An elderly female patient, aged 73-year-old, was admitted to our hospital for unexplained acute abdominal pain and bloating after the occurrence of vomiting. Upon admission, the patient was observed to have an abdominal bulge and total abdominal tenderness accompanied by rebound pain and muscle tension. The patient had a medical history of total colectomy in combination with an ileal pouch-anal anastomosis (IPAA) for the treatment of functional chronic constipation or chronic idiopathic constipation (CIC) 2 years before hospital admission.
General physical examinations were as follows: heart rate: 120 bpm; blood pressure: 85/50 mmHg; Laboratory tests revealed a white blood cell (WBC) count of 17 × 109 / L, and lactic acid (LA) level of 6.3 mmol / L; Abdominal enhanced computed tomography (CT) showed dilation, as well as gas and liquid accumulation in the distal portion of the small intestine, ventral to the distorted stomach. It was observed that a segment of the small intestine was prolapsed via the defected lesser omentum, passing the retrogastric lesser curvature to enter the ventral part of the stomach. CT images in the abdomen also revealed a hypodensity in some fragments of the small intestine, liquid accumulation around the liver and spleen, as well as pelvic effusion (Fig. ).
Based upon the abdominal CT findings, the patient was diagnosed with having a lesser omental hernia complicated with intestinal obstruction, acute diffuse peritonitis, and septic shock.
The patient was immediately treated with an emergency laparotomy. During the procedure, ascites, of approximately 1500 ml liquid with blood, were observed. Notably, a fragment of the small intestine protruded from the lesser retrogastric curvature of the stomach into a defected lesser omentum (Fig. a) and appeared necrotic and black. The defected omentum was approximately 3 × 4 cm in size (Fig. b), with the necrotic fragment of the small intestine measuring approximately 200-cm in length. The necrotic portion of the small intestine was resected, anastomosis was performed, and the defected lesser omentum was closed. The patient was subsequently transferred to the intensive care unit (ICU). The tracheal intubation was removed 2 days after the operation, and the patient was transferred to a local hospital for further treatment.
The risks and benefits of the surgical procedures were explained to the patient, and written informed consent was obtained.


A 61-year-old man (height, 157 cm; weight, 56 kg) was diagnosed with recurrent hepatocellular carcinoma with cirrhosis in the right hepatic lobe and was scheduled for laparoscopic hepatectomy. He had no clinical cardiopulmonary or brain disease.
The operation was performed under combined general and epidural anesthesia. Anesthesia was induced with propofol 70 mg and fentanyl 100 μg. After administration of rocuronium 30 mg, tracheal intubation was performed. Anesthesia was maintained with desflurane, a 40 to 50% oxygen–air mixture, and continuous infusion of remifentanil 0.15 μg × kg−1 × min−1. The arterial blood pressure, pulse oximetry, capnography, and central venous pressure were monitored continuously. Volume-controlled ventilation was adopted to obtain an end-tidal CO2 (EtCO2) level of 30 to 40 mmHg.
The patient was placed in the head-down position during surgery, and intra-abdominal pressure was maintained to 10 cmH2O. During the pneumoperitoneum, the tidal volume was adjusted to 500 ml, and the respiratory rate was adjusted to maintain the EtCO2 at 30 to 40 mmHg. The fluid management strategy was adjusted to maintain CVP about 5 mmHg.
Laparoscopic hepatic resection was started after clamping the branches of the vascular pedicle, commonly known as the Pringle maneuver. During the hepatic resection, the EtCO2 dropped from 40 to 21 mmHg, and ST elevation was observed in lead II and ST depression was observed in lead V5 of the electrocardiogram (Fig. , middle). At this time, the electrocardiogram showed sinus rhythm and the blood pressure was almost stable; however, the central venous pressure slightly increased from 7 to 13 mmHg. After the operation was stopped, arterial blood gas analysis showed a divergence between the partial pressure of CO2 (67.4 mmHg) and EtCO2 (21 mmHg). Although gas embolism was strongly suspected, coronary artery spasm could not be ruled out because the ST change in leads II and V5 was suspected to be associated with the right coronary artery. The electrocardiographic changes improved shortly thereafter (Fig. , lower), and the surgery was resumed after administration of a coronary vasodilator (nicorandil, 3 mg/h) and β-blocker (landiolol, 5 mg). The surgery was completed without further problems.
After the surgery, the patient’s hemodynamic state was stable and tracheal extubation was performed smoothly 20 min postoperatively. Although the patient could speak and had alert consciousness, he exhibited muscle weaknesses in the right arm and leg. Obvious cerebral bleeding was not detected by emergency computed tomography immediately after surgery; however, magnetic resonance imaging performed the next day revealed cerebral infarction in the broad area of the left cerebral cortex (Fig. ). Transthoracic echocardiography was performed to determine the cause of the cerebral infarction, but no intracardiac defects were found. The patient was able to walk independently with a cane and was discharged 21 days after the surgery.


The patient was a 41-year-old man (height 174.2 cm, body weight 60 kg) with dextro-TGA who underwent balloon atrioseptostomy treatment at birth because of desaturation. He also had a Mustard procedure (interatrial baffle) at 10 months of age and required surgical repair for pulmonary vein stenosis at 2 years of age. At 41 years of age, he developed severe systemic RV failure and pulmonary edema (Fig. ). He was treated with inotropic agents, mechanical ventilation, intra-aortic balloon pumping, and continuous hemodiafiltration. His hemodynamic status was stabilized with these treatments, but he remained inotrope-dependent, and his condition gradually worsened despite optimal medical therapy. After a medical team preoperative meeting, he was scheduled for a VAD implantation of the RV as a bridge to orthotropic cardiac transplantation.
Preoperative cardiac catheterization indicated elevated pulmonary arterial wedge pressure and severely impaired systemic RV function with infusion of dobutamine (3 μg/kg/min) and carperitide (24 ng/kg/min), a recombinant atrial natriuretic peptide with vasodilating and diuretic activity (Table ). Echocardiography identified the dilated RV, preserved pulmonary ventricle (morphological left ventricle), and increased baffle flow velocity (Table ). Chest radiography and computed tomography scan showed a severely dilated RV (Figs. and ).
In the operating room, a continuous monitoring of electrocardiography, SpO2, systemic arterial pressure via a right radial artery catheter, bispectral index (BIS; Medtronic, Minneapolis, MN), and regional cerebral oxygen saturation at the right and left forehead (INVOS™ 5100C, Somanetics, USA) was initiated before anesthesia induction. After administration of 100% oxygen, general anesthesia was induced slowly by intravenous administration of 3 mg of midazolam, 0.5 mg of fentanyl, and 50 mg of rocuronium. Additionally, dobutamine (3.3 μg/kg/min), nicorandil (1.1 μg/kg/min), which has the dual properties of a nitrate and a potassium channel opener, and carperitide (33 ng/kg/min) were continuously administered to minimize anesthetic-induced cardiac depression. During anesthesia induction and tracheal intubation, his circulatory and respiratory status remained stable. After tracheal intubation, a transesophageal echocardiography probe was inserted. Then, a central venous catheter and right heart catheter were inserted via the right internal jugular vein. The latter catheter (Swan Ganz catheter) was guided to the right pulmonary artery under fluoroscopic control because of his unique anatomy with interatrial baffle.
His anesthesia depth was controlled at a BIS of 40–60 by a continuous infusion of propofol (3–5 mg/kg/h), remifentanil (0.2–0.3 μg/kg/min), and rocuronium (7 μg/kg/min).
A standard median sternotomy was performed. Because his heart was heavily adherent, the cardiac surgeons had difficulty in adhesiolysis. The systemic aorta and systemic atrium were cannulated, and cardiopulmonary bypass (CPB) was instituted. At first, the patient’s aortic valve was replaced with a bioprosthetic valve for moderate aortic valve regurgitation. Subsequently, the trabeculae carneae of the RV, which could disturb the flow to the inflow cannula, were resected via the RV apex; the inflow cannula was positioned at the apex of the RV. The outflow cannula graft was anastomosed to the ascending aorta, and then a Jarvik 2000 VAD (Jarvik Heart, Inc., New York, NY, US) was implanted.
At the weaning of the CPB, infusion of dobutamine (3.3 μg/kg/min) and inhalation of nitric oxide (20 ppm), to decrease afterload of the pulmonary LV, was started. The CPB weaning was not difficult, and the VAD was successfully commenced at a pump speed of 10,000 rpm (3–5 L/min). The aortic cross-clamping, CPB, surgery, and anesthesia lasted 200, 296, 628, and 807 min, respectively. Estimated blood loss and urine output were 2051 and 2390 mL, respectively. Overall, 900 mL of crystalloid, 900 mL of colloid, 960 mL of packed red blood cells, 560 mL of fresh frozen plasma, and 200 mL of platelet concentrate were administered. After completion of operation, the patient was transferred to the intensive care unit with ventilator support under propofol sedation.
On postoperative day (POD) 2, the patient was weaned from mechanical ventilation. On POD 5, after our surgeons decreased the VAD dial from 3 to 2, the patient developed pulmonary congestion with respiratory distress, decreased arterial oxygen saturation, and elevated pulmonary artery pressure (PAP) (Table ). Noninvasive positive-pressure ventilation (NPPV) was adopted, and intensified diuretic therapy was started. Additionally, the intensivists returned the VAD dial from 2 to 3. A few days later, he recovered from congestive heart failure, and then, NPPV was stopped. Following this, the patient did well hemodynamically and had good VAD performance. Another important point for postoperative management of VAD implantation is to prevent thrombosis. In this case, continuous infusion of heparin was administered for anticoagulation. The heparin infusion adjusted to an activated partial thromboplastin time (APTT) ration of 1.5–2.0 (or 40–50 s). Actually, the infusion rate or heparin was 15,000–20,000 units per day.
The patient was discharged from the hospital on POD 60. He is now eagerly awaiting heart transplantation. Table shows his hemodynamic data, and Fig. shows his chest radiography on POD 90.


