT ) examination was performed to evaluate other primary or metastatic lesions . It revealed that no other accumulated lesions were identified , and the accumulation of 18F fluorodeoxyglucose ( FDG ) was in the gallbladder ( SUVmax 7.8 ) and lymph nodes ( SUVmax 13.4 ) ( Fig.1c , d ) . On the basis of these findings , the most likely diagnosis was a gallbladder NEC that was confined to the regional hepatic hilar lymph nodes metastasis . Finally , we decided to perform surgical resection prior to chemotherapy because of concerns about complications developing from mechanical obstruction of the hepatic hilum by the enlarged lymph node . She underwent cholecystectomy , hepatic hilar lymphadenectomy , extrahepatic biliary duct resection , and hepaticojejunostomy . The bulky lymph nodes were totally resected as “ en bloc ” . There were no apparent residual lesions surgically . The postoperative course was uneventful and she was discharged on the tenth day after surgery . Macroscopically , the tumor was 58 × 42 mm in size and was located in the fundus , which contained a yellowish gallstone ( Fig.2a ) . A portion of the hepatic hilar lymph nodes ( 71 × 37 mm ) was also excised separately ( Fig.2b ) . Microscopic examination of the gallbladder revealed a moderate to well differentiated tubular adenocarcinoma infiltrating from the mucosa to the muscular layer , but not the serosal surface , without any NEC components ( Fig.2c , d ) . The tumor cells in the gallbladder are slightly positive for synaptophysin and CD56 , but negative for chromogranin A ( Fig.2e – g ) . The resection margin from the liver bed was negative for tumor cells . The epithelium around the carcinoma showed intestinal metaplasia with the goblet cells ( Fig.4a ) , which area was stained by alcian blue ( Fig.4b ) . On the other hand , the hepatic hilar lymph nodes were composed of small round tumor cells with hyperchromatic nuclei and scant cytoplasm ( Fig.3a ) . Some of the tumor cells were large and had vesicular nuclei . The tumor cells were arranged in sheets , cords , or in a trabecular or rosette fashion and were interspersed with focal necrosis . They were immunohistochemically positive for CD56 , synaptophysin , and chromogranin A ( Fig.3b–3d ) . The mitotic count was 24 per 10 high - power microscopic fields , and the Ki-67 proliferation index was 70–80 % , consistent with NEC . The surgical dissection margin of the hepatic lymph nodes was microscopically cauterized within the tumor cells . There was no invasion to the extrahepatic biliary duct . As the result of thorough pathological re - evaluation by total segmentation , a negligible area of adenocarcinoma was detected in the lymph nodes ( Fig.3e , f ) . The adenocarcinoma component and the intestinal metaplastic epithelium in the gallbladder were both positive for CDX2 ( Fig.4a ) , but the neuroendocrine component in hilar lymph nodes was negative for CDX2 ( Fig.4b ) . Postoperatively , the patient received three cycles of carboplatin ( area under the curve of 5 on day 1 repeated every 21 days ) and etoposide ( 80 mg / m2 on days 1 through 3 repeated every 21 days ) . During the first course , grade 4 neutropenia occurred and it was managed with prophylactic fluoroquinolones . After 4 months , multiple recurrences in the para - aortic lymph nodes were detected , which was pathologically demonstrated via EUS - FNA to be NEC . The patient underwent second - line chemotherapy with amrubicin ( 24 mg / m2 on days 1 through 3 repeated every 21 days ) . Grade 4 neutropenia and anemia developed during the courses , and she needed to receive pegylated granulocyte colony - stimulating factor and red blood cell transfusion . However , she died of progressive disease 8 months after surgery .


A 45 - year - old woman presents to her general practitioner because of left - sided neck and shoulder pain . The pain was mild and non - specific and the patient 's history was unremarkable . She denied a history of smoking , excessive alcohol use and radiation exposure . Physical examination demonstrated mild left sided cervical lymphadenopathy . Routine blood tests revealed borderline elevated calcium of 10.5 mg / dL and subsequent work up exhibited a markedly elevated parathyroid hormone level of 286 pg / mL , so the patient was referred to otolaryngology for further evaluation . Thyroid ultrasound showed a hypoechoic nodule in the left lower lobe of the thyroid . CT scan of the neck revealed a 2 cm hypodense nodule on the posterior inferior aspect of the left lower thyroid and sestamibi scan showed increased uptake along the lower pole of the left thyroid lobe . Elevated PTH along with an aberrant parathyroid gland on imaging suggests primary hyperparathyroidism . Historically , hyperparathyroidism is associated with bone disease , renal stones and neuromuscular dysfunction , however , with the current screening modalities , most patients are caught early and often asymptomatic.3 Primary hyperparathyroidism is most commonly caused by a parathyroid adenoma . Infrequent causes include parathyroid hyperplasia , which would affect all four glands and rarely caused by parathyroid carcinoma . Markedly elevated serum PTH and calcium levels leading to severe renal and bone manifestations are helpful in the diagnosis of cancer , however , it is usually discovered operatively based on local invasion and metastases.3 The primary indication for parathyroidectomy , historically , is for symptomatic patients . Currently , since most patients are caught earlier , there are newer indications for surgery . These include an asymptomatic patient with any of the following : glomerular filtration rate < 60 mL / min , bone density T - score < −2.5 at any site and/or previous fractures , age < 50 , and serum calcium 1.0 ng / dL above the upper limit of normal.3 This patient presented with pain , markedly elevated PTH , and was younger than 50 years old , so it was decided that surgery was the best choice in management . The patient was brought to the operating room and underwent a parathyroidectomy . The surgeon found the parathyroid gland to be firm and densely adherent to the thyroid capsule and overlying strap muscle , making it difficult to dissect . There was no visible invasion into the capsule , surrounding muscle or regional lymph nodes . The resected specimen was noted to be brownish grey in colour with scattered necrotic foci , and irregular texture . On postoperative pathology , the specimen was confirmed positive for parathyroid carcinoma with capsular invasion , focal tumour necrosis , reactive fibrosis and local skeletal muscle invasion ( figures 1 and 2 ) . Margins were resected . Immunohistochemical stains showed increased Ki-67 reactivity as well as strong Bcl-1 ( cyclin D1 ) reactivity , which support the diagnosis of parathyroid carcinoma ( figure 3 ) . Additionally , P57 staining was negative . Although most reports of parathyroid carcinomas are associated with marked hypercalcaemia , non - functioning cancers in patients tend to behave more aggressively.1 Owing to the severity and uncertainty of the lesion , the patient was followed up postoperatively for repeat imaging to determine if residual tumour remained . Repeat sestamibi and positron emission tomography ( PET ) scan revealed residual activity along the surgical area so the patient subsequently underwent a second operation for a radical left neck dissection and left hemithyroidectomy . The patient recovered very well postoperatively and it has now been 3 years since the second surgery . The patient continues to do very well and is followed up every 3 months to monitor serum PTH and calcium levels . She no longer reports of neck and shoulder pain . Sometimes the patient 's blood tests show marginally elevated PTH levels , however , she remains eucalcaemic and follow - up nuclear scans and PET scans continue to be negative . The patient will continue to be monitored every 3 months indefinitely .


