A 35-year-old male with Down syndrome and hyperkinesis rapidly became tetraparetic. Cervical radiographs revealed atlantoaxial subluxation (AAS) [Figure and ]. The T2-weighted magnetic resonance (MR) showed cervical canal stenosis with an intramedullary signal change at the C1 level []. Computed tomography (CT) of the head also documented a subacute cerebral infarction in the right cerebellum and left occipital lobe [Figure and ].
Three-dimensional CT angiography (3D-CTA) showed a complete right VA occlusion at the C2/3 level, a left C2 origin of the posterior inferior cerebellar artery (PICA), and hypoplasia of the bilateral C2 pedicles and C2 lamina [Figure –].
Because traditional screw-placement techniques could not be utilized, the atlantoaxial fusion involved placing a C2 transverse foramen-penetrating screw was accomplished.
Subsequent to C1 laminectomy, a right atlantoaxial transarticular screw was inserted, aided by neuronavigation using a unique trajectory through the C2 transverse foramen. Although the screw was placed in the same direction as a standard atlantoaxial transarticular screw, a lateral entry point was utilized to penetrate the transverse foramen. A left C1 lateral mass screw was then placed under the special attention to the left C2 origin of PICA with the partial drilling of the C2 vertebral body. Finally, a C2 interlaminar screw placement, rod connection, and iliac bone grafting were performed.
The postoperative course was uneventful. Cervical X-rays showed adequate bilateral atlantoaxial screw placement [Figure and ]. The T2-weighted MRI documented decompression of the spinal cord at the C1 level [], while the 3D-CTA demonstrated preservation of the left PICA []. The patient wore a cervical orthosis for 3 postoperative months, during which time he regained his ability to ambulate and perform the activities of daily living. The CT/CTA 12 months postoperatively revealed solid bony fusion without stroke recurrence [Figure –].


A 73-year-old woman developed AAAD 6 years ago. At onset, computed tomography (CT) showed a patent FL extending from the ascending aorta, which had enlarged to a diameter of 5.0 cm, to left common iliac artery (LCIA). She underwent emergency HAR because of a primary entry tear located in the ascending aorta. Open distal anastomosis was performed under circulatory arrest. The intima and adventitia were sandwiched and reinforced with a felt strip, and the synthetic graft was secured with running sutures. Postoperative CT showed a patent FL extending from the aortic arch to LCIA and reentry tears in the RSCA (), abdominal aorta, and LCIA. Three years later, aortic angiography showed strong flow from the reentry tear of RSCA to FL of the aortic arch (); there were no new tears at the distal anastomosis site. Six years after onset, a follow-up CT showed a 26-mm-diameter aneurysm (enlargement of 6 mm/6 years) in the RSCA and a 55-mm-diameter aneurysm (enlargement of 15 mm/6 years) at the distal part of arch with saccular dilatation. Additionally, CT revealed a reentry tear in the RSCA, which was 2 cm distal to the right common carotid artery bifurcation, abdominal aorta, and LCIA. In arterial and venous phase CT, aortic arch thrombosis was detected; in addition, the area extending from abdominal aorta below the level of celiac artery to LCIA was found patent. Although CT revealed aortic arch thrombosis, we understood that reentry flow from the RSCA to FL was an important factor for aortic dilatation. We chose to perform reentry occlusion rather than redo-TAR because it is less invasive. The occlusion method involved transcatheter arterial embolization (TAE) as a distinct approach from the covered stent placement because of difficulties in performing the procedure without cervical debranching.
In TAE, the right brachial artery and right femoral artery were cannulated to obtain therapeutic and angiographic routes, respectively. Intraoperative angiography was performed, which showed reentry flow from the RSCA to FL of the brachiocephalic artery (BCA) without diffusion throughout the FL of the aortic arch (). Using 0.014-inch guidewire, a 5-Fr cobra-type guiding catheter (Elway, Terumo Clinical Supply, Kakamigahara, Japan) was inserted into the RSCA and a microballoon catheter (Attendant LP, 4.5 mm, Terumo Clinical Supply) was advanced into the FL through the tear. After microballoon occlusion of the inlet port, 2.0 ml of 5% dextrose solution was flushed and 0.5 ml of glue [mixture of equal parts of N-butyl-2-cyanoacrylate (NBCA) and ethiodized oil] was subsequently injected (B-glue technique) (). The balloon was deflated 50 s after injecting the glue and removed without resistance or glue migration; afterward, a detachable microcoil (5 mm diameter×12 cm length; Cashemere, Johnson and Johnson, Tokyo, Japan) was placed proximal to the glue (). The whole procedure was uneventful. CT performed immediately after TAE showed that the FL of the aortic arch was completely thrombosed, and a follow-up CT performed 2 years later showed that the FL reduced in size. Surprisingly, the FL of the abdominal aorta below the level of celiac artery was thrombosed and decreased in size ().


Patient: 20-year-old male, nursing school student.
Chief concern: delusion, auditory hallucination.
History of present illness: X-3rd year April: As the patient was to begin work after graduation from a local high school, he was requested to undergo company training for 1 year in another prefecture. At the training field, he was reprimanded for mistakes at work. He endured but after consultation with parents, resigned from the company. X-2nd year September: he worked at a hospital as temporary staff. X-1st year April, while working at hospital, entered nursing school. From X-1st year November, the patient began to experience persecution mania and hypochondriacal delusions hearing voices of criticism from colleagues such as “Your face looks ugly. Your body is ugly.”
When you forget your homework, he felt as has been ridiculed from everyone. He began to think that they had been published as “guy to a strange question.”
Around this time, he began to hear voices of criticism. From X-1st year one December: As the frequency of the delusion of being laughed at rose, he visited a psychiatrist and was diagnosed with Social Anxiety Disorder and received medication. Year X February, nursing practice began and voices from classmates criticizing the patient became aggravated and hence he visited another psychiatrist, and was diagnosed as adjustment disorder, and received dosages of SSRI (selective serotonin reuptake inhibitor) and sulpiride. Subsequently while walking, heard voices of criticism from passerby, the sound of refrigerators sounded like criticisms and while driving, from all drivers of oncoming vehicles, the individual heard voices of “Don't drive such cars and I am scared of your face.”
With sleeplessness and loss of appetite, since there was 7 kg drop in weight in 1 week, during year X June, he visited our clinic for the first time.
Past history: Nothing in particular.
Family composition:father, mother the patient, three in all.
Psychological examination:
Self-Rating Depression Scale (SDS): 56 points (normal 35±5).
State-Trait Anxiety Inventory (STAI): Trait anxiety score: 75 points (normal 33–43) State anxiety score: 70 points (normal: 32–40).
Tokyo University Egogram: TEG:N type, (Figure : Left is at time of initial examination).
We are recognized by configuring the frame in the others, education and home and social environment has relocated various information in accordance with their importance. In other words, cognitive frame of individuals, may vary due to others, education and social environment. Based on various information, regarding what kind of information is to be linked together and composed into a frame, based on relationships with others and the passing of time, they change along with the level of importance for oneself., , , ,
As for the patient at the time of initial examination, interpersonal relationship anxiety was strong, and SDS (Self-rating Depression Scale), STAI(State-Trait Anxiety Inventory) were found at a high value, and although not in a state of practical training, patient resisted taking a break from work.,
Why does not the patient take rest despite the fact that the patient shows symptoms? If you look from the others, it indicates that there is a confusion of the patient's frame.
In order to subjectively support self-assessment, if one is to interview thoroughly from beginning to end, delusion and auditory hallucination and insecure status, there is the possibility that one maintains a negative confused frame.
A man can recognize outer things with a lot of frames based on their past experiences. However, it is quite different from person to person which should be taken important, and it is also different, which a frame should be taken to understand the outer things. A person with a frame A consists of several elements, in the case to accept information from the frame B as it is, you must rewrite the components of aligning manner frame A. For this purpose, it is necessary to make conscious the positive information of being happy, joyful, and comfortable which comes in line with emotion and moreover, by adding new information, it is important that to act so that new frame with consistency can be created.
If it is possible that one acquires information about when issues did not occur, or when it was being handled at that time, it will mean that the patient maintains a calculation processing possible frame of past in memories of the brain. As the doctor in the clinic asked him that when he was free from delusion or sufferings, he replied that it was before October of the year X-1. By asking how it was being properly handled, and having a more objective view of the difference of what the patients himself had decided regarding the difference between past cognition frame, and current confused frame will lead to a clue for problem solving.
Regarding this method of questioning to the patients, it has been advocated in Solution-Focused Brief Therapy (SFBT). SFBT is a one of psychotherapy, without pursuing the cause of the problem, patients are able to support in order to build a new frame toward solving the problem., ,
Although it was difficult for patients to participate in practical training, there was a strong desire on his father part for him to graduate. Within the frame of the patient, if the importance of the father was high and within the framework with the father, which is taken in by the patient, if there is information included which is that the patient must follow one's superior is suppressed by a hierarchical relationship, then this would mean the continuation of a state that the individual is unable to express oneself within this hierarchical relationship.
We indicate schematically, the relationship between self and others of the frame in Figure . Self and the other of the frame must maintain an appropriate sense of distance so as to calculation processing as possible to each other (Figure A).
If this were to be expressed simply in a type of schematic format, the patient without forming a comprehensive frame with consistency, there become the possibility of generating delusion by continuing the contamination of the frame in the entered status (Figure B).
When we take in information from another's frame which is of high importance to the patient, we hypothesized that when the patient is unable to form a consistent frame and when the individual has to maintain the state where other's frame is in a state of contamination, there is a possibility that delusions will occur. For the delusion to disappear, the individual must set a target of not being fettered by others and to enhance the presence of the state that is possible to continue a new frame of composition with consistency (Figure ).
That one's frame may be contaminated by frames sorted in the order of importance of degree of information maintained by others, and that oneself is contaminated by another's frame, means that one may be led to be forced to live a life, which is contaminated by goals set by others. For the delusion to disappear, a perspective of providing data processing with consistency and to cancel frame contamination is required.
From among the experience of interviews by physicians to patients, below are perspectives of the patient's mental dialog and environment and status.
X-3rd year: Within the time that he resided out of the prefecture and was committing mistakes at work, the leader said that “…is no good. I do not want to teach him”.
From an oncoming vehicle “Do not ride such a car. Your appearance to the eyes is not good.”
He harbored delusions that colleagues are criticizing him as a lazy man who takes off from work due to a psychiatric illness. By maintaining that frame that it is important that one exercises self-inhibition in accordance with hierarchical relationships, the contamination from other's frame continued.
An egogram is an analysis, which was created by John M. Dusay who is learned from Eric Burn founded the Transactional Analysis. An egogram is the 5 ego states of an individual. The CP (Critical Parent) is critical, responsible, and uses words such as should, must, always, ridiculous, demanding, and critical. The NP (Nurturing Parent) is sympathetic, protective, helpful, and uses words like good and is nurturing. The A (Adult) is rational, logical, objective, and not uses words accompanied by feelings. The FC (Free Child) can express feelings and thoughts naturally and uses want, will not, happy, fun. The AC (Adapted Child) is adaptable, cooperate, grateful. CP, NP, and FC, AC is, in a growth environment from early childhood to lead to the current, are thought to be due to whether the individual has received what message from the surrounding. People in relationships with parents and others, has been wearing the method of the most appropriate and feel judged reaction.
Based on the egogram analysis result, the heart adapting to others (AC: adapted child) is high, and the heart of the FC: free child seems to be low.
The above frame contamination hypothesis for which the current symptoms occur between patient and others was proposed. The patient was fettered by frame information from others, and exercised self-inhibition and since one continued to persevere, it became a factor to generate delusions. As a common goal to do what one enjoys, one was able to get out of frame contamination, and the goal became how to change so that one can think about manifesting one's own capability.
As a method of supporting one's new formation of frame and for the individual himself to understand the contamination state of frame, three chairs were prepared. (i) patient, (ii) the driver of the oncoming vehicle, (iii) chair of the third party. Patient sits on these chairs one by one, and by becoming that person, expressed so that one's feelings could be conveyed to the other imaginary person. This is the time of everyday clinical practice, you can even use a bet instead of a chair (Figure ). Patients who sat in a chair of the driver, he can fully become a driver, told that he want to say to the patient. To return to the chair of the patient, what feelings, asked whether there is no possibility that you want something retorted. Initially, he is unable to reply anything, but the words from the perspective of the third party was “You do not have to listen to the words of the oncoming vehicle” or “why not talk back”. Ever since that work with the three chairs was conducted, it became a chance to restore from an objective perspective, and ever since that time, the delusion from the driver of the oncoming car disappeared. It became possible to recognize the respective positions of the frame, then he might have made to allow objective self-awareness.
Yamazaki has pointed out, in schizophrenia patients, there was a positive correlation between confidence and pain level. There is a need to reach out to meta cognition to control the thinking. The memory of the individual, as a short-term memory, with repeated stimulation from hippocampus, is transferred as long-term memory to the cerebral neocortex. On the other hand, Susumu Tonegawa et al. by optically handling the specific brain cell of the hippocampus, has succeeded in switching “bad memory to enjoyable memory.” and as for the connection from hippocampus to amygdala, it was explained as plasticity. This case might be an example to show the plasticity of the brain.,
I wonder what factors to enhance the inhibition of brain plasticity. From one point of view with daily dialog, people maintain presence. Based on the content of self-dialog, the memory of delusion may become adamant and the level of the confidence of the patient toward delusion strengthens.
So then, by setting the target outside of the current frame, with I as noun and in progressive affirmation tense, and by expressing in words the goal of the direction one selects: affirmation, was able to enhance the presence of that which makes possible the continuation of one's new frame composition.
It required several times of 10 minutes treatments until the patient was able to create affirmation by themselves, but finally the patient was able to create it. Affirmation is “Since one is able to have time to enjoy, my heart is affluent. I currently reflect on myself and have come closer to an enjoyable life.”
Within 8 weeks of delusion from the first treatment, the SDS and STAI 4 months later normalized (Table ). With egogram, FC is increased, and AC is decreased (Figure ). This means that he was able to self-expression for others (Figure ). To advocate affirmation, it was effective to maintain and build a new frame as memory information.
In patients where the delusion state was fixed, it is difficult to find cases where improvement was seen, but there is need to look at the mechanism of cognition from the standpoint of cognitive science and information field, and there are cases of delusion for which it can be supported so that one can select according to the individual's target (Figure ).
Patient and patient's family and medical staff is, to each other the information necessary in order to enhance the function of the patient wishes, each person can understand the most important part of that will look to introspective.


