An 80-year-old, non-smoker, female patient presented to the outpatient Clinic of the Department of Oral Medicine and Oral Pathology, School of Dentistry, National and Kapodistrian University of Athens, Greece for evaluation of an asymptomatic, exophytic nodule located on the lower lip. The patient had first noticed the lesion 4 months ago and since then it has been invariable. Her medical history was unremarkable and the last blood tests where within normal limits. On clinical examination, a well – circumscribed, penduculated, painless soft nodule was noted on the left side of the lower lip (Fig. ). The lesion was covered by normal mucosa and measured approximately 1.5 x 1cm. The remaining oral mucosa was normal. With a provisional diagnosis of a mucocele, the lesion was excised under local anesthesia and sent for histopathological examination.
Microscopic examination of 5-mm-thick, formalin-fixed, paraffin-embedded tissue sections stained with hematoxylin-eosin revealed numerous, variably sized clear cystic spaces, some of which contained amorphous eosinophilic material, interspersed in a fibrous connective tissue stroma. These spaces were surrounded by vacuolated epithelioid histiocytes with a signet-ring like appearance intermixed with few multinucleated giant cells (Fig. a, b). Although the lesion was reminiscent of liposarcoma, no nuclear atypia was noticed and a foreign body granulomatous reaction was speculated; however polarized light microscopy did not reveal any birefringent material. Before setting a final diagnosis, the patient was contacted and asked if she had been subjected to any aesthetic procedure in the perioral area in the past. At that time, she recalled that she had received hyaluronic acid injections in both nasolabial folds and the lower lip 1.5 year before, however the histopathological features were compatible with silicone, a different filler from the one she thought she had received. The combination of the patient’s history and the microscopic examination set the final diagnosis of a FBG to silicone. Nine months after the excisional biopsy, no recurrence has been reported.


A 48-year-old, non-smoker, female patient presented to a private oral medicine clinic with an asymptomatic, well-defined submucosal firm nodule on the upper lip, of 4 months duration. Her medical history was non – contributory while she had been subjected to hyaluronic acid filler injections in the ipsilateral nasolabial fold six months before her visit to the clinic. On clinical examination, a well - circumscribed submucosal nodule measuring approximately 2 x 1 cm was noticed on the left upper lip mucosa. The lesion was covered by normal-appearing mucosa and was painless and soft on palpation (Fig. a). The remaining oral mucosa was within normal limits. With a provisional diagnosis of foreign body granuloma and a differential diagnosis of salivary gland and neural tumor, the nodule was excised with no reported recurrence 4 months later. Histopathologically, pools of amorphous, basophilic material compatible with hyaluronic acid that were surrounded by epithelioid macrophages and mild lymphocytic inflammation were observed (Figs. b, c), confirming the tentative diagnosis of a FBG to hyaluronic acid filler.


The patient was an 8-year-old right-handed girl who fell from eight feet onto her outstretched and supinated left upper extremity. She immediately experienced elbow pain and swelling. In the emergency department, she was unable to move her elbow without significant pain. Initial radiographs showed a left radial neck fracture and a nondisplaced olecranon fracture (). Elbow range of motion was 40° shy of full extension to 110° of flexion, supination 15° shy of neutral and pronation of 30°. Reduction of the radial neck fracture was attempted via closed reduction under fluoroscopic guidance. Follow-up radiographs showed <30° angulation and 1 mm of translation of the radial head (). Her left arm was placed in a well-padded posterior A-frame splint. She was sent home in the splint and returned to clinic one week later. One week after injury, radiographs were taken and then her splint was removed. A long arm cast was placed (). Two weeks after injury, left elbow radiographs showed no change in alignment ().
Three weeks after injury, the cast was removed and physical examination revealed full extension with 90° of flexion and a pronosupination arc of 40°, both limited by pain. Radiographs demonstrated minimal displacement of the olecranon fracture, but no change in radial neck fracture alignment (). She was prescribed range of motion exercises with the assistance of a physical therapist. Four weeks after injury, physical examination revealed pronosupination between −10° and 20°, with almost full pronation. She was without pain. Radiographs demonstrated healing radial neck and olecranon fractures (). Eleven weeks after injury, physical examination revealed extension to 90°, flexion to 30°, supination 15° from neutral, and pronation to 20° from neutral, all limited by pain. In addition to continued healing of fractures, radiographs demonstrated a new finding of synostosis at the PRUJ (). Continued physical therapy was recommended, and the family was informed that surgical resection of the synostosis may be needed to improve her range of motion. She was lost to follow-up for almost two years, at which point she returned to our clinic.