A 16 - year - old female suffered from an abdominal pain at right upper quadrant , lasting for more than 10 days . Shortly ahead of her medical consultation , 4 ascaris - like worms were vomited out , individually with a length of about 10 cm . She had a previous onset of ascariasis , during which low - grade fever ( 38.4 ° C ) occurred without apparent jaundice , diarrhea , or anemia . Physical examination revealed tenderness at right upper quadrant . Her total leukocyte count was 11.2 G / L consisting of 5.2 % eosinophils . Serum and urine amylase were 386 and 928 U / L , respectively . In terms of liver functionality , the level of total bilirubin rose up to 23.2 μm / L , meanwhile the hepatic enzymes were similarly elevated ( alanine aminotransferase 163 U / L ; aspartate aminotransferase 96 U / L ) . Abdominal ultrasound described the enlargement of the gallbladder , upper segment of common bile duct ( 1.5 cm in diameter ) and intrahepatic bile duct ( 1.3 cm in diameter ) . Furthermore , the intrahepatic bile duct was also discovered to be filled with echogenic and banded substances . Based on such evidences , she was clinically diagnosed as biliary ascariasis with a concomitant manifestation of biliary duct infection . Through a laparoscopic exploration , the enlarged gallbladder and common bile duct were visually confirmed , as well as the massive storage of worms within the biliary tract . Subsequently , a 1 cm incision was made on the common bile duct in order to facilitate the extraction of the pathogenic worms , which were then placed into a specimen bag laparoscopically ( Fig.1 ) . Once the contained worms were virtually cleared out under laparoscope , chodedochoscopy was employed to seek for more hidden worms inside the biliary system ( Fig.2 ) . After finishing the removal of ascarides , the biliary duct incision was well sutured , with a T - tube placed in situ ( Fig.3 ) . Eventually , a standard laparoscopic cholecystectomy was performed , followed by the removal of specimen bags and drainage tube placement ( Fig.4 ) . The total amount of worms inside the common bile duct summed up to more than 100 ( Fig.5 ) . Postoperatively , she was treated with oral antihelminthic drugs for 3 days . The T - tube was rinsed with saline every day , and during the first 3 days , 6 more worms were additionally washed out . The patient experienced a smooth postoperative recovery and was finally discharged from hospital without any complications .


A 51 - year - old man was referred to our hospital due to severe congestive heart failure and ventricular arrhythmias in March 2008 . He had been suffering from heart failure and ventricular tachycardia for years despite receiving the conventional treatment ( ie , furosemide , lisinopril hydrate , pimobendan , warfarin potassium , carvedilol , metildigoxin and amiodarone hydrochloride ) . His height was 161 cm and body weight was 83 kg . Blood pressure was 110/60 mm Hg . The fasting blood glucose was 107 mg / dl and HbA1c was 6.3 % . The chest x - ray showed cardiomegaly with a cardiothoracic ratio of 0.67 ( figure 1A ) . ECG , as shown in video 1 , revealed a diffused hypokinetic left ventricle with markedly dilated left ventricle dimension ( end - diastole : 95 mm ) and reduced EF ( 0.11 ) . The coronary angiogram was normal . A myocardial biopsy revealed that over 50 % of cardiomyocytes were replaced by fibrosis ( figure 2 ) . An implantable cardioverter - defibrillator was implanted . Due to the typical facial appearance and thickening of hands , he was referred to the endocrinology department . The plasma level of GH was 8.2 ng / ml and IGF-1 was 504 ng / ml . MRI demonstrated a macroadenoma in the pituitary . Thus , he was diagnosed as acromegaly . He was treated with octreotide long - acting - release ( LAR ) for 8 months . Thereafter , he underwent trans - sphenoidal surgery in January 2009 ( figure 3 ) . The plasma levels of GH and IGF-1 were decreased with octreotide LAR , but basal plasma levels of GH were always more than 4 ng / ml and plasma IGF-1 levels were above the appropriate age range ( figure 3 ) . After surgery , both plasma levels of GH and IGF-1 further decreased . Basal plasma levels of GH were mostly less than 0.5 ng / ml and IGF-1 levels were within normal ranges ( figure 3 ) . With the treatment of LAR , the cardiac function improved partially ( cardiothoracic ratio=0.58 ; EF=0.20 in September 2008 ) . After surgery , the cardiac function improved drastically ( cardiothoracic ratio=0.47 ; EF=0.55 in April 2009 ; figures 1B and and2B).2B ) . Frequency of ventricular arrhythmias decreased and pimobendan was tapered off .