An 82-year-old woman with a past history of chronic kidney disease and thyroid cancer (post-thyroidectomy) was admitted to our hospital due to a 1 week history of nausea, appetite loss, and diarrhea. Three days before the onset of symptoms, she visited a nearby clinic complaining of a chronic cough. The physician prescribed levofloxacin suspecting infection. A few days later, the diarrhea started, which brought her to stop taking the levofloxacin 3 days before admission. She had no history of smoking, recent traveling, and no particular family history.
On examination, vital signs were stable. There were no significant findings except bilateral pitting edema in the lower extremities, which had manifested in the past week. The laboratory data indicated a low serum albumin level of 1.6 g/dL, which was 3.1 g/dL 2 months ago. Medications included aspirin, lansoprazole, and levothyroxine. The aspirin and lansoprazole had been prescribed for at least 2 years, but we could not find out why.
Our first differential diagnoses for this patient were antibiotic-associated diarrhea or Clostridium difficile infection. For antibiotic-associated diarrhea, we suspected levofloxacin to be the cause. The patient had already stopped taking it. For C. difficile infection, the possibility was less likely as C. difficile antigen/toxin test results were both negative. We decided not to add any medication, and the symptoms spontaneously improved in a few days. She was discharged on the fifth postadmission day.
However, 4 days later, the patient was readmitted to our hospital due to the recurrence of diarrhea. The serum albumin level decreased to 1.2 g/dL. Stool occult blood was positive, but gram stain, culture, and fat stain of the stool showed no particular findings. There was no proteinuria, liver dysfunction, or any sign of hypermetabolism that could lead to the low serum albumin. An enhanced CT scan of the abdomen showed bowel wall thickening and fat stranding. There were no signs of vascular obstruction, pancreatitis, or endocrine tumors. Suspecting protein leakage from the small intestine and colon, we performed a Technetium-99m human serum albumin scintigraphy. It showed protein leakage from the small intestine (Figure A-C) proving the existence of protein-losing enteropathy. Fasting and total parenteral nutrition were initiated, which did not improve the diarrhea, indicating that it did not result from malabsorption. To identify any structural disorders, an endoscopy of the stomach, duodenum, and colon was performed. No obvious abnormalities were revealed from the stomach and duodenum. Diffuse edema was observed throughout the colon (Figure A) as well as a few polyps. Biopsy was taken from multiple regions. There were no signs of malignancy, amyloidosis, or eosinophilic gastroenteritis. Mild inflammation was found in samples taken from the duodenum. Samples of the ascending colon showed subepithelial collagen bands more than 10 μm in thickness as well as lamina propria inflammation (Figure B,C). With these findings, we reached the diagnosis of collagenous colitis.
We discontinued aspirin and lansoprazole, and after the introduction of loperamide, the diarrhea and serum albumin level improved.


A 42-year-old man with schizophrenia experiencing worsening fatigue over 2 weeks was referred to our hospital. He had been drinking approximately 4 liters of distilled spirits per week for a year. The patient lived alone, and consumed only various types of junk food instead of balanced meals or vegetables.
Physical examination revealed facial pallor and leg edema bilaterally. His body temperature was 37.2°C, pulse rate was 102 beats/min, blood pressure was 101/64 mm Hg, and respiratory rate was 16 breaths/min. Laboratory tests revealed that his hemoglobin level was 2.8 g/dL; he had macrocytic anemia with hemolysis and pancytopenia (Table ). A peripheral smear revealed that the anemia was megaloblastic. After admission, additional tests showed that his vitamin B12 level was within normal range but that his folic acid level was below the lower limit of normal. Other findings were otherwise normal. He was diagnosed as having folic acid deficiency anemia due to excessive alcohol consumption, and his hemoglobin level improved by administration of folic acid and cessation of alcohol.
We inquired why the patient never finished his vegetables during his meals. He responded that he had not felt the need to eat vegetables, although this did not mean that he disliked them. We discussed folic acid deficiency anemia due to excessive alcohol consumption with him, along with the cause of his symptoms, worsening fatigue, and admission. We also listened attentively to his narrative and expressed understanding toward his thoughts. Afterward, he realized that ceasing alcohol consumption and eating vegetables as part of a balanced meal were indispensable for preventing recurrence of folic acid anemia and staying in good health.
Although the patient had been drinking approximately 4 liters of distilled spirits per week, he was not a constant consumer of alcohol and did not show any signs or symptoms of withdrawal after admission to our hospital and cessation of alcohol use. We diagnosed the condition of the patient as pre-alcoholism, a recently proposed disorder. We subsequently discussed the patient's condition with his father, whereupon we discovered that the patient's alcohol abuse was partially caused by his father's purchasing of bottles of distilled spirits for the patient. Furthermore, his father was divorced and had been living with a woman out of wedlock at her house, leaving the patient alone at home. We communicated directly with his primary care doctor regarding public and social support and assistance. We found that the patient had never applied for social support for which he was eligible under the Basic Act for Persons with Disabilities. We advised the patient on how to obtain support from his primary care doctor and other mechanisms. The patient currently continues to eat vegetables and balanced meals, and has avoided alcoholic beverages completely since the two years after his discharge from our hospital.