Two years after injury, physical examination of the elbow revealed 135° of flexion and full extension, but complete loss of pronosupination with the forearm fixed in 10° of supination. Radiographs demonstrated healed radial neck and olecranon fractures, and an extensive bony synostosis at the PRUJ (Figures and ). At that time, surgical treatment of the synostosis was offered, but the patient was again lost to follow-up for six months. Two years six months after injury, she again returned to our clinic, and physical examination was unchanged from prior. CT scan () confirmed extensive bony synostosis at the proximal radioulnar joint. She was again offered a multitude of treatment options, including surgical resection, and family chose nonsurgical management with physical therapy. She has not returned to our clinic since.


A 42-year-old man of Armenian descent was admitted to the internal medicine service complaining of intermittent fever and night sweats for one month. The fevers continued for >36 hours, peaked at 40°C, and were associated with diffuse myalgias, rigors, and diaphoresis. He also reported drenching night sweats and a 20 lb. weight loss over the previous month. He does not smoke and drinks alcohol sparingly. His past medical history and family history were unremarkable. His review of systems was otherwise unremarkable. He is married with two children and works at a petroleum tank farm with exposure to benzenes and industrial solvents. His physical exam upon admission was significant for fever of 39.1°C, marked diaphoresis, tenderness to palpation in the lower extremities bilaterally, blanching maculopapular rash on the legs bilaterally and left forearm, and subcentimeter mobile, nontender inguinal lymph nodes bilaterally. Myalgias and fevers continued throughout the hospital stay. His myalgias were only moderately relieved by the aggressive use of opiates and NSAIDs. The patient continued to complain of the same symptoms throughout his hospital stay during which he was evaluated for fever of unknown origin.
Laboratory evaluation was significant for ESR 66 mm/hr, C-reactive protein 10.79 mg/L, creatinine kinase 34 U/L, and lactate dehydrogenase 117 U/L. His complete blood count, liver, kidney and thyroid function tests were all within normal limits, as were his serum electrolytes, iron studies, uric acid, amylase, proteins, and immunoglobulins. Serial blood, urine, and sputum cultures, including mycobacterium, were negative. Serologic testing was negative for HIV, EBV, CMV, HBV, HCV, and Syphilis. A PPD was also negative. His EKG, chest X-ray, and abdominal sonography were normal. Testing for the following autoimmune factors was negative: ANA, anti-dsDNA, RF, anti-smith, anti-RNP, anti-SSA, anti-SSB, and CCP.
A malignancy work-up included bone marrow examination. Core biopsy, aspirate, flow cytometry, molecular pathology, immunohistochemistry, and cultures (for tuberculosis, bacteria, and fungi) were all unrevealing. Flow cytometry of peripheral blood was normal, no atypical cells were identified by peripheral smear, and there was no M-spike detected in serum or urine. Whole body PET/CT scan showed hypermetabolic retroperitoneal enlarged lymph nodes in the left paraaortic region at the level of the renal vessels (largest 1.7 × 2.5 cm) and minimally active lymph nodes in the following regions: right axillary region (1.8 cm), right lower paratracheal region (1.5 cm), right upper lung (8 mm), retrocaval, common iliac, internal iliac and obturator regions bilaterally and left external iliac (all subcentimeter), and the inguinal region bilaterally (largest 1.2 cm).
CT-guided aspiration biopsy of the retroperitoneal periaortic lymph node () showed atypical lymphoid proliferation of small lymphocytes, which were polyclonal by flow cytometric analysis. Surgical consultation was requested for an excisional biopsy of the periaortic lymph node; however, this was deferred due to unacceptable risk related to anatomical location of the node.
The patient was given the presumptive diagnosis of a low-grade lymphoproliferative disorder and in addition to careful expectant management, an empiric trial of prednisone was started despite the risk of losing diagnostic lymph node architecture. The patient was discharged and had outpatient follow-up one week later. Over the next several weeks, the patient noted a subjective improvement in his symptoms. However, attempts to taper the prednisone dose resulted in a relapse of fevers and myalgias.