In January 2009 , a 57 - year - old woman emergently presented with acute shortness of breath . She had a 1 - month history of progressive shortness of breath and a gradual decrease in exercise capacity secondary to mild dyspnea . She reported no additional symptoms . At age 40 , she had been diagnosed with a stage IIA , T1bN1 , left - sided breast cancer . Initial treatment had included a lumpectomy and axillary node dissection . She subsequently underwent 4 cycles of DOX therapy ( 75 mg / m2 ) , followed by 8 cycles of cyclophosphamide , methotrexate , and 5 - fluorouracil . Multigated acquisition scans before and after chemotherapy showed normal cardiac function . After chemotherapy , she underwent left whole - breast radiation with an axillary boost . Because the tumor had been estrogen receptor - positive , her subsequent medical regimen consisted only of anti - estrogen therapy . She took tamoxifen for 5 years , and , ever since , the aromatase inhibitor letrozole . In the 17 years after chemotherapy , she had been active and in relatively good health . In addition to her other symptoms , she now presented with tachycardia , tachypnea , and hypertension . She had marked jugular venous distention , an S3 , pulmonary rales , and trace peripheral edema . Initial laboratory values were within normal limits except for an elevated level of N - terminal pro - brain natriuretic peptide ( > 2,000 pg / mL ) . Results of investigation into the new - onset cardiomyopathy included normal cardiac enzyme levels , an electrocardiogram ( ECG ) that revealed no ischemic changes , and a coronary angiogram of normal appearance . The ECG showed sinus tachycardia with frequent premature ventricular complexes , left - axis deviation , left atrial enlargement , and low - voltage QRS complexes with nonspecific ST changes ( Fig.1 ) . A 2 - dimensional echocardiogram revealed a left ventricular ejection fraction ( LVEF ) of 0.20 , severe diffuse left ventricular ( LV ) hypokinesis , and a mildly dilated left atrium . To better define the cause of the LV systolic dysfunction , cardiovascular magnetic resonance ( CMR ) was performed . It confirmed the LVEF of 0.20 . The T2 - weighted sequence showed slow flow secondary to LV dysfunction , and no myocardial edema ( Fig.2A ) . Late gadolinium enhancement disclosed diffuse myocardial thinning and no scarring ( Fig.2B ) . The patient was treated medically . Her symptoms progressively improved during therapy , which consisted of a β - blocker , an angiotensin - converting enzyme inhibitor , digoxin , and a diuretic . The therapy was slowly tapered , and her LVEF increased from 0.20 to 0.55 during an 8 - month period . All medications except for low - dose metoprolol were discontinued after 1 year , and she remained asymptomatic .


A 61 - year - old male patient had a history of chronic obstructive pulmonary disease under regular bronchodilator treatment . In 2014 , he suffered from severe productive cough with mucus sputum for several months and unintentional body weight loss 6 kg within 6 months . After sputum analysis and chest imaging examinations in May 2014 , he was diagnosed of squamous cell carcinoma in right upper lobe lung ( cT3N2M0 , stage IIIa ) . Then he received neoadjuvant chemoradiotherapy ( etoposide 70 mg [ 45 mg / m2 ] + cisplatin 79 mg [ 50 mg / m2 ] ; 4500 cGY in 25 fractions ) from June to July 2014 . In October 2014 , surgical intervention was arranged . Because the tumor was located at right hilum and invaded main bronchus and major vessels , video - assisted thoracoscopic surgery with right side intrapericardial pneumonectomy was performed . Postoperatively , pathological exams revealed squamous cell carcinoma , T3N0M0 , stage IIB . The postoperative course was smooth but he suffered from severe cough and right chest pain one month later . Laboratory exams revealed leukocytosis ( white blood cells = 21,860 μL ) and elevated C - reactive protein to 23.94 mg / dL. Chest X - ray showed cavitary lesion and computed tomography showed pleural effusion and fluid collection with mottled gas appearance in the dependent portion of right hemithorax ( Fig.1A ) . According to the patient 's history , results of laboratory exams , and imaging findings , postpneumonectomy empyema was diagnosed and bronchopleural fistula was highly suspected . After admission , chest tube drainage was inserted and bronchoscopic tissue glue sealing was performed . However , persistent air leakage was presented and we decided to repair the bronchial stump with flap coverage . Because the patient just received neoadjuvant chemoradiotherapy a few months ago , the flaps harvested from chest area were not appropriate because the pedicle arteries might have been injured by irradiation . After discussing with the plastic surgeon , we decided to repair the bronchial stump by a TRAM flap . Intraoperatively , the patient was placed in supine . Right side exploratory thoracotomy was performed and the bronchial stump was located . The superior epigastric vascular artery and right rectus abdominis muscle was identified and the location of the TRAM flap was marked on the skin ( Fig.2A ) . Then the TRAM flap was harvested from right rectus abdominis ( Fig.2B ) and was deepithelialized ( Fig.2C ) . Through a subcutaneous tunnel , the TRAM flap was moved toward the right thoracic space with no tension or kinking on the pedicle ( Fig.2D ) . Then the TRAM flap was fixed to posterior chest wall to cover the bronchial stump ( Fig.2E ) and the tissue glue was also applied to the bronchial stump under bronchoscope . The donor site of flap was closed with mesh repair . The postoperative course was smooth and the air leak was diminished gradually . Then the patient was discharge under stable condition and was free from air leak after following for 12 months ( Fig.1B ) . The patient provided written informed consent for publication of this report and all accompanying images .