A 33-year-old man (height, 176 cm; weight, 71 kg) visited our hospital with a chief complaint of respiratory discomfort. The patient reported a history of smoking (20 cigarettes per day) between 20 and 31 years of age; otherwise, his medical and family histories were unremarkable. Computed tomography detected pleural effusion and an anterior mediastinal tumor. A detailed examination led to the diagnosis of thymoma (stage IVb: pleural dissemination involving the superior vena cava [SVC] and brachiocephalic vein). The patient exhibited a partial response to radiation therapy and chemotherapy; thus, the implementation of right EPP and partial replacement of the SVC were scheduled with the aim of achieving cytoreduction by removing as much of the thymoma as possible.
Preoperative respiratory function test results were as follows: vital capacity (VC), 5.51 L; %VC, 113.6%; forced expiratory volume in 1 s (FEV1), 4.6 L; and FEV 1.0%, 85.5%. Blood gas testing revealed a pH of 7.422; partial pressure of carbon dioxide (PaCO2), 40 mmHg; partial pressure of oxygen (PaO2), 96.9 mmHg; and bicarbonate (HCO3−), 25.6 mmol/L. No abnormalities were observed in preoperative cardiac function. Chest radiography revealed a mediastinal tumor shadow, but no abnormalities were detected in the lung fields.
On arrival to the operating room, the epidural catheter was inserted at the level of thoracic vertebrae 7/8 successfully. General anesthesia was induced by using remifentanil (1.0 μg/kg/min), rocuronium (40 mg), and propofol (target-controlled infusion [TCI], 3.0 μg/mL). The airway was secured using a 37-Fr left-sided double lumen tube (Smiths Medical, Minneapolis, MN, USA), which was inserted at a point above the bifurcation of the trachea via a bronchoscope. Anesthesia was maintained using propofol (TCI 3.0 μg/mL) and remifentanil (0.4–0.8 μg/kg/min), under 40–100% oxygen. Monitoring tools included a five-lead ECG system, pulse oximeter, and expired gas monitor. Bispectral index (BIS™, Medtronic PLC, Dublin, Ireland) was used to monitor the depth of anesthesia. Hemodynamic monitoring was performed via direct measurement of arterial pressure and measurement of central venous pressure. The chest lining was cut, the right phrenic nerve was separated, and the right diaphragm was removed. The left brachiocephalic vein was bypassed to the right atrial appendage, and the right brachiocephalic vein was bypassed to the SVC. The portion of the SVC with suspected residual tumor was dissected. After the lung hilum was treated, both the tumor and the right lung were removed; some injury to the trachea was repaired. The right diaphragm and pericardium were reconstructed using a GORE-TEX® sheet (W.L. Gore and Associates, Newark, NJ, USA). The procedure was performed while visually observing the left lung. As the anterior junction line was maintained, a left-sided chest drain was not inserted. The initial dose of 0.2% ropivacaine (5 mL) was injected into the epidural space when the chest incision was closed. Then, a continuous infusion of 0.2% ropivacaine (5 mL/h) without narcotics was initiated for postoperative analgesia. No abnormalities were observed in terms of intraoperative ECG and hemodynamics. The duration of anesthesia was 10 h and 12 min; the operative time was 8 h and 5 min. The infusion volume was 3550 mL, blood loss volume was 1540 g, and urine volume was 2120 mL.
Following surgery, bronchoscopic observation of the trachea under anesthesia revealed minimal phlegm. After the patient awoke from anesthesia and began to breathe spontaneously, his pulse oximetry reading was maintained at 100% and he did not complain of postoperative wound pain; thus, the patient was extubated. However, immediately after extubation, labored respiration began and breathing rate markedly increased. Pulse oximetry decreased to 84% under the administration of 6 L/min of oxygen via face mask. There was little sputum or hemosputum, but subcutaneous emphysema was evident in the right subcutaneous area and streak of the large pectoral muscle. The patient exhibited normal breath sounds in the left lung. Further, there was no air leak from the chest tube without kinks, clogs, or regurgitation during inspiration of the chest tube system. The measurements of arterial blood gases were 7.207 for pH, 68 mmHg for PaO2, and 64 mmHg for PaCO2; accordingly, the condition was diagnosed as hypoventilation-associated hypoxemia/hypercapnia. Hypercapnea cannot be explained by intraoperative opioid use because we did not include opioids for postoperative continuous epidural analgesia. In terms of hemodynamics, the patient’s blood pressure was elevated, and his heart rate had increased. There were no signs of strider or wheeze; additionally, the patient did not complain of pain, was able to breathe deeply as instructed, and exhibited clear consciousness. To improve oxygenation, the use of a bi-level positive airway pressure mask was initiated; however, the patient’s respiratory discomfort remained and his pulse oximetry reading only minimally improved (to 92%). Chest radiography revealed a mediastinal shift, which was suspected to have arisen due to impending tension pneumothorax associated with malfunction of the chest drain (Fig. ). Thus, suction pressure of the chest drain was increased from − 7 to − 15 cmH2O, which immediately improved respiratory discomfort. Chest radiography also revealed improvement of the mediastinal shift and adequate dilation of the left lung (Fig. ).
Arterial blood gas analysis revealed pH 7.256, PaO2 250.3 mmHg, and PaCO2 60.3 mmHg during the administration of 5 L/min of oxygen via face mask; thus, the patient was transferred out of the operating room. During the administration of 4 L/min of oxygen via face mask on arrival to the intensive care unit (ICU), arterial blood gas parameters were pH 7.352, PaO2 200.3 mmHg, and PaCO2 44.9 mmHg. Because no recurrence of breathing discomfort was observed, the patient was discharged from the ICU the following day. There were no postoperative complications after the patient exited the operating room. The patient was discharged from the hospital on the 16th postoperative day without additional complications.


A 62-year-old male weighing 75 kg and with a height of 162 cm complained of discomfort in the throat. Preoperative laryngoscopy revealed a large laryngeal polyp attached to the right vocal fold that synchronously swung inward into the trachea and outward to the larynx with inspiration and expiration, respectively (Fig. ). The space between the vocal cords was too narrow due to the presence of the polyp for an endotracheal tube to be inserted. In addition, a surgical procedure could not be performed if the polyp moved into the trachea after endotracheal intubation. Thus, we decided to reduce the volume of the polyp by using a flexible bronchoscope through the LMA and then to perform total removal of the polyp by using a rigid laryngoscope with endotracheal intubation. If the airway did not remain patent by such airway management, we planned to perform temporary tracheostomy for removal of the polyp using a rigid laryngoscope.
The patient was not given premedication, and routine noninvasive monitoring including blood pressure, percutaneous oxygen saturation (SpO2), and end-tidal CO2 was performed in the operating room. SpO2 was 97% on room air, and oxygen was delivered by a facemask at 7 L/min in the operating room. During anesthesia that was induced with incremental administration of propofol (total dose of 170 mg), spontaneous ventilation was manually assisted and was followed by manual positive pressure ventilation without any airway obstruction. However, complete airway obstruction occurred immediately after a size 4 LMA (LMA Supreme™, Teleflex Co., NC, USA) was inserted. Maneuvers including changing the LMA position and increasing and decreasing the volume of cuff air did not improve the difficult airway. A flexible laryngoscope revealed airway obstruction due to the polyp lodged between the vocal cords (Fig. ), and the polyp could not be moved by pulling with forceps through the LMA. Spontaneous respiration returned, but the airway was still not patent even though the maneuvers were repeatedly tried. SpO2 decreased to 88%, and the LMA was removed. Soon after the removal, patency of the airway was dramatically improved and SpO2 returned to 100%. Transient tracheostomy was then carried out under general anesthesia with 2.0% of sevoflurane in 40% oxygen with assisted spontaneous ventilation and injection of 250 μg fentanyl. Resection of the polyp was successfully performed using a rigid laryngoscope. The tracheostomy was closed on postoperative day 5, and the patient was discharged on postoperative day 7.


A 22-month-old female (70 cm, 9.9 kg) with MMAemia was admitted to our hospital to receive living donor LT (LDLT) from her mother. Three days after her normal birth, metabolic acidosis and seizures appeared, and genetic tests revealed a MCM defect, which is one of the most common types of abnormalities in Japanese people. Despite a protein-restricted diet, vitamin B12 and l-carnitine supplements, and treatment with anticonvulsant agents, her symptoms were poorly controlled. She was transferred to our hospital with continuous infusion of glucose, vitamin B12, and l-carnitine. Her preoperative arterial blood gas (ABG) data were within normal ranges (Table ). Preoperative plasma MMA (P-MMA) was 157 nmol/ml (normal range 0.35 ± 0.22 nmol/ml). Hepatic and renal functions were within the normal ranges.
On the day of the operation, after fasting for 6 h, the patient was transferred to the operating room with continuous glucose, vitamin B12, and l-carnitine infusion. General anesthesia was induced and maintained with sevoflurane, fentanyl, remifentanil, and rocuronium. After tracheal intubation, a catheter for continuous hemodiafiltration (CHDF) was inserted to facilitate further intraoperative treatment of metabolic acidosis. Although metabolic acidosis with elevated lactate and NH3 occurred during the anhepatic phase, all improved promptly after graft reperfusion (Table ). LDLT was completed without the use of CHDF or sodium bicarbonate administration for metabolic acidosis. The operation time and anesthetic time were 9 h 45 min and 12 h 40 min, respectively. The total fluid infusion was 1175 ml, including transfusion of 1 unit of red blood cells and 1 unit of fresh frozen plasma. Total urine output was 135 ml, and a small amount of bleeding occurred.
The patient was transferred to the ICU under sedation with midazolam. She was extubated on postoperative day (POD) 3, and P-MMA improved to 18.7 nmol/ml on POD 7. She was discharged on POD 80.


We obtained comprehensive consent beforehand from the patient, and we obtained consent to report the clinical experience and publish the accompanying images.
The patient was a 58-year-old woman suffering from lower abdominal pain and vomiting, which gradually worsened from the start of December 2017. An upper gastrointestinal endoscopy revealed multiple gastric ulcers and scars, and lower gastrointestinal endoscopy revealed inflammation in the large intestine. The patient had undergone surgery in 1997 for cervical carcinoma, followed by postoperative radiotherapy that involved irradiation of her pelvis and stomach. On the basis of the symptoms, endoscopy findings, and medical history, the patient was diagnosed with refractory multiple gastric ulcers, enterocolitis, and paralytic ileus due to late radiation-induced sequelae.
As a result of frequent vomiting, the patient had become unable to ingest orally. She was hospitalized in October 2018 and fasted before being placed under central venous nutrition control. Hyperbaric oxygen therapy was started to treat the intractable multiple gastric ulcers and ileus. Thirty treatment sessions were scheduled over a period of approximately 1–2 months. Pentazocine and tramadol were administered to treat the abdominal pain, but these achieved poor results.
At hospitalization, the patient was 155 cm tall and weighed 43 kg. Although she exhibited abdominal distention, no muscular defense or rebound pain was observed. On percussion, the bowel sound was attenuated. A blood examination revealed anemia, slight liver dysfunction, low protein levels, and hypoalbuminemia. An abdominal X-ray showed several small intestinal niveau and extension of the colon and small intestine by intestinal gas (Fig. a).
The patient experienced increased lower abdominal pain during bowel movements and felt relieved after defecation. Consequently, we hypothesized that her abdominal pain was due to poor peristalsis of the intestinal tract and that blocking the sympathetic nerve of the intestinal tract would help normalize the peristaltic movement and relieve the pain. The pain was strongest in the lower abdomen at the level of the 12th thoracic nerve. An epidural catheter was inserted via the lumbar1–2 intervertebral space, and continuous epidural anesthesia with 0.2% ropivacaine at 4 ml/h was administered for 1 week, resulting in good control of the lower abdominal pain and defecation. This allowed the tramadol, which promotes constipation, to be discontinued. A block of the inferior mesenteric artery plexus with ethanol was performed, resulting in an immediate improvement in the patient’s bowel movements and defecation, and a reduction in lower abdominal pain, now measured as 3 on a numerical rating scale (NRS = 3). An abdominal X-ray was performed after the block procedure, showing the number of intestinal niveau and the amount of gas had decreased, as compared to that before the block (Fig. b). The control of lower abdominal pain was effective, and defecation was noted. Tube feeding was started 4 days after the inferior mesenteric artery plexus block, and oral feeding was started 2 days later.
Twelve days after the block, the patient’s lower abdominal pain increased to NRS 8 and there was recrudescence of the vomiting. An abdominal computed tomography (CT) scan showed dilation of the small intestine, as well as the formation of niveau; however, no bowel obstruction or disruption of blood flow was observed (Fig. a).
An upper gastrointestinal contrast examination with contrast medium (Gastrografin®, Bayer Yakuhin Ltd., Osaka, Japan) showed relatively good peristaltic movement of the large and small intestine but poor gastric peristaltic movement. A large amount of food residue was also observed. An epidural catheter was inserted via the thoracic 6–7 intervertebral space for innervation of the upper gastrointestinal tract, including the stomach and small intestine, and continuous epidural anesthesia with 0.2% ropivacaine at 4 ml/h was started. This alleviated the abdominal pain, and the vomiting disappeared.
Approximately 2 weeks later, continuous epidural anesthesia was stopped, and a splanchnic nerve block with ethanol was performed (Fig. c). This resulted in an improvement in the lower abdominal pain to NRS 1, as well as an increase in food intake. The following day, CT showed a large improvement in the ileus (Fig. b). An upper gastrointestinal contrast examination showed that peristaltic movement of the upper gastrointestinal tract had improved (Fig. ). The subsequent course was good, and the hyperbaric oxygen therapy was completed. The patient was discharged from hospital at the end of January. At the outpatient visit 2 weeks later, the general condition of the patient was good and she could orally intake her normal diet.


