A 31-year-old male was referred to a quaternary intensive care unit (ICU) for consideration for extracorporeal membrane oxygenation (ECMO) due to severe biventricular heart failure refractory to inotropic support (a cardiac index of 1.3 on noradrenaline and dobutamine infusions). He had presented with shortness of breath, extreme lethargy and abdominal pain, and was hypotensive and tachycardic.
His history was significant for a diagnosis of an iron overload state after presenting with lethargy 4 months prior. At diagnosis his serum ferritin was 2541 μg/L (reference range (RR) 30–500) with a transferrin saturation (TS) of 90% (RR 10–45). Laboratory investigations revealed normal hematologic, renal, and liver function. Hepatitis serology was negative and subsequent extensive imaging revealed no evidence of malignancy. Genetic testing revealed H63D heterozygosity for the HFE gene, which is inconsistent with hereditary hemochromatosis with iron overload. While awaiting venesection he developed diabetic ketoacidosis which required admission and stabilization with an insulin infusion. His glycated hemoglobin (HbA1c) was 15% and c-peptide 0.07 nmol/L (RR 0.30–2.30). He was diagnosed with diabetes mellitus secondary to iron overload with significant beta cell insufficiency and was transitioned to twice daily premixed insulin. Given the above presentation, the decision was made to proceed to liver biopsy to investigate the extent of iron overload. A liver biopsy identified extensive intrahepatocyte iron but minimal inflammatory cell infiltrate and minimal fibrosis with a hepatic iron index of 13 (RR <2). His liver function tests were normal.
Our patient, of Serbian origin, reported no family history of iron overload syndrome, endocrinopathy or cardiomyopathy. There was no history of excess alcohol intake, recreational drug use, or toxic environmental exposures.
A physical examination on admission to the ICU revealed a patent airway. His respiratory rate was 15 breaths/minute, oxygen saturation 98% on 4 liters of oxygen via nasal prongs, and good air entry to bilateral lung fields but slightly reduced at the right base without crackles or wheeze. On a noradrenaline, dobutamine, and amiodarone infusion his blood pressure was 90/64 mmHg with a pulse rate of 105 beats per minute with cardiac monitoring revealing a sinus tachycardia. A cardiovascular examination was significant for a hyperdynamic apex beat with heave, a jugular venous pulse at 2–3 cm and dual heart sounds with nil murmurs. A neurological examination was significant for a Glasgow coma score of 14 (eyes 3 motor 5 verbal 6). His abdomen was soft on palpation with tenderness to the right upper and lower quadrant and no guarding. A peripheral examination was significant for a tanned complexion and the absence of peripheral edema.
Laboratory investigations on admission did not account for the patient’s critical clinical state revealing normal hemoglobin concentration, platelet count, renal function and serum electrolytes. His liver function was mildly deranged with an elevated alanine transaminase (88 units/ L, RR 12–15) and bilirubin (62 umol/L RR, ≤ 23) and decreased albumin (30 g/L, RR 33–46). His C-reactive protein (CRP) and neutrophil count were mildly elevated, 9 mg/L (RR ≤ 5) and 10.27 109/L (RR 1.90–8.00) respectively, with a normal white blood cell count (12.03 109/L, RR 3.90–12.70). Antinuclear antibody and rheumatoid factor test results were negative. A high-sensitivity Troponin I test result was mildly elevated (64 ng/L, RR ≤ 26). Midstream urine and blood culture were negative.
A computed tomography scan demonstrated a dilated heart with associated pleural effusions, ascites, and liver congestion. A transthoracic echocardiogram revealed normal left ventricular (LV) size with severe global systolic dysfunction with an ejection fraction of 5–10%, spontaneous echo contrast, and normal wall thickness. The right ventricular (RV) size was normal with severely reduced function. Mild to moderate mitral and pulmonary regurgitation were noted along with a trivial pericardial effusion.
He had a prolonged ICU stay due to progressive multi-organ dysfunction. He was intubated and ECMO support was initiated on day 2 and biventricular assist devices (BiVAD) were inserted on day 8. An endomyocardial biopsy revealed myocyte intracytoplasmic iron deposition (Fig. and ). This result together with the global nature of the systolic dysfunction was consistent with iron overload as a cause for the cardiomyopathy. There was no echocardiographic or histopathologic evidence to suggest myocarditis and hemodynamic instability precluded coronary angiography.
Serum ferritin (SF) level was 12,361 μg/L and TS was 99% on day 2. Iron chelation therapy was commenced on day 6 with desferrioxamine, initially subcutaneously. Shortly after its commencement, increasing inotropic requirements and bilateral lung infiltrates felt to represent pulmonary edema were noted and desferrioxamine was ceased as a precaution. It was restarted on day 21 once his clinical condition had stabilized and up-titrated to a maximum dose of 4200 mg (60 mg/kg) administered via a 24-hour intravenous infusion and was subsequently well tolerated with rapid removal of iron burden. SF levels peaked on day 13 at 18,676 μg/L and TS was > 99% before decreasing to 1055 μg/L by day 59 with TS also decreasing to 65%.
By the fifth week after presentation, it was considered that he may have developed diabetes insipidus on the basis of a marked unexpected increase in urine output, but because of his parlous clinical state on BiVAD it was not possible to confirm with a water deprivation test at that time. A trial of desmopressin did not result in convincing improvement.
Investigation of his anterior pituitary function revealed isolated hypogonadotropic hypogonadism. Testosterone replacement was commenced with testosterone 1% gel 2.5 g topical daily with subjective improvement in energy levels and sense of wellbeing.
Our patient was listed for heart transplantation and discharged home on day 69 with BiVAD in situ after progressive improvement in his physical capacity with intensive inpatient rehabilitation. Desferrioxamine was continued at home via nightly 10-hour continuous subcutaneous infusions. Our patient was readmitted on day 89 with urosepsis, which was successfully treated with antibiotic therapy. At this time, he was noted to have improved left ventricle function on an echocardiogram, estimated to be only mildly reduced on a technically difficult study. Serial outpatient echocardiograms, both resting and stress, demonstrated myocardial recovery with normal LV size and resting systolic function (visual LV ejection fraction of 55–60%) and normal RV size and low-normal systolic function. With exercise, there was good augmentation of both LV and RV function and a normal hemodynamic response. Successful BiVAD explant occurred, 141 days after initial implant with SF 163 μg/L and TS <1% 12 days prior. Left ventricular biopsy at this time demonstrated less intracytoplasmic iron deposition compared with the initial biopsy (Fig. ). Post BiVAD explant, desferrioxamine was ceased as a potential cause of worsening renal tubular acidosis. Cardiac magnetic resonance imaging (cMRI) completed 2 weeks post BiVAD explant demonstrated normal biventricular systolic function but a myocardial T2* time of 12.3 milliseconds (normal > 20 milliseconds) consistent with residual myocardial iron loading. A formal water deprivation test was performed and was normal, therefore desmopressin was ceased.
As the patient’s history was significant for a diagnosis of hemochromatosis, JH was suspected given his age and absence of family history. Targeted gene sequencing was then performed across 39 genes and 11 promoter regions using a custom “AmpliSeq” panel (Life Technologies, Mulgrave, Victoria, Australia) and an Ion Torrent™ Personal Genome Machine™ (Life Technologies) as previously described []. Following alignment of the sequencing with the Human Genome version 19 (HG19), our patient’s heterozygosity for the HFE H63D was confirmed, and no other mutation were present in the HFE gene. Variant analysis identified homozygosity for a variant c.G959T (NM_213653) in exon four of the HFE2 gene (aka HJV) resulting in a p.G320V mutation (rs74315323). This DNA change was confirmed by Sanger sequencing. The G320V mutation has previously been reported in multiple cases of juvenile onset hereditary hemochromatosis []. No other mutations known to be associated with iron overload were identified in our patient, nor were there any other novel or rare single nucleotide polymorphisms in the coding regions of sequenced genes.
At follow-up 12 months after his presentation with severe biventricular heart failure the patient has made a near-complete recovery and had returned to work. His SF level was 29 μg/L. CMRI, previously contraindicated due to the implanted ventricular assist devices, 20 months after he presented with severe biventricular heart failure, demonstrated T2* time had returned to normal in the myocardium (41 milliseconds) and liver (19 milliseconds). The study also demonstrated normal biventricular function with mild biventricular dilatation and the absence of myocardial fibrosis. He remains on insulin and testosterone replacement and 3-monthly venesections were commenced.