A 36 - yr - old previously healthy Sri Lankan male who takes care of a horse presented to the medical casualty ward with fever , arthralgia and myalgia for one day . He complained of mild dysuria but had normal urine output . He did not have chest pain or shortness of breath . Further inquiry revealed that he was treated for leptospirosis during a febrile illness in the past . On examination , patient was afebrile , anicteric . His blood pressure was 90/60 mmHg and pulse rate 76 bpm . Rest of the examination was unremarkable . Initial investigations performed on the day of admission revealed neutrophil leukocytosis , mild thrombocytopaenia and microscopic haematuria ( Table 1 ) . Renal function and liver enzymes were within normal limits . Urine analysis revealed pus cells 05 – 06 /hpf , red cells 30 – 35 /hpf . CRP ( C - reactive protein ) was 75 mg / dl . A clinical diagnosis of leptospirosis was made and he was started on intravenous penicillin in addition to adequate hydration . On the second day of illness , he developed hypotension with tachycardia and dyspnoea . ECG revealed sinus tachycardia with ST depression in leads V4 – V6 [ Figure 1 ] . His CXR ( chest x ray ) showed gross cardiomegaly and bilateral pulmonary shadows [ Figure 2 ] . CVP ( central venous pressure ) was 16 cmH2O and 2D echocardiogram revealed dilatation of all four chambers , severe global hypokinesia and ejection fraction of 20 % . Troponin I was 12.77 ng / ml ( normal range < 0.40 ) . He was diagnosed to have early and severe myocarditis . Patient was transferred to ICU ( intensive care unit ) as he needed inotropic support . Intravenous antibiotics including penicillin , meropenem and levofloxacin were continued . Patient was electively ventilated on the 3rd day of illness due to severe respiratory distress . On the same day , he developed rapid atrial fibrillation [ Figure 3 ] unresponsive to digoxin and intravenous amiodarone . Platelet count dropped to 10 × 103 μ / L and he was given platelet transfusions to prevent bleeding [ Table 1 ] . We started intravenous methylprednisolone based on previous studies showing a mortality benefit in severe leptospirosis complicated with myocarditis [ 11 ] . His serum creatinine increased to 362 μ mol / L by the 5th day of illness and ALT ( alanine transaminase ) and AST ( aspartate transaminase ) were markedly elevated up to 2726 U / l and 7438 U / l respectively . Dengue and Mycoplasma infections were excluded . Blood cultures were negative . Leptospira IgM antibody performed on the 5th day of illness was positive ( IgG negative ) . Patient developed refractory shock and died of persistent ventricular tachycardia despite optimal treatment in the ICU .


A 71 - year - old woman with known diastolic congestive heart failure ( CHF ) presented to the ER with exacerbation of CHF and a decreased level of consciousness . Brachial blood pressure ( BP ) was measured at 55/40 mmHg . The patient had four recent admissions with exacerbation of CHF . Her medical history was also significant for autoimmune hepatitis , but preserved liver function ; esophageal varices with a bleeding episode ; and long - term corticosteroid therapy complicated by adrenal insufficiency , type 2 diabetes mellitus and osteoporosis . Recent echocardiography had revealed moderate concentric left ventricular hypertrophy with diastolic dysfunction , and mild to moderate mitral regurgitation . Cardiac catheterization in a recent admission demonstrated 50 % stenosis in the second diagonal artery , with mild diffuse disease in the other coronary arteries . Right ventricular endomyocardial biopsy had ruled out myocarditis and infiltrative cardiomyopathies , but healing ischemic microinfarcts with atheroemboli were observed . Previous BP values were also low ; systolic BP was between 60 mmHg and 65 mmHg , and diastolic BP was between 40 mmHg and 45 mmHg . Following intubation , dopamine was started for hypotension management and was later replaced with noradrenaline . The patient developed atrial flutter but successfully converted to sinus rhythm with two direct current electric shocks . Cardiology consultation resulted in admission to the coronary care unit ( CCU ) . On admission to the CCU , BP was measured at 56/36 mmHg in the left arm but was not detectable in the right arm . An arterial line was inserted via the femoral artery , and BP was measured at 191/92 mmHg . BP values were consistently much higher through the femoral arterial line than the cuff on the arms , and was higher in the left arm than in the right arm . For instance , on the first day post - CCU admission , BP at one point was measured at 170/80 mmHg through the arterial line , while cuff readings on the arms were 83/74 mmHg on the left and 60/39 mmHg on the right arm . To investigate the inconsistency between brachial and femoral BP values , a computed tomography ( CT ) scan of the thorax was obtained using 1.25 mm slices , both before and after intravenous contrast injection with sagittal and coronal planar reformatting of maximum - intensity projection images . Analysis of the initial unenhanced CT images showed densely calcified plaque or thrombus at the origins of both subclavian arteries and the right common carotid artery . The CT angiogram showed absence of flow in the right subclavian artery , a very tight stenosis at the origin of the left subclavian artery and a tight stenosis at the origin of the right common carotid artery . Both vertebral arteries showed normal calibre and flow ( Figure 1 ) . Further management following the insertion of the femoral arterial line was based on femoral BP readings with diuretics and BP - lowering agents . The patient was eventually discharged in stable condition . She remained stable during the eight months between discharge and the time the present report was written , without further exacerbation of CHF or related ER visits .