A 36-year-old man who had been involved in a traffic accident was admitted to our hospital 6 hours after the accident with complaints of pain in the left shoulder. On physical examination, the left clavicle was prominent and there were no neurovascular injuries. The patient's medical history was unremarkable, and he had no notable comorbidities. Radiography revealed a left comminuted midshaft clavicle fracture with a bone fragment separated from the main fracture by soft tissue (Fig. A).
Emergency surgery involved our novel double ligature technique designed specifically to treat comminuted midshaft clavicle fractures (Fig. B). The procedure required 4 steps and no specialized surgical instruments. The length of the clavicle was restored by reducing the main fracture; temporarily, bone-holders were used to hold the fracture in position. The anatomical position of the bone fragment was stabilized. A clavicle locking compression plate of adequate length was used to fix the main fracture. The anatomical position of the bone fragment was fixed using double-stranded absorbable coated VICRYL Plus antibacterial sutures (Fig. B). When suturing the bone fragment, the needle was kept close to the bone surface to avoid neurovascular injury.
Postoperative radiographs showed good fracture reduction (Fig. C). At the 1-year follow-up, radiography revealed fracture union with abundant callus formation across the fracture site and absence of a fracture line (Fig. D). The patient had normal function in the injured shoulder.


A 65-year-old male was inter-hospital transferred to the vascular surgery service due to sudden onset of pain, tenderness and loss of elasticity in the femoral mass and hyperemia over the thigh greater saphenous vein (GSV). Although the non-pulsatile, soft femoral mass was present for a year, the patient was not investigated because of asymptomatic course and his lack of intention to reach a consultation. Physical exam was unremarkable except local status, where a 6-cm globular, partially-compressible, painful lump was determined under the left inguinal ligament ( and ). The mass was non-adherent, constant in upright and supine position, with some cyanosis over the median-inferior aspect. Hyperemia and tenderness over the GSV varicosities in the medium and lower third of thigh was noticed. The blood analyses were unremarkable. Doppler duplex scan showed occlusive thrombotic masses in the thigh and upper third of calf segments of GSV, with a fixed apex extending 5 mm into the common femoral vein (CFV). Near the SFJ was visualized a 6-cm eccentric fusiform dilation of GSV, completely occluded with thrombotic masses. The diagnosis of left lower limb ascending SVT, stage III, according to Verrel’s classification and giant thrombosed SFJ aneurysm type IA (Bush’s classification) was established. The patient was set on low molecular weight heparin (LMWH) and brought into the operating room, where a left CFV thrombectomy, SFJ thrombosed aneurysm removal and GSV excision were performed.
Under spinal anesthesia, a 3.5-cm longitudinal incision over the left inguinal crease was made and the external iliac vein controlled with a rubber loop. The incision was extended downward to thigh, slightly medial to the aneurysm with its cautious mobilization and ligation of all SFJ tributaries. GSV was set on rubber band distal to the aneurysm (). The CFV was dissected down to its bifurcation and controlled with a rubber band proximal to deep femoral vein. Transversal venotomy on GSV at 8 mm distal from SFJ has been done, with direct thrombus removal from CFV lumen, isotonic saline lavage and full content aspiration from the rubber-isolated venous segment. A Satinsky clamp was tangential applied over CFV and saphenous stump, partially preserving axial venous outflow, and a sparing-edge resection with lateral venorrhaphy has been performed. The CFV incision was closed with 5–0 Polypropylene running suture (PROLENE®, Ethicon). Afterward, the rubber bands were released and the aneurysm was fully excised (). A total saphenectomy by means of separate incisions on thigh and ankle was performed, the so-called Narath procedure, due to the tortuous path of the thrombosed GSV. The operation lasted 125 min, with an estimated 150-mL intraoperative blood loss.
The patient was transferred back to the ward and kept under direct anticoagulation. The postoperative course was uneventful, and he was discharged on the sixth postoperative day. The 1 and 3 months’ follow-up went uneventful, with full functional recovery and satisfaction.


The patient was a 41 year-old male with a history of AIDS who presented for evaluation of asymmetric SNHL. He reported progressive left-sided hearing loss for the prior four months with intermittent tinnitus. The patient had no evidence of facial weakness or auricular vesicles on the affected side. An audiogram confirmed profound left-sided SNHL as well as mild right-sided SNHL. A MRI showed abnormal enhancement within the left IAC concerning for a vestibular schwannoma (A and B). Upon closer examination, there was also bifrontal leptomeningeal enhancement which raised suspicion for viral or opportunistic etiology given the patient's immune status (most recent CD4 cell count was 4). A lumbar puncture was positive for varicella zoster via polymerase chain reaction (PCR) testing. The patient was treated with a three week course of intravenous acyclovir. A post-treatment MRI showed resolution of both the IAC and bifrontal enhancement, further confirming the infectious etiology (). A repeat audiogram showed unchanged, profound left-sided SNHL. At no point in the treatment course did the patient develop facial weakness or auricular vesicles.


A 22-month-old girl diagnosed with Sandhoff disease was referred to our hospital with chief complaints of spasticity and swallowing difficulty as well as difficulty with head control. She was born at full term through normal vaginal delivery. She was able to stand while holding on to something at 8 months of age, which suggested normal development. However, developmental arrest occurred at 13 months of age. Spasticity and genu recurvatum were observed while standing and holding on to something. The patient showed a progressive motor regression pattern, and at 18 months of age, she could barely maintain a propped sitting position. At 20 months of age, she showed symptoms of aspiration while swallowing and prolonged feeding time.
Brain magnetic resonance imaging scans obtained at 15 months of age did not show delayed myelination or abnormal enhancement (). Developmental regression was similar to that in GM2 gangliosidosis, such as Tay-Sachs disease and Sandhoff disease. The patient underwent hexosaminidase assay in white blood cells, which showed increased hexosaminidase A (%) and decreased total hexosaminidase. The total hexosaminidase A & B and hexosaminidase A levels were 321.2 nmol/hr/mg (reference range, 620–1,000 nmol/hr/mg) and 74.3% (reference range, 55%–72%), respectively. Based on these findings, the patient was diagnosed with Sandhoff disease. However, the patient did not show cherry red spot on fundoscopy.
At the time of admission, physical examination revealed grade 3 and 2 muscle strength in the upper and lower extremities, respectively. Neurological examination showed sustained ankle clonus and increased deep tendon reflexes in all extremities as well as hypertonicity and decerebrate posture manifested by an exaggerated extensor posture of all extremities, while crying and/or when she was irritable (). In terms of spasticity, her four extremities scored grade 2 based on the modified Ashworth scale (MAS).
Overall, the patient had developmental regression. Especially, she showed a delay in development by 1 month in gross-motor domain, by 3 months in language and fine motor domain, and by 2 months in personal-social interaction domain in the Denver Developmental Screening Test II.
Dietary assessment revealed that the patient irregularly ingested a soft and blended diet of 70–130 kcal, five times a day, and the mean eating duration was approximately 1 hour. She had difficulty in eating and she showed signs of aspiration (e.g., coughing, gagging). Moreover, she had a poor feeding posture with inadequate trunk and head support.
Oral motor function assessment showed that the patient had increased tone and decreased movement of the tongue and hypersensitivity in the oral and perioral areas. The patient underwent videofluoroscopic swallowing study (VFSS), and was given barium-containing free water, yogurt (thick liquid), and rice porridge (soft). In the oral phase, motor control, including lip sealing, tongue control, and mastication, was inadequate with delayed oral transit time (1.3 seconds) and premature bolus loss []. In the pharyngeal phase, a delayed swallow reflex was observed without aspiration or penetration during or after swallowing ().
The patient's height and body weight were 85.0 cm and 11.6 kg, respectively. Her weight-for-height Z-score (−0.3) was in the 15th–50th percentile of the World Health Organization (WHO) growth standards []. Nutritional evaluation showed that the patient needed a regular daily intake of 989 kcal. However, she could only consume 700 kcal/day, which was less than the required caloric intake. The patient was given supplementary balanced nutrition twice a day.
The patient received an intensive dysphagia rehabilitation program for 30 minutes a day, five times a week, for 6 weeks, and it comprised both direct and indirect interventions, such as oromotor facilitation, thermo-tactile stimulation, and lip strengthening, and compensatory techniques, such as postural modification and alteration of the feeding utensil to facilitate swallowing []. She was given anti-spasticity drugs for managing spasticity and achieving a stable posture during feeding. After the treatment, she was fed in a semi-reclined position, which reduced the signs of aspiration and the amount of food or liquid leakage from the mouth.
However, her nutritional status showed no improvement, with her daily calorie intake decreasing to 600 kcal/day after 4 weeks of admission. At 6 weeks postadmission, her total intake further decreased to 392 kcal/day. Her body weight continuously declined from 11.6 kg to 10.5 kg, and her weight-for-height Z-score (−1.6) decreased to the 3rd–15th percentile of the WHO growth standards, which was a sharp decrease of one major percentile line in a short period [].
Gastrostomy was therefore recommended, but her parents refused the procedure. She was then referred to another hospital for treatment of deconditioning due to dehydration, and she received gastrostomy.


A 19-year-old man presented to our department with progressive visual deterioration for 6 months. Ophthalmological examination revealed bitemporal hemianopsia and reduced visual acuity that was more apparent in his right eye (visual acuity: right eye, 0.2; left eye, 0.6). Hormonal evaluation revealed values within normal ranges except for hypogonadism [testosterone 0.04 ng/mL (normal, 2.67–10.12 ng/mL)]. Brain magnetic resonance imaging (MRI) showed a 3.8×3.1×4.5 cm sized highly enhancing mass expanding the sella and extending into the suprasellar cistern, compressing the optic chiasm, and also displacing A1 segments of the anterior cerebral arteries superiorly and anteriorly, suggestive of a pituitary macroadenoma. The tumor was hypointense on T1-weighted images and hyperintense on T2-weighted images. Intense and homogenous enhancement are presented (). Based on the clinical and radiological features, the tumor was assumed to be a pituitary macroadenoma with optic neuropathy, and transsphenoidal approach (TSA) was initially scheduled for elective surgery. However, we performed an emergency TSA because his vision rapidly deteriorated during preoperative systemic evaluation for elective surgery. TSA surgery revealed that the tumor had a rubbery-firm consistency, hypervascularity, and massive bleeding. Because of unexpected severe bleeding that needed several units of blood transfusion and confusing pathology, surgery was prematurely stopped after only a partial resection for pathological diagnosis and application of several hemostatic agents to control bleeding.
We planned a second stage transcranial approach for decompression of the optic nerves and chiasm after digital subtraction cerebral angiography. The cerebral angiogram showed multiple feeders from both internal carotid arteries. The tumor blush was noted in the mid- and late-arterial phases (). We could not perform a tumor embolization because of multiple small feeders from both internal carotid arteries. Consecutively, the tumor was approached through a right fronto-temporal craniotomy to prevent permanent visual loss. At surgery, the tumor was soft, highly vascular, and appeared to be originating from the pituitary stalk. We achieved gross total resection of the suprasellar mass to reduce compression of the optic apparatus. The pituitary stalk could not be preserved due to intrinsic adhesion of the tumor. On the other hand, we removed the intrasellar mass subtotally because of uncontrolled bleeding from the remnant attached to both cavernous sinuses. Subsequent pathology revealed a pituicytoma with epithelioid features. Microscopic examination showed a hypercellular tumor, composed of predominantly epithelioid cells with a vague storiform and perivascular architecture. The epithelioid tumor cells had pale eosinophilic cytoplasm and ovoid nuclei with small nucleoli. The tumor cells were positive for thyroid transcription factor (TTF)-1 and S-100 protein, and were focally positive for glial fibrillary acidic protein (GFAP), which suggested the glial nature of the tumor cells. Positive immunostaining for TTF-1 and morphologic features support the diagnosis of a pituicytoma with epithelioid features (). Postoperatively, the patient developed panhypopituitarism and diabetes insipidus. Levothyroxine, hydrocortisone, and DDAVP were given. In the postoperative period, the patient's visual acuity and field defect improved. A postoperative MRI with gadolinium enhancement showed the residual tumor adherent to both cavernous sinuses (). We decided to manage the residual tumor with gamma knife radiosurgery. The follow-up magnetic resonance scans showed the residual tumor to be stable.