An 8-year-old male patient with a history of SCD maintained on long term erythrocytapheresis (LTE) for primary prevention of stroke due to a history of increased transcranial Doppler velocities presented with several days of fatigue, decreased oral intake, chest pain, and palpitations. Imaging studies showed a large right-sided pleural effusion with underlying atelectasis or consolidation (). A chest tube was inserted for drainage of the pleural fluid, which continued to have significant output for several weeks. The pleural fluid had features consistent with chylous effusion, including elevated triglycerides, positive for chylomicrons, and milky appearance.
Enhanced computed tomography (CT) venogram was performed (); followed two weeks later by conventional venogram, which showed right internal jugular (IJ) vein thrombus with SVC extension. The patient did not respond to dietary therapy, consisting of a low fat diet, showing little improvement in the pleural drainage. An interventional radiology lymphangiogram was inconclusive because the contrast was very slow moving. A thoracic magnetic resonance image (MRI) showed two separate lymphatic ducts draining the lymph from cisterna chyli to the right and left subclavian veins (). This represented a normal congenital variant with the (left) thoracic duct smaller in caliber. There were two draining sites at the terminal part of the (left) thoracic duct, with the accessory draining site inferior and posterior to the main opening. The terminal part of the main (right) thoracic duct at the level of confluence of the right IJ and right subclavian vein could not be delineated.
A thrombophilia workup looking for traditional factors revealed the following:
The etiology of his thrombus was likely from the presence of a central line used for LTE in the setting of a known hypercoagulable state of SCD and heterozygous factor V Leiden mutation. He was therefore placed on long term anticoagulant therapy using low molecular weight heparin. Aspirin was also added. The pleural drainage remained significant so he was made “nothing by mouth” (NPO) and given total parenteral nutrition for 3 weeks. A bilateral upper extremity venogram 2 weeks after presentation showed a persistent clot in the SVC and multiple collaterals. The tip of the CVAD was in the right brachiocephalic vein. He was then started on octreotide and the dose was increased but provided no improvement in the chest tube output. He subsequently underwent vascular surgery procedures including thrombectomy—which was unsuccessful as the vascular surgeon was unable to cross the subclavian lesion with both a Kumpe catheter and a soft angle Glide wire—followed by balloon angioplasty of the SVC and left innominate vein. The SVC and left innominate vein showed resolution of stenosis, however there was still occlusion of the subclavian vein with several collaterals. At the same time, his CVAD was removed. He was discharged with the chest tube in place.
He returned to the hospital 2 weeks later due to persistent drainage, erythema, and pain around the chest tube site, for which he was treated with 10-day course of clindamycin. Following discharge, he returned 2 weeks later for a reversed pleuroperitoneal (PP) shunt placement with perioperative transfusion, and measures to prevent acute chest syndrome. The shunt was a single valve, 15.5 French, Denver (Beckton, Dickinson and Company, Franklin Lakes, NJ, USA) PP shunt, used in this case in a reverse fashion such that the valve opened from pleural cavity to the abdominal cavity (, and ). (This particular PP shunt is typically designed to drain malignant abdominal ascites into the chest cavity).
The pressure gradient necessary to open the valve is 3 cm of water, but this can be overcome by compressing the bulb which houses the one-way valve, forcing flow from chest to abdomen. This pressure gradient is noted on the packing insert for the shunt and is outlined within the instruction manual for the Denver shunt on the manufacturer, Beckton, Dickinson, and Company’s (Franklin Lakes, NJ, USA) website. The patient continued with monthly simple transfusions, and hydroxyurea was instituted. Following the PP shunt placement, he required one hospitalization for re-accumulated chylothorax and had a thoracostomy tube placed. Significant drainage was felt to be secondary to the obstruction of the PP catheter and to non-adherence regarding compressing the shunt reservoir bulb daily in order to prevent obstruction of its one-way valve. The PP catheter was cleared by pressure on the shunt bulb, which was continued at home a few times daily. Repeat imaging with Duplex ultrasound showed no change in the thrombus, consistent with fibrotic changes. The PP shunt was removed about 6 months after placement, and he has remained free of pleural effusion (). The decision to remove the shunt was based on an asymptomatic period of about 6 months, parent comfort level, and the surgeon’s past experience with PP shunts. He has continued to be managed with hydroxyurea, with dose escalation to the maximally tolerated dose, and he has transitioned off transfusions.


An 18-year-old female presented in December 2015 with acute chest pain. A computed tomography (CT) scan of her chest revealed a pericardial effusion which was negative for malignancy. The presumptive diagnosis was viral pericarditis. In February 2016, she developed recurrent left-sided chest pain and was found to have cardiac tamponade. An enhancing mass was identified in the right atrium on imaging (Figure ). She underwent a pericardial window procedure which revealed a vascular tumor invading the pericardium. The frozen section of the specimen was consistent with sarcoma. In March 2016, she underwent pericardiectomy with biopsy of the tumor revealing angiosarcoma of the right atrium. After the procedure, she was started on a neoadjuvant cycle of doxorubicin (25 mg/m2, one to three days) and ifosfamide (1.8 g/m2, one to five days). She was then treated with four other cycles of doxorubicin and ifosfamide followed by four cycles of paclitaxel 80 mg/m2 weekly for three of four weeks. Follow up imaging revealed an increase in the tumor size with interval development of small volume metastasis to the right lung. In November 2016, she underwent the surgical resection of the right atrial tumor after she was found to have metastatic lung nodules. The pathology showed angiosarcoma with the treatment effect and evidence of invasion of the cardiac muscle and fibrous connective tissue. New pulmonary nodules were evident on subsequent imaging which led to further chemotherapy treatment. She initially received a cycle of gemcitabine 900 mg/m2 followed by four cycles of gemcitabine 1500 mg/m2 and dacarbazine 500 mg/m2. A week prior to receiving her fifth cycle, she developed severe chest tightness and was found to have left-sided pneumothorax requiring surgical management with left-sided video-assisted thoracoscopic bullectomy. The pathology was negative for metastasis. Currently, she is doing well with plans to resume further chemotherapy.


A 39-year-old male reported concerns of progressive right calf swelling for two years. A lower extremity magnetic resonance image (MRI) revealed a mass suspected to be a sarcoma. Fine needle aspirate of the mass was consistent with low-grade monophasic synovial cell sarcoma. A staging CT of his chest showed multiple small bilateral pulmonary nodules. He underwent three cycles of neoadjuvant cyclophosphamide, doxorubicin, and dacarbazine followed by amputation above the right knee. After the surgery, he underwent 10 more cycles of cyclophosphamide, doxorubicin, and dacarbazine with complete resolution of the pulmonary nodules. On follow-up CT of his chest two and a half years later, a left lower lobe metastatic lung nodule was noted. He was re-started with chemotherapy with ifosfamide, mesna, and pegfilgrastim (Neulasta). After three cycles, his chest CT showed disease progression with bilateral pulmonary metastases. The left and right video-assisted thoracoscopy with nodule resections were done, and the surgical specimen pathology was consistent with metastatic synovial sarcoma. At this time, given his progressive disease with chemotherapy, the decision was made to start pazopanib. Two weeks after receiving pazopanib for three months, he was admitted for chest pain and was found to have a pneumothorax which was managed by talc pleurodesis. Pazopanib was resumed, and after receiving it for 29 months, it was temporarily stopped due to uncontrolled diarrhea. Four months later, he developed chest tightness while playing golf and was found to have a recurrent hemothorax six months after the initial one (Figure ). Both hemothoraces required emergent evacuation and blood transfusions. The examination of the pleural fluid was negative for malignancy. After resolution of his second hemothorax, pazopanib was resumed, and currently, he is doing well.


A 20-year-old male presented in August 2016 with distal left thigh pain of a few months duration. A left lower extremity MRI revealed distal femoral metadiaphysis mass with surrounding periosteal reaction. The biopsy of the mass revealed osteoblastic osteosarcoma. A staging CT of his chest showed a 3 mm right upper lobe lung nodule. He underwent three cycles of neoadjuvant cisplatin (25 mg/m2, one to three days) and doxorubicin (25 mg/m2, one to three days). Two weeks after his first cycle, he developed a left pneumothorax, which recurred two weeks later. Given his increased risk for the recurrent pneumothoraces, the pleurodesis was performed. In December 2016, he underwent radical resection of the left distal femur with left total knee arthroplasty and distal femur replacement. The resected tumor showed 50% necrosis. Therefore, the decision was made to pursue three additional cycles of ifosfamide/doxorubicin alternating with ifosfamide/cisplatin. The cumulative doses of ifosfamide, cisplatin and doxorubicin were 27 g/m2, 80 mg/m2 and 150 mg/m2, respectively. Three days prior to receiving his cycle two of ifosfamide/cisplatin, he started to have right-sided chest pain and was found to have bilateral pneumothoraces on imaging (Figure ). Being hemodynamically stable, he was initially given his planned chemotherapy cycle of ifosfamide/cisplatin followed by chest imaging. A CT of his chest showed three bilateral subpleural cystic lesions which were not demonstrated on prior imaging. He underwent bilateral video-assisted thoracoscopy with lung nodule resection and pleurodesis. The follow-up imaging confirmed the resolution of his pneumothoraces. Currently, he is doing well with plans to perform a chest CT every two months in the first year to detect incidental asymptomatic recurrent pneumothoraces.


A 68-year-old woman presented with increased right upper limb weakness for one week's duration. There were no sensory symptoms. Her vital signs were normal. Examination showed slurring of speech with decreased power in the right upper limb proximal muscle strength (Medical Research Council (MRC) score of 4) compared to the left (MRC 5). Muscle power in the distal upper limbs was equal. Power was also decreased in the right proximal lower limb compared to the left. The patient had a past medical history of old ischaemic stroke in 2006, hypertension, dyslipidaemia, Graves’ disease, and immune thrombocytopaenia (ITP), which was diagnosed incidentally in 2008. There was no bleeding manifestation of the ITP on diagnosis; her platelet was repeatedly below 100 x 109/L at that time. There were no immature or abnormal white cells, no schistocytes, and no abnormal platelet morphology on blood film. Coagulation tests were not prolonged. Antiphospholipid antibodies (lupus anticoagulant and anticardiolipin), anti-double-stranded DNA, and anti-Smith antibodies were negative. Complements (C3 and C4) were normal. Human immunodeficiency virus (HIV) and hepatitis C antibodies were not detected. Helicobacter pylori screening was not done.
Computed tomography (CT) of the brain showed hypodensity in the left corona radiata and old infarcts with a background of small vessel disease (Figure ). A decision was made by the neurologists not to proceed with magnetic resonance imaging (MRI) of the brain in view of the multiple old strokes. A diagnosis of right ataxic hemiparesis was made. An ultrasound of her carotid arteries showed moderate left and mild right carotid artery stenosis. Platelet level at the onset of stroke was 119 x 109/L (reference range 150-400 x 109/L). Total white cells were 6.98 x 109/L and haemoglobin 14.4 g/dL. Thrombophilia screenings revealed levels of Factor V Leiden, proteins C and S, and antithrombin were not deficient. She was not on prednisolone. After consultation with a haematologist, the decision was made to start clopidogrel. She underwent a one-month duration of rehabilitation. While on clopidogrel, her platelet count dropped to a nadir of 59 x 109/L. There were no clinical symptoms or signs of bleeding manifested. Antiplatelet therapy was continued. She was discharged ambulant with a walking frame.
Two months later, she presented with acute right-sided lower limb weakness and difficulty in walking, which was new to her. CT brain did not show any acute haemorrhage. Multiple chronic lacunar infarcts were seen in bilateral thalami, internal capsules, corona radiata, and pons. MRI with diffusion-weighted imaging (DWI) did not show the presence of an acute infarct. There were multiple chronic infarcts. Multiple microhaemorrhages were also seen. Magnetic resonance angiography (MRA) showed diffuse flow irregularities in the anterior and posterior circulations due to atherosclerosis without significant flow-limiting stenosis. She was diagnosed with right ataxic hemiparesis and DWI-negative stroke with microhaemorrhages. Her platelet count was 41 x 109/L, and the clopidogrel was suspended. She was started on prednisolone, 60 mg daily, as advised by the haematologist. Subsequent platelet counts were 43 x 109/L and 51 x 109/L before the clopidogrel was restarted with esomeprazole. Her platelet remained stable at 88 to 126 x 109/L during the course of rehabilitation, and her prednisolone was gradually tapered to 20 mg daily upon discharge.
Three weeks after discharge from above-mentioned admission, she was admitted for non-specific breathlessness. Initial investigations showed that her blood gases and chest x-ray were normal. A CT scan was performed because the patient complained of right-sided weakness with deconditioning of her activities of daily living, to the point where she needed a wheelchair for ambulation. CT showed no acute intracranial haemorrhage or territorial infarct. A 0.4 cm hyperdense lesion was noted in the left corona radiata that corresponded to a prior punctate haemorrhage (Figure ). Her platelet count was 127 x 109/L. She was discharged uneventfully with clopidogrel and same previous prednisolone dose of 15 mg daily.
Literature review
We reviewed recently published reports on adult ischaemic stroke in ITP over the past five years (from 2012 onwards) using PubMed search and hand search with Google. Keywords of ischaemic stroke and ITP were used. There were seven reports published [-], and we included our report in the table summarised below (Table ).