A 61 - year - old male was referred to the emergency department by his general practitioner in April 2010 for investigation of loose bowel motions and an episode of black stool . The patient had a history of insulin - dependent type II diabetes mellitus , hypertension , ischaemic heart disease with two previous ischaemic events , obstructive sleep apnoea , depression , schizophrenia and a previous incisional hernia repair . On examination , he was morbidly obese ( BMI 45 ) and was noted to have marked hepatomegaly . This was not associated with any recent weight loss , haematemesis , jaundice or abdominal pain . The patient denied previous blood transfusions , usage of intravenous drugs and did not drink alcohol . A faecal occult blood test was negative , and the patient ’s last colonoscopy 2 years prior was unremarkable . He was referred to our tertiary centre for further management after an ultrasound scan ( USS ) displayed an ovoid mass of mixed echogenicity arising from the liver , measuring 12 × 9 cm . A computed tomography ( CT ) scan confirmed a malignant appearing , pedunculated lesion attached to segment IV ( Fig.1 ) . A subsequent magnetic resonance imaging ( MRI ) confirmed that on T2 weighted imaging ( WI ) , the lesion was isointense to the liver peripherally with central branching hyperintensities ( Fig.2a ) which corresponded to the hypointensities seen on T1WI ( Fig.2b ) . Enhancement of the lesion was noted in arterial phase ( Fig.3a ) , during portal venous phase ( Fig.3b ) and at 2 min ( Fig.3c ) , with some central areas of non - enhancement . The lesion becomes slightly hypointense on delayed images at 10 ( Fig.3d ) and 20 min compared to the surrounding liver . Laboratory investigations revealed a mildly elevated gamma - glutamyl transpeptidase of 137 IU / L ( normal 5–50 IU / L ) . Hepatitis screen , alpha - fetoprotein , carcinoembryonic antigen and cancer antigen 19–9 were all unremarkable . The patient underwent a subsegmental resection of the 15 cm segment IVb mass in June 2010 . There was severe hepatic steatosis , but no cirrhosis . The patient was discharged postoperative day seven without complications . Pathology of the resection specimen confirmed SFTL . The specimen displayed a pale tan nodular appearance with a firm and rubbery cut surface . Histological examination revealed fascicles of spindle cells in storiform arrangement with a pushing margin . There was evidence of extracellular collagen deposition , areas of myxoid stroma and branching vessels with hyalinisation . The specimen displayed a high mitotic rate of up to 9 per 10 high - power fields ( HPF ) with no necrotic or haemorrhagic features . Immunohistochemistry showed positive staining for CD34 , CD99 and BCL-2 . The tumour was negative for c - Kit , CD31 , SMA , desmin , cytokeratins ( AE1 / AE3 , MNF116 and Cam 5.2 ) , EMA and S100 . The margins were clear . The non - neoplastic remainder of the liver displayed pericellular fibrosis indicative of steatohepatitis . The patient was followed - up regularly every 4 to 6 months with CT scans by the local general practitioner who liaised with the consultant surgeon . There were two episodes of re - admissions for further investigation of recurrent right upper quadrant pain between 2011 and 2013 . Multiple MRI scans performed during this period revealed expected postsurgical changes with no tumour recurrence . However , in May 2016 , the patient presented to his local emergency department with progressively worsening right upper quadrant pain and increasing dyspnoea with an oxygen demand . CT of his chest , abdomen and pelvis revealed extensive tumour recurrence adjacent to the previous resection site ( Fig.4 ) . In addition , there was a clinically significant right - sided pleural effusion and a pleural mass at the right lung base measuring 3.8 cm ( Fig.5 ) . Pleurocentesis was performed , draining 1400 ml of serosanguineous fluid . Cytology was negative for malignant cells . The case was discussed extensively in a multi - disciplinary setting , and it was decided given the patient ’s two sites of disease and significant perioperative risk that he was not a candidate for radical reoperation . There were also no suitable chemo- or radiotherapeutic therapies available . The patient was subsequently referred to the palliative team for management of his symptoms and discharged back to the community . He was still alive 1 month after discharge .


A 41 - year - old man with weight loss , nausea , vomiting , and abdominal pain was referred for an abdominal CT scan to rule out intraabdominal pathology . A dedicated CT of the abdomen was performed at our institution according to our standard venous phase protocol . Following ingestion of positive oral contrast material ( barium sulfate suspension 2.1 % w / v , Mallinckrodt ) and injection of 125 ml of iopromide , 300 mg I / mL ( Ultravist , Bayer HealthCare ) , helical CT was obtained with a 65 - s delays using a 64 - slice GE Lightspeed VCT scanner ( GE Medical Systems ; Milwaukee , WI ) . Axial sections of the abdomen showed a large ( 18×22×22 cm ) heterogeneous retroperitoneal mass probably arising from the left adrenal gland containing multiple areas of macroscopic fat ( Fig.1 ) . The patient had no documented clinical or laboratory evidence of adrenal hormonal excess . On the basis of the clinical history and CT findings , the patient underwent surgical resection of the left adrenal mass , which was found on pathologic examination to represent a low - grade adrenocortical carcinoma .


A 76 - year old woman presented with a 24 - month history of enlarging mass involving the back history of trauma . Physical examination showed a mass of an 3x4 cm in diameter , localized in the right inter - scapular region . The mass was ulcerative helophytic , grayish in colour , hard in consistency and easily bleeding on manipulation . The remainder of the examination was unremarkable ; no lymphadenopathy and no abdominal masses were felt . After resection , the histological examinations of the specimens have concluded for basal cell carcinoma . A local recurrence was observed 18 months later ; the patient was admitted to our institution for Lumpectomy ( Figure 1 ) . Histopathological examination revealed a syringomatous pattern infiltrating the dermis ( Figure 2 , Figure 3 ) , subcutis and skeletal muscle . The neoplastic epithelial cells were arranged in interconnecting cords with microcystic areas . Nests , cords , and tubules of the tumour extended into the dermis and into the adjacent muscle . Many lobules showed squamous differentiation . Sclerosis of stroma around the cords was present . Tumour cells were not connected to the epidermis . The immunohistochemical analysis showed positivity for anti - CK7 ( Figure 4 ) , AE1 / AE3 and negativity for anti CEA and anti CK20 . Based upon her histological and immunohistochemical presentation , the diagnosis of syringomatous eccrine carcinoma was established . Radiotherapy of the involved area was performed ( 70 Gy , 35 sessions )