A 38 year old female, housewife, came to our outpatient department with chief complaints of pain and swelling over right knee since 6 months. Pain was mild and activity related to start with and progressed to moderate and continuous. There was no history of precedent trauma, no history of fever, weight loss and anorexia. Patient had not solicited any treatment for this. On examination, there was diffuse bony swelling with crunchy ‘feel’ over right femoral condyles more localized to left side, extending to popliteal fossa. Overlying skin and muscles were free and mobile. Patient was unable to squat and walk painfree with knee ROM halted to 50 degree flexion but no fixed flexion deformity and full terminal extension possible.
On plain radiographs, a distinct expansile radiolytic lesion was found in lateral femoral condyle, with articular step off , but no cortical breach on medial, lateral or posterior side, with thinned out nonsclerotic margin, graded as Campanacci Grade 2 (). MRI was done, which reaffirmed heterogeneous hyperintense lesion measuring 55x41 mm in epimetaphyseal region of lateral femoral condyle, with no soft tissue involvement(&). A confirmatory biopsy was taken with all precautions for future procedure. Biopsy track was marked so as to include in approach during resection.
On confirmation of GCT in biopsy, a marginal resection and curettage with articular reconstruction and PMMA cementing for skeletal support was planned. Under spinal anesthesia, with tourniquet, an anterolateral parapatellar approach was taken, with view of future need of knee arthroplasty. After adequate visualisation of tumor extent and articular margin, marking was done for wide resection (&). Surgical mops were placed before opening the marrow, to avoid surrounding tissue contamination. Cortical breakout of lateral femoral wall occurred midway and curettage was done till the extent of viable bleeding bone. Cauterization of margins was carried out followed by denaturation of margins using 5 % Phenol soaked mop(&). Articular margin of lateral knee joint was reconstructed after elevation of subchondral bone and fixation using 1.8 mm threaded K wires (). Bone defect was again curetted and prepared for cementing. PMMA cement, dual dose, was prepared using vacuum mixing technique, and the bone defect was filled with PMMA cement(). Threaded K wires were cut short, with ends for future retrieval. Closure was done in layers after tourniquet release and adequate hemostasis control.
Patient was advised immediate ROM exercises on postoperative day 1 and allowed Full weight bearing with support. Patient could gain 90 degree flexion of knee with 10 degree terminal extension lag and Straight leg Raise possible (-).
After 3 months, Postoperative radiology was done to see status of distal femur(). Chest xrays were taken every 3 months. Patient was followed for 2 years and has shown no signs of recurrence, cement subsidence or K wire loosening (Figure 15-17).


A 34-year-old, 47 kg male farmer presented to the emergency department with a history of consumption of around 150 ml of plant growth stimulant (nitrobenzene 20%) about 8 h before admission with suicidal intention. On examination, he was pale, irritable, tachypneic, and there was bitter almond-like pungent smell from patient's mouth. Blood pressure was 100/70 mmHg with pulse rate of 128/min and respiratory rate of 28/min. Arterial blood gas blood samples were dark-brown, which was suggestive of respiratory alkalosis. Electrocardiogram showed sinus tachycardia. X-ray chest was within normal limits. He was treated with gastric lavage (with normal saline), IV fluids, and IV methylene blue 50 mg. His kidney and liver function tests were normal on the day of admission. His serum cholinesterase enzyme level was 10,778 U/L. After 24 h of admission, the patient developed hypoxia (O2 saturation 86%), icterus, and decrease in urine output of about 100 ml in the last 6 h. Withdrawn blood for investigation was dark brown, which showed following serum values: total bilirubin 2.8 mg/dl (direct 1.0 mg/dl and indirect 1.8 mg/dl), serum glutamic oxaloacetic transaminase 121 U/L, serum glutamic pyruvic transaminase 45 U/L, alkaline phosphatase 45 U/L, creatinine 11.1 mg/dl, sodium 150 mEq/L, potassium 3.5 mEq/L, lactate dehydrogenase 780 U/L, and reticulocyte count of 4.0%; blood urea 279 mg/dl, hemoglobin 5.8 g/dl, total leukocyte count 11,800/mm3, and platelet count 7.54 lakh/mm3. Hemodialysis was initiated on an urgent basis through double-lumen internal jugular vein catheter with blood transfusions and was transferred to nephrology ward for the same. Peripheral blood smear showed normocytic, normochromic red blood cells that demonstrated anisocytosis and teardrop cells consistent with hemolysis. Coombs tests, both direct and indirect were negative. Urine was deep brown colored, and dipstick test was positive for hemeprotein. His methemoglobin level was sent and was found high (16.8%). Moreover, afterward, his G6PD enzyme level was found deficient. Hence, a diagnosis of methemoglobinemia in a G6PD-deficient patient due to compounds methylene blue and nitrobenzene with acute kidney injury was made. He was treated with ascorbic acid 500 mg three times a day along with supportive treatment. He was dialyzed on alternate days for the next 10 days with repeated blood transfusions. On the 11th day, his urine output gradually improved to 1000 ml and kidney functions started recovering. He was discharged after 20 days with following parameters: hemoglobin: 10.6 g/dl, total leukocyte count: 6600/mm3, and platelet count: 1.7 lakh/mm3. Serum creatinine was 1.1 mg/dl with normal serum electrolytes. Serum lactic dehydrogenase level was 186 U/L with normal liver function test.


A 68-year-old female presented to an outside hospital complaining of long-standing right knee pain. There was no history of trauma and her past medical history was otherwise unremarkable. Four months prior, she had undergone bilateral knee intra-articular high molecular weight hyaluronic acid injections. Physical examination of her right knee revealed full but painful range of motion and tenderness especially on the medial compartment. Radiographs of the knee revealed radiographic characteristics of osteoarthritis including joint space narrowing and sclerosis (). The patient underwent total knee arthroplasty for management of knee osteoarthritis. Intraoperatively, there were extensive arthritic changes in all three compartments. At that time, the surgeons observed that the lateral part of the synovial membrane in close proximity to the quadriceps muscle was found to be thickened and had an associated “fatty mass.” A specimen was sent for pathology, but at the same time, the findings were attributed to reactive synovitis, secondary to knee arthritis and the ongoing total knee arthroplasty (posterior stabilized design) proceeded per routine (). One week postoperatively, pathology results showed a biphasic malignancy composed of a mixture of spindled mesenchymal cells with admixed glandular epithelial elements. Immunohistochemically, the tumor was positive for vimentin, CD99, keratins AE1/AE3, keratin 7, epithelial membrane antigen, focally positive for S100, keratin 19 and keratins 8 and 18 of the epithelial-like cells. The aforementioned morphologic and immunohistochemical findings were consistent with a biphasic SS (). The patient was subsequently referred to the Musculoskeletal Oncology Department at the University of Athens School of Medicine for consultation and further management. An MRI of the right knee showed a large soft-tissue mass on the anterolateral side of the distal thigh. The mass was extending into the substance of the vastus lateralis, presenting a heterogenous fusiform morphology. The mass was 7.2 × 8 × 6.2 cm, with irregular contrast enhancement. There was no evidence of regional cortical infiltration or any signs of an intramedullary inflammatory lesion (). Further evaluation of the patient with a computed tomography scan of the chest, abdomen and pelvis as well as a bone scan did not provide any evidence of metastatic disease. After appropriate preoperative planning, limb salvage surgery with endoprosthetic reconstruction was undertaken (). The patient was reoperated 28 days following the first operation. Given the fact that the knee joint was considered highly contaminated, a wide extra-articular tumor resection, including the site of the previous arthroplasty was mandatory. Accordingly, an extended medial fusiform incision including the previous incision and the patella was performed (). En-bloc resection of the tumor included the entire knee joint (). Nevertheless, the regional neurovascular structures were preserved and the residual bone defect was reconstructed using a modular knee megaprosthesis (METS modular implant system; Stanmore Implants, Borehamwood, UK) (). Histology of the resected specimen confirmed the diagnosis of classic biphasic SS, whereas it demonstrated tumor-free wide surgical margins. In the early postoperative period, the extensive soft tissue resection resulted in wound closure complications and exposure of the endoprosthesis. The defect was treated successfully using a gastrocnemius rotational flap. The latter technique provided sufficient coverage to the knee endoprosthesis avoiding further complications or infection (). After wound healing, the patient was referred to the Medical Oncology Department to proceed with adjuvant therapy, but she declined any further treatment including chemotherapy or radiotherapy. She was therefore advised to stay under close medical surveillance. At the last follow-up, 8 years postoperatively, the patient demonstrated no signs of local recurrence or systemic disease. Additionally, there was no evidence of implant loosening (), while she ambulated satisfactorily with a walking stick.