A 63-year-old Japanese woman was referred to our hospital after suffering from rectal prolapse with a mass and rectal bleeding for 2 years. An examination revealed complete rectal prolapse of the entire thickness of the rectum with a soft, ulcerated tumor, 7 cm in diameter, included in the prolapse (Fig. ). The tumor and prolapse were easily reduced manually; the distance from the anal verge to the tumor was 5 cm. The anal sphincter tone was slightly diminished. The patient’s laboratory data were normal except for anemia (hemoglobin level, 5.9 g/dL). Tumor markers were within normal limits: carcinoembryonic antigen was 2.8 and carbohydrate antigen 19-9 was 6.2. A computed tomography scan revealed that the lower rectum was filled with a tumor measuring 7 × 6 cm, which was enhanced with contrast medium (Fig. ). There was no evidence of direct invasion of the tumor around the rectum, and no evidence of lymph node involvement or distant metastasis. A gastrografin enema revealed that the tumor was located in the posterior wall of the lower rectum (Fig. ). Colonoscopy showed a large villous tumor in the lower rectum. The cauliflower shape of the tumor caused the edge to protrude laterally from its base, and the rim of the tumor appeared friable (Fig. ). Biopsies of the tumor revealed adenocarcinoma. These findings suggested that the large, partially ulcerated tumor was not more than a T1 stage. We defined her cancer as clinical stage 1; cT1, cN0, cM0 according to the Union for International Cancer Control Classification of malignant tumors, 7th edition. Therefore, we did not consider neoadjuvant chemoradiotherapy. Thus, we planned to perform Lap-LAR. To preserve the anal sphincter and to retract the part of the cauliflower-shaped tumor protruding over the wall of the rectum, ensuring a negative distal margin, we also planned to use a prolapsing technique.
Our patient was placed in the lithotomy position under general anesthesia, and five ports were inserted. We dissected the lymph nodes from the origin of the inferior mesenteric artery. We preserved the left colic artery and ligated and divided the superior rectal artery. The sigmoid colon and the rectum were mobilized using the total mesorectal excision technique, and the dissection was extended distally to expose the entire circumference of the levator ani muscle (Fig. ). The proximal colon was transected using an endoscopic stapler. Then, we grasped the stump of the rectum using a forceps introduced anally and gently withdrew the stump under laparoscopic assistance. The distal rectum was easily everted and pulled outside of the anus (Fig. ). We transected the distal rectum 1.5 cm distal to the lower edge of the lesion under direct visualization, using the same stapler (Fig. ). An intraoperative frozen section revealed that the surgical margin was negative for tumor involvement. We reduced the distal rectum, through the anus, back into the pelvis (Fig. ). Then, we performed a minilaparotomy with a 4-cm incision at the umbilical port site to extract the proximal colon. We resected an extra 10 cm of proximal colon to create the proper length for an anastomosis and attached a 29-mm anvil head. We performed an end-to-end anastomosis using a double-stapling technique with a circular stapler. The operative time was 194 minutes, and the blood loss was 10 mL.
On gross examination of the resected specimen, a cauliflower-shaped soft tumor with an ulcer was located in the lower rectum. The tumor measured 7 × 8 × 3 cm, and the distal margin of the resected rectum was more than 1.5 cm from the tumor. Histological examination of the tumor showed moderately differentiated tubular adenocarcinoma without regional lymph node metastasis. Almost the entire tumor was intramucosal, with focal invasion of the submucosal layer (stage 1; pT1, pN0, pM0) (Fig. ). Our patient had an uneventful postoperative course. She had no fecal incontinence or constipation. Twelve months after surgery, she is doing well with no evidence of recurrence of either her rectal prolapse or her cancer.


A 63-year-old woman diagnosed with alcoholic cirrhosis was referred to our hospital for LDLT. The blood tests and physical examination revealed that liver cirrhosis was graded Child-Turcott-Pugh classification C and her calculated model for end-stage liver disease (MELD) score was 17. Preoperative CT scan and endoscopy revealed that she had portosystemic collaterals, such as right spleno-renal shunt and duodenal varix (Fig. a, b). She had mild dyspnea on exertion as well as fatigue. Chest radiographs and computed tomography showed mild cardiomegaly (chest-thoracic ratio, 56%); however, no abnormal findings were seen in the lung field. Arterial blood gas (ABG) analysis showed mild hypoxemia at room air (pH, 7.468; partial pressure of carbon dioxide [pCO2], 38.3 mmHg; partial pressure of oxygen [pO2], 83.0 mmHg), although a radiolabeled technetium macroaggregated-albumin (99mTc-MAA) perfusion scan showed an insignificant right-left shunt of 3.8%, indicating the absence of hepatopulmonary syndrome (HPS; Fig. c). Echocardiography revealed tricuspid regurgitation (TR) with estimated mPAP of 54 mmHg, TR-peak pressure gradient value of 62.2 mmHg, and pulmonary vascular resistance (PVR) of 520 dynes s/cm5 suggesting pulmonary hypertension (Fig. ). Heart contractility was normal with normal ejection fraction values of 65%. The patient proceeded to cardiac catheterization, which revealed a high mPAP value (36 mmHg), high pulmonary vascular resistance (476 dynes s/cm5), and normal pulmonary capillary wedge pressure (PCWP; 9 mmHg). The patient’s cardiac output (CO) was 4.20 L/min, and cardiac index (CI) was 2.91 L/min/m2 (Table ). Accordingly, she was diagnosed with liver cirrhosis accompanied by moderate-grade PPH. We commenced treatment with oral tadalafil (20 mg/day), an oral once-daily PDE5 inhibitor, for moderate PPH. The patient tolerated the tadalafil therapy well. Twenty-five days after starting tadalafil, a second preoperative echocardiography demonstrated good response to tadalafil and improved PPH with an estimated mPAP of 22 mmHg, TR-peak pressure gradient value of 26.3 mmHg, and PVR of 184 dynes s/cm5.
Thirty-two days after the initiation of tadalafil, she underwent LDLT with a left lobe graft from her daughter. The graft-versus-recipient weight ratio was 0.76%. Dobutamine hydrochloride (3 μg/kg/min) was administered temporally after graft reperfusion. The pre-explant portal vein pressure was 25 mmHg during surgery and decreased to 17 mmHg after reperfusion. The operation time was 9 h and 56 min, while the total blood loss was 1200 mL. Immunosuppression consisted of methylprednisolone and tacrolimus. An intravenous systemic infusion of prostaglandin E1 (7 ng/kg/min) was started after graft reperfusion and continued intra- and postoperatively instead of tadalafil [–]. No hemodynamic events occurred during the operation.
The mPAP values were continuously monitored using a cardiac catheter intra- and postoperatively, and values rapidly decreased to 22 mmHg 2 days after the LDLT (Table ). After weaning and discontinuation of the prostaglandin E1, the mPAP value remained 23 mmHg. After mPAP stability was confirmed, the cardiac catheter was removed. Since the mPAP value was effectively reduced, we decided to not subject the patient to a further course of tadalafil. She showed a lot of ascites and hyperbilirubinemia several weeks after LDLT, suggesting mild small-for-size syndrome. This syndrome was gradually resolved by treatment with diuretics and liver graft function gradually improved without rejection (Fig. ), while a surgical site infection by gram-positive bacillus occurred and she was treated with a course of antibiotics. After LDLT on POD 60, Doppler echocardiography revealed that the TR had disappeared with lowered estimated mPAP, TR-PPG, and PVR value from 54 to 24 mmHg, 62.2 to 27.6 mmHg, and 520 to 234 dynes s/cm5, respectively (Fig. and Table ), suggesting an effective retrieval of right heart function. Right heart catheterization 62 days after the LDLT showed that the mPAP value remained at 22 mmHg with a CO of 4.56 L/min and CI of 3.5 L/min/m2, suggesting that the PPH had attenuated (Table ). ABG analysis showed improved oxygenation at room air (pH 7.393; pCO2, 30.8 mmHg; pO2, 111.0 mmHg). The patient was discharged 70 days post-LDLT in good condition with no signs of cardiac insufficiency and good liver graft function. She has shown a good clinical course for over 2 years after the LDLT without any evidence of PPH.
An association between portal hypertension and pulmonary hypertension was first reported by Mantz and Craige []. PPH is defined as elevated PAP accompanied by hepatic disease and portal hypertension, while the key finding is clearly an elevated calculated PVR []. The criteria for the diagnosis of PPH include an elevated resting mPAP value ≥ 25 mmHg, an elevated PVR of ≥ 120 dynes s/cm5, normal PCWP (≤ 15 mmHg), and evidence of portal hypertension []. However, more recent studies have proposed that the PVR value for the diagnosis of PPH should exceed 240 or 250 dynes s/cm5 [, ]. The most typical pulmonary symptoms include fatigue, exertional dyspnea, syncope, and chest pain; however, these symptoms are absent in about 60% of patients at the time of diagnosis []. Mild hypoxemia at rest due to diffusion limitations and TR may be present on examination. Our patient met the diagnostic criteria of PPH.
PPH is most commonly diagnosed 4–7 years after the diagnosis of portal hypertension [], and the longer the portal hypertension persists, the greater the risk of PPH exists [, ]. The prognosis of patients with PPH is poor, with a mean survival of 15 month []. Death occurs due to liver failure, infection, or right heart failure. As mentioned in the “” section, liver transplantation in patients with moderate to severe PPH is associated with significantly higher mortality rate [, ]. Therefore, several reports have recommended that preoperative estimation of PPH severity by using cardiac catheterization is necessary for the patient selection and preoperative treatment of patients with moderate PPH using vasodilators [, , ]. Following these recommendations, there have been several reports of successful liver transplantation for patients with moderate to severe PPH using vasodilators in the perioperative period as a bridging therapy, similar to the case reported herein.
Several agents have been used to treat PPH prior to liver transplantation, including epoprostenol [], bosentan [], sildenafil [], iloprost [], and a combination of these agents []. Prostanoids including prostaglandin E1 (alprostadil) and prostacyclin (epoprostenol) are the most widely used and most effective agents for bridging therapy [–]. Another agent is the endothelin receptor antagonist, bosentan. Its adverse effect of hepatic dysfunction has limited its use for decompensated liver disease, although it has been seen in only a few patients. Increasing evidence of the efficacy of the PDE5 inhibitor, sildenafil, is emerging, and it has been used for patients with PPH. PDE5 inhibitors boost the effect of endogenous nitrous oxide by inhibiting the breakdown of the messenger substance cyclic guanosine monophosphate, leading to pulmonary vasodilatation and inhibition of vascular smooth muscle proliferation. Selective pulmonary vasodilators rather than systemic vasodilators have demonstrated relatively few adverse effects []. Additionally, they are generally well tolerated and have been used successfully for the treatment of pulmonary hypertension []. Tadalafil, another PDE5 inhibitor, is a once-daily oral medication that has shown comparably significant pulmonary vasorelaxation in patients with pulmonary hypertension []. In our case, we observed successful resolution of PPH using tadalafil without any complications or evidence of toxicity and with good tolerability. Including the present case, only a few reports have described LDLT for adult patients with PPH [–] and a few reports have described a combination use of PDE5 inhibitor (sildenafil) and other drugs as bridging therapy in LDLT [–].
The patient in this case experienced a rapid improvement of PPH after LDLT. It is debatable whether PPH is reversible after liver transplantation. Most patients with PPH show improved or normalized PAP and can be weaned from vasomodulating medication, which usually takes months []. In our case, PPH was rapidly resolved after LDLT. In fact, in our case, we had planned switching back to tadalafil after LDLT; however, the resolution of PPH was more rapid than we had expected. On the other hand, some of patients require long-term treatment due to persistent and progressive pulmonary hypertension after liver transplantation []. One speculation for this contradiction is that reversibility might depend on PPH stage. Pathoetiologically, in PPH, vasoactive substances initially cause pulmonary constriction functionally, and subsequently cause endothelial proliferation, and vessel obliteration propagates PPH []. Progressive PPH may be organic and irreversible, and its rapid resolution after liver transplantation as seen in our case may be partly attributed by earlier stage PPH. In addition, the responsibility to preoperative treatment with a vasodilator may reflect the stage of PPH. Another speculation is the coexistence of HPS. It has been reported that individual postoperative courses cannot be predicted by the severity of PPH []. In some cases, concurrent or sequential onset of PPH with HPS is seen, although its mechanisms are opposite []. HPS is a pulmonary vascular dilative process, while PPH is a pulmonary vascular constrictive/obliterative process resulting from portal hypertension []. Therefore, PPH might be masked by vasodilation of occult HPS and unmasked by the resolution of HPS after liver transplantation. In our case, occult HPS was absent. Although these are only speculations, these points should be considered and preoperative estimation of HPS and/or responsibility to vasodilator may be important for appropriate selection of liver transplantation candidates.