Although very atypical in presentation, the diagnosis of familial Mediterranean fever was considered given the robust response to steroids and his Armenian descent. Genetic studies were performed and an empiric trial of colchicine 0.6 mg daily was also initiated. The patient reported a near immediate relief of symptoms and was then able to be tapered off of prednisone completely. One month later, the MEFV genetic results were returned, which confirmed the diagnosis. His genetic tests were significant for a complex heterozygous genotype with the three mutations: E148Q, P369S, and A744S. The patient's mother was also genotyped to determine allelic distribution and risk of inheritance. The patient's mother's test was significant for heterozygosity at the A744S locus. The patient's father was not willing to undergo genetic counseling or testing but denies any symptoms that might be attributed to FMF. Thus, the father's presumed haplotype E148Q/P369S is likely not sufficient to produce any symptoms or clinical phenotype.
Three months later, a follow-up PET scan was performed to evaluate the patient's previously identified lymphadenopathy (). The study revealed near resolution previous paraaortic lymph node and resolved axillary and pelvic lymphadenopathy. However, new extensive hypermetabolic mediastinal and hilar lymphadenopathy were identified, revealing new right upper paratracheal node (1.7 cm), enlarging right lower paratracheal node (1.6 cm), subcarinal node (2.7 cm), and bilateral hypermetabolic hilar lymphadenopathy. At this point, several core needle biopsies of the subcarinal and peritracheal lymph nodes were performed under CT-guidance. Pathologic examination showed nonspecific reactive heterogeneous population of lymphocytes and was negative for granulomatous and amyloidal disease. Molecular pathology, immunohistochemistry, and flow cytometry were unremarkable.
Despite these findings, the patient continued to do well and remained symptom-free on colchicine.


A 50-year-old immunocompetent Hispanic male patient presented in April 2017 to the California Hospital Medical Center in Los Angeles with dizziness, nausea, headache, and a 2-week history of flu-like symptoms. Routine chest radiograph showed no abnormalities. Suspected bacterial meningitis was treated with vancomycin and ceftriaxone. Neurological examination revealed cranial nerves II through XII intact, no sensory or motor deficits, stable gait, DTRs 2+ bilaterally, and a negative Babinski sign. Serum lab results showed white blood cell count of 17,000/mm3. The patient had lumbar puncture done which revealed xanthochromic CSF fluid with a lymphocytic pleocytosis: WBC count of 234/mm3 (94% lymphocytes), glucose of 17 mg/dL, and CSF protein of 90 mg/dL. CT of the head showed ventricular enlargement and hydrocephalus with basal cistern patterns, but he did not require a shunt. Also, mild volume loss with small chronic ischemic disease was noted. Considering the CT of the head, dexamethasone was initiated, and the evaluation to establish the etiology of the meningitis was performed. Initial negative laboratory results were as follows: influenza A or B virus; CSF cryptococcal antigen; HIV-1/2 Ag/Ab screen; blood cultures; CSF cultures; and PCR for Mycobacterium tuberculosis. However, 6 days later the patient's condition worsened, and he was transferred to the ICU. The patient was not responding to the antibiotic and corticosteroid treatment, and his condition deteriorated rapidly over the next few days. Coccidioidal meningitis was confirmed with CSF Coccidioides complement fixing antibody titer of 1:2048. Treatment with IV fluconazole 1200 mg daily was then initiated. Neurological assessment demonstrated altered mental status; the patient was alert, oriented x1, responding to his name only, unable to follow commands, was able to move all extremities but had decreased grip strength bilaterally, held arms in flexion, and had difficulty feeding himself. Blunted left nasolabial fold was noted as a new manifestation. CT of the head demonstrated slightly improved hydrocephalus when compared to the previous exam. MRI of the brain showed meningeal enhancement in the basilar cisterns suggestive of basilar meningitis or a granulomatous process and 9 mm acute infarct in the right globus pallidus. Several days after initiation of fluconazole, follow-up neurological exam exhibited no improvement; the patient's motor strength gradually decreased with intact sensation and withdrawal to stimuli. MRI of C-spine () and T-spine without contrast revealed areas of signal changes in the cord secondary to myelitis and inflammation. MRI of L-spine without contrast showed crowding of the nerve roots in the lower lumbar spinal canal, suggestive of arachnoiditis, and explained the cause of the patient's significant neurological decline. The patient's motor strength decreased to 3/5 in proximal upper extremities and 0/5 in distal upper extremities with very poor hand grasp bilaterally. The patient lost bladder control, and his lower extremities were paralyzed completely even though his mentation improved.