A 4 month old male patient presented to the Tata Memorial Hospital with complaints of redness and swelling at medial canthus of the left eye, which extended along the upper and lower eyelids (). Magnetic resonance imaging (MRI) of the orbit showed a homogenous lesion of 2.2 × 2.0 × 2.2 cm in the extraconal compartment of medial aspect of left orbit. The lesion was limited to the orbit without any intracranial extension, or extension into the ethmoid air sinuses ( and ). Biopsy was suggestive of alveolar rhabdomyosarcoma, which was positive for PAX3-FKHR fusion gene. Metastatic workup done with whole body positron emission tomography-computed tomography (PET-CT) was negative. The patient was treated with multi-agent chemotherapy as per the IRS-IV protocol []. The alveolar histology and suboptimal response after induction CTh mandated the use of radiation therapy for local control. In view of the expected morbidity of EBRT, it was decided to treat this patient using interstitial brachytherapy.


A 35-year-old man presented to the clinic with a facial disfiguring anomaly. Physical examination revealed a median cleft of upper lip and nose (Tessier no 0). Nasal cartilage and bones were widened resulting in a lateral displacement of the ala nasi and deep midline depression []. A broad nasal root and duplicated nasal septum were found. The external nares of the two halves were patent and wider than normal in horizontal dimension. In addition, a true orbital hypertelorism was also noticed at the orbital region. A diagnosis of median cleft face syndrome was made. Median cleft of the upper lip was repaired successfully by an inverted V-shape technique with special emphasis on muscular layer and vertical length of the lip []; however, correction of bifid nose and hypertelorism are yet to be carried out because of challenges to be encountered in their reconstruction.


A 30-year-old female had a midline cleft of the nose and upper lip (Tessier no 0). She was a street beggar by occupation and married to a deaf and dumb man with five children. Clinical examination revealed midline cleft of the nose apex, absence of cartilaginous part of nasal septum and columella []. There was also an incomplete midline cleft of the upper lip with associated lip incompetence []. An inverted V-shaped technique was used to repair the lip defect which resulted in an improved lip competence [].


A 14-year-old male had a cleft nose (Tessier no 0) and an incomplete median cleft of the upper lip (Tessier no 0). There were both agenesis of cartilaginous part of nasal septum and columella []. No history of difficulty in breathing was given and both nares were patent. The upper lip showed a furrow at midline and underdeveloped when compared with the thicker lower lip. There was well-pronounced lip incompetence. The palate appeared clinically normal, except for the presence of a rudimentary premaxilla. Median cleft lip was repaired in layers by inverted V-shaped technique. Reconstruction of columella attempted with an internally nasal dorsal flap supported by conchal cartilage harvested from the left ear. A rubber nasal stent was placed to further improve the nasal patency [].


A malnourished 7-month-old male child presented with median cleft of upper lip (Tessier no 0) and dysmorphic nose. The premaxilla, columella, and nasal septum were completely absent. There was a Squit of the left eye, hypotelorism, and slight frontal bossing []. Midfacial hypoplasia was also noticed. No other abnormality was detected. A diagnosis of premaxillary agenesis type holoprosencephaly (HPE) was made; however, the patient was lost to follow-up. Therefore, no surgical repair could be done.


A 58-year-old woman from Greece with a history of >20 years of chronic kidney disease of unknown origin since her mid-30s received her first deceased kidney transplantation at 48 years of age. Concomitant diseases included hypothyroidism, repeated thrombotic occlusions of her dialysis shunt and a transient ischaemic attack at the age of 41 years. Family history regarding inherited kidney diseases, thromboembolic events and/or malignancy was unremarkable. The patient developed a rapid and irreversible graft failure 18 months after her first kidney transplantation. Diagnostic kidney biopsy revealed TMA in the transplanted kidney, interpreted as potentially CNI-associated as tacrolimus was part of her immunosuppressive regimen. After another 10 years on haemodialysis, a second deceased RTX was performed under continuous control of haemolytic parameters and complement factors. Despite absence of haemolysis and complement consumption over the first 2 weeks after RTX, onset of graft function was delayed. Subsequently, the patient presented with reduction of urinary volume and rising serum creatinine levels of >300 µmol/L estimated glomerular filtration rate according to chronic kidney disease epidemiology collaboration (eGFR CKD-EPI)-CKD-EPI 12 mL/min/1.73 m2] (Figure ). On Day +21, laboratory findings finally revealed both a Coombs-negative haemolytic anaemia (haemoglobin 4.9 mmol/L, platelets 93 × 109/L, haptoglobin <0.1 g/L, fragmentocytes 1%, lactate dehydrogenase 10.5 mmol/L) and consumption of complement factors [C3 0.83 g/L, ref. range 0.9–1.7; complement component 4 (C4) 0.07 g/L, ref. range 0.18–0.49] representing clinical recurrence of aHUS. Accordingly, a subsequent kidney biopsy showed pre-glomerulary and intra-glomerulary TMA. Triggering infections, especially Shiga toxin-producing bacteria, streptococcus and CMV were not detected. Complement analysis revealed increased levels of soluble complex of complement component 5b and component 9 (C5b-9) (sC5b-9 655 ng/mL; ref. range <320 ng/mL), also known as the soluble form of the membrane attack complex (MAC), and CFH autoantibodies (IgG anti-CFH 74 U/mL; ref. range <60 U/mL; method ELISA). Specific mutation analysis, using a targeted complement gene panel (including ADAMTS13, C3, CFB, CFD, CFH, CFHR1, complement factor H related 2 (CFHR2), CFHR3, CFHR5, CFI, DGKE, MCP, MMACHC and THBD), yielded a homozygous deletion of the CFHR1 and CFHR3 genes, which was confirmed by multiplex ligation-probe amplification (Figure ). Additional risk polymorphisms or rare variants were not detected. Based on the clinical and genetic diagnosis of post-transplantation aHUS, plasmapheresis (n = 6) was initiated. Furthermore, the patient received the complement component 5 (C5) convertase inhibitor eculizumab, starting with a loading dose of 900 mg weekly for 4 weeks, followed by 1200 mg every 14 days. To eliminate additional triggers, we switched the initial immunosuppressive regimen from tacrolimus/prednisolone/mycophenolate mofetil (MMF) to a CNI-free protocol consisting of belatacept/prednisolone/MMF and eculizumab. Eight weeks after switch of immunosuppression, haematologic remission with normalization of haptoglobin and platelets as well as normalization of C3 and C4 could be obtained (Figure ). Simultaneously, renal graft function recovered and remained stable at a moderate level of kidney function with an eGFR (CKD-EPI) of 30–32 mL/min/1.73 m2 during an 18-month follow-up under continued belatacept and eculizumab administration. Re-biopsy of the transplanted kidney on Day +52 showed only slight residual activity of TMA. Interestingly, an attempt to discontinue eculizumab therapy after 19 weeks resulted in a new rise of serum creatinine levels and decreasing platelet counts, whereas immediate re-initiation of eculizumab administration led to a prompt haematological remission (Figure ). Retrospective measurements of CFH autoantibody titres from samples taken 6 months after failure of the first allograft and immediately before second kidney transplantation were negative.


A 67-year-old woman with epigastric pain presented to Gangnam Severance Hospital. Her symptoms had begun 2 weeks earlier, and she had been diagnosed with esophagitis at another hospital. After 2 weeks of fasting, she started oral feeding; however, epigastric pain recurred, and she was transferred to our hospital. Her medical history included type 2 diabetes mellitus and well-controlled hypothyroidism. She had a history of drinking 2 glasses of wine 3 times per week for 50 years. Her body temperature was 36.4°C and blood pressure was 143/69 mm Hg. Her abdomen was soft without tenderness. Laboratory tests showed a leukocyte count of 7,570/μL (neutrophils, 68.0%) and a C-reactive protein level of 79.7 mg/L. No bacterial growth was observed in blood or sputum cultures.
Esophagogastroduodenoscopy (EGD) was performed (). Although there were multiple esophageal perforations, the muscular layers were intact; thus, a large amount of pus was drained internally, resulting in effective drainage without penetrating the muscular layer of the esophagus. Moreover, contrast-enhanced chest computed tomography (CT) revealed diffuse edematous wall thickening with submucosal areas of air density in the esophagus. Air bubbles were also seen in the thickened wall of the esophagus ().
On chest CT, bilateral pleural effusions were noted, but there was no evidence of fluid collection in the mediastinum, and the patient’s heart function was normal. These findings suggested a diagnosis of acute phlegmonous esophagitis.
Intravenous antibiotics and other drugs to control the patient’s diabetes were administered, and fasting was recommended. However, because early enteral nutrition was considered necessary for long-term medical management and L-tube insertion could induce a friable esophageal wall injury, a feeding jejunostomy and enteral feeding were started on the fifth hospital day. Thereafter, the patient gradually recovered and was discharged on the 10th hospital day.
We then evaluated the patient with EGD and a chest CT scan by three weeks at our outpatient clinic. After 2 months, the phlegmonous esophagitis had significantly improved on EGD, but there was an esophageal stricture that could not be passed with a scope. Because the patient experienced symptoms of dysphagia, we performed esophageal ballooning and stent insertion. Two weeks after esophageal stenting, the dysphagia had resolved significantly; the stent was removed and the patient was able to tolerate oral feeding. She had no complaints of dysphagia and showed no recurrence of the infection during 14 months of follow-up.