An 80-year-old woman (height, 142 cm; weight, 48 kg) with severe aortic stenosis was scheduled to undergo AVR. A subjective symptom was exertional dyspnea. Exercise tolerance was 2METs. Preoperative transthoracic echocardiography (TTE) revealed the aortic valve to be tricuspid, with a valve area of 0.57 cm [], maximum flow rate of 5.0 m/s, maximum pressure gradient of 101 mmHg, and average pressure gradient of 64 mmHg. Severe calcification was observed in all leaflets and aortic annulus. Left ventricular wall motion was normal, and the ejection fraction was 77.5% (modified Simpson’s method). As well as TTE, TEE showed severe calcification of the aortic leaflets and annulus (Fig. a). TEE revealed the left coronary ostium intact (Fig. b). Similarly, preoperative coronary angiography did not reveal significant stenosis (Fig. ).
Anesthesia was induced with intravenous administration of midazolam, remifentanil, and rocuronium and was maintained with intravenous remifentanil and rocuronium and desflurane inhalation. Desflurane inhalation was stopped and intravenous propofol started just prior to establishment of cardiopulmonary bypass (CPB). Intraoperative TEE revealed severe calcification around all leaflets and the valve annulus, but left ventricular wall motion was normal. CPB was established by cannulating the ascending aorta and right atrium, and the ascending aorta was clamped following cannulation of the aortic root. Cardioplegic solution was administered via the cannula, followed by dissection of the aortic root upon asystole. During AVR, cardioplegic solution was administered from each coronary ostium via a selective coronary artery cannula. A biological valve (19-mm diameter; Trifecta™ Valve) was replaced after disconnecting the native valve and careful decalcification of the annulus. Withdrawal from CPB was uneventful and did not require vasopressors. TEE showed minor paravalvular leakage and good left ventricular function without dysfunction.
About 20 min after withdrawing CPB, signs of left heart failure appeared; systolic blood pressure was <70 mmHg, and mean pulmonary pressure was >40 mmHg. Despite administration of dobutamine (5 μg/kg/min) and adrenaline (0.1 μg/kg/min), hemodynamics did not improve. TEE showed regional wall motion decreases of the left ventricular anterior and septal walls. The electrocardiogram showed wide QRS and extensive ST elevation especially in V4 and V5. There was a high-brightness massive shadow at the left coronary ostium (Fig. , left) where the color flow on Doppler showed a mosaic image (Fig. , right). The patient was diagnosed with acute left heart failure owing to decreased left coronary perfusion. CPB was immediately resumed, and CABG to the left anterior descending artery with the large saphenous vein was performed. After CABG, regional wall motion at anterior walls was still moderately hypokinetic but wall thickness was on improving trend. Motion of septal walls improved markedly and became normal with catecholamines. TEE showed remnant of high-brightness massive shadow at the left coronary ostium with no mobility, and the color flow on Doppler showed a mosaic echo remain.
CPB was withdrawn with administration of dobutamine (5 μg/kg/min) and adrenaline (0.1 μg/kg/min). Hemodynamics was stabilized following CPB (Fig. ).
Details of the operation were as follows: operative time, 331 min; duration of anesthesia, 403 min; duration of extracorporeal circulation, 177 min; duration of aortic interruption, 63 min; volume of infusion: blood transfusion (3300 ml), red blood cell solution (6 units), and fresh frozen plasma (10 units); urine volume, 475 ml.


An 85-year-old man who had undergone ascending aortic replacement developed large amounts of sputum due to postoperative bronchopneumonia. At 16 days postoperatively, an MT with a Portex Mini-Trach® 2 Kit (Smith Medical International: Ashford, Kent, U.K.) was uneventfully performed to alleviate sputum retention, although he was still on warfarin for new onset of sustained arterial fibrillation and arterial flutter. At that time, he was placed on a prothrombin time-international normalization ratio of between 2 and 3. At 22 days, the amount of sputum increased and was, for the first time, accompanied by hemosputum. Fiberoptic bronchoscopy (FOB) revealed a large clot due to bleeding around the insertion site of the MT tube, but there was no bleeding from the bronchial tree. His respiratory condition gradually deteriorated, and his oxygen saturation decreased. After removing the MT tube to avoid interference, tracheal intubation with the ETT (internal diameter of 8.0 mm) was performed. However, immediately after this procedure, the patient’s respiratory condition deteriorated catastrophically and his lung could not be ventilated with a self-expandable respiratory bag. Cardiac arrest soon followed, and cardiopulmonary resuscitation was performed. Direct laryngoscopy reconfirmed that the ETT was securely positioned in the trachea. An FOB examination performed during resuscitation revealed a massive blood clot completely obstructing the ETT. The FOB was used to push the clot away from the ETT toward the right main bronchus. Thereafter, his left lung was successfully ventilated and spontaneous circulation resumed. Any attempts to remove the clot by drawing it out through the ETT consequently failed because it was too big or too solid. Fortunately, oxygenation was preserved via one-lung ventilation during these procedures. Finally, it was decided to replace the ETT after removing the original with the clot still just inside. The clot was subsequently secured with the FOB and basket forceps and pulled into the ETT, after which, both were removed and a new ETT successfully inserted (Fig. ). Thereafter, other smaller clots and blood were removed with the FOB and absence of bleeding from the bronchial tree confirmed. Open tracheostomy was performed 14 days later. The patient was weaned from mechanical ventilation at 48 days after this event and discharged in satisfactory condition with no psychiatric or neurological damage.
Mini-tracheostomy is performed widely to remove accumulated sputum [] and acute obstructions of the airway []. There is no clear evidence, however, suggesting the superiority of MT over other sputum clearance methods such as medical or physiotherapies. In a review of the management of sputum retention, Beach et al. noted that an MT might be useful along with physiotherapy in adults following thoracic surgery. Its utility in other situations, including an acute care setting, remains unclear []. Although an MT is considered less invasive and more easily performable than conventional tracheostomy, it carries the risk of a number of complications [–]. Catastrophic airway obstruction due to clotting has been reported, but in most cases, this has occurred during or immediately after insertion of an MT tube [, ]. Late bleeding after MT tube insertion can therefore be considered a rare occurrence: indeed, in one case, the latest bleeding time was reported as occurring at approximately 38 h after insertion of an MT tube []. In the present case, bleeding appeared to occur at 6 days after insertion, and meanwhile, the patient had not complained of hemosputum. Fiberoptic bronchoscopy revealed a massive clot in the tracheal wall around the insertion site of the MT tube, but not in the lower bronchi (Fig. ). It was assumed that this clot, which became detached upon tracheal intubation, was obstructing ventilation in the trachea. The etiology of this late bleeding at the insertion site in the present case is unknown at this stage, but we cannot exclude the possibility that it was due to the anti-coagulant effect of the warfarin. Mini-tracheostomy tube insertion is not contraindicated in anticoagulated patients in Japan. However, the present case suggests that MT tube insertion carries the risk of abnormal bleeding at the insertion site in such patients. This indicates the need to be aware of the potential of such an event when performing MT tube insertion in patients receiving anticoagulants.
A number of methods are used to remove clots from the lower airway, including suction, forceps under FOB, a rigid bronchoscope, an arterial embolectomy catheter, and fibrinolytic drugs to the airway.
Bodenham reported the development of a unique suction technique, which involved combining the ETT with a Y-connecter as a suction catheter []. If unsuccessful, a number of other options are available. These include rigid bronchoscopy, an arterial embolectomy catheter (i.e., number 6 Fogarty catheter inflated with 1.5 ml of air) [], and topical thrombolysis. This latter option involves the application of 3000 to 12,000 units of streptokinase [, ] or 2500 units of urokinase [] mixed with normal saline under visualization of the clot via FOB. Replacement of a clot-bearing ETT with a new one offers another option but can only be considered if the condition of the patient allows. Only patients in whom respiratory and/or circulatory conditions are not compromised may be eligible for ETT tube replacement. These techniques are summarized in Table .