A 47-year-old male (58 kg, 178 cm) with ischemic cardiomyopathy, left ventricular ejection fraction of 10%, congestive hepatopathy, anasarca, and cardiac cachexia was transferred to our institution for consideration of advanced therapies. Pertinent past medical history included ST-elevation myocardial infarction, post multiple percutaneous coronary interventions (last coronary stents placed approximately 5 months prior), chronic obstructive pulmonary disease, and recently diagnosed left lower extremity deep vein thrombosis (DVT). Important home medications included clopidogrel 75 mg and apixaban 5 mg daily. Clopidogrel was continued on admission, while anticoagulation for DVT was maintained with a heparin infusion instead of apixaban.
Over the next 5 days, despite optimal medical therapy, he developed cardiogenic shock requiring emergent intra-aortic balloon pump placement and subsequent percutaneous Impella CP® device placement. Initial platelet count of 87 × 103/μL decreased to 32 × 103/μL after 8 days of heparin infusion. His 4Ts score was intermediate, and heparin-platelet factor 4 enzyme-linked immunosorbent assay (PF4 ELISA) was strongly positive with an optical density of 3.3. Heparin was replaced with bivalirudin infusion due to high suspicion of HIT.
The serotonin release assay (SRA) test was performed with the result unavailable preoperatively. Although later reported negative, the validity of the test was questionable as it was performed while the patient was on clopidogrel with a P2Y12 platelet reactivity units (PRU) test of 104 at the time. The diagnosis of HIT in this patient was established on the basis of significant HIT antibody positivity and clinical 4Ts score.
After 3 days on bivalirudin treatment, the patient’s platelet count remained stable at 40 × 103/μL. His P2Y12 PRU test result finally rose > 200 after discontinuation of clopidogrel, indicating return of normal platelet function. Thus, he was taken for urgent HeartMate 3® LVAD implantation and removal of percutaneous Impella CP® device that day. Bivalirudin infusion was stopped on call to the operating room, and cangrelor with heparin was used for anticoagulation on CPB. Following a midline sternotomy and creation of LVAD driveline tract, a loading dose of cangrelor (30 mcg/kg) was administered over a minute, followed immediately by a continuous infusion of cangrelor at 4 mcg/kg/min. First intraoperative P2Y12 PRU test was drawn prior to heparin administration. Full dose heparin (300 units/kg) was given 10 min after cangrelor administration. Once activated clotting time (ACT) reached above 450 s, full CPB was commenced after cannulation. ACT was monitored every 30 min and maintained at a goal of > 450 s throughout CPB.
After implantation of LVAD, the patient was successfully weaned from CPB. Cangrelor infusion was discontinued 10 min prior to heparin reversal with protamine. Second intraoperative P2Y12 PRU test was drawn after discontinuation of cangrelor. In addition to transfusion of 2 units of platelets to promote return of platelet function, 2 units of packed red blood cells (PRBC) and 2 units of fresh frozen plasma (FFP) were also transfused prior to chest closure. Final intraoperative P2Y12 PRU test was drawn following blood product transfusion. Postoperative thromboelastography revealed satisfactory coagulation status. The patient was then taken to the intensive care unit on intravenous dobutamine 8 mcg/kg/min, epinephrine 0.02 mcg/kg/min, vasopressin 0.04 units/min, norepinephrine 5 mcg/min, and 40 ppm of inhaled nitric oxide. The HeartMate 3® LVAD was set at 4900 rpm, yielding a flow of 3.8 L/min.