A 52-year-old man presented to Asan Medical Center with a recurrent mediastinal mass incidentally found on follow-up chest computed tomography (CT) (). The patient had undergone the excision of an anterior mediastinal sarcoma 6 years ago at another hospital. That mass measured 150 mm×100 mm, and was completely removed through a median sternotomy combined with a left thoracotomy. His past medical history revealed total thyroidectomy due to thyroid cancer and paroxysmal atrial fibrillation that had persisted for the previous 6 years.
Preoperative transthoracic echocardiography (TTE) revealed severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 22% accompanied by mild mitral and tricuspid insufficiency. In addition, a newly developed anterior mediastinal mass measuring 35 mm×30 mm abutting the aortic arch was observed. The mass, which had abroad base attached to the right brachiocephalic vein, encircled both the right brachiocephalic and left common carotid arteries.
We planned complete en bloc excision of the invaded tissue, followed by reconstruction of the aortic arch and superior vena cava (SVC). After a redo median sternotomy, cardiopulmonary bypass (CPB) was established by cannulating the ascending aorta and right atrium. The aorta was cross-clamped, and then 1 L of cold del Nido cardioplegic solution was administered via the aortic root. A left-sided Maze procedure with cryoablation was performed through a left atriotomy. After closure of the left atriotomy, the entire tumor, including the invaded SVC, right brachiocephalic vein, and aortic arch, was resected en bloc under total circulatory arrest at a nasopharyngeal temperature of 21°C (). First, the right brachiocephalic artery was anastomosed to a 4-branched vascular graft (Hemashield Platinum Woven Double Velour Vascular Grafts 24 mm; Maquet Holding BV & Co. KG, Rastatt, Germany) to secure immediate unilateral antegrade cerebral perfusion. Then, anastomoses of the descending thoracic aorta, left common carotid artery, and proximal ascending aorta were performed, in order. The left subclavian artery was anastomosed under beating-heart CPB after the release of aortic cross-clamping (ACC). The SVC was then reconstructed using a bovine pericardial patch tailored in a tubular shape. Weaning from CPB was smooth, and normal sinus rhythm was restored. The intraoperative frozen biopsy revealed a negative resection margin, free of tumor cells.
The total circulatory arrest time, lower body ischemic time, ACC time, and CPB time were 13 minutes, 23 minutes, 78 minutes, and 132 minutes, respectively. The patient was transferred to the intensive care unit and extubated after 12 hours. The patient was transferred to the general ward on postoperative day (POD) 2 and was discharged on POD 9 without complications. Postoperative TTE showed no changes in overall cardiac function compared to the preoperative exam, except for slightly alleviated LV dysfunction, with an EF of 28%. Postoperative CT showed no evidence of a residual tumor, and confirmed the presence of a well-reconstructed arch, arch vessels, and SVC without architectural distortions ( ). The pathologic examination revealed a myxofibrosarcoma with resection margins free of tumor cells (pT1bN0M0, stage IA according to the American Joint Committee on Cancer seventh edition). The patient has been followed up a tour outpatient clinic for the last 9 months, and no evidence of tumor recurrence has been found. Recent follow-up TTE revealed normalized LV systolic function, with an EF of 63% and sinus rhythm. The patient’s resting pulmonary hypertension was relieved, and the extent of mitral and tricuspid insufficiency was reduced.


A 31-year-old woman presented for evaluation of pain in the left forearm, right hand, right knee, right hip, and lower back following a fall sustained 3 days prior to presentation. She had a past medical history notable for end-stage renal disease (ESRD) for which she has been receiving maintenance hemodialysis for the past 15 years, hypertension, diabetes, and congestive heart failure. She was wheelchair bound due to disabling peripheral neuropathy and chronic leg pain. She reported that she had fractured her left wrist about 3 weeks prior to presentation. She also experienced femoral fracture about a year ago, that was managed conservatively.
Physical examination revealed a blood pressure of 153/81 mm Hg and pulse rate of 101 bpm. There was moderate swelling and tenderness over the right distal femur with limited range of motion of the right knee due to pain. Left forearm splint due to previous fracture was in place. Tenderness was also noted over tip of the right index finger. There was no distal neurovascular deficit in the extremities. Medications included aspirin of 81 mg per day, lisinopril of 40 mg per day, carvedilol of 25 mg twice a day, sevelamer carbonate of 800 mg thrice a day with meals, and insulin regimen. The patient reported non-compliance with medications, diet, and hemodialysis treatment.
Initial laboratory values were significant for hemoglobin of 8.5 g/dL (12–15 g/dL), white blood cell count of 6.2 thou/mm3 (4–10 thou/mm3), platelet count of 222 thou/mm3 (150–450 thou/mm3), blood urea nitrogen of 36 mg/dL (6–20 mg/dL), and creatinine of 5.72 mg/dL (0.4–0.9 mg/dL). Serum intact PTH was found to be significantly elevated at 1735 pg/mL (15–65 pg/mL (goal 150–300 pg/mL for ESRD)) with serum calcium level of 9.5 mg/dL (8.4–10.2 mg/dL) and phosphate of 5.7 mg/dL (2.7–4.5 mg/dL). Serum 25-hydroxy vitamin D level was 24 ng/mL (>20 ng/mL).
X-ray of the right lower extremity showed diffusely decreased osseous mineralization and a comminuted distal femoral fracture (). Similarly, X-ray of the left upper extremity revealed significant diffuse osteopenia, and X-ray of the right hand showed findings concerning for possible fracture of the distal phalanx of the index finger just proximal to the subungual tuft versus aggressive erosion at this site was reported for the right hand (). Computed tomography (CT) scan of the abdomen and pelvis showed remarkable diffuse severe demineralization of the bones, with florid changes of renal osteodystrophy, prominent subligamentous resorption in the sacroiliac joints bilaterally, and widespread brown tumors ().
With normal serum calcium, high serum phosphate together with severely high PTH level, and history of non-compliance with medications and the dialysis treatment, the diagnosis of secondary (renal) hyperparathyroidism was made. Chart review revealed a history of long-standing severe hyperphosphatemia in the past explaining the presence of severe hyperparathyroidism despite current mild hyperphosphatemia (possibly now evolving toward more autonomous PTH secretion).
Typical imaging stigmata of hyperparathyroidism including diffuse demineralization, insufficiency fractures, and brown tumors supported the diagnosis in this young woman.
Her fractures were managed with non-operative treatment given her poor baseline functional status and severe hyperparathyroidism. The patient refused surgical parathyroidectomy. A high-dose phosphate binder (i.e. sevelamer carbonate) and also an oral calcimimetic (i.e. cinacalcet) were started for management of hyperphosphatemia and hyperparathyroidism. We reinforced compliance with low phosphate diet, medications, and hemodialysis treatment.


A 69-year-old man was admitted to our department in July 2015 due to fever, urticarial rash, and arthralgia. He had suffered from urticarial rash since 2003 but visited our department in August 2012 for the first time. The urticarial rash appeared over the entire body, including the trunk and both upper and lower extremities. It had aggravated episodically without noticeable factors. It was not painful but was accompanied by severe pruritus. It was accompanied by fever of up to 39℃ that persisted throughout the day, arthralgia, myalgia, leukocytosis, and elevated CRP and erythrocyte sedimentation rate (ESR). The episodes have lasted over 1 week. The urticarial symptoms were not found in his family.
Laboratory findings were as follows: leukocytes 10600/µL (reference range, 4800–10800/µL), hemoglobin 9.4 g/dL (12– 18 g/dL), platelets 258000/µL (130000–450000/µL), ESR 63 mm/hr (0–20 mm/hr), CRP 13.6 mg/dL (0–0.3 mg/dL), ferritin 360.77 ng/mL (4.63–274.66 ng/mL), complement (C) 3 158 mg/dL (90–180 mg/dL), C4 48.7 mg/dL (10–40 mg/dL), immunoglobulin (Ig) G 611 mg/dL (700–1600 mg/dL), IgA 124 mg/dL (70–400 mg/dL), IgM 154 mg/dL (40–230 mg/dL), and IgE 18.7 IU/mL (0–100 IU/mL). Liver and renal functions were in normal ranges. Blood and urine cultures were negative. Anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, rheumatoid factor, and cryoglobulin were also negative. Serum and urine immunoelectrophoresis showed no evidence of monoclonal gammopathy.
He had undergone a thorough examination in our hospital before this presentation. Skin histology revealed neutrophilic and eosinophilic inflammation without evidence of vasculitis. Computed tomography showed subpleural nodular consolidation in the lower left lung and bilateral pleural effusion. Positron emission tomography additionally revealed spleno-megaly, lymphadenopathy, and bone marrow hypermetabolism. A transthoracic needle biopsy for the subpleural nodule showed chronic granulomatous inflammation with organization. At that time, the possibility of adult-onset tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), an autoinflammatory disease, was considered based on his manifestations. However, a tumor necrosis factor receptor superfamily 1A (TNFRSF1A) gene mutation was not detected. Additionally, TNF-α antagonist, etanercept (Embrel®, Immunex Corporation, Seattle, WA, USA) 50 mg, which is known to be effective for TRAPS, was subcutaneously administered once, and he did not respond.
Over three years before successful treatment, he was unresponsive to various combinations of anti-histamines and various doses of systemic glucocorticoids, colchicine, cyclosporine, dapsone, and methotrexate. The observation that he had signs of systemic inflammation and did not respond to any conventional medications indicated the possibility of another autoinflammatory disease, such as Schnitzler's syndrome. However, Schnitzler's syndrome could not be diagnosed, because of the absence of monoclonal gammopathy. Despite the lack of diagnostic criteria for the typical TRAPS and Schnitzler's syndrome, we still did not exclude the possibility of autoinflammatory disease. Recent European guidelines suggest a diagnosis of IL-1-mediated autoinflammatory disease in such a situation. Therefore, an IL-1 receptor antagonist, anakinra (Kineret®, Swedish Orphan Biovitrum, Stockholm, Sweden) 100 mg, was subcutaneously injected on a daily basis. Fever, arthralgia, and urticaria were resolved within 24 hours of the first injection. The patient was very satisfied with the anakinra injections. Thus, antihistamines were tapered off in a few days, and systemic steroids were gradually tapered. Inflammatory markers, such as CRP and ESR, were normalized for the first time after ten days (). Transient increases in leukocytes, CRP, and ESR were observed shortly after anakinra injection, which may be associated with slight aggravation of Schnitzler's syndrome by the reduction of steroid doses. However, as the anakinra treatment was continued, the inflammatory markers returned to normal ranges although the steroids were further tapered. Prednisolone was tapered to a dose of 5 mg/day after one month. The treatment with anakinra was well tolerated, except for a mild reaction at the injection site.
Unfortunately, due to economic problems, anakinra was discontinued after 56 days of treatment. Two days later, his symptoms recurred. The systemic steroids were again increased. Three months after discontinuation of anakinra, he died due to pneumonia.