A 52-year-old man was found to have pulmonary adenocarcinoma of the right upper lobe with invasion to upper thoracic vertebral bodies. Complete tumor resection was planned via right upper lobectomy and total vertebrectomy (Th2–4) with corresponding costectomy. Prior to surgery, catheter embolization was tried to prevent massive bleeding from the tumor and around the vertebrae, but it failed. Accordingly, total vertebrectomy following bilateral video-assisted thoracoscopic surgery was scheduled for ligation of feeding intercostal arteries and exfoliation of the tumor.
After administration of 100% oxygen, general anesthesia was induced with propofol, fentanyl, remifentanil, and rocuronium. For maintenance of anesthesia, we used propofol and remifentanil in consideration of motor evoked potential monitoring. An arterial line was placed in the left radial artery and a pulse oximeter attached to his left hand.
The intrathoracic procedure in the right and left lateral decubitus positions was completed uneventfully. Then, the patient was turned to the prone position for total vertebrectomy approached via a posterior midline incision. When the surgical procedure reached the area around the vertebral bodies, arterial systolic blood pressure suddenly dropped from 90 to 43 mmHg. Because we suspected massive hemorrhage from vessels around the vertebrae, we asked the surgeons to interrupt the operation. At the same time, we performed rapid infusion and transfusion and administered phenylephrine. Then, his blood pressure was restored to the previous value and the operation was resumed. After a short time, his blood pressure dropped again (Fig. ) without any sign of bleeding at the surgical site, so we considered other reasons for the low blood pressure. Despite extremely low pulse pressure in the left radial artery, we could palpate the right radial artery, so we started to monitor the pressure of the right radial artery. We found an interarm pressure difference and the possibility of reduced blood flow in the left upper limb. We suspected left subclavian artery malperfusion due to the surgical procedure at that time. We were also afraid of malperfusion of an unmonitored aortic arch branch, the left common carotid artery, because we thought that resection of intercostal arteries and exfoliation between the upper thoracic vertebral bodies and posterior mediastinum tissues caused impaired fixation of the descending aorta and aortic arch, which might easily result in ventral displacement under the influence of pressure from the dorsal side. We considered whether to add a cerebral regional oxygenation (rSO2) monitoring, but attachment of rSO2 sensors to his forehead was difficult in the prone position. The bispectral index and motor evoked potentials of the upper extremities were unchanged. Therefore, the operation continued with intermittent malperfusion of the left arm, and when it was prolonged, we asked the surgeons to release the compression. The malperfusion was observed over 10 h until closure of the thoracic cavity and never observed after that. The total time of operation was 23 h (the prone position lasted over 17 h) and intraoperative blood loss was 4220 ml.
The patient was transported to our ICU under mechanical ventilation and extubated 30 h after his ICU admission. He did not have any signs of cerebral ischemia or left arm neurological or ischemic damage.
Postoperatively, we reviewed enhanced computed tomography scans of the patient, and a slightly compressed left subclavian artery between the first rib and anterior scalene muscle was pointed out (Fig. ). However, he had never felt any clinical symptoms previously. His condition was finally diagnosed as accidental arterial TOS resulting from the surgical procedure and his position during the operation. Further diagnostic test such as CT angiography was not performed because of its little value for his postoperative treatment.
TOS is a disorder with signs and symptoms produced by compression of nerves or vessels, or both, at the thoracic outlet. The most common type is neurogenic TOS, and vascular types (arterial or venous) are relatively rare []. For anesthetized patients, TOS is a very critical condition because they cannot complain about their symptoms. Vascular types of TOS may be recognized as an interarm blood pressure difference, loss of the plethysmographic waveform, edema, and obstruction of IV lines in the affected limb, but neurogenic TOS cannot be noticed during general anesthesia.
There may be two major causes for the intraoperative occurrence of TOS, the position of the patient and compression of the thorax mainly due to surgical maneuvers. Mouton et al. [] reported a case of positional arterial TOS in the left lateral park bench position for neurosurgery, and they continued the operation after repositioning of the patient. Kim et al. [] reported a case of arterial TOS that occurred due to pressure applied to the surgical site during spine surgery in the prone position. In that position, the thorax tends to be compressed by the patient’s own weight and TOS symptoms seem likely to appear with compressive force from the dorsal side.
In our case, in addition to the prone position, the patient’s upper limb positioning might have affected the occurrence of TOS. Our patient’s upper limbs were fixed with shoulders in the 90° abducted position and elbows flexed to 90°, as for the Roos test, a diagnostic stress test for TOS []. This arm positioning stretches the neurovascular bundle and can provoke TOS symptoms. If we had noticed TOS and its mechanism, we could reposition his upper limbs to avoid malperfusion. The compression from the surgical site, together with positional risk factors, was considered to be the cause of the left subclavian artery malperfusion. We assumed that the ascending aorta and aortic arch were pressed and displaced ventrally during resection of the vertebrae and contributed to malperfusion in the current case. This is because the left radial artery pressure decreased even while surgeons did not compress his thorax during exfoliation between the upper thoracic vertebral bodies and posterior mediastinum tissues.
Because the arterial TOS in our case was not continuous but intermittent, we continued the operation after we noticed the malperfusion of the left subclavian artery. However, even if arterial compression is intermittent, there is a risk of intimal damage, aneurysm formation, and thrombosis due to repeated compression of the artery. If arterial TOS is accompanied by neurogenic TOS, severe peripheral nerve injuries may arise silently during the long period of general anesthesia. Accordingly, preoperative risk assessment based on the patient’s anatomical factors, positional risk during the operation, and surgical confounding is very important, not to mention early detection once it happens. For prevention of intraoperative TOS, it might be better to fix patient’s upper limbs along the trunk, if the patient has some risk factors of intraoperative TOS. For early detection of pulselessness in one side of an upper limb, it might be useful to monitor pulse waveform of bilateral upper limbs using pulse oximeters and/or arterial lines. Once TOS is suspected, careful repositioning of the patient may be effective to reduce compression of the neurovascular bundle.


The patient was a 68-year-old man of 166 cm height and 60 kg weight who was diagnosed with an esophageal carcinoma (T3N1M0, stage III). We performed video-assisted thoracoscopic esophagectomy followed by posterior mediastinal gastric tube reconstruction. There was no indication of coagulopathy prior to surgery. The activated partial thromboplastin time (APTT) was 27.2 s (reference range 23–35 s), prothrombin time (PT) was 108.0% (reference range 75–130%), and platelet count was 24.4 × 104/μL (reference range 14–34 × 104/μL).
Anesthesia was provided using a combination of general and epidural anesthesia. For the latter, the epidural catheter was inserted at the Th6–7 level and advanced approximately 5 cm into the epidural space. We did not observe any neurological symptoms, hemorrhage, or dural puncture during catheter implantation. Propofol and fentanyl were administered intravenously to induce anesthesia, and endotracheal intubation was carried out after rocuronium administration. Anesthesia was maintained using oxygen/air/desflurane with additional rocuronium as needed. For intraoperative analgesia, a total of 20 mL of 1.5% lidocaine was administered via the epidural catheter. Following video-assisted thoracoscopic resection of the esophagus, we reconstructed the gastric tube through laparotomy and performed cervical esophageal anastomosis using the posterior mediastinal route. In addition, we also performed regional lymphadenectomy (in three nodal regions) and enterostomy. The operation time and anesthesia time were 405 and 536 min, respectively. Blood loss during surgery was 221 mL.
After surgery, the patient was moved to the general intensive care unit and was extubated the following day; no neurological deficits were observed at this point. Two days after surgery, APTT, PT, and platelet count were within normal limits. However, high levels of d-dimer (36.9 μg/mL; reference range 0–0.9 μg/mL) indicated a need to prevent thrombosis, and we decided to administer enoxaparin sodium (Clexane™, SANOFI, Tokyo, Japan), a low-molecular-weight heparin, as an anticoagulant. At that time, fibrinogen level was 419 mg/dL (reference range 150–350 mg/dL), APTT was 29.1 s, PT was 81.4%, and platelet count was 5.4 × 104/μL. The epidural catheter was removed 2 h before the scheduled administration of enoxaparin sodium. The patient was placed in the decubitus position for catheter removal, and the catheter was removed smoothly without resistance.
Fifteen minutes after catheter removal, the patient complained of a complete lack of strength in both of his lower extremities. The patient had a manual muscle testing score of 1 (out of a possible 5), and he reported a lack of touch sensation and cold sensation below Th4. Due to this unexpected development, an emergency magnetic resonance imaging (MRI) scan was performed 2 h after catheter removal, which indicated a possible spinal epidural hematoma spreading from Th3 to Th6 (Fig. ). As shown in Fig. , the hematoma was pressing the spinal cord toward the ventral side. The patient experienced involuntary movements in his lower extremities during MRI scanning. Three hours after catheter removal, we began emergency surgery to remove the hematoma. Within an hour, we had confirmed and removed a hematoma that spanned from Th3 to Th7; the hematoma had spread to another spinal segment since the MRI scan had been performed. After surgery, the patient demonstrated gradual improvements in touch sensation, cold sensation, and motor function. The patient was able to walk 2 days after hematoma removal, and involuntary movements ceased after 7 days.
Catheter-associated spinal epidural hematomas can occur during catheter placement or removal, and incidence has been reported to range from 2 to 20 cases per 100,000 epidural procedures [, , ]. Despite their relatively low incidence, these hematomas are widely recognized by anesthesiologists as a possible deleterious complication of epidural anesthesia. Furthermore, the development and progression of hematomas associated with epidural anesthesia is relatively slow and is generally characterized by symptoms such as dorsalgia, impaired motor function (paraplegia), and sensory abnormalities; intense pain also occurs in many cases []. In the present case, the patient rapidly developed paraplegia and sensory abnormalities without any intense back pain. Rapid diagnosis was facilitated through the use of T2-weighted MRI, which produced clear visualization of the hematoma. Previous investigations of the time course of spinal epidural hematoma development reported that paraplegia can occur as early as 1 h after catheter removal, with some cases developing symptoms after more than 24 h [, ]. In contrast, the case described here is unusual in the rapid manifestation of neurological symptoms after catheter removal.
The epidural cavity, which lies between the lamina externa and lamina interna, contains loose connective tissue, adipose tissue, and venous plexuses. Therefore, the veins in the epidural cavity constitute the primary source of epidural hematomas. In the report by Gulur et al., epidural hematomas occurred in patients with abnormal coagulation parameters after the epidural catheter had been removed [], indicating the importance of conducting follow-up examinations. Although our case patient did not develop paraplegia or sensory abnormalities during the 2 days when the epidural catheter was implanted, these symptoms rapidly developed after catheter removal, suggesting that a venous plexus was damaged during the removal process. This supposition was supported by the absence of arterial hemorrhage or arteriovenous malformation during surgery. However, it is interesting that the degree of hemorrhage from a vein could result in such rapid onset of neurological symptoms.
The following abnormal coagulation parameters during the perioperative period have been identified as risk factors for epidural hematoma occurrence: APTT >35 s, international normalized ratio of PT >1.5, and platelet count <10 × 104/μL []. However, our case patient fulfilled none of these criteria for abnormal parameters. The levels of d-dimers, a fibrin degradation product, generally increase in patients with thrombotic disease or after undergoing surgery []. Despite the usefulness of d-dimer levels in the exclusion of deep-vein thrombosis [], there is also a need to perform ultrasonography of the veins in the lower extremities for accurate diagnoses. Although our case patient underwent ultrasound scanning, the field of view did not indicate any sign of thrombosis.
Studies have shown that patients with epidural hematomas should undergo surgical intervention within 8 h from the onset of symptoms to allow for neurological recovery []. In our case patient, we had detected and surgically evacuated the hematoma within 4 h after catheter removal. It is likely that the rapid response and surgical intervention were crucial in facilitating neurological recovery.
It should be noted that the increasingly prevalent use of postoperative anticoagulation therapy in recent years has provided the option of utilizing nerve blocks in place of epidural anesthesia. Peng and Wang reported that the use of a thoracic paravertebral intercostal nerve block was able to achieve satisfactory postoperative analgesia in esophageal cancer patients []. In our institution, however, analgesia control for thoracoabdominal surgery is generally performed using epidural anesthesia. The guidelines of the American Society of Regional Anesthesia and Pain Medicine for anticoagulant therapy recommend the use of a low-molecular-weight heparin (such as enoxaparin sodium) at least 4 h after epidural catheter removal []. In accordance with this practice, we had planned to remove the epidural catheter before administering the anticoagulant.