A 57-year-old woman was scheduled for spine surgery. Her preoperative examination was unremarkable, and there were no abnormal findings on blood tests, chest X-ray, and 12-lead electrocardiogram.
Induction of anesthesia was performed with 200 μg of fentanyl, 80 mg of propofol, and 40 mg of rocuronium. Oxygen, air, desflurane, and remifentanil were used to maintain anesthesia. While moving the patient to a prone position, we noticed that her left neck was slightly enlarged (Fig. ). Using an ultrasound, we found that the left lobe of her thyroid gland was enlarged heterogeneously, with hypoechoic areas and microcalcifications (Fig. ). The margin of the left lobe was somewhat irregular, and a mass approximately 1 cm in diameter with a calcification and an acoustic shadow was detected (Fig. ).
An otolaryngologist was immediately consulted, and suspected chronic thyroiditis and papillary adenocarcinoma of the thyroid, and recommended a detailed postoperative examination. Thyroid hormone levels were not measured preoperatively.
Because the patient had no symptoms suggestive of hyperthyroidism or hypothyroidism, no abnormalities on preoperative 12-lead electrocardiogram, and an uneventful course of anesthesia up to that point, we determined that the ultrasound findings would not affect her surgery and decided to continue as scheduled. Total operative time was 143 min, and total anesthesia time was 210 min. She was transferred to the ward after extubation, and the perioperative and postoperative course was unremarkable.
Six days after surgery, the patient underwent otolaryngologic examination and thyroid-specific laboratory testing. The anti-thyroglobulin antibody was high at 562 IU/mL (normal values 0–28 IU/mL) and the anti-thyroid peroxidase antibody was also high, at 40 IU/mL (normal values 0–16 IU/mL). Her thyroid hormones (free triiodothyronine, free thyroxine, and thyroid-stimulating hormone) were within the normal range. Aspiration biopsy cytology revealed chronic thyroiditis (Hashimoto’s disease) and papillary thyroid adenocarcinoma. The left lobe of the thyroid was resected for thyroid carcinoma 7 months after the first surgery, and the patient is currently being followed up in the otolaryngology department.


A 6-years-old, nulliparous, intact English Bulldog female was referred to the University of Antioquia Veterinary Teaching Hospital (Small animal clinic). The dog weighed 24.3 kg, had complete immunoprophylaxis and antiparasitic treatments, and was fed with commercial dog food. The owner reported no previous hormonal treatment, and 3 months had elapsed after its last standing estrus, that lasted 21 days. Two weeks before the consultation, the dog started with fetid vaginal discharge.
Rectal temperature, respiratory rate, heart rate, and capillary refill time were 38.3°C, 25 rpm (with increased vesicular murmur), 135 b.p.m., and 1 s, respectively, with a strong pulse, rhythmic, and concordant. The oral mucosa was found slightly pale, wet, and brilliant. The dog exhibited a docile attitude, had a 2.5 Body condition score (in a 1–5 scale), and was down although she was able to feed with commercial concentrate and drink water. An increased size of mammary glands, edematous vulva, and vulvar secretion of fetid sanguine-purulent aspect were observed. At palpation, the patient exhibited abdominal pain.
The dog was referred to with the results of blood cell counts (The blood cell counts are presented in ). A blood sample was taken by radial vein puncture for measurements of plasma proteins, activated partial thromboplastin-time, ALT, and creatinine, using an IDEXX Pro Cyte Dx® automated equipment (DEXX Laboratories, Westbrook, MA, USA). The results of blood cell counts were indicative of normocytic normochromic anemia. Also, a vaginal cytology smear was prepared on microscopic slides and stained with Hematoxylin & Eosin, resulting in predominant degenerated polymorphonuclear neutrophils, and erythrocytes. All exams were performed in the Clinical Pathology Laboratory, School of Veterinary Medicine, University of Antioquia. No hormonal measurements were performed.
At the abdominal ultrasound examination, both ovaries showed increased size with fine-heterogeneous hyperechoic structure, a 3.0 × 2.5 cm cyst not compromising the ovarian silhouette. The uterine wall was tight, exhibiting irregular contour. Also, homogeneous intramural cystic structures and a hypoechoic luminal fluid associated with cystic walls were found (). A presumptive diagnosis of open pyometra was established. Ovariohysterectomy was prescribed, and the dog was prepared for surgery.
For preparation, the dog was subjected to 12 h of solid food and 8 h of liquids fasting. According to the protocol of University of Antioquia Veterinary Teaching Hospital: Pre-anesthesia was performed with Tramadol (Tramadol, MK, 2 mg/kg/SC), Acepromazine (Tranquilan, Zoo laboratories, 0.02 mg/kg/IM), Meloxicam (Meloxic, Provet, 0.2 mg/kg/EV), Dipyrone (Colivet, Provet 28 mg/kg/EV). Cefalotine (Cefalotine, Vitalis, 20 mg/kg/IV) was administered before initiating the surgery. Anesthesia induction was achieved with Propofol (Propofol 1% MCT/LCT, Fresenius Kabi, 2.6 mg/kg/IV). The deep anesthetic level was maintained with 2 CAM isoflurane. Also, a lumbosacral epidural blockade was done with epinephrine-free Lidocaine (Lidocaine, Virbac Laboratories, 1 mg/kg). The surgical plans were according to the conventional approach through line alba. All the surgical plans were performed with no complications.
The uterus presented a slightly symmetrical distention, occupied with purulent material. The ovaries were found polycystic, measuring 3.0 × 2.5 cm, with normal color and aspect (). In a sagittal cutting of the right and left ovaries, hair, and bone tissue (), and polycystic structures were found, respectively. Samples taken from the uterus and both ovaries were fixed in 10% formaldehyde and were sent to the Laboratory of Animal Pathology, the University of Antioquia, and processed for histopathological evaluation with hematoxylin-eosin staining. Diagnosis was performed by an experienced pathologist with more than 20 years in microscopic histopathologic diagnoses.
Post-operative treatment included: Ampicillin, Metronidazole, Ranitidine, Tramadol, and Meloxicam at the recommended doses and treatment schedule. Also, 0.5% of topical chlorhexidine was prescribed for the healing of the surgical incision. The sutures were removed on the 20th post-operative day. The dog recovered with no complications up to the 20th post-operative day.
The histopathological exam evidenced a GCT in the left ovary, GCT in a solid tubular pattern containing Call-Exner bodies, tubular structures typical of a Sertoli pattern, surrounded by abundant stromal tissue (). The neoplastic cells exhibited scare cytoplasm, cytoplasmic projections with rounded or oval nuclei, hyperchromatic or clear, having one or several nucleoli. Similarly, two mitotic figures per 400X field were observed.
In the right ovary, a well-differentiated teratoma was found (, ) that included fragments of perichondrium-containing hyaline cartilage (), trabecular and compact bone (), smooth muscle, sweat glands, hair follicles, stratified cylindrical, and simple plane epithelium. Abundant cavities covered by a stratified keratinized flat epithelium, containing abundant keratin, and supported by a dense connective tissue and adipose tissue were found (). Finally, a dentin-pulp complex containing dentine, pre-dentine, odontoblasts, and pulp was found (). Accordingly, the definite diagnosis was teratoma of the right ovary, GCT of the left ovary, and open-cervix pyometra.


In January 2018, a 65-year-old Japanese man visited a hospital with the chief complaint of abdominal pain. CT showed edema and thickening of the intestinal wall from the descending colon to the rectum (Fig. ). The blood examination results included a white blood cell (WBC) count at 6500/μl and the C-reactive protein (CRP) level at 13 mg/dl. The patient was admitted to that hospital based on the suspicion of enteritis. The result of a fecal culture was negative. Despite fasting and antibiotic treatment, the patient's condition did not improve. The differential diagnoses were ulcerative colitis, amyloidosis, vasculitis, malignant lymphoma, and venous thrombus, but no definitive diagnosis was obtained. On the 48th hospital day, dilatation of ascending colon to transverse colon was observed (Fig. ). A long tube was inserted through the nostril to treat the intestinal obstruction. Strong narrowing of the descending colon to rectum was revealed by an enema X-ray examination (Fig. ).
On the 57th day of hospitalization, the patient was transferred to our hospital for the treatment of colonic stenosis and bowel obstruction. On the same day, an emergency transverse colostomy was performed. We tried to resect bowel, however, the sigmoid colon and mesentery were too rigid and edematous to resect (Fig. ). Prednisolone was started with the diagnosis of mesenteric panniculitis. Hemorrhage occurred 2 weeks after the transverse colostomy surgery. Colonoscopy showed circumferential ulceration, and achieving hemostasis by colonoscopy was considered too difficult (Fig. ). With the intervention of radiology, coiling for the arteriovenous fistula was performed, and hemostasis was obtained (Fig. ).
The patient was discharged from our hospital at 51 days after the transverse colostomy surgery. Six months later, colonoscopy showed neither ulceration nor stenosis in the rectum, indicating that the rectum could be preserved in the next surgery (Fig. a). However, the severe stenosis in the descending and sigmoid colon remained unchanged (Fig. b).
Ten months after the creation of the transverse colostomy, we performed a subtotal colectomy, ileorectal anastomosis, and ileostomy creation (Fig. ). The sigmoid colon and mesentery were not so rigid compared to the findings in the first surgery, and we were able to resect intestine and mesentery (Fig. ). Because the length of the remnant rectum was only 7 cm, it was difficult to anastomose the right colon to the remnant rectum. The histopathology evaluation revealed phlebitis and venulitis, fibrinoid necrosis, and normal arteries (Fig. ). These findings were diagnostic of MIVOD with myointimal hyperplasia of mesenteric veins. The patient’s postoperative course was uncomplicated. The ileostomy is scheduled to be closed 8 months after the second surgery.