A 57-year-old African-American male was diagnosed with AIH 5 years ago. At his initial presentation, he was incidentally found to have leukopenia, thrombocytopenia, and elevated liver enzymes. The patient then underwent comprehensive laboratory and radiological workup to determine the underlying etiology. His initial laboratory investigation revealed WBC of 3,000/mm3, hemoglobin of 15.2 g/dL, platelets of 97,000/mm3, creatinine of 0.97 mg/dL, AST of 123 units/L, ALT of 83 units/L, alkaline phosphatase of 457 units/L, bilirubin of 1 mg/dL, albumin of 4.4 g/dL, and prothrombin time of 15 s. Viral hepatitis profile for A, B, and C was negative. Serology for ANA, c-ANCA, ds-DNA, liver-kidney microsome IgG, proteinase 3 antibody, myeloperoxidase antibody, smooth muscle antibody, and HIV were negative. P-ANCA and single-stranded DNA were positive. Serum electrophoresis showed elevated IgG level of 2,970 mg/dL (reference range: 751–1,560). He also underwent bone marrow biopsy due to leukopenia and thrombocytopenia, which revealed no evidence of lymphoproliferative disorder. CT scan of abdomen revealed hepatosplenomegaly. He also underwent liver biopsy, which showed active hepatitis with sinusoidal T-cell infiltrates (Fig. , Fig. ). Patient clinical presentation was secondary to possible AIH (according to Revised Original Scoring System of the International Autoimmune Hepatitis Group). He was initially treated with high-dose steroids without clinical or biochemical improvement. He was then observed clinically with frequent monitoring of his liver function tests. His medical history was significant for hypertension and chronic pancreatitis. He was not taking any routinely prescribed medications. He had a prior history of smoking as well as alcoholism. Family history was significant for acute leukemia in the father and brother.
After approximately 5 years of close clinical follow-up, the patient presented with generalized abdominal pain and worsening liver enzymes. His bilirubin increased from 0.9 mg/dL to 4.5 mg/dL, alkaline phosphatase increased to 1,098 U/L from baseline of 400 U/L with liver transaminase staying close to his baseline of 100–150 U/L. The patient underwent magnetic resonance cholangiopancreatography (MRCP), which revealed intrahepatic biliary dilatation and stricture at the porta hepatis. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a 2-cm stricture in the common bile duct extending into the right intrahepatic biliary tree. Biopsy confirmed the diagnosis of cholangiocarcinoma (Fig. ). CT scan of chest, abdomen, and pelvis revealed no distant metastasis. The patient was evaluated by the liver transplant team but was deemed unqualified for liver transplant due to recurrent cholangitis at the time of initial evaluation. The patient was not a surgical candidate due to his extensive underlying liver disease. The patient was then started on systemic chemotherapy with gemcitabine and cisplatin. He successfully completed 6 cycles of treatment. PET scan after 6 cycles of treatment showed no evidence of malignancy. The patient is currently being followed by the transplant team for possible liver transplant in the future.


A 45-year-old gentleman presented with a 6-week history of progressive decline in function and easy bruising. He had mild ataxia along with binuclear horizontal diplopia. Acute lymphocytic leukemia was suspected due to high leukocytes count (79.1 × 109/L) and abnormal cells (53.4 × 109/L) on blood smear in favor of blast cells. Platelet count was low (22 × 109/L). Sugar coating along the brainstem was ruled out using MRI brain with gadolinium. Thus, an urgent LP was planned to assess tumor seeding within the CSF after correcting platelets to 51 × 109/L. A diagnosis of Burkitt lymphoma was made thereafter. Nevertheless, within 6 hours of the LP, the patient experienced initial left leg pain which was treated empirically. As bilateral numbness developed, an MRI spine was ordered and a diagnosis of spinal hematoma was made []. By the time this was obtained the patient was experiencing severe paraparesis and transferred to our centre for urgent intervention. On arrival, the patient posed a challenge owing to his medical instability; however, due to the urgency of the neurosurgical situation and given the patient's age, we provided both medical and surgical treatment simultaneously. The surgical intervention was planned for T11–L3 decompression, which took place approximately 24 hours post LP. Intraoperatively, the conus medullaris and cauda equina were severely compressed from multi-compartmental hemorrhages with the largest one within the subdural space []. Despite aggressive surgical and medical management, the patient remained paraplegic and died 3 months after surgery.


A 65-year-old woman with 4 days of neck and shoulder pain that affected her sleep in addition to left arm numbness was seen in our Pain Management Department. Prior to her arrival, the patient had taken some medications (specific details were not clear), but the pain did not improve and became intolerable. The patient had a history of hypertension that had not been treated regularly, and her highest blood pressure was 180/100 mm Hg. All of the patient's examinations and treatments were approved by the ethics committee of 903 Hospital.
Upon arrival, the patient's vital signs showed hypertension with a blood pressure of 170/92 mm Hg; her other vital signs were normal. Physical examination showed a normal spine and extremities. There was slight tenderness over the cervical and the corresponding paravertebral area. The Spurling test, Jackson test, and left Eaton test were all positive. Sensation to pain and muscular tension of the extremities were normal bilaterally, and motor strength was grade 4/5 in the upper and lower extremities bilaterally. The biceps and triceps reflexes were normal bilaterally, and the Hoffmann sign was negative.
When she arrived, the patient underwent an MRI scan that showed multiple disc herniation at cervical 3/4, 4/5, and 5/6, and the epidural sac was compressed by the disc herniation (Fig. ).
The initial diagnosis was cervical spondylosis and primary hypertension. It was decided to treat the patient conservatively with loxoprofen 60 mg twice a day, nifedipine sustained release tablets 10 mg daily, and an intravenous drip of 250 mL of 20% mannitol daily.
Two days later, the patient manifested clusters of tiny blisters along the C4 and C5 dermatome; the vesicular fluid was clear and there was no tenderness, suggesting the patient might have a concurrent acute herpes zoster infection. The antiviral drug famciclovir 0.25 g was started 3 times a day. The next day, the patient under went a nerve block procedure with an epidural puncture at the C7 to T1 space, and a catheter was inserted. The patient received an injection of 3 mL of the following mixture through the epidural catheter: 5 mL of 2% lidocaine, dexamethasone 10 mg, vitamin B1 100 mg, vitamin B6 100 mg, mecobalamine 1 mg, and 2 mL 0.9% saline, total volume 12 mL). The patient was observed for 10 minutes after the injection, and there were no signs of spinal anesthesia; the remaining volume of the mixture was subsequently injected and the catheter was removed.
The following day, the patient's pain had decreased and the clusters of blisters were somewhat reduced in size. A second epidural puncture and injection were performed, and the patient received the same nerve block mixture as before. The patient then showered and began to complain of body soreness, slight weakness, and a headache. Bilateral lung wheezing was heard on physical examination, and the patient was given 1 capsule of amoxicillin. However, the patient experienced severe pain of the shoulder, neck, and head accompanied by a low-grade fever (37.8°C), fatigue, and nighttime muscle aches. The patient also fell 1 time on the ward. Blood was tested due to these aggravated symptoms, and the white blood cell count was 24.27 × 109/L, neutrophil percentage was 92.41%, erythrocyte sedimentation rate (ESR) was 66 mm/h, hyperallergic C-reactive protein (CRP) was over 10 mg/L, and general CRP was 193.8 mg/L, suggesting an acute inflammation. The patient underwent a chest x-ray and cervical/thoracic MRI scan and was started on intravenous cefperazone/sulbactam 2 g twice a day and fosfomycin sodium. One day later the patient still complained of severe shoulder pain and headache; physical examination revealed C4 to T8 tenderness and neck stiffness; however, limb strength was normal. The MRI scan indicated epidural inflammation from C6 to T8 and an abscess formation (Fig. ).
The patient was moved to the intensive care unit to receive more intensive antibiotic treatment with vancomycin 1 g every 12 hours combined with imipenem/cilastatin sodium 1 g every 8 hours for anti-inflammation. Famciclovir was also changed to gentinovir 0.15 g twice a day for antiviral treatment. The patient's neck and back pain significantly improved after 4 days of anti-inflammation therapy, and the MRI scan showed significant absorption of the abscess (Fig. ). This therapeutic regimen was continued for 17 days, during which the white blood cell count decreased to 5.11 × 109/L, the neutrophil percentage decreased to 57.3%, the ESR decreased to 76 mm/h, the hyperallergic CRP decreased to 4.71 mg/L, and the general CRP was less than 10 mg/L. The patient's neck and back pain disappeared, and the clusters of blisters scabbed over. On physical examination, there was slight tenderness to percussion but no pressing pain or neck stiffness. After 3 weeks of anti-inflammation therapy, the antibiotics were gradually weaned. After over a month of anti-inflammation therapy, the epidural abscess was completely absorbed and the patient was discharged from the hospital (Fig. ).