The patient was a 34 - yr - old man who presented with complaints of fever and a chronic cough . He was a smoker and had a history of pulmonary tuberculosis that had been treated and cured . A computed tomographic ( CT ) scan revealed multiple tiny nodules in both lungs . A thoracoscopic lung biopsy was taken from the right upper lobe . The microscopic examination revealed a typical LCH . The tumor cells had vesicular and grooved nuclei , and they formed small aggregations around the bronchioles ( Fig.1 ) . The tumor cells were strongly positive for S-100 protein , vimentin , CD68 and CD1a . There were infiltrations of lymphocytes and eosinophils around the tumor cells . With performing additional radiologic examinations , no other organs were thought to be involved . He quit smoking , but he received no other specific treatment . He was well for the following one year . After this , a follow - up CT scan was performed and it showed a 4 cm - sized mass in the left lower lobe , in addition to the multiple tiny nodules in both lungs ( Fig.2 ) . A needle biopsy specimen revealed the possibility of a sarcoma ; therefore , a lobectomy was performed . Grossly , a 4 cm - sized poorly - circumscribed lobulated gray - white mass was found ( Fig.3 ) , and there were a few small satellite nodules around the main mass . Microscopically , the tumor cells were aggregated in large sheets and they showed an infiltrative growth . The cytologic features of some of the tumor cells were similar to those seen in a typical LCH . However , many tumor cells showed overtly malignant cytologic features such as pleomorphic / hyperchromatic nuclei and prominent nucleoli ( Fig.4 ) , and multinucleated tumor giant cells were also found . There were numerous mitotic figures ranging from 30 to 60 per 10 high power fields , and some of them were abnormal . A few foci of typical LCH remained around the main tumor mass . Immunohistochemically , the tumor cells were strongly positive for S-100 protein ( Fig.5 ) and vimentin ; they were also positive for CD68 ( Dako N1577 , Clone KPI ) , and focally positive for CD1a ( Fig.6 ) , and they were negative for cytokeratin , epithelial membrane antigen , CD3 , CD20 and HMB45 . The ultrastructural analysis failed to demonstrate any Birbeck granules in the cytoplasm of the tumor cells . Now , at five months after lobectomy , the patient is doing well with no significant change in the radiologic findings .


A 37 - year - old African American female with a past medical history significant for stage 1 sarcoidosis presented to our facility with a chief complaint of shortness of breath . Ten years prior , she presented with bilateral uveitis and lupus pernio ( LP ) on her right ear and was subsequently diagnosed with sarcoidosis . She was successfully treated for these conditions and her sarcoidosis remained quiescent until three years ago , when , at an outside institution , she was discovered to have laryngeal involvement . She was treated with prednisone 60 mg daily for several months and eventually tapered to 10 mg daily . Her sarcoidosis remained well - controlled on this maintenance dose of prednisone until six months prior , at which time she self - discontinued her prednisone in favor of the homeopathic treatment Nopalea cactus juice , which unsubstantially claimed to have anti - inflammatory properties [ 4 ] . Subsequently , she developed dyspnea on exertion progressing to dyspnea at rest . During this time her voice became increasingly hoarse and she experienced frequent episodes of difficulty swallowing . In our emergency department , her physical examination was concerning for respiratory distress as she presented with inspiratory stridor and hoarseness . She also had chronic - appearing , indurated lesions on her right ear . Given that she had signs of upper airway disease for impending respiratory failure , an emergent bedside laryngoscopy was performed , revealing an obstructed airway with the epiglottis retroflexed over the glottis and significant edema in the arytenoids and aryepiglottic folds . She was immediately treated with high - dose intravenous dexamethasone and taken emergently to the operating room ( OR ) to secure her airway for concern for complete upper airway obstruction , which was confirmed with direct visualization of her larynx in the OR . She was intubated for a surgical airway , and after taking biopsies from the lingual surface of her epiglottis , a # 4 cuffed Shiley ™ tracheostomy was placed . Her respiratory status immediately stabilized , was extubated , and transferred to our medical intensive care unit . Her tracheostomy was exchanged to a # 4 cuffless Shiley on postoperative day 5 . During this time she was transitioned from intravenous dexamethasone to prednisone 60 mg daily . Biopsies ultimately revealed non - necrotizing epithelioid granulomas consistent with sarcoidosis ( Figure 1 ) . She was prescribed this high - dose prednisone for three months , and after receiving education for self - tracheostomy care , she was discharged home . At her subsequent one - month and three - month follow - up visits , she denied any further respiratory issues . Repeat laryngoscopies showed significant improvement in the edema in the arytenoids and aryepiglottic folds , but the epiglottis continued to obscure the glottis despite therapy with high - dose prednisone . Methotrexate was initiated while prednisone was tapered to 10 mg daily ; however , this regimen failed and her prednisone dosage was increased to 20 mg daily to reduce edema . Because she declined surgical treatment , she will continue with medical management with immunosuppressive therapy to facilitate eventual de - cannulation .


A 71 - year - old African - American woman presented to the hospital with worsening exertional dyspnoea associated with orthopnoea and lower extremity oedema for 3 weeks . She had a long - standing history of hypertension and documented G6PD deficiency with prior episodes of haemolysis . She was a former cigarette smoker and had family members with G6PD deficiency , hypertension and diabetes mellitus . Vital signs measurement revealed a blood pressure of 150/73 mm Hg , pulse rate of 70 bpm , respiratory rate of 24 breaths / min , temperature of 36.6 ° C and 97 % saturation on room air . She was comfortable at rest . Her physical examination showed distended jugular veins , inspiratory crackles in bilateral lung bases , a laterally displaced apical impulse and bipedal oedema . The ECG showed left ventricular hypertrophy and inferolateral T - wave inversions . Chest radiography revealed cardiomegaly and mild pulmonary oedema . The metabolic panel and troponin levels were normal but the B - type natriuretic peptide was increased at 826.5 pg / mL. Echocardiography showed a dilated left ventricle with an ejection fraction ( EF ) of 30 % and mild right ventricular systolic dysfunction . Coronary artery catheterisation revealed normal coronary circulation . Ethacrynic acid at 50 mg daily was chosen for diuresis . She improved after a day but still had dyspnoea , so we added spironolactone . Subsequently , metoprolol succinate and losartan were included in the regimen . Repeat chest radiography showed resolution of pulmonary oedema . The patient 's laboratory results during her hospital stay did not show signs of haemolysis nor worsening kidney function . She did not develop ototoxicity and was discharged home asymptomatic .