This case was a 3-year-and-11-month-old male child, with no obvious abnormality at birth. However, the milk coffee spot was noted at the right face (Fig. a) at 2 month old, which was not treated. At the age of 1 year, the right frontal bulge was observed (Fig. a), which was gradually increased. After admission to the hospital, the head CT scan showed that, the local diploic space on the right side of the frontal bone was thickened, showing a glass-like density. Based on these detection results, the child was diagnosed as abnormal skull proliferation, and the skull replacement surgery after adulthood was recommended. At the age of 2 years, the length of lower extremities was found to be unequal. The X-ray showed that the right lower extremity was longer than the left lower extremity (Fig. b), and the correction with appropriate insole was recommended then. During 2016–2019, the head CT examination showed that the thickening range of the local diploic space on the right side of the frontal bone was enlarged, and the X-ray showed that the unequal length of the lower extremities increased from 2.9 cm to 3.7 cm. On January 4, 2019, in another hospital, the child received the osteophyte blocking at the distal right femur and proximal right tibia. Thereafter, the child was admitted to our hospital for the suspected McCune-Albright syndrome (MAS). Physical examination findings were as follows: height, 95.0 cm; and weight, 14.1 kg. Moreover, the right frontal bone bulging, milk coffee spot on the right face, local bulging at the midline of the right rib, and flaky nodules on the right hand and right thigh were observed (Fig. c). Furthermore, the right lower extremity was about 3.5 cm longer than the left lower extremity.
According to the auxiliary examinations, normal findings were obtained from the blood and urine routine tests, the liver and kidney function assessments, and the blood electrolyte and bone metabolism detections. The growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were within the normal range. The sex hormone levels were as follows: estradiol (E2), < 5.00 pg/ml; luteinizing hormone (LH), 0.16 mIU/ml; follicle stimulating hormone (FSH), 0.58 mIU/ml; prolactin (PRL), 11.33 ng/ml; testosterone (Testo), < 0.03 ng/ml; 8 am cortisol, 472.00 nmol/L (133–537 nmol/L); and 8 am adrenocorticotropic hormone (ACTH), 5.15 pmol/L (1.6–13.9 pmol/L). The case was with normal thyroid function, negative for thyrotrophin receptor antibody (TRAb), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). The head CT detection showed local diploic space thickening on the right side of the frontal bone, with frosted glass-like density shadow. Superior orbital fissure and inferior orbital fissure were observed, while the optic nerve canal was not widened. Moreover, the accessory structures such as optic nerve and extraocular muscle were normal. Based on these findings, the bone fiber abnormal proliferation syndrome and osteofibroma had been considered (Fig. d). The X-ray showed that, the lower extremities were unequal in length, and the right lower extremity was obviously longer than the left one. There were no obvious abnormalities in the morphology, structure and density of the bilateral femur and tibia. Moreover, no abnormalities were found in the surrounding soft tissues. Ultrasound detection indicated that, the right rectus abdominis (8 mm in thickness) was significantly thicker than the left side (about 5 mm). For the analysis of the bone age, the head and hook bones were enlarged, and the fifth metacarpal ossification center was visible. The dermatoscopy indicated mild papillary hyperplasia. The skin CT detection showed hyperplasia at the lesion, with thickened epidermis, and papillary hyperplasia. Biopsy was performed based on the samples of the milk coffee spots, and the thickened nodular skin from the hands and feet, which were subjected to the DNA extraction and detection of disease-causing genes. The results showed that, there was a heterozygous point mutation 49G > A (p.Glu17Lys) in the exon region of the AKT1 gene (Fig. e). In silico algorithms including SIFT (/), PolyPhen-2 (), and Mutation Taster () were performed to predict this variation, and the predictive values were 0.01, 1.00 and 0.999 respectively, suggesting the pathogenicity of this mutation. Genetic testing results confirmed the diagnosis of PS.


Ms A is a 64-year-old, married, domiciled, formerly employed woman who experienced insidious onset of worsening thought disorder, tangential thinking, paranoia, and verbal aggression toward her family starting 12 years prior to the current admission. On admission, thought content was consistent with persecutory paranoid delusions, namely that her family intended to harm her.
Psychiatric history included new-onset depressive symptoms 17 years prior to the current admission and, initially, was treated on an outpatient basis with bupropion. Due to prominent neurovegetative symptoms (eg, sadness, anhedonia, lethargy), she was subsequently treated off label with amphetamine/dextroamphetamine. Around approximately the same time period, when the patient was in her mid- to late 40s, she also developed new-onset alcoholism.
Medical history was significant for traumatic brain injury six years prior to the current admission, as she sustained two subdural hematomas secondary to a major fall; however, there was no evidence of lasting neurologic injury per chart review. Five years prior to the current admission, the patient was evaluated for CADASIL following discovery of white matter changes on brain MRI consistent with the pattern commonly observed in CADASIL. Genetic analysis was subsequently performed on the Notch3 gene. Direct DNA sequencing revealed a nucleotide substitution of A (TAT) to G (TGT) resulting in a change from tyrosine to cysteine at codon 1021 in exon 19 and thus confirmed CADASIL diagnosis. Chart review of the diagnostic neurological workup indicated that the patient was guarded regarding her medical diagnosis and did not want her family members to accompany her to her appointments. When asked during the current admission, the patient exhibited limited insight into her medical illness, reporting that she was not definitively diagnosed with CADASIL.
Brain MRI with and without contrast 10 months prior to admission revealed diffuse areas of patchy and confluent T2 hyperintense signal in the supratentorial and infratentorial white matter, including the bilateral anterior temporal lobes and external capsules. Chronic hemorrhagic infarctions were noted within the posterior right frontal lobe and inferior left parietal lobe (Figure ). Multifocal areas of chronic microhemorrhage were observed within the brainstem and bilateral thalami. Subsequent brain MRI without contrast 5 months later further revealed new foci of susceptibility hypointensity indicative of chronic microhemorrhages in the lateral right cerebellar hemisphere and cerebellar vermis.
Clinical correlates around the same time of the brain MRI included worsening thought disorganization with paranoid ideation; the patient's primary care physician (PCP) also noted the onset of perseverative and persecutory thoughts regarding her family. The patient's PCP suggested the possibility of mania with psychosis possibly related to CADASIL. Until her current hospitalization, the patient herself maintained that she was unaffected by the CADASIL.
One month prior to the current admission, the patient experienced an acute exacerbation of paranoid ideation involving members of her extended family plotting to do her harm. She became verbally aggressive, exhibiting pressured speech and thought disorganization. She was initially admitted to a local hospital and treated with bupropion. Adderall was discontinued, and the patient was released to the care of her family; she discontinued bupropion when discharged. Four days later, she experienced a severe manic episode with mood-congruent psychotic symptoms, including prominent agitation, flight of ideas, and emotional lability.
During the current inpatient psychiatric hospitalization, physical examination, EKG, laboratory examination results (comprehensive metabolic panel, urinalysis, and lipid profile) were normal. Her CBC was remarkable for mild anemia, and follow-up testing was remarkable for anisocytosis, consistent with a prior diagnosis of autoimmune hemolytic anemia.
Ms A also underwent extensive neuropsychological testing. Results were not consistent with dementia, but rather were notable for deficits mainly in executive functions (eg, cognitive inhibition, cognitive flexibility, perseverative tendencies), as well as working memory, processing speed, and word retrieval. Learning and memory functions were well within normative limits. There was no significant decline in cognitive functions when compared to a prior evaluation 10 months earlier.
Symptoms of mania and psychosis responded to a treatment regimen of quetiapine (titrated up to 125 mg per day) and lithium carbonate 900 mg a day (level 0.84 mEq/L). Paranoid ideation decreased, and thought processes became increasingly linear and goal-directed, though she remained perseverative. Furthermore, insight improved and the patient began to understand her psychiatric illness as a manifestation of CADASIL. Psychoeducation with the patient and her family helped to improve their communication. The patient was ultimately discharged to her family and agreed to work with an outpatient psychiatrist for follow-up care.


A 37-year-old man presented with progressive limitation of activities as a result of bilateral motor weakness of the lower extremities for several weeks. He had no history of strenuous sporting activity or low back pain. Neurological examination revealed motor weakness in iliopsoas and quadriceps muscles, and muscle power was rated at a manual muscle testing level of 2. He had no urinary dysfunction or lower extremity sensory dysfunction.
A plain radiograph showed local kyphosis at L1-L2 as a result of severe degenerative change at the L1-2 disc level and wedging of the vertebral body at L1 (Figures and ). Magnetic resonance imaging (MRI) revealed severe degenerative disc change and severe canal stenosis at L1-2 (Figures and ). Computed tomography (CT) revealed SBO and spondylolysis at L1 and no other malformations (Figures –).
He was diagnosed with cauda equina syndrome at the L1-2 level related to SBO and spondylolysis at L1. Posterior lumbar interbody fusion at L1-2 was performed (). After surgery, his symptoms improved promptly, and he was able to walk with a cane on his discharge.