A 62-year-old woman (height, 155 cm; weight, 45 kg), with a fracture of the left clavicle due to a traffic accident, was scheduled to undergo open reduction and internal fixation. She had bilateral pneumothorax and was equipped with chest drains in the bilateral thoracic cavity. In addition, she had been undergoing artificial dialysis for 10 years because of severe renal dysfunction. Considering the potential complications of general anesthesia, we decided to induce only regional anesthesia without general anesthesia.
We had to relieve the pain of the supraclavicular nerve and the fifth and sixth cervical nerves (C5 and C6) for the left clavicle fracture surgery. The most appropriate methods include both a left cervical plexus nerve block and a brachial plexus nerve block. However, since the cervical plexus nerve block is associated with a risk of phrenic nerve paralysis, we opted for a selective supraclavicular nerve block.
In the operating room, the patient was connected to several monitors. We performed the selective C5 and C6 blocks by injecting 0.75 % levobupivacaine (10 mL) around the C5 and C6 between the anterior and middle scalene muscles using a high-frequency linear probe of a LOGIQ e Premium system (GE Healthcare Japan, Tokyo, Japan). After these injections, we confirmed that the local anesthetic did not spread around the fourth, seventh, and eighth nerves by using the LOGIQ e Premium system.
The selective supraclavicular nerve block was administered by injecting 0.75 % levobupivacaine (10 mL) from the head side into the space beyond the pectoralis major muscle that was 2 cm lateral to the left sternal edge by means of the high-frequency linear probe (Figs. and ). Twenty minutes after applying the blocks with a pinprick test, the breast resection was performed without using any sedative. The perioperative course was uneventful and did not require additional analgesics. There were no changes caused phrenic nerve paralysis on the postoperative chest X-rays.
Prior to this case, there have been no reports in literature on the use of a selective supraclavicular nerve block at the subclavian site. Hence, we mainly performed the cervical plexus nerve block to anesthetize the selective supraclavicular nerve. However, as the cervical plexus nerve block may lead to phrenic nerve paralysis, it cannot be performed in patients with bilateral pneumothorax.
The supraclavicular nerve arises from the third and fourth cervical nerves and emerges beneath the posterior border of the sternocleidomastoid muscle. The supraclavicular nerve branches into the medial, intermediate, and lateral supraclavicular nerves at the sternocleidomastoid and descends into the posterior triangle of the neck beneath the platysma and deep cervical fascia (Fig. ) []. These branches run parallel beyond the pectoralis major muscle. In this case, we selectively blocked the supraclavicular nerve by injecting local anesthetic at the site of the pectoralis major muscle. The selective supraclavicular nerve block reported by Valdés-Vilches and Sánchez-del Águila [] is performed via the supraclavicular approach and has the risk of phrenic nerve block if more than required volumes are injected.
Administering a nerve block at the site of the pectoralis major muscle enables the procedure to be performed safely and easily. In addition, we may be able to use this approach for performing selective supraclavicular nerve block in patients with severe complications such as bilateral pneumothorax and hemorrhagic diathesis. In the future, we may be able to perform selective supraclavicular nerve block for perioperative analgesia of patients with such complication. For example, the nerve block may be used effectively in surgeries for clavicle fracture and anterior rib fractures.
There have been no reports in the literature on the use of selective supraclavicular nerve block in clavicle fractures. Therefore, it is uncertain whether adequate anesthetic volumes and concentration would achieve a satisfactory result. In particular, administering a small volume at the site may not be able to block lateral supraclavicular nerves.
In addition, there were no cadaver studies showing the spread of dye or something. Therefore, we must eventually perform some cadaver studies to confirm the spread.


We performed a superficial dissection of the face of a 73-year-old at death Caucasian male, a fresh frozen cadaver, and performed anatomical measurements with a microcaliper (Mitutoyo, Kanagawa, Japan). At the angle of the left mandible, the left facial artery was located and carefully dissected to follow its branches, i.e., the superior labial artery and the CoAs. An unusual third CoA, which ascended obliquely from the columellolabial junction toward the right of the SC, i.e., across the midline mediosuperiorly (Figure ), was located in the philtrum along with two other CoAs that symmetrically ascended in a vertical fashion (the columellolabial junction of the right vertical CoA was 0.76 mm in diameter and that of the left vertical CoA was 0.91 mm in diameter, respectively), following the pattern of a common columellar variation []. The columellolabial junction of the oblique variant was more distal from the SC than that of the left vertical CoA, i.e., 1.32 mm in diameter (Figure ). Further dissection of the oblique CoA revealed an unusual direct aastomosis with the infraorbital artery (Figure ).


An 11-year-old female patient of Samoan (Polynesian) descent presented with left SCFE and acute rheumatic fever. The patient had progressive severe pain in the left hip, difficulty walking, and loss of appetite. The patient did not report skin lesions or symptoms of pharyngitis/respiratory infection. Both parents and siblings were healthy with no reported family history of diabetes, coronary heart disease, asthma, or cancer.
The patient was transferred to a tertiary medical center for hip surgery. At that time, patient’s review of systems showed polydipsia and polyuria which revealed concern for diabetes insipidus. She had no headaches, emesis, or visual complaints. Further endocrine work-up also revealed adrenal insufficiency, likely growth hormone deficiency, and hypothyroidism. Patient also presented with musculoskeletal abnormalities including hip deformity, arthralgia, and gait problems, all consistent with SCFE. On examination, patient had varus on the right side, 3+ patellar and Achilles Tendon reflexes on the left side, and 3+ right/1+ left suprapatellar reflexes. Gait examination was limited by SCFE but was noted to be non-ataxic and narrow-based. Patient had normal hip abduction and adduction. All other systems reviewed were negative for findings (full skin was not examined due to patient fatigue but was negative for café-au-lait macules at axilla, upper back, and legs). Endocrine findings and other notable lab values are reported in Table .
Magnetic Resonance Imaging (MRI) of the brain following endocrine workup revealed a suprasellar mass of 1.6x1.2x1.2 cm in the upper infundibulum which was deviated to the left and thickened inferiorly (Figure ). The pituitary gland was enlarged to 6 mm. Differential diagnosis included diencephalic astrocytoma (including pilocytic and pilomyxoid astrocytoma), craniopharyngioma, germ cell tumor, Langerhans cell histiocytosis, and pinealoma.
Transsphenoidal biopsy confirmed germinoma, with germinoma cells predominantly occupying the posterior pituitary. Immunohistochemistry was performed on the cells and tested positive for sal-like protein 4 (SALL4), octamer-binding transcription factor 4 (OCT4), and cluster of differentiation 117 (CD117), and negative for pan-cytokeratin, soluble protein-100 (S-100), and cluster of differentiation 1a (CD1a). Serum alpha-fetoprotein (AFP) was 6 ng/mL and serum beta-human chorionic gonadotropin (β-HCG) was reported to be <1 IU/L. Cerebrospinal fluid levels of AFP and β-HCG were <0.5 ng/mL and 2 IU/L, respectively. These findings confirmed a diagnosis of germinoma. No component of embryonal carcinoma, yolk sac tumor, choriocarcinoma, or teratoma was identified. Patient had no café-au-lait lesions on her skin or other stigmata of neurofibromatosis type 1. Other etiologies to consider included Langerhans cell histiocytosis and lymphocytic hypophysitis. However, there was no other evidence of systemic disease.
The patient underwent the following therapeutic interventions. Her left-sided SCFE was pinned as well as the right side, prophylactically. To treat endocrine abnormalities, the patient was started on desmopressin, hydrocortisone with stress dosing (10 mg/m2/day), and levothyroxine. The germinoma was treated with four cycles of carboplatin (600 mg/m2/dose x 1 dose) and etoposide (150 mg/m2/dose x 3 doses), with each cycle consisting of 21 days. Chemotherapy was followed by 18 gray whole ventricle irradiation with a 12 gray boost to the primary site.
Following treatment, the patient has done well clinically. MRI of the brain done 32 months from diagnosis showed no suspicious parenchymal, dural, or leptomeningeal lesions (Figure ). The pituitary gland was decreased in volume and unchanged. The patient has had no further orthopedic problems and remains on hormone supplementation (somatotropin, hydrocortisone, desmopressin, levothyroxine, and estradiol).