A 36 - year - old female presented at the emergency department with aggravating right upper abdominal pain for 2 hours . The patient was diagnosed hepatitis B virus ( HBV ) carrier for several years and non - alcoholics . No other specific personal and familial medical history was noted . Initial blood pressure was 100/60 mmHg , pulse rate 70 / min , respiration rate 20 / min , body temperature 37.5 ℃ . The laboratory findings were white blood cell 12,000 / mm3 ( poly : 70 % ) , hemoglobin 12.8 g / dL , platelet 198,000 / mm3 , prothrombin time 14.3 seconds , international normalized ratio 1.11 , aspartate aminotransferase 22 IU / L , alanine aminotransferase 12 IU / L , total bilirubin 0.5 mg / dL , alkaline phosphatase 134 IU / L , lactate dehydrogenase 295 IU / L , gamma - glutamyl transpeptidase 26 IU / L , protein / albumin 6.4/4.0 g / dL , uric acid 5.0 mg / dL , blood urea nitrogen / creatinine 16.6/0.7 mg / dL. And serum viral markers were HBsAg ( + ) , anti - HBs ( - ) , anti - HBc ( + ) , HBeAg ( - ) , anti - HBe ( + ) , HBV - DNA < 20 IU / mL , anti - HCV ( - ) and anti - HIV ( - ) . The patient 's serum α - fetoprotein ( AFP ) was 676.5 ng / mL and carbohydrate antigen 19 - 9 ( CA19 - 9 ) < 0.6 U / mL. She took an abdominal CT scan , which showed a 9 cm sized necrotic mass with internal hemorrhage at the right hepatic lobe and ruptured to peritoneum ( Fig.1A ) , so an emergency hepatic central bisectionectomy was done ( Fig.2A ) . The initial histological diagnosis was cHCC - CC with spindle cell metaplasia of cholangiocarcinoma element ( Fig.2B ) . The serum AFP was decreased to 7.67 ng / mL at time of discharge . Regarding as cHCC - CC , postoperative adjuvant chemotherapy with tegafur / uracil ( UFT ) was administrated for 3 months . 3 months later , follow - up abdominal CT scanning showed previously unseen a 5.5 cm sized left subphrenic mass with mild enhancement in delayed image ( Fig.3A , B ) and AFP was increased to 312.06 ng / mL. She underwent laparoscopic splenectomy with mass excision . On histologic examination , mesenchymal elements consisted of a proliferation of primitive - appearing mesenchymal spindle - shaped cells , intimately admixed with the epithelial elements in a highly cellular pattern . Cytoplasm was more abundant than that of mature fibroblasts , and the nucleus was elongated and plump . These cells blended progressively with areas of less intense cellular mesenchymal proliferation , and with relatively acellular , fibrous septa . Osteoid was present either within the primitive mesenchyme , near the fibrous septa or pseudocapsule , or admixed within the epithelial elements . Osteoid foci contained cells morphologically identical to osteoblasts ( Fig.4A ) . The immunohistochemistry stains showed expression of hepatocyte , β - HCG , AFP , vimentin , CK7 , CK19 , CD56 and β - catenin and negativity for CEA.(Fig.4B , C , D , E , F , G ) . Metastatic hepatoblastoma was confirmed by histologic examination with immunohistochemistry stains , so immunohistochemistrically re - examination of previous surgical specimens was also confirmed as hepatoblastoma . Follow - up abdominal CT scan performed 1 month after reoperation showed a newly onset 1.7 cm sized subtle enhancing soft tissue mass in splenic bed , and positron emission tomography ( PET ) showed multiple FDG uptake(max SUV > 3.80 ) in left upper and lower quadrant area of abdomen , paralumbar area including right subphrenic area ( Fig.5A , B , C ) . Follow - up AFP was 162.69 ng / mL. Systemic chemotherapy started with cisplatin ( 60 mg / m2 ) , 5 - fluorourasil ( 5 - FU ) ( 600 mg / m2 ) , vincristine ( 1.5 mg / m2 ) and total 3 cycles of chemotherapy were done every 4 week . Entecavir 0.5 mg was also started for chemoprophylaxis of CHB . After the 3rd chemotherapy cycle , follow - up abdominal CT and PET scan showed progression of multiple intraperitoneal metastasis with large amount of intraperitoneal fluid ( Fig.6A , B ) and follow - up AFP was further increased to 254 ng / mL. So chemotherapy regimen was changed to carboplatin ( 350 mg / m2 ) with doxorubicin ( 30 mg / m2 ) every 3 weeks . The patient experienced neutropenia after the new regimen , but recovered shortly after treatment with granulocyte colony - stimulating factor ( G - CSF ) . After second carboplatin with doxorubicin chemotherapy , follow - up AFP was increased 1510.19 ng / mL , but abdominal CT scan showed that amount of ascites was decreased ( Fig.7 ) . Because of radiologic improvements , third and fourth chemotherapy were performed . After 4th chemotherapy , follow - up abdominal CT revealed progression of multiple intraperitoneal metastatic masses , newly developed hepatic metastasis and large amount of intraperitoneal fluid ( Fig.8 ) . A diagnostic paracentesis was performed and showed white blood cell 310 / mm3 ( poly 20 % , lymph 80 % ) , protein 3.6 g / dL and albumin 2.3 g / dL on ascitic fluid analysis . The serum albumin was 3.1 g / dL and serum - ascites albumin gradient ( SAAG ) was 0.8 g / dL. The AFB stain and culture were all negative in ascitic fluid . The AFP was 6881.93 ng / mL on serum . Regarded as peritoneal carcinomatosis , the patient underwent conservative treatments including the use of repeated therapeutic paracentesis for 1 month before death .