A 33-year-old male with a past medical history of hypertension, depression, and alcohol abuse presented with complaints of nausea, vomiting, and abdominal pain. He had a history of tobacco and alcohol abuse. He was drinking six cans of beer and a half-pint of vodka daily for the last six months. He did not have any significant medical issues in his family and family history was negative for any cancers. His temperature was 97.8° F, blood pressure was 136/88 mmHg, pulse was 87/minute, and respiratory rate was 14/minute. Physical examination was positive for moderate tenderness in the epigastrium on deep palpation.
Initial workup revealed laboratory values as mentioned in Table .
CT scan of the abdomen was done, which showed peripancreatic fat stranding around the pancreatic head consistent with mild acute uncomplicated pancreatitis. CT scan of the abdomen also revealed multiple clustered nodes in the central mesentery with fatty haziness which is also known as "misty mesentery" and ground-glass appearance of the mesenteric fat representing mesenteric panniculitis (Figure ).
The pancreas was obscured by bowel gas and was not visualized well (Figure ).
The patient was started initially on conservative management for suspected acute pancreatitis. He was kept nothing-by-mouth and was started on intravenous fluids and intravenous pain medications. On the second day after admission, all laboratory abnormalities were improving. AST and ALT levels had normalized. The lipase level was down to 926 U/L. The patient was still having abdominal pain, but it was now around the umbilicus and not in the epigastrium. Nausea and vomiting remained persistent. On the third day, his lipase level came down to 267 U/L and had normalized. Complete blood count, metabolic panel, and hepatic function remained unremarkable. Lactic acid was checked and returned normal.
An abdominal X-ray was done and came back negative for small bowel obstruction and showed a small amount of stool in the ascending colon (Figure ).
Due to persistent abdominal pain, nausea, and vomiting, a gastroenterology consultation was obtained. His symptoms were believed to be secondary to mesenteric panniculitis seen on the CT scan and not secondary to acute pancreatitis. The patient was started on 40 mg of oral prednisone daily. After starting prednisone, his symptoms completely resolved within 36 hours. He started tolerating diet and was discharged home with a gastroenterology follow-up. He was prescribed prednisone oral taper over a period of two weeks.
The patient was closely followed after discharge and had a repeat CT scan of the abdomen done at six months, which showed the complete resolution of the ground-glass appearance of the fat but the adenopathy persisted (Figure ).
The patient was completely asymptomatic by this time but had unfortunately continued to drink alcohol although he had cut down his frequency of drinking to three to four days in a week but had not cut down on the amount of alcohol. On a repeat CT scan of the abdomen, the patient was again found to have findings of mesenteric panniculitis with persistent adenopathy. He was eventually released from gastroenterology care.


A 14-year-old girl was admitted to our hospital with sudden abdominal pain. Diffuse tenderness with abdominal guarding was observed on admission. The body height (BH) and body weight (BW) were 157 centimeters (cm) and 49.0 kilograms (kg) on admission, respectively. A blood test revealed slightly elevated counts of white blood cells (WBC: 12.0 ×109/L) and C reactive protein (CRP: 0.56 mg/dL, reference range: ≤ 0.3 mg/dL), and the FOBT was negative (). We performed an abdominal sonography, which revealed peritoneal fluid accumulation and the HH sign in the duodenal bulb (). CT revealed edematous changes and wall defects in the duodenal bulb, which indicated a perforated DU. An antiulcer drug and antibiotic agent were administered, with concomitant fasting. Eight days after admission, we performed an endoscopy and identified ulceration in the duodenal bulb, on the basis of which, the patient was diagnosed with DU.


A 13-year-old boy was presented to our hospital with upper abdominal pain lasting for 3 months. The BH and BW were 151.5 cm and 40.4 kg on admission, respectively. A blood test revealed anemia (hemoglobin 8.6 g/dL) with a slight elevation of CRP level (1.25 mg/dL), and the FOBT was negative (). An abdominal US scan revealed the presence of the HH sign () and the absence of free air and ascites that usually indicate a perforated DU. CT revealed wall hyperplasia in the duodenal bulb, consistent with a DU. An endoscopy revealed a microhemorrhage in the anteriorly located DU. Five days after the initiation of the antiulcer drug, we performed a US and found that the HH sign had diminished (data not shown). He experienced two recurrent episodes, and in both, the HH sign, which was observed in the symptomatic period, diminished in the post-treatment period ().


A 12-year-old girl suffering from upper abdominal pain for several months was presented to our hospital. The BH and BW were 150 cm and 39.4 kg on admission, respectively. Her blood tests were normal (WBC 7.4 ×109/L, hemoglobin 13.0 g/dL, CRP 0.17 mg/dL), and the FOBT was negative (). A US scan revealed the HH sign in the right epigastric region, consistent with her symptomatic site (). An endoscopy revealed DU on the anterior wall of the duodenal bulb. After the first episode, she experienced four recurrent episodes. In each, a pretreatment US scan revealed the HH sign, which disappeared in response to the treatment ().


An 11-year-old boy was hospitalized for epigastric pain. The BH and BW were 133 cm and 34.6 kg on admission, respectively. The thickness of the duodenal bulb wall was 5.4 mm (which slightly exceeded the 5 mm limit) and the hyperechoic line was clearly visible, consistent with the HH sign (). Blood tests were normal (WBC 6.4 ×109/L, hemoglobin 13.8 g/dL, CRP <0.02 mg/dL), and the FOBT was negative (). We observed ulceration with highly mucosal edema, and the duodenal lumen was obstructed by the edematous change. The HH sign diminished after the initiation of the antiulcer drug (data not shown).


A 13-year-old boy was presented to our hospital with complaints of dizziness and upper abdominal pain. On admission, the BH and BW were 153 cm and 38.3 kg, respectively. Blood testing revealed anemia (hemoglobin 9.2 g/dL), and the FOBT was positive (). Since melena was observed on hospitalization, we performed a US, which revealed a mass-like region surrounded by a blood vessel () that appeared to be connected to the duodenum. The HH sign was not observed. No remarkable findings were found in the CT image. In the endoscopy, the ulcer was identified at a site between the anterior and posterior bulb. A US performed 20 days after treatment revealed that the mass-like lesion disappeared.


A 36-year old male presented to the ED with generalized weakness, confusion, and fatigue starting one week prior. The symptoms were associated with some episodes of nausea, vomiting, and loose semisolid stools. The patient reported shortness of breath that had progressed to rest over the past weeks. He denied any fever but reported some chills. He denied any chest pain, palpitations, lower extremity swelling, abdominal pain, or other complaints. The patient has routine weekly labs which showed hyponatremia (sodium = 122 mmol/dL, baseline 130 mmol/dL) so he was sent for evaluation to the emergency room by his cardiologist. The patient has a past medical history of nonischemic cardiomyopathy diagnosed at age 16. A transthoracic echocardiogram done about 9 months prior showed a left ventricular ejection fraction of less than 20% and severe concentric left ventricular hypertrophy. The patient had an automatic implantable cardioverter-defibrillator (AICD) placement 8 years prior for primary prevention of sudden cardiac death. The patient had been on a chronic milrinone infusion delivered through a peripherally inserted central catheter (PICC) line for the past 3 years. This was initiated as a bridge to transplant. However, during transplant evaluation, he was noted to have secondary pulmonary hypertension and would need a combined heart and lung transplant, and no transplant center in the state would accept his insurance for a combined transplant. Besides cardiomyopathy, he also has a history of chronic atrial fibrillation, congenital hydrocephalus with ventriculoperitoneal shunt (since the age of 2), and spinal stenosis. Of note, the patient was taking apixaban, bumetanide, magnesium oxide, allopurinol, digoxin, metolazone, eplerenone, and carvedilol.
On exam, the patient had a red, swollen left upper extremity at the site of his PICC and white nail beds on the left hand and cool extremities, but no lower extremity edema. The patient was afebrile, had an elevated heart rate of 109 beats per minute (bpm), an elevated respiratory rate of 26 breaths per minute, and SpO2 was 96% on 2 L nasal cannula. All other vitals were within normal limits.
Labs on admission are as follows: WBC: 10.9 × 103/mcL; sodium: 123 mmol/L; potassium: 4.7 mmol/L; chloride: 90 mmol/L; bicarbonate: 22; BUN: 27 mg/dL; creatinine: 0.9 mg/dL; glucose: 102 mg/dL; INR: 1.56; total bilirubin: 4.12 mg/dL; alkaline phosphatase: 166 units/L; AST: 44 units/L; and ALT: 27 units/L. The patient was initially diagnosed with viral gastroenteritis and his symptoms of nausea, vomiting, and diarrhea resolved within 2 days. As the team was preparing to discharge the patient, 2 sets of blood cultures taken at admission came back positive for Candida dubliniensis. The patient's WBC count increased from 11.0 to 15.2 with continued stability in his vital signs other than an increase in his heart rate to 120 s bpm. A chest X-ray on admission showed no acute abnormalities, stable cardiomegaly, and an AICD in place. An electrocardiogram (EKG) showed atrial flutter. CT scan of the head showed a left VP shunt with mild ventriculomegaly of the lateral and third ventricles unchanged since 2017. No evidence of intracranial hemorrhage was found. A lumbar puncture obtained clear CSF that was sent to microbiology. The CSF cultures had no growth. The patient was started on empiric micafungin 100 mg IV daily and vancomycin.
A blood culture of the PICC line and a culture of the catheter tip was positive for Candida dubliniensis as determined by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Minimum inhibitory concentrations (MICs) for antifungals are listed in .
The PICC line was removed and a right-sided internal jugular vein (IJV) central line was placed. Vancomycin was discontinued after one day once the culture grew yeast. A negative blood culture of C. dubliniensis was drawn 4 weeks after the first positive culture. Micafungin was continued for a total of 6 weeks after the initial positive culture.
Transesophageal echocardiogram (TEE) () showed a new finding of echogenicity of one of the three leads consistent with lead vegetation. Consistent with a TEE done 8 months ago, there was minimal thickening of the aortic valve, mild thickening of the mitral valve with moderate to severe mitral regurgitation, and moderate to severe tricuspid regurgitation. One of the leads had a mobile echodensity measuring 0.4 × 1.3 cm, consistent with lead vegetation. No valvular vegetations were identified on TEE. The findings of the TEE were consistent with AICD fungal septicemia. An AICD lead extraction was done one week after admission at an outside facility with a temporary transcutaneous pacer placed, after which the patient returned to our inpatient facility for placement of a replacement AICD two weeks later. Blood cultures done at the outside facility were negative. Blood cultures from the right and left arms done at our facility after AICD implantation returned Staphylococcus aureus on 2/2 sets sensitive to cefazolin, oxacillin, tetracycline, and trimethoprim/sulfamethoxazole. The right-side IJV central line was removed and a left-side IJV central line was placed with negative blood cultures after placement. The micafungin was recommended to be continued for four weeks after new AICD placement and cefazolin was started for two weeks due to the right-sided IJV central line MSSA infection. A vascular surgeon was consulted for optimal line access with the least infectious risk. The vascular surgeon recommended a PICC line. A replacement PICC line was placed three weeks later and the patient was discharged the next day with a PICC line for milrinone, cefazolin, and micafungin infusion.