A 65-year-old married woman visited our emergency room of Obstetrics and Gynecology Department, Soonchunhyang University Cheonan Hospital, due to a chief complaint of lower left abdominal pain which started 3 days before her visit and aggravated on the day of visit. Her obstetric history was the patient has had 2 term births, 0 preterm births, 2 abortions, 2 living children and had menopause 10 years ago. At the time of visit, her systemic condition was favorable. Her height was 162 cm and weight was 61 kg. Vital signs were normal with a blood pressure of 110/60 mm Hg, pulse rate of 60 beats/min, body temperature of 36.0°C, respiratory rate of 19 breaths/min, and no apparent specific signs. There was slight abdominal distension, but no tenderness or rebound tenderness on abdominal palpation. In pelvic examination, no vaginal bleeding or discharge was noted.
In radiologic assessment, transvaginal and abdominal ultrasound showed a normal uterus and a 13 × 9 cm sized multicystic tumor with irregular surface of the left ovary (Fig. A). Abdominal and pelvic computed tomography scans revealed a 16 × 9 × 14 cm sized multiseptated cystic mass with large enhancing solid portion in the left ovary, and malignancy was suspected (Fig. B). In addition, there was a finding of mild dilation of the right distal ureter caused by the compression of the left ovarian mass, and there were no findings of ascites, pleural effusion, and lymph node enlargement. Test results were normal in peripheral blood smear, blood coagulation, liver function, renal function, urinalysis, and C-reactive protein, and her chest x-ray and electrocardiogram were normal. The test for serum tumor markers revealed normal levels of cancer antigen 125 (CA-125) at 8.69 IU/mL (range 0–35 IU/mL) and carbohydrate antigen 19–9 at 3.29 U/mL (range 0–34 U/mL). The patient underwent exploratory laparotomy with a suspicion of borderline or malignancy of an adnexal mass. A white-gray 17 × 9 cm sized cystic tumor was detected in the left adnexa, having a torsion of 720° in a counterclockwise direction or no necrosis (Fig. ). Uterus, right ovary, large intestine, bladder, small intestine, and liver were normal in inspection and palpation of abdominal organs. There were no presentations of ascites or nodules within the peritoneal cavity. We carried out laparotomy because there was the possibility of ovarian malignancy, but torsion of the left ovary was observed. So, we decided to conduct frozen biopsy of left ovary for confirming malignancy before performing staging surgery. Salpingo-oophorectomy on the left side was performed after washing cytology from the peritoneal cavity, and the result of an emergent frozen section biopsy confirmed a borderline Brenner tumor associated with a benign mucinous tumor. Subsequently, total hysterectomy and right salpingo-oophorectomy were performed. The operation was completed without additional procedures such as pelvic lymph node dissection.
Gross pathologic findings revealed that the left ovary showed a well-demarcated oval mass composed of both solid and cystic components, measuring 17.0 × 16.0 × 8.5 cm in dimensions. The cystic area showed multilocular appearance and it contained mucin materials. On microscopic examination, the cyst wall was lined by a single layer of benign mucinous cells, which was consistent with benign mucinous cystadenoma. The solid area displayed round to oval tumor cell nests within fibrous stroma and the tumor cells had fine chromatin pattern, obvious nucleoli, and longitudinal grooving with no cytologic atypia or mitotic activity. Histologic features of solid area were benign Brenner tumor (Fig. ). Therefore, we diagnosed this ovarian tumor as benign mixed Brenner-mucinous tumor.
The patient was discharged in good condition on the 15th postoperative day without specific complications.


In March 2015, a 31-year-old Caucasian man presented at the Surgery Department complaining of weight loss (approximately 5% of body weight during the previous 2 mo) and abdominal pain. His father underwent liver resection for unspecified liver neoplasm 12 years before but no other significant family history of illness or tumor emerged. The patient had no history of alcohol abuse or hepatitis; he had been followed for arterial hypertension and treated with ramipril and nebivolol.
Physical examination revealed a palpable large abdominal mass in the right upper quadrant, with no evidence of ascites or splenomegaly. Laboratory findings revealed a high level of gamma-glutamyl transferase (349 U/L) and a mild leukocytosis (13.8 × 103 cells/mm3); serology findings for hepatitis B and C, autoimmune hepatitis and human immunodeficiency virus were negative. Serum findings for alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were within normal range.
The CT scan showed a large, lobulated, multinodular mass (22 cm × 13 cm × 25 cm), with few round calcifications mainly in the central part, involving entirely the right hemi-liver, partially the Couinaud’s segment 4, and the caudate lobe. After administration of iodinated contrast material, the tumor showed non-homogeneous, early enhancement in the arterial phase, with subsequent washout in the portal and delayed phases. The CT images also demonstrated an extensive infiltration of the right portal branch and of the right and middle hepatic veins, with a consequent spontaneous hypertrophy of the left lobe (Figure ).
The surgical procedure, consisting of a virtual resection, was planned[]. The quantitative analysis of CT images showed a total liver volume of 5797 cm3 and a tumor volume of 3879 cm3 with a hypertrophic remnant left liver lobe (Couinaud’s segments II and III) of 1329 cm3. The future liver remnant, thus, was 69%, markedly over the safe cut-off[]. Based on these radiological findings, a right trisectionectomy extending to the caudate lobe was proposed.
On laparotomy, careful exploration of the abdominal cavity ruled out no extra-hepatic manifestations; intraoperative ultrasound revealed another 2 cm nodule in segment II. The remaining left lobe did not show any histological alterations at intraoperative biopsy. Hepatoduodenal ligament was dissected to isolate and ligate the right hepatic artery, portal vein and bile duct as well as the biliary and vascular elements for segments IV and I (Figure ). After transection of the right portal vein, that appeared infiltrated by the tumor, the hepatic parenchyma was dissected between segments II/III and segment IV by using Cavitron ultrasonic surgical aspirator and argon diathermy. Afterwards, the nodule at the hepatic segment II was treated by radiofrequency ablation.
Postoperative course was uneventful, except for a 4.5 cm fluid collection on the cut surface of the liver that was successfully treated by percutaneous drainage. The patient was discharged on postoperative day 21 with a completely preserved liver function.
Gross appearance: The right hepatic lobe was almost entirely occupied by a multinodular mass with homogeneous whitish cut surface, partial necrosis and calcifications. The lesion had a greatest diameter of 19 cm and was 0.5 mm far from the surgical margin (Figure ).
Microscopic and immunohistochemical features: Histologically, the neoplasm showed an organoid arranged tumor of well-defined nests of epithelioid and spindle cells with focal necrosis, surrounded by hypercellular stroma with areas of osseous metaplasia and calcifications. The cellular nests were oval, elongated, and irregular with rounded edges. The epithelioid part of the tumor was composed of monomorphous polygonal and spindle-shaped cells, round to oval nuclei with finely stippled chromatin and no appearance of nucleoli. The cytoplasm was eosinophilic in most areas, with few cells containing clear cytoplasm (Figure ). The cellular nests showed positive staining for markers of epithelial differentiation (CAM 5.2, AE1/AE3, EMA (focal), β-catenin (both membrane and nuclear), WT1 (both membrane and cytoplasmatic), GPC3 (focally cytoplasmatic) and CD56 (diffuse) and negative staining for hepatocyte antigen EpPar1 (hepatocyte paraffin 1), CK7, CK19, CD34, CD99, chromogranin and desmin.
The calcifications were most commonly within or adjacent to cellular nests. The mitotic index was 10 mitotes/10 high power field (40 × objective). The stroma surrounding the cellular nests showed a myofibroblastic nature, with spindled cells with long tapered cytoplasmic processes, positive staining for smooth muscle actin and negative staining for citokeratins and EpPar1. Bile ducts entrapped in the fibrous stroma were normal and were highlighted by CK7 and CK19 immunohistochemical stains (Figure ). The neoplastic cells infiltrated the surrounding hepatic parenchyma and peri-hepatic soft tissue. Vascular invasion of a portal vein branch was demonstrated.
Differential diagnosis: The differential diagnosis of a biphasic tumor, with a spindled and epithelioid component, variable calcifications and osseous metaplasia includes in the first instance synovial sarcoma, mixed epithelial and mesenchymal hepatoblastoma and calcifying NSET. Desmoplastic small round cell tumor (DSRCT) is also a diagnostic consideration in a young patient. In addition, the possibility of sarcomatous variants of hepatocellular carcinoma or cholangiocarcinoma should be considered. However, these tumors lack the nested, organoid architecture of NSET, typically showing a greater cytological atypia.
Areas predominantly composed of epithelioid nests may resemble islands of fetal hepatoblastoma cells. However, the neoplasm in this report lacked the fetal and/or embryonic hepatoid features of the epithelial component of mixed hepatoblastoma, and neither the spindled nor the epithelioid lesional cells stained with the hepatocyte-specific tissue stain EpPar1.
The overall histology and immunohistochemical features supported the diagnosis of NSET, a very rare tumor defined as a non-hepatocytic and non-biliary tumor of the liver consisting of nests of epithelial and spindled cells with associated myofibroblastic stroma and variable intralesional calcification and ossification[,,].
For a comprehensive report, molecular analysis was performed. Reverse transcriptase-polymerase chain reactions for SYT-SSX and EWS-WT1 were negative in our case. Such findings, combined with the histological appearance, allowed us to rule out the hypothesis of synovial sarcoma and DSRCT, respectively.
In September 2015, the patient underwent a CT scan, which showed several liver lesions (maximum diameter of 17 mm), and also a positron emission tomography (PET) that documented a pre-sacral nodule (SUV = 5). After discussion within the Multidisciplinary Tumor Board (MTB), since surgery was judged not feasible, a liver chemo-embolization (DCBeads + doxorubin) was performed. Although the arteriography showed a higher number of the lesions, only five nodules were treated with the chemoembolization. Due to an increase in the gamma-glutamyl transferase level (944 U/L), no further treatment was practicable.
In November 2015, a re-assessment with a CT scan showed a local progression and an increased number of abdominal lymphoadenopathies. Hyperbilirubinemy (10.2 mg/dL) was also observed with a dilatation of the intrahepatic biliary duct. Therefore, a trans-cutaneous biliary catheter was positioned, with consequent improvement of the hepatic and biliary function. The patient was re-evaluated within the MTB and we hypothesized a regimen with ifosfamide/mesna, platin and anthracycline according to ifosfamide/cisplatin/pirarubicine (commonly known as the IPA) schedule. Due to the correlation of the histological features of the disease with the hepatoblastoma, as described in literature[-], four courses of cisplatin (100 mg/m2) and ifosfamide/mesna (3 g/mq) were administered, omitting doxorubicin because of the liver impairment.
Anyway, infections of the biliary catheter, with fever and abdominal pain, affected the treatment, and required both antibiotics and a dose modification of the chemotherapy schedule. In fact, cisplatin alone was administered in the second course and ifosfamide/mesna was added again from the third course, reducing by 50% of its total dose. The patient received a total of four cycles of chemotherapy.
In April 2016, a restaging CT scan showed a progressive disease, represented by an increase of the hepatic lesion (5 cm vs 2.4 cm) and of the pre-sacral nodule (2.6 cm vs 1.7 cm). Ascites was also documented (Figure ). Unfortunately, the worsening of the clinical status, the rise in total bilirubin up to 27.4 mg/dL and alterations of sodium and potassium prevented further administration of chemotherapy and the patient died in June 2016.