A 60 - year - old white Brazilian man , with controlled hypertension and stage 2 obesity presented to our institution with a complaint of progressive fatigue with moderate to light exertion of approximately 1 year ’s duration . During that period , he had undergone myocardial perfusion scintigraphy without evidence of obstructive ischemic disease . He had no clinical evidence of systolic heart failure . He had undergone biological mitral valve replacement 3 years previously for mitral valve stenosis and had undergone ablation of atrioventricular nodal reentry tachycardia 18 months previously . At the time of valve replacement , there was no reported evidence of pulmonary arterial hypertension . The patient ’s medication list included aspirin 100 mg / day , carvedilol 50 mg / day , atorvastatin 10 mg / day , and losartan 25 mg / day . His echocardiogram showed normal function of a mitral prosthesis , global left ventricular systolic function within normal limits ( left ventricular ejection fraction 62 % measured using the Teichholz method ) , stage I diastolic dysfunction , and mean pulmonary arterial systolic blood pressure of 50 mmHg . In the 6 - minute walk test , the patient walked 104 meters ( Table 1 ) . Catheterization of his right heart chambers and pulmonary arteries confirmed the diagnosis of pulmonary hypertension ( Table 2 ) . During the follow - up period , therapy with nifedipine and sildenafil was not tolerated secondary to orthostatic hypotension . The patient was referred for radiofrequency ablation of the pulmonary artery trunk for the treatment of refractory pulmonary hypertension . The procedure was performed in the catheterization laboratory with direct visualization using fluoroscopy and radiopaque contrast dye . The patient remained under unconscious sedation . Catheterization of the right femoral artery via the standard Seldinger technique was performed using an 8 - French valved short sheath after subcutaneous injection of a local anesthetic . Subsequently , this sheath was replaced with a steerable long sheath ( Agilis ® ; St. Jude Medical , St. Paul , MN , USA ) using the standard over - the - wire technique . Unfractionated heparin was administered intravenously , targeting an activated coagulation time between 250 and 350 seconds . Electroanatomic reconstruction of both the right ventricular outflow tract and pulmonary artery was performed using the EnSite Velocity Cardiac Mapping System ( St. Jude Medical ) under direct fluoroscopic visualization , and a merger was made with the formatted image obtained by performing cardiac computed tomography angiography ( Fig.1 ) . The Agilis ® sheath was advanced into the right ventricular outflow tract just before reaching the pulmonary valve . Through this long sheath , we introduced an ablation catheter with an open irrigated tip ( St. Jude Medical ) . The parameters used for each application according to our protocol were as follows : power of 5 W , maximum temperature of 48 ° C , 60 - second duration in each spot , maximum impedance variation of 10 % from baseline values , and an irrigation flow rate of 17 ml / minute , which created a circle in the pulmonary artery trunk . The patient was discharged the next morning . No noteworthy changes before or after the procedure or before discharge in the patient ’s radiographic or echocardiographic laboratory parameters were seen . The patient ’s blood pressure in both the right heart chambers and the pulmonary artery were determined using catheterization before and at 3 and 6 months after the procedure . The results are shown in Table 2 . At the patient ’s 3 - month follow - up examination , he showed an improvement in functional class for fatigue with major exertion . He also demonstrated an increased distance walked in the 6 - minute walk test and reduction of the pressures in both the right cavities and the pulmonary artery . Currently , with 6 months of clinical follow - up , he has maintained his improvement in functional classification and is pedaling his bicycle .


A 35 - year - old woman was admitted with a 5 - day history of increasing drowsiness , fatigue , personality changes , generalised weakness and deteriorating mobility . Her medical history included a 10 - year history of schizo - affective disorder , lithium - induced diabetes insipidus and hypothyroidism . Her medications included sodium valproate 1 g twice daily , carbamazepine , quetiapine and lithium . On admission , the patient was drowsy , difficult to rouse ( sleeping all night and in the afternoon ) . Her Glasgow Coma Scale ( GCS ) was 14/15 , her abbreviated mini - mental test score was 6/10 and she was noted to be slow in her responses . Neurological examination showed reduced power in her lower limbs ( 3–4/5 ) in a pyramidal distribution , and brisk reflexes with intact sensation in all modalities . Cardiovascular , respiratory and gastrointestinal examinations were unremarkable and there were no demonstrable features of hepatic disease . Routine biochemistry was unremarkable . The patient 's alanine transaminase was 7 u / L ( 1–15 ) , alkaline phosphatase 61 u / L ( 30–130 ) , γ - glutamyl transferase 17 u / L ( < 45 ) and bilirubin was 6 μmol / L ( < 21 ) . She had normal serum B12 and folate levels , and normal thyroid function tests . Serum lithium levels were within the therapeutic range . Her serum ammonia was 47 μmol / L ( 11.2–35.4 ) and valproate concentrations were elevated 140 mg / L ( 50–100 ) . Brain imaging including CT and MRI did not show any haemorrhage or intracranial mass . Lumbar puncture demonstrated clear cerebrospinal fluid ( white cell count < 1×106 / L , protein 0.25 g / L ( 0.2–0.4 ) ) . EEG demonstrated mild variable slowing and irregularity of background activity ( likely due to medication ) . The differential diagnosis included encephalitis , Guillain - Barré syndrome and acute disseminated encephalomyelitis ( ADEM ) , which were excluded through our investigations . In view of the raised valproate and ammonia levels , a diagnosis of valproate hyperammonaemic encephalopathy ( VHE ) was made at this point The dose of sodium valproate was reduced by half rather than being completely withdrawn . This was due to the complex and challenging nature of managing the patient 's schizo - affective disorder . Within 3 days , there was evident clinical improvement in her mental status . The patient was able to sit and communicate with the team , and her abbreviated mental test score improved to 10/10.The serum ammonia normalised and valproate levels decreased to the therapeutic range . After 4 days she was discharged home . Results of investigations of her urea cycle were awaited . Three weeks postdischarge , the patient was clinically stable in terms of mental functioning , having had no further episodes of confusion or drowsiness . However , she continued to have fatigue and walking difficulties ( due to residual leg weakness ) . Results of her serum amino acids revealed that our patient had carnitine deficiency evident by low acyl - carnitine , low free serum carnitine ( 14.2 μmol / L , normal range : 23–52 ) and low total serum carnitine ( 19.9 μmol / L , normal range : 27–63 ) . She was started on oral carnitine 1 g twice daily . Within 2 weeks , her symptoms resolved completely with normalisation of serum carnitine levels ( free carnitine 25.2 μmol / L and total carnitine of 41.3 μmol / L ) . The sodium valproate was initially stopped completely , but due to a serious relapse of the patient 's schizo - affective disorder , it was restarted and she is now well on valproate 1 g once daily and long - term carnitine supplements .