A 54-year-old gentleman, known case of hypertension diagnosed during an acute ischemic stroke event without residual weakness, was discharged on anti-hypertensive medications that included perindopril-indapamide (10 mg/2.5 mg). After 10 days of commencement of his medication, he started to have gait imbalance that was aggravated and eventually resulted in a fall but without any loss of consciousness. He sought emergent medical attention. On presentation, he was conscious, alert, oriented and gave a complete history of his presentation. There was no history of vomiting and diarrhea. On examination, he had moist mucous membranes and normal skin turgor without postural hypotension and no signs of overload like raised jugular venous pressure (JVP), peripheral edema or shortness of breath. Later, during his stay in the emergency department, his gait disturbance was increased, associated with dysarthria and he had one episode of generalized tonic-clonic seizures. Due to the history of a recent stroke, an urgent CT scan of the brain was done and found to be unremarkable for any acute brain insult as shown in Figure below.
On blood investigations, his serum sodium level was found to be severely low with a value of 100 mmol/l (NR: 136-145 mmol/L) and a repeat value of 101 mmol/L. Potassium level was also low while the bicarbonate level was high with a value of 2.5 mmol/l (NR: 3.5 mmol/L-5.1 mmol/L) and 34.5 mmol/l (NR: 22-29 mmol/L) respectively. Serum osmolality was 244 mmol/kg (NR: 275-295 mmol/kg) correlating with the hypo-osmolal state, and urine osmolality was in the normal range 342 mosm/kg (NR: 150-1150 mosm/kg). Keeping in mind the most common side effect of thiazide diuretics to cause mild to profound hyponatremia, perindopril-indapamide was withheld.
The patient was started on 3% hypertonic saline infusion for sodium correction. Potassium replacement was given as well. His sodium level along with the rest of the electrolytes also improved and no further drop was observed (Table ). The patient improved symptomatically over the course of hospital stay without any complications.


The patient was a 64-year-old man who felt numbness of the tongue 30 minutes after eating fugu prepared by an unqualified person. He then felt hotness of the left side of his face and head, followed by left hemi-paresthesia of the left upper and lower extremities. He visited a local medical clinic and was transferred to our hospital with suspected fugu intoxication. He had obesity and dyslipidemia. On arrival, 150 minutes after eating the fugu, his consciousness was clear, his blood pressure was 146/89 mmHg, his heart rate was 65 beats per minute and his percutaneous oxygen saturation was 97% under room air. He complained of left hemi-paresthesia but there were no physical findings. Both electrocardiography and chest roentgenography revealed no specific findings. A venous blood gas analysis revealed the following: pH, 7.40; PCO2, 41.8 mmHg; HCO3-, 26.7 mmol/L; base excess, 1.0 mmol/L; and lactate, 0.9 mmol/L under room air. The main result of a blood analysis was total cholesterol, 261 mg/dL. We did not measure serum TTX level because it could not be measured in our hospital or at any available commercial based biochemical laboratory company. Initially, he refused to undergo a cerebral radiological study, including magnetic resonance imaging (MRI). He underwent gastric irrigation with charcoal and laxative administration. At approximately four hours after eating fugu, his hemi-paresthesia spontaneously subsided and he felt an abnormal sensation on the left side of his head. He was admitted to our hospital for observation. The post-admission course was uneventful. He agreed to undergo brain MRI and MR angiography, which revealed no specific findings (Figure ). He was discharged on the second day of hospitalization without complaint.


A 7-year-old boy with a past history of T-cell ALL presented ~ 3 months after 5/6 matched allogeneic hematopoietic stem cell transplant for evaluation of increasing serum creatinine levels. His initial presentation had included a high white count of 133,000/µL with 71% blasts and mild anemia. Peripheral blood flow cytometry showed T-cell ALL, which was confirmed by bone marrow biopsy. There was no initial testicular or CNS involvement. Induction chemotherapy included treatment with cytarabine, vincristine, daunorubicin, prednisone, and methotrexate. Risk assessment, performed after completion of induction therapy placed this patient in the high-risk group, as he had minimal residual disease (MRD). He proceeded directly to consolidation therapy without waiting for count recovery and he received cranial radiotherapy during the delayed intensification phase of treatment. Maintenance chemotherapy was begun ~ 7 months after initial presentation and was complicated by several episodes of fever and neutropenia, acute appendicitis requiring laparoscopic appendectomy and a bone marrow relapse of T-cell ALL.
As per protocol, the patient began intensive reinduction chemotherapy for children with a bone marrow relapse after standard induction therapy. He received the following agents: vincristine, doxorubicin, prednisone, ifosfamide, etoposide, clofarabine, cytoxan, and nelarabine. After ~ 1 month of therapy, preparations commenced for stem cell transplant. Total body irradiation was a component of his pre-transplant conditioning as was high-dose cytarabine and clofarabine. 14 months after initial presentation the patient received a 5/6 matched stem cell transplant. His post-transplant course was complicated by a central nervous system event that occurred ~ 2 weeks after transplant which resembled HUS/TTP and resulted in deafness and paraplegia.He received GVHD prophylaxis with mycophenolate mofetil (MMF) and tacrolimus.
Immediately following stem cell transplant the serum creatinine was normal at 0.7 mg/dL and rose gradually over a period of 6 – 8 weeks peaking at 2.5 mg/dL. Concurrently, the patient began to gain weight and develop significant total body edema. His blood pressure remained normal. He did not complain of any diarrhea or skin lesions though skin GVHD was confirmed by biopsy and endoscopy showed grade 1 GVHD of the stomach ~ 60 days after stem cell transplant; these resolved after treatment with several weeks of solumedrol. At the time of the initial nephrology evaluation, post-transplant medications included only physiologic hydrocortisone and mycafungin, a nephrotoxin. He was also maintained on keppra for seizure prophylaxis and nadolol for history of a prolonged QTc thought secondary to cardiac toxicity from preparative regimens.
A renal ultrasound showed normal size kidneys with slightly increased echogenicity and mild pelvicalyceal dilatation. Liver function tests and electrolytes were normal apart from a low phosphorous of 2.7 mg/dL. A phosphate-wasting tubulopathy was confirmed by urine and serum studies, which showed a TRP of 53%. Complement levels were normal with C3 of 203 mg/dL and C4 of 42 mg/dL and an ANA screen was negative at < 1 : 40. Serial protein/creatinine ratios were 3.8 – 10.0 suggesting nephrotic range proteinuria, though the serum albumin was consistently > 3.5 mg/dL. A 24-h urine collection showed 4.7 mg/kg creatinine, presumably so low due to muscle wasting and paralysis, and 14.6 mg/kg protein. There was no hematuria. As a result of this patient’s persistent and moderately impaired renal function as well as his proteinuria, a renal biopsy was pursued since there were some entities in the differential diagnosis which would potentially change management. Differential diagnosis at the time included progressing CKD, GVHD, bone marrow transplant-associated HUS/TTP, radiation nephritis, BK nephropathy, CMV nephritis, calcineurin inhibitor toxicity, and tubulointerstitial nephritis.


A 24-year-old man suffered a car accident, arriving at the emergency room (ER) in a comatose state with a Glasgow Coma Scale (GCS) of 4/15, miotic pupils, decerebrate posture when painful stimuli were applied and spontaneous hyperventilation. A CT scan showed changes compatible with diffuse axonal injury, confirmed further by MRI ().
The patient was transferred to the intensive care unit (ICU). An intraparenchymal fiberoptic device was placed in the left parietal lobe for intracranial pressure (ICP) monitoring. He spent 45 days in the ICU, during which he developed several medical complications, including nosocomial pneumonia, septic shock, and ventilator dependency.
He was transferred to a rehabilitation facility in a patent vegetative state with nocturnal mechanical ventilation requirements. He has never experienced epileptic seizures, had no symptoms of infections, and his laboratory values were normal.
We decided to administer Cerebrolysin 30 ml/day for ten days. The Argentinian regulatory office had recently approved the drug, and we had no prior experience of its use in traumatic brain injury (TBI), so we decided to adopt the dosage recommended in the literature [-].
Our therapeutic approach was based on the pathophysiology of traumatic brain injury and, in particular, of the diffuse axonal injury. Diffuse axonal injury (DAI) had been traditionally considered an acceleration-deceleration injury resulting in widespread neuronal damage: small petechial hemorrhages in the corpus callosum and dorsolateral pons quadrants and axonal disruption (clusters and Wallerian degeneration) associated with brain edema, which could be seen on CT and MRI scans [].
Nevertheless, recent evidence has shown that DAI is present with any type of brain injury, focal or otherwise, especially in those patients dying immediately after TBI as well as those who remained in a persistent vegetative state or severely disabled [,].
The cytoskeletal damage of DAI was initially assumed to occur rapidly, due to the transmission of shear forces throughout the brain. Modern research shows that tearing of the axons occurs rarely; a progressive disruption of the axonal membrane is the norm, not only in severe but also in moderate and mild TBI cases. Mitochondrial disruption could play a central role in this process []. Very recent evidence has pointed out that axonal damage and degeneration are not always associated with neuronal death, as it was assumed up to now. It may be possible for neurons to survive such insults and even attempt to regenerate, providing a further chance of recovery []. This means neuroplasticity and neurotrophic action, which was indicative of the Cerebrolysin administration [].
A transcranial Doppler (TCD) was performed in order to establish cerebral blood flow velocities in the Circle of Willis and to calculate cerebral perfusion pressure (CPP) using Belfort's formula () [].
By the 7th day of Cerebrolysin administration, the patient began to respond to simple orders and could be weaned from nocturnal mechanical ventilation.
A new TCD was performed, which showed a significant improvement in blood flow velocities and CPP as compared to baseline ().
On the 45th Cerebrolysin administration, the patient was able to perform a MiniMental State Examination, scoring 18 points out of 30 He also presented pyramidal signs of the four extremities with a vicious position in flexion of both upper arms.
We decided to perform another Cerebrolysin treatment cycle with the 10 ml/day dosage for 21 days, the dose recommended for cognitive disorders, three months after the first administration []. We also decided to administer botulinum toxin in the upper extremities and the vocal cords. After the second Cerebrolysin treatment cycle, the patient improved the MMSE score to 25/30, and a full cognitive battery was performed, including Benton's test and verbal fluency (). He also improved his motor abilities, gained weight and muscular mass. Occupational therapy was reinforced.
A third Cerebrolysin treatment cycle was scheduled after another three months using the same dosage. After that, the patient improved his cognitive abilities, resulting in an MMSE of 28/30 (faults in recalling) and improvement in Benton's test and verbal fluency ().
A fourth Cerebrolysin cycle was performed with improvement in mood and attention, meanwhile memory and verbal fluency did not change.


A 76-year-old Chinese male, former smoker, with no other significant past medical history or other high-risk behavior and not on medications presented to the hospital for worsening right lower extremity swelling, erythema, and pain. The swelling suddenly started 3 days ago, with occasional cough and dyspnea on exertion. He denied trauma or injury to the area, fever, chills, chest pain, nausea, vomiting, abdominal pain, and dysuria. He did mention some unintentional weight loss. Physical exam was pertinent for right leg swelling, decreased breath sounds on right side, and abdominal distension.
Laboratory analysis revealed mild leukocytosis with normal differentials, mild anemia (Hb 10.6 g/dl), and a normal platelet count of 386 K/μl. His creatinine was elevated. HIV and hepatitis testing were negative. Epstein–Barr virus (EBV) serology signified a past infection. HHV-8 serology testing was not available. Bilateral Doppler ultrasound results were negative for deep vein thrombosis, and a ventilation-perfusion (VQ) scan revealed a low probability for pulmonary embolism.
Renal ultrasound demonstrated moderate hydronephrosis on the right and mild hydronephrosis on the left, with no evidence of calculi in the kidney, ureters, and bladder. Computed tomography (CT) and a following positron emission tomography (PET) scan revealed a mass like encasement of the proximal right ureter and bladder (Figures and ), along with retroperitoneal lymphadenopathy on the right side. Moderate to large pleural effusion was noted on the chest CT scan. Subcutaneous lymphedema was seen on magnetic resonance imaging (MRI) of the right lower extremity. His ejection fraction was normal on echocardiogram. Patient refused a lumbar puncture. He did not have any neurological symptoms.
Urine cytology revealed atypical urothelial cells. Patient underwent cystoscopy and right ureteroscopy, demonstrating bullous edema and erosion at the bilateral trigone areas and in the right mid-distal ureter. Bladder biopsy was taken and a right ureteral stent was placed. The patient also underwent a diagnostic and therapeutic thoracentesis.