A 39-year-old Chinese man was hospitalized for right thigh cellulitis. He had a past medical history of poorly controlled type 2 diabetes mellitus. Based on clinical, biochemical, and radiological assessment, he was also concomitantly diagnosed with Child's C liver cirrhosis which was attributed to alcoholic liver disease. The values of initial laboratory tests are represented in . The ultrasonography of abdomen revealed small amount of ascites and patent portal vein. On day 9 of hospitalization, the patient suffered a massive hematemesis. After adequate resuscitation, an urgent upper GI endoscopy was performed by an experienced procedurist. During endoscopy, gastroesophageal varices (Sarin's GOV-2) with large gastric component (at the cardia and fundus) toward the greater curvature were visualized (). A white spot, the “nipple sign,” was visible at one of the gastric varices, suggesting it to be the point of hemorrhage. The gastric varices were injected with the commercially prepared mixture of the N-acetyl-2-cyanoacrylate and Lipiodol (Laboratoire Guerbet, Aulnay-sous-Bois, France) in 0.5 ml : 0.8 ml ratio. The procedurist and nurses adhered to the institutional protocol of intravariceal injection of N-acetyl-2-cyanoacrylate. A total of 5 ml of the mixture was injected in 5 separate aliquots at 5 different locations with complete obliteration (). Additionally, three variceal ligation bands were applied to the varices in the lower esophagus. Although prophylactic antibiotic therapy (intravenous ceftriaxone) was administered, patient developed fever five days after the variceal treatment. This fever was attributed to a new urinary tract infection (UTI) with growth of pan-sensitive Escherichia coli in urine. A computed tomography of the abdomen was performed which again showed small amount of ascites, but no localized intra-abdominal collection was observed. Additionally, radiological appearances of the pancreas were unremarkable. The patient was discharged well after treatment of the UTI. Nonselective beta-blocker therapy (tablet propranolol) was initiated before discharge. The patient was advised to complete the courses of antibiotics (namely, five more days of cloxacillin for cellulitis and ten days of ciprofloxacin for UTI).
A follow-up endoscopy was performed after 10 days of the index endoscopy where complete obliteration of the gastroesophageal varices was ascertained. The patient remained well for next 6 months until he was rehospitalized for high spiking fever. He did not report any epigastric pain. The abdomen was soft and not tender. The patient had been abstinent from alcohol for last 6 months. The values of initial laboratory tests are shown in . Parenteral antibiotic therapy (ceftriaxone) was administered. Growth of pan-sensitive Escherichia coli was noted in the aerobic blood culture. A computed tomography (CT) of the abdomen and pelvis was performed in view of nonresolving fever despite clearance of bacteremia in subsequent blood cultures. The CT scan (Figures and ) showed a retrogastric abscess (5.1 cm × 3.4 cm × 4.3 cm in size) adjacent to the left diaphragmatic crus and pancreatic tail. The previously injected N-butyl-2-cyanoacrylate was still visible around the gastric cardia, in the perigastric varices, and in the left adrenal vein. Also, there was a new partial thrombosis of the left renal vein. As compared to the abdominal imaging six months ago, there was no ascites. Additionally, there were no radiological features of acute or chronic pancreatitis. An infectious disease specialist was consulted who suspected inadequate penetration of the abscess with cephalosporin. The antibiotic therapy was switched to carbapenem, and a conservative nondrainage approach was undertaken for two reasons: the bacteremia had already cleared, and the size of the abscess was relatively small for drainage. Another CT scan was performed after one week which confirmed interval reduction in the size of retrogastric abscess (now 4.8 cm × 2.4 cm × 4.5 cm). After clinical improvement, the patient was subsequently discharged thirteen days after hospitalization. Further antimicrobial therapy was administered at the outpatient parenteral therapy centre. Two CT scans (Figures and ) were repeated at one month intervals, which showed gradual resolution of the retrogastric abscess to a small nonliquid lesion. Overall, the patient received three months of antibiotics. Over next one year of follow-up, there was no clinical or radiological recurrence of the retrogastric abscess.


An 83-year-old man presented to the emergency department (ED) with upper abdominal chest pain with newly deranged liver function tests (LFTs) and raised inflammatory markers. On examination, he was found to be tender in the right upper quadrant as well as in the epigastrium. His LFTs were as follows: unconjugated and conjugated bilirubin were both 26 and 14 µmol/L, respectively; ALP, GGT, ALT, and AST were 333, 557, 194, and 158 U/L, respectively. His white cell count was 13.9 × 109/L, and CRP was 105 mg/L. A computed tomography (CT) scan was performed due to his atypical presentation to the emergency department, which showed cholecystitis with a distended gallbladder containing a 21 mm solitary lamellated calcified calculus. This was then confirmed on abdominal ultrasound, which, in addition to the above findings, showed that there was no evidence of choledocholithiasis or biliary duct dilatation.
The patient underwent LC, performed by a senior surgical trainee with an intraoperative cholangiogram showing no filling defects in the biliary ducts and free flow of contrast into the duodenum. During the operation, the gallbladder was inadvertently opened whilst dissecting it from the liver bed, resulting in spillage of the large calculus. While retrieving the gallbladder specimen in an endoscopic bag, the spilled calculus was left inadvertently in the peritoneal cavity. The operator did not realize that the spilled stone was unretrieved. The patient made an uneventful, gradual recovery and was discharged on postoperative day 1. Macroscopic histopathology report revealed a partially opened gallbladder with no gallstone within the lumen, suggesting that the spilled large calculus was not retrieved from the peritoneal cavity. Microscopically, it was consistent with acute and chronic cholecystitis with muscle hypertrophy and fibrosis of the wall.
The patient re-presented to the emergency department 3 weeks after discharge with central abdominal pain, anorexia, and vomiting. He had been experiencing these symptoms since day 3 of discharge, and they had been getting worse until the time he re-presented. In spite of these symptoms, he was systemically well. Examination of the abdomen revealed minimally distended abdomen with tenderness in the periumbilical region. These symptoms and signs suggested that he had small bowel obstruction. However, in the setting of recent cholecystectomy, we wanted to rule out the possibility of a biliary injury. His LFTs and inflammatory markers were normal. His symptoms were further evaluated with a CT scan, which showed evidence of SBO with transition point in the right iliac fossa. The obstruction was from a laminated calcified structure applying extrinsic compression on a loop of small bowel. With the knowledge of the index operation and the pathology report of the retrieved specimen, it was suspected that this structure was the unretrieved gallstone. This calculus was associated with a surrounding phlegmon, evidenced by intense inflammatory change on the CT scan ().
The patient underwent laparoscopy in view of the CT scan findings. Laparoscopy identified a large phlegmon compressing on the distal ileum causing obstruction with distended proximal and collapsed distal small bowel loops (). Dissection of the phlegmon revealed a small abscess cavity and the unretrieved gallstone at its center (). The abscess was drained and the gallstone retrieved (), which resulted in a resolution of the small bowel obstruction. The patient made a gradual recovery and was subsequently discharged on postoperative day 4, at which point he was tolerating solid diet with return of normal gastrointestinal function.