Patient was coagulopathic due to impaired liver function. Fibrinogen was 180 mg/dL and international normalized ratio (INR) was 1.7 on postoperative day 1, for which he received transfusion of 2 units PRBC, 2 units of FFP, and 10 packs of cryoprecipitate. No platelet transfusion was given as platelet count was 102 × 103/μL. Anticoagulation with bivalirudin was eventually restarted on postoperative day 2. Transition to warfarin therapy was achieved by postoperative day 13, with a goal INR of 2–3. The patient’s platelet count recovered to > 150 × 103/μL by postoperative day 4 and remained within normal limits thereafter. There were no thromboembolic complications or major bleeding during his postoperative course, and he was discharged home on postoperative day 35. He continues to do well on device support.


We describe a case of a 29-year-old man with a history of IDU who presented to the hospital with fever and chills a few days after an inadvertent needle stick while injecting heroin. Avoiding medical care at first, he eventually came to the Emergency Department when he developed swelling around the punctured skin over the inferior aspect of the left cubital fossa. Upon initial evaluation, he had a temperature of 37.3°C, heart rate of 104 per minute, and respiratory rate of 38 per minute. The inferior aspect of the left cubital fossa was warm, erythematous, and with a 3.5 cm × 3.5 cm well-circumscribed area of fluctuance and induration. Laboratory evaluation revealed a hemoglobin of 10.9 gm/dl and white blood cell count of 10.6 k/cumm with a neutrophilic predominance but no immature granulocytes. His absolute neutrophil count was 9.1 k/cumm (normal 1.5–6.5 k/cumm). The comprehensive metabolic panel showed normal renal function and transaminases but elevated total bilirubin (4.5 mg/dl). His chest radiograph showed patchy infiltrates throughout the mid and upper right lung field with possible small right pleural effusion. Blood and sputum cultures were ordered, and he was started on broad-spectrum antibiotics consisting of vancomycin 1.5 gm IV every 8 hours (∼15 mg/kg), piperacillin-tazobactam 4.5 gm IV every 8 hours given as an extended infusion, and levofloxacin 750 mg IV once daily. He underwent incision and drainage of the cubital abscess. His antibiotics were tailored to oxacillin 2 gm IV every 4 hours as blood and sputum cultures revealed growth of methicillin-susceptible Staphylococcus aureus. On hospital day 6, his condition rapidly deteriorated due to sepsis (persistent fevers, tachycardia, and hypotension with rising white blood cell count), and a new 4 cm × 3 cm area of fluctuance was noticed on the left superior pectoralis region. He was transferred to the intensive care unit. A transesophageal echocardiogram (TEE) revealed a multilobed lesion on the superior and septal leaflets of the tricuspid valve, with lesion dimension approximating 3 cm on the superior cusp. CT of the chest with intravenous contrast demonstrated extensive bilateral cavitary lung lesions likely reflecting septic emboli, reactive mediastinal and hilar lymphadenopathy, and a large left-sided pleural effusion. A loculated component along the left upper lung insinuated through the chest wall into the left pectoralis muscle, raising the possibility of empyema necessitans (Figures and ).
Incision and drainage was performed with subsequent indwelling catheter placement for drainage of pectoralis major EN. For the left-sided pleural effusion, a chest tube was placed and it drained serosanguinous fluid. The cardiothoracic surgery service evaluated the patient and recommended ongoing antibiotic therapy with close clinical and radiographic surveillance. CT of the chest, when repeated, showed no interval change in multiple bilateral cavitary lesions, and a surveillance TEE done two weeks later identified persistent tricuspid vegetations with minimal regurgitation. As the CT of the chest was stable and the patient was clinically improving, surgery to replace the tricuspid valve was deferred with plans to treat the patient with six weeks of oxacillin.
The patient completed six weeks of intravenous oxacillin and was later started on suppressive antibiotic therapy with oral dicloxacillin 500 mg twice daily given the fact that he had high disease burden and had not undergone surgical intervention. Follow-up transesophageal echocardiogram (TEE) done soon after completing six weeks of antibiotic treatment showed that the tricuspid valve lesions had stabilized, if not minimally regressed in size, but tricuspid insufficiency had progressed to a moderate range. Magnetic resonance (MR) cardiac imaging reconfirmed sclerosis/thickening of the tricuspid valve leaflets, with moderate-to-severe tricuspid valve regurgitation. Surveillance radiography with CT of the chest showed that the cavitary lesions throughout the lungs had resolved. Unfortunately, at this point, the patient was lost to follow-up.