The affected individual was a 15-month-old boy who passed away due to aspiration pneumonia. He was born to consanguineous parents, who were first-degree cousins. The child presented at the age of 3 months with lethargy, protracted vomiting, hypotonia, and decreased level of consciousness and was admitted to the pediatric intensive care unit (PICU). Arterial blood gas analysis revealed a pH of 7.02 (normal range: 7.35–7.45), pCO2 of 17.6 (normal range: 35–45) mm Hg and [HCO3] of 5.3 (normal range: 20–28) mmol/L. The acute attack had been managed with hydration and administration of IV bicarbonate in order to correct the acidosis. Other routine laboratory investigations revealed no abnormalities with a hemoglobin of 11.3 (normal range for 3–6-month-old infants: 9.5–14.1) g/dL, total white blood cell count of 6700/mm3 (normal range for 3–6-month-old infant: 6000–17,500/mm3), blood urea nitrogen of 15 (normal range: 5–20) mg/dL, creatinine of 0.5 (normal range: 0.2–0.5) mg/dL, sodium of 135 (normal range: 135–145) mEq/L, potassium of 4.6 (normal range: 3.5–5) mEq/L, and blood sugar of 92 (normal range: 65–99) mg/dL. Liver function enzyme levels were also within normal range. Analysis of the CSF revealed no abnormalities. Evaluation for metabolic disease using tandem mass spectrometry revealed elevated levels of propionylcarnitine (10.3 μmol/L, normal range < 2.5 μmol/L) and increased propionylcarnitine/acylcarnitine ratio (0.53, normal range < 0.13). Methylmalonic acid level was not determined. The patient was subsequently discharged with L-carnitine, vitamin B12 and chronic alkaline therapy.
In subsequent evaluations the patient had an improvement in the overall condition. However, growth parameters were not within normal range. Weight being 6 kg and length being 66 cm were both lower than one percentile for age. The patient also failed to reach developmental milestones. At the age of 9 months, he had head lag and was not able to sit alone, could not transfer objects hand to hand and did not say two-syllable words. Furthermore, he had two other episodes of acute attacks, which had led to hospital admission. At the age of 15 months, he presented with tachypnea, fever, cough, and decreased level of consciousness. Chest x-ray was in favor of aspiration pneumonia. Intravenous antibiotics were administered and alkaline therapy was started. However, the patient showed no clinical response to the treatment.
To determine the causative genetic mutation in the family, an unbiased next generation DNA sequencing which covered the entire coding exons (whole exome sequencing, WES) was carried out. Peripheral blood was obtained from parents and was used to isolate genomic DNA. WES was done utilizing next generation sequencing on an Illumina NextSeq500 (Illumina, USA). The results were subsequently analyzed with BWA aligner [], GATK [] and ANNOVAR []. To identify common probably pathogenic mutations in the couple, carrier screening was performed on annotated data. Filtering was accomplished based on local (sample size: 1183 unrelated individuals) and other available population databases (such as ExAC browser, gnomAD and Kaviar VARiants).
WES was performed with a mean target coverage of 100×. Results revealed a novel heterozygous missense mutation in MUT gene (c.1055A > G, p.Q352R) in both male and female partners. Homozygous mutations in this gene are compatible with MMA and since MMA has an autosomal-recessive pattern of inheritance, this finding suggests that the child had probably had MMA by inheriting both mutated alleles.
To confirm the presence and the pattern of inheritance of the novel identified mutation, peripheral blood samples from the couple and their parents and siblings were taken; DNA was extracted and used for Sanger sequencing. QIAamp DNA Blood Mini kit (Cat No./ID: 51104, Germany) was used for genomic DNA extraction. The following primers were used to amplify exon five of MUT gene as well as its flanking intronic sequences to look for the mutation—Forward: 5′ TCAGCACTACAGGGAAGCTAG 3′ and Reverse: 5′ GACCTAACGTTACTATTTTAGGTTGT 3′.
The amplified DNA was sequenced from both directions using Sanger Sequencing kit (ABI BigDye Terminator Cycle Sequencing Kit, Applied Biosystems®, USA) according to the company protocol. Sanger sequencing confirmed the presence of mutation in heterozygous form in both parents. The parents’ siblings were either heterozygous carriers or homozygous for the wild type allele (Fig. ). This mutation is a variant of uncertain significance and has not previously been reported. However, bioinformatics software programs such as Polyphen, SIFT, LRT, Mutation Taster, FATHMM, Radial SVM, and Mutation Assessor software have predicted that this variant will be damaging. Moreover, comparative amino acids alignment using multiple sequence alignment revealed that this amino acid is highly conserved among different species (Fig. ).
Ovarian stimulation was performed using the antagonist protocol. The couple underwent intra-cytoplasmic sperm insemination. Among four retrieved oocytes, three were fertilized and produced three 8-cells embryos on day three. One blastomere from each cleavage stage embryo was isolated and transferred into a sterile 0.2-mL PCR tube containing 5 μL of PBS and kept at − 80 °C in this condition until testing. DNA amplification across the exon 5 of the MUT gene of each of the blastomeres was done using whole-genome amplification (WGA) reaction.
Whole-genome amplification reaction was done by REPLI-g Single Cell kit (QIAGEN). Briefly, samples were mixed with 3 μL of denaturation buffer and incubated at 65 °C for 10 min, followed by inactivation by adding 3 μL of stop solution. Then, master mix containing REPLI-g sc DNA polymerase was added to the denatured DNAs. Finally, the mixture was incubated at 30 °C for 8 h followed by heat inactivation at 65 °C for 3 min. The products were kept at 4 °C until PCR amplification. DNA amplification of one of the embryos failed. DNA amplification was successful with the other two blastomeres. There was no amplification in the medium blank controls ran simultaneously.
PCR was performed on the products for the amplification of the exon 5 of the MUT gene. Sanger sequencing was then performed on the PCR products to determine the MUT genotype of the embryos using 3130xl Genetic Analyzer (Applied Biosystems). Among the two successfully amplified blastomeres, one was diagnosed as homozygous for the wild-type allele and the other was homozygous for the mutated allele (Fig. ). The unaffected embryo was then transferred. Single embryo transfer (SET) resulted in a successful implantation and clinical pregnancy confirmed by detection of gestational sac and fetal heart at 4–5 weeks after embryo transfer by transvaginal ultrasonography. The embryo was confirmed as unaffected (homozygous wild type) after prenatal diagnosis done by amniocentesis at 15 weeks of gestation.


A 43-year-old male with idiopathic pulmonary fibrosis underwent double-lung transplant (LT) at our institution in July 2014. His immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisone. His early post-LT course was complicated by one episode of humoral rejection (at 17 months post-LT) treated with high dose steroid therapy, one episode of acute cellular rejection (at 19 months post-LT) treated with thymoglobulin at the dosage of 125 mg per day for 6 days, and a persistent acute cellular rejection a month later treated with another course of thymoglobulin at the same dosage. During these treatments, he also received pre-emptive valganciclovir in consideration of minimal Cytomegalovirus (CMV) blood replication. Then, 22 months after-LT, he required admission for fever and bilateral pneumonia. A chest computed tomography (CT) showed persistent ground glass opacities, with tree-in-bud appearance, of the right middle and lower lobes (a). Laboratory results showed an elevated C-reactive protein of 78.8 mg/L (normal range 0–5 mg/L) and a normal white blood cells count. Blood cultures turned negative. The forced expiratory volume in one second (FEV1) was 1.73 L and the forced vital capacity (FEV1) of 2.16 L. Empirical antibiotic and antifungal therapy with meropenem, linezolid, and liposomal amphotericin B was started with mild clinical improvement. A broncho alveolar lavage (BAL) showed no growth on bacterial and fungal cultures, and galactomannan on BAL was negative. Lung transbronchial biopsy (TBB) showed no signs of acute rejection but was notable for acute bronchitis with aggregates of round and oval elements suggestive for fungi at the PAS staining. PCR 18S-sequencing was performed on the fresh tissue and identified Malassezia restricta. The patient was then started on voriconazole, with a significant progressive improvement in respiratory function, with an increase in both FEV 1 (2 L) and FVC (2.55 L). During the antifungal treatment, the tacrolimus dosage was adjusted according to the serum concentration and aimed at trough levels of 8–10 ng/mL. After 12 months, a new lung-TBB (36 months after-LT) showed the persistence of Malassezia restricta on PCR 18S-RNA molecular identification. At an 18-month follow up (42 months after-LT), both lipid-enriched culture and 18S-RNA on biopsy were negative for fungal pathogens, and the chest-CT-scan showed a notable improvement of radiographic findings (b). At a 2-year follow up (4 years after-LT), voriconazole was discontinued and the patient maintained a stable respiratory function. He had no infection recurrence at his 3-year follow up.


A 52-year-old female presented with a lung nodule in the right lower lobe one year after living related donor kidney transplant (KT) for nail-patella syndrome in February 2020. Her post-KT course was uncomplicated, and her immunosuppressive regimen was based on tacrolimus, mycophenolate mofetil, and steroid. On a routine CT scan, a solitary pulmonary nodule with a small satellite lesion was accidentally found at 2 months post-KT (a). A positron emission tomography (PET) revealed high 18-Fluorodeoxyglucose-avidity with a value of standardized uptake value (SUV) of 12.3. The patient did not show any respiratory symptoms and the physical examination and laboratory results were unremarkable. Blood cultures were not performed as the patient was afebrile and the main diagnostic hypothesis was the neoplastic disease. To rule out a malignant aetiology, a CT guided transthoracic needle biopsy was performed. Histologic analysis of the specimen found granulomatous inflammation with multinucleated giant cells containing oval forms positive on PAS and Grocott staining. After deparaffination of the tissue section, we performed PCR 18S-RNA-sequencing. 18S-sequencing analysis was most consistent with the genus and species Malassezia restricta. After three-month antifungal therapy with itraconazole, a follow up CT scan showed a complete resolution of the lung nodule (b). Due to pharmacokinetic interaction between itraconazole and calcineurin inhibitors, frequent adjustments of tacrolimus dosage were needed based on through levels (max 19 ng/mL–min 7.1 ng/mL) to avoid nefrotoxicity. Renal function remained constant without any rise of creatinine levels. Maintenance therapy with oral itraconazole was continued for a month further.