A 46-year-old woman (53.6 kg, 152 cm tall, and ASA PS II) was scheduled for a colostomy closure. She gave written informed consent and approved the reporting of her case. Thirteen months prior to colostomy closure, she had been treated for generalized peritonitis following Hartmann’s operation for perforation of the sigmoid colon cause by colorectal cancer. Hartmann’s operation was under combination of general and epidural anesthesia. And she received general anesthesia without epidural for her generalized peritonitis. Both of their anesthetic procedures were uneventful. The patient was receiving outpatient chemotherapy. Right after finishing the treatment, the patient was planned to administer to have colostomy closure surgery. She also had a history of asthma, which was treated with inhaled budesonide. She had no other past medical history. At presentation, she was not taking any herbal preparations or anticoagulants and there were no contradictions for epidural anesthesia.
Epidural catheterization was performed in the right lateral position. After skin preparation with 0.5 % chlorhexidine, epidural space was identified by loss of resistance technique with normal saline using a 17-gauge Tuohy needle at the T10–11 interspace, and a 20-gauge epidural catheter (Perifix® Soft Tip catheter) was threaded 5.5 cm and taped securely. Catheter insertion was smooth, and no blood or cerebrospinal fluid leakage was seen. The conduct of the epidural insertion was unremarkable, and following a test dose, there was no evidence of subarachnoid block.
General anesthesia was induced by target-controlled infusion (TCI) of propofol at a target plasma concentration of 3 μg/ml. Rocuronium (0.7 mg/kg) was administered after loss of response to verbal commands. Remifentanil was initiated at a rate of 0.3 μg/kg/min, and propofol was adjusted to maintain a BIS index of 40–60. Ten minutes before skin incision, 6 ml of 0.2 % ropivacaine and 100 μg of fentanyl were administered through the epidural catheter. A mobile disposable negative-pressure infusion pump (Coopdech Syrinjector, Daiken Medical, Osaka, Japan) primed with a total volume of 120 ml anesthetic (113 ml of 0.2 % ropivacaine, 300 μg of fentanyl, and 2.5 mg of droperidol) was used for continuous epidural infusion at a rate of 5 ml/h starting 10 min after skin incision. The surgical procedure itself was uneventful, and recovery was satisfactory. The patient reported no pain at the surgical site, and no lower extremity paralysis was observed immediately after the operation.
However, 28 h after entering the PACU, she developed paralysis in her right lower extremity and paresthesia in her right trunk, and epidural continuous infusion was stopped. However, symptoms remained 12 h after onset, and the epidural catheter was removed after confirming no sign of coagulopathy. Dysuria appeared 17 h after onset. Examination by a neurologist revealed paraparesis (impaired lower extremity movement, particularly in her right leg), decreased thermal nociception on the right dermatome T6–12, hyperesthesia below the right dermatome T12, and bladder and rectal dysfunction. Two days after onset, an emergent thoracolumbar spine magnetic resonance imaging (MRI; 1.5T system, Ingenia, Philips Medical Systems, Best, The Netherlands) demonstrated intramedullary hyperintensity, particularly in the gray matter, extending from T5–T9 on T2-weighted and diffusion-weighted MR images (Fig. ). No space-occupying lesion, such as hematoma or abscess, and no intracranial lesion, such as hemorrhage or infarction, were seen. Due to her history of asthma, contrast-enhanced MRI was not performed. The following day, the lumbar puncture was performed after confirming no sign of coagulopathy, and inflammation within the spinal cord was indicated by celebrospinal fluid (CSF) pleocytosis and elevated IgG index, but no viral infection was detected. The drug-induced lymphocyte stimulation test for ropivacaine showed no allergic history. On the basis of the above results, she was diagnosed with acute transverse myelitis.
High-dose IV methylprednisolone treatment was initiated (first treatment: 1 g daily for 3 days). Paresthesia on the right side and bladder and rectal disturbances slightly recovered, and she began to walk using a standard pick-up walker. Additional high-dose IV methylprednisolone treatments (second: 1 g daily for 3 days and third: 500 mg daily for 3 days) resulted in gradual improvement of sensorimotor symptoms. On the other hand, D-dimer concentration was elevated from 6.2 μg/ml before the first treatment to 13.7 μg/ml after the second treatment. After the second treatment, no lower limb deep venous thrombosis was observed by color Doppler ultrasound imaging of the lower extremity. After the third treatment, however, dyspnea occurred and her D-dimer concentration was elevated to 31.1 μg/ml, and she was examined by pulmonary scintigraphy, which showed ventilation-perfusion mismatching in both lungs (right posterior, right superior, right anterior-basal, right lateral-basal, right posterior-basal, and left lateral-basal segments), indicative of multiple pulmonary embolisms. Heparin therapy to maintain activated partial thromboplastin time with the therapeutic target range of 50–70 s was initiated. Two days after initiating heparin treatment, symptoms of dyspnea disappeared. Following establishment of a therapeutic prothrombin time/international normalized ratio with warfarin, the heparin was ceased.
Forty-seven days after onset, paraparesis of the right lower extremity had recovered. Results of manual muscle tests (MMTs) were 3/5 for iliopsoas, 3/5 for hamstrings, 4/5 for quadriceps, and 5/5 for other muscles, and she could walk with a medical cane. Forty-nine days after onset, thermal nociception and hyperesthesia had diminished (although incompatibility still existed) and bladder and rectal disturbance had recovered. Further, she was independent in defecation. Fifty-one days after onset, results of MMTs were 5/5 for iliopsoas and hamstrings; furthermore, she could walk without a cane.
Transverse myelitis is, rare with only 1–8 cases per million per year reported [], a focal inflammatory disorder of the spinal cord, resulting in motor, sensory, and autonomic dysfunction. Longitudinal case series of acute transverse myelitis reveal that approximately one third of patients recover with little to no sequelae, one third are left with moderate degree of permanent disability, and one third have severe disabilities []. Transverse Myelitis Consortium Working Group proposed diagnostic criteria, as well as a diagnostic approach algorism when we see patients with neurologic deficits corresponding to a spinal disorder [].
According to the algorism, the first priority is to exclude an extra axial compressive etiology. The working group suggests to conduct gadolinium-enhanced MRI within 4 h after recognizing the deficits to rule out the compressive etiology like hematoma or abscess. These complications were highly possible in this case; therefore, we should have performed MRI much earlier, though in this specific patient with a history of asthma, possible anaphylactoid reaction precluded the use of contrast agents [].
The second priority is to define the presence or absence of spinal cord inflammation. Non-inflammatory causes of myelopathy include ischemia, radiation, epidural lipomatosis, or fibrocartilagious embolism. In this case, we confirmed CSF pleocytosis and elevated IgG index, so we considered some inflammatory reaction as its pathogenesis.
The third priority is to define the extent of demyelination by using brain contrast MRI and visual evoked potential. If myelination of the brain or the brain with optic nerve is detected, multiple sclerosis, acute disseminated encephalomyelitis, or disease-associated acute transverse myelitis are possible diagnosis. Myelination of the optic nerve or tract may indicate neuromyelitis optica. If only the spinal cord was demyelinated, the diagnosis is acute transverse myelitis due to idiopathic or disease-associated etiology. We could not use a contrast medium because of the reason mentioned above, but by checking non-contrast MRI and visual evoked potential (VEP; delayed VEP was observed on 43 days after onset), we have concluded that this patient had acute transverse myelitis with some reasons.
Once diagnosis of transverse myelitis is established, it is useful to clarify the cause to decide on therapeutic strategy and assess prognosis. However, even after several years of follow-up, 15–36 % of transverse myelitis patients cannot be given a more specific diagnosis [].
What is possible causes inducing the acute transverse myelitis in this patient? The relationship between anesthesia and acute myelitis is controversial, with only a few published studies addressing a possible association.
We speculate mainly two reasons to cause acute transverse myelitis in this patient. One of the reasons is the neurotoxicity derived from local anesthetics. It is reported that histologic damage in the nerve roots and the spinal cord was less severe after injection with epidural local anesthetics than with intrathecal local anesthetics in rats []. And it was also reported that the inadvertent intrathecal administration of intended epidural local anesthetic can occur in a clinical situation []. Considering these reports and the devastating spinal cord injury in this case, we speculate that the tip of the epidural catheter could exist in the intrathecal not in the epidural space; as a result, the local anesthetic continued to affect the spinal cord and induced the devastating damage.
The other predicted pathogenesis is an autoimmune reaction induced by chemical stimulation like local anesthetic or mechanical stimulation by a catheter or an epidural needle, which in turn caused acute transverse myelitis. According to the algorithm, autoimmune disease like multiple sclerosis, acute disseminated encephalomyelopathy, or neuromyelitis optica must be considered as a differential diagnosis.
One of the reason why we would speculate the cause as an autoimmune reaction is that elevated IL-6 was detected in the CSF (179 pg/ml, normal <4.0 pg/ml) and serum (5.82 pg/ml, normal <4.0 pg/ml) in this patient. Additionally, a delayed VEP may suggest the existence of potential autoimmune disease such as neuromyelitis optica. A case with neuromyelitis optica arising after a spinal anesthesia with bupivacaine was reported []. Originally, the patient might have autoimmune disease potentially, and it might become apparent after the surgery by the trigger of anesthesia or surgery itself, or it might be merely an innocent by-stander. Fortunately, she could have recovered with little sequelae; however, we cannot deny with certainty her remission of autoimmune reaction by unknown etiology. Further continuous observation by neurologist should be necessary in this case.
Interestingly, Gutowski and Davies published a case with acute transverse myelitis after general anesthesia without epidural anesthesia [], and this case shows that transverse myelitis may arise coincidentally after the surgery in which no local anesthetic procedure has been used. This case arises some caution to anesthesiologists, that epidural or spinal anesthesia may be just innocent by-standers even when we see patients with some neurologic disorders after epidural or spinal procedures. Despite the absence of evidence, administration of high-dose IV methylprednisolone is the first treatment to hasten recovery, reduce activity, and restore neurologic function [].
In addition to acute transverse myelitis, we have also faced with multiple pulmonary embolisms in this case. Known etiologic factors predisposing to venous thromboembolism include reduced mobility, malignant disease, and history of venous thromboembolism []. Cancer patients are considered at a significantly increased risk of developing venous thromboembolism, particularly while receiving systemic chemotherapy []. Female sex is another reported predisposing factor for thrombosis []. The patient in this case was a woman with a history of colorectal cancer who had received outpatient chemotherapy and reduced mobility due to transverse myelitis. In addition, intermittent pneumatic leg compression was performed, but pharmacological prophylaxis was not performed in this case. Combined prophylaxis could prevent from developing pulmonary embolisms [].


35-year-old, gravida 3 para 0 woman was admitted for the anatomical survey of her fetus at the 21st week of pregnancy. During the US examination, we detected 11 × 10 mm solid mass between tongue and palate. This solid mass was homogeneous and originated from the bottom of the mouth The mass has no abnormal vessel architecture by Doppler US ().
There was no cleft lip. We decided to perform MRI to reveal extension of solid mass and rule out other head and neck anomalies (). Lips and hard palate were visualized as intact by both US and MRI. The parents had refused prenatal invasive genetic tests. The couple was informed about the possible risks in the pregnancy. Polyhydramnios did not occur in the remained pregnancy period that could be common. Before cesarean section (C/S) the neonatologists were informed about oral solid mass which might obstruct the airway of the neonate, and the possible need for the EXIT (ex-utero intrapartum treatment) procedure [].
The baby was delivered by cesarean section in 37 weeks and 4 days of gestation due to breech presentation. The baby's weight was 2690 gram and had 7 and 9 Apgar scores. In the first neonatal examination of the baby, there was a white, 2 × 2 cm solid mass between the tongue and palate in the mouth (). It has smooth surface. There was another pink coloured adjacent soft tissue mass that was evaluated as accessory tongue. Postnatal karyotype analysis was reported as 46 XX. Therefore, considering the relation between epignathus and congenital heart diseases, the postnatal echocardiography was performed and it revealed mild atrial septal defect and mild tricuspid insufficiency []. In the postnatal exam, she had low-set ear and flattened-based nose. The postnatal MRI revealed a 26 × 13 × 10 mm soft tissue mass, which has left paramedian location and seemed hyperintense in the T1 planes and isointense in the T2 planes. She underwent surgery in the neonatal period to excise oral solid mass. In the operation, following the excision of oral mass, incomplete cleft palate was surprisingly seen in the soft palate. In the histopathologic examination of the mass, the fat tissue was painted by S100 and surface epithelium with pancreatin []. Final histopathologic diagnosis was mature cystic teratoma. She underwent another surgery to excise accessory tongue and repair of incomplete soft palate cleft when she was 14 months old. Postoperative follow-up is normal after second operation.