A 6-year-old female patient presented to our hospital with a history of a 2.0 × 2.5 × 3.0-cm mass in the deep soft tissues of her right lower extremity. She denied any other associated symptoms including pain, obvious swelling, and local fever. A mass 2.3 cm in diameter in the deep soft tissues of her right lower extremity was visible by color Doppler ultrasound (Fig. A). This feature was suggestive of capillary hemangioma (Fig. B). An excision biopsy was performed on June 3, 2015. During surgery, a clearly circumscribed tumor without obvious capsule was observed. Biopsy revealed ASPS measuring approximately 2.5 × 1.5 × 1.3 cm; tumor thrombolysis was observed in blood vessels and almost all margins were positive. Microscopically, the tumor cells showed a diffuse arrangement of cells or pseudoalveolar architectures separated by thin, well-vascularized fibrous septa (Fig. A). The tumor cells exhibited pleomorphism with oval to polygonal shape, with abundant cytoplasmic granules and eosinophilic deposits with irregular nuclei (Fig. B). Immunohistochemically, the tumor cells were positive for transcription factor E3 (TFE3) (Fig. F) (which confirmed the histological diagnosis of ASPS), myogenic determination factor 1 (MyoD1) (Fig. E), and (focal) PAS-D (Fig. C), with negativity for desmin and synaptophysin. The Ki-67 proliferating index was about 20% (Fig. D). Postoperative magnetic resonance imaging (MRI) revealed abnormal signals in the right calf measuring approximately 1.4 × 0.83.2 cm. T1 imaging showed a low signal whereas T2 imaging showed a slightly higher signal intensity. Tumor parenchyma was markedly enhanced after enhancement scanning (Fig. A). Other parts of the patient, including her chest and abdomen, showed no abnormalities. A second enlarged resection was performed on June 24, 2015. Twenty days after the operation, the patient was treated with three-dimensional conformal radiation therapy. Under the Varian linear accelerator, 6 MV X-ray external irradiation was applied to the area of the tumor bed. The total dose was 5000 cGy at 200 cGy each time, 5 times a week. The patient developed no adverse reactions to radiotherapy or any abnormal blood indicators, except grade 1 skin toxicity in the radiation field. MRI after radiotherapy showed longer T1 and T2 abnormal signals without marked enhancement consistent with postoperative changes, accompanied by exudation of the surrounding soft tissue (Fig. B).
Routine follow-up has been performed since the end of radiotherapy, and the patient has been followed-up for 3 years by MRI examination of the right lower extremity. The MRI performed on July 10, 2018, revealed no local tumor recurrence (Fig. C). No chronic toxic side effects, such as limited joint activity, and no evidence of distant metastatic spread were observed. The patient remains under regular surveillance.


A 49-year-old woman with a history of Hashimoto’s thyroiditis presented with a rapidly growing neck mass and upper airway compression symptoms. No B symptoms were present. The hematological test showed a white blood cell count within the normal range (51.5 × 102/μL). Interleukin-2 receptor (801 U/mL) and lactate dehydrogenase (228 U/L) levels were elevated, although serum thyroxine and thyroid-stimulating hormone levels were within their normal ranges. An elevated thyroid peroxidase antibody of 271.4 IU/mL was detected. Ultrasonography revealed a mass measuring 2.0 × 1.0 × 1.0 cm in the right lobe of the thyroid; the border of the nodule was indistinct. The patient underwent a right thyroidectomy after a core needle biopsy revealed a diffuse large B-cell lymphoma. Following the final histological diagnosis of primary thyroid BL, the patient received rituximab, cyclosphosphamide, doxorubicin, vincristine, and prednisone for 2 weeks, as well as rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone including prophylactic intrathecal methotrexate for 3 months. Adjuvant treatments involving 22 cycles of linear accelerator (LINAC) therapy, 40 Gy each, were administered after the chemotherapy. Thirty months after the initial diagnosis, the patient had no evidence of recurrent disease.
The tumor cells were composed of round, intermediate-sized lymphoid cells admixed with scattered tingible body macrophages imparting a “starry sky” appearance (Fig. ). The nuclei were uniform and round-to-oval-shaped. The chromatin was coarsely clumped and had medium-sized paracentral nucleoli, while the cytoplasm was basophilic. Mitotic figures (12 per high-power field) were identified; there was no coagulative necrosis, although extrathyroidal extension was observed. Hashimoto’s thyroiditis was identified in the non-tumoral thyroid tissue.
Diffuse membranous immunostaining for CD10, CD20, and CD79α, as well as diffuse nuclear staining for MUM-1 (Fig. a) and p16 (Fig. b), were noted in the tumor cells. The expression of MDM2 was focal and confined to the tumor cell nuclei (Fig. c), although the cells were negative for Bcl-2, Bcl-6, and p53. The Ki-67 labeling index exceeded 90% (Fig. ). The EBER in situ hybridization test was negative (Fig. ). Ninety-six percent of the tumor cells were found to have MYC/IgH gene fusion as determined by FISH (Fig. ).
The clinicopathological features of 21 thyroid BLs are summarized in Table . The median age at diagnosis was 39.3 years with a male-to-female ratio of 13/8. The majority (94.4%) of these patients presented with a thyroid mass; patients also presented with a rapidly growing nodule (66.7%), dyspnea (61.1%), dysphagia (16.7%), and thyrotoxicosis (5.6%). Four of the 14 described patients (28.6%) showed B symptoms (e.g., systematic symptoms of fever, night sweats, or weight loss). None of the reported patients presented with immunosuppressive conditions or the endemic form of BL. Regarding the treatment modalities, all of the 20 patients for whom data were available (data for 1 were missing) received multidrug chemotherapy regimens; 12 received chemotherapy only, 7 received chemotherapy with combined surgery, and 1 was administered chemotherapy combined with surgery and adjuvant radiotherapy (LINAC).
Five of 7 patients with thyroid BL (71.4%) had morphologic evidence of Hashimoto’s thyroiditis. Regarding immunohistochemical features, all patients who were tested for CD10 (n = 14), CD20 (n = 18), and CD79a (n = 5) were positive for these respective proteins. IgM was positive in the lone patient who was tested. Additional factors measured are shown in Table . The Ki-67 labeling index exceeded 90% in all 19 patients for whom such staining was performed. We demonstrated that our patient had focal immunoreactivity for MDM2, but none of the other patients had been tested for this protein. All 12 patients who were tested for EBER in situ hybridization showed negative results, and flow cytometry immunophenotyping demonstrated CD10-positive monotypic B-cell populations in all 5 tested patients; moreover, MYC gene translocation was detected using FISH in all 12 patients whose samples were tested.
Of 19 patients with available clinical outcome data, 14 (73.7%) were alive with complete remission, 1 (5.3%) was alive with persistent disease, and 4 (21.1%) died of the disease. Three of the 19 patients lacked follow-up data; hence, the median follow-up of the 16 remaining patients was 46.5 months (range, 0.5–361 months). Kaplan-Meier survival analysis showed that the 12- and 60-month overall survival rates were 87.5 and 70.7%, respectively (Fig. ).


A 30-year-old male patient with nausea, vomiting, and abdominal pain complaints lasting for a few days presented to our clinic. In his anamnesis, he had several previous abdominal pain attacks which healed themselves. He had not had any abdominal surgery or medicine use before. Clinical examination revealed a tender and distended abdomen. Plain X-ray of the abdomen showed air-fluid levels of small bowel type. On the other hand, abdominal CT revealed dilatation and wall thickness in the terminal ileum (). No abnormality was observed in laboratory parameters. An exploratory surgery with a laparotomy method was decided with “acute mechanical intestinal obstruction” prediagnosis. During the laparotomy, a cocoon-like fibrous tissue of about 20 cm diameter was observed around the ileum. Small bowel was relieved through cutting the fibrous membrane. Since the circulation was normal in bowel segment, no resection was made. The patient was discharged on the fourth day after the operation.


A 47-year-old male patient presented to our hospital with the complaints of constipation, nausea, and vomiting for three days. No significant medical or clinical record was apparent in his medical past, including any previous abdominal operations or medication use. Clinical examination revealed signs of only abdominal distension. Plain abdominal X-ray indicated air-fluid levels while abdominal CT showed proximally dilated clustered terminal ileum and cecum. Laboratory parameters were normal, and exploratory laparotomy was carried out. During laparotomy, a cocoon-like fibrotic tissue with a diameter of about 10 cm was found to surround internally herniated ileum and cecum (). Bowel loops were relaxed after cutting the fibrous structure. Since the circulation was normal in the affected bowel segment, resection was not made during the laparotomy. The patient was discharged five days after the operation with no complications.


A thirty-eight-year-old female patient applied to our hospital with the complaints of swelling, vomiting, and constipation for a week. She had sigmoid colon tumor diagnosis two months ago and underwent left hemicolectomy. Clinical examination revealed only distended abdomen. Plain X-ray of the abdomen indicated air-fluid levels while abdominal CT showed clustering of proximally dilated ileum and cecum. Laboratory findings were normal (Figures and ). Exploratory laparotomy showed pronounced adhesion in the abdomen. It was observed that small bowels, colon, stomach, and liver were adhered as surrounded en bloc by a fibrous capsule in a way that anatomic boundaries could not be distinguished (Figures and ). No area was observed for adhesiolysis or resection in the patient diagnosed to have ACS. Due to continuous vomiting and lack of oral intake, percutaneous gastrostomy (PG) was applied for palliative purposes. Abdominal fascia was extremely rigid and not suitable for closing. The skin was closed with primary suture, and the patient was monitored in surgical oncology department in postoperative period. The patient became ex on the 37th postoperative day.


A sixty-four-year-old female patient applied to our hospital with the complaints of abdominal swelling, vomiting, and constipation which had been continuing for three days. Her history revealed TAH+BSO+pelvic and para-aortic lymph node dissection due to endometrium cancer a month ago. Clinical examination showed only abdominal distension. No feature was observed in plain abdominal X-ray and abdominal CT examinations. Laboratory parameters were normal (Figures and ). Exploratory laparotomy was decided for the patient. Advanced level adhesion was observed in the abdomen during laparotomy. The small bowels, colon, stomach, and liver were adhered and surrounded en bloc by a fibrous capsule in a way that anatomic boundaries could not be distinguished (Figures and ). No area was found appropriate for adhesiolysis or resection in this ACS patient. Percutaneous gastrostomy (PG) was applied to the patient with palliative purposes because of her continuous vomiting and lack of oral food intake. Abdominal fascia was extremely rigid and was not suitable for closing. The skin was closed with primary suture. The patient became ex on the 25th postoperative day.