A 69-year-old man, with a more than 30-year history of chronic obstructive pulmonary disease (COPD) and peptic ulcer disease (PUD), was admitted because of fever, cough and dyspnea on exertion. Increased levels of acute-phase proteins, D-dimer (7030 ng/ml), hypoxia, and hypercapnia were found. Pulmonary embolism was suspected, but the investigation was negative. After 5 days, upper gastrointestinal (GI) bleeding occurred; however, endoscopy did not reveal the source of bleeding. A deformation of the duodenal bulb was observed. Abdominal ultrasound (US) revealed the presence of a heterogeneous, restricted fluid-solid mass in the liver hilus, close to the body of the pancreas. The patient was treated with antibiotics, metronidazole, bronchodilators, diuretics, H2-blockers, fraxiparine and transfusion of 2 units of packed red blood cells.
The patient was transferred to the department of gastroenterology and internal medicine, 4 weeks after the first symptoms. He complained of dull, middle epigastric postprandial pain, loss of appetite, and an approximately 20 kg loss of weight within the last 5 to 8 weeks. On physical examination, sparse pulmonary rales, midepigastric pain and pleural edema were observed. Laboratory tests showed hypochromic anemia, thrombocytosis and elevated levels of acute-phase proteins ().
The US revealed a hypoechoic lesion with hyper-echoic surroundings in the left hepatic lobe, which was suspected to be an abscess (), and the presence of air in the extrahepatic and intrahepatic bile ducts (). Abdominal computed tomography (CT) showed the presence of air in dilated intrahepatic bile ducts and the gallbladder, and the presence of a hypodense lesion in the left hepatic lobe (). During gastroscopy, a small amount of hemorrhagic erosion on the posterior wall in the lower part of gastric body, two ulcers (3 and 9 mm long), and a linear scar (12 mm long) on the anterior wall of the prepyloric region were found. The histological examination showed chronic gastritis without Helicobacter pylori infection. The clinical picture, imaging studies, and laboratory tests suggested a liver abscess and biliary duct fistula at the upper GI tract; thus, the patient was transferred to the department of surgery for further treatment.
During the operation, the surgeons found ‘an old’ wide pyloric ulcer perforation with a left subhepatic abscess and inflammatory infiltration of the hepatoduodenal ligament. After abscess evacuation, the cholecystectomy was performed. The intraoperative cholangiography showed proximal dilatation of the extrahepatic bile duct, no visible passage of contrast medium through the distal part of the common bile duct (CBD) into the duodenum, and the gastrobiliary fistula between the proximal CBD and stomach (). Then, the CBD was dissected and ligated in the distal part. Surgeons performed an antrectomy, combined with a truncal vagotomy and Billroth II gastrojejunostomy. The anastomosis between the dilated common hepatic duct and proximal jejunum was created. After 3 weeks, the patient was reoperated on because of leakage from the biliary anastomosis and intraperitoneal bleeding. The bleeding vessel was ligated and the anastomosis between the common hepatic duct and jejunum was repaired.


A 77-year-old white male presented sporadic rectal bleeding in April 2016. Rectal examination revealed a mass in the lower rectum. A broad-based rectal polyp measuring 10 mm and located approximately 6 cm from the anal verge was seen on colonoscopy, and a transanal polypectomy was performed. Histopathology diagnosed a 3.3-mm anorectal melanoma with positive stains for Melan A on immunohistochemistry, ulceration, high mitotic index, and inadequate positive resection margins (pT3bR1). Other malignant primary sites and distant metastases were ruled out. The patient underwent revised surgery that consisted of APR with bilateral inguinal lymphadenectomy, following the consensus of the interdisciplinary tumor board. Surgery and recovery were uneventful. The final tumor stage was pT3bN0 (0/15) M0R0, stage IIb (UICC). No perineural invasion was revealed. Neither BRAF nor KIT mutations were identified on genetic analysis. No adjuvant treatment was given according to international guidelines. The follow-up consisted of alternately brain + thoraco–abdo–pelvic Computed Tomography (CT) and positron-emission tomography (PET) scan, every 3 months. Six months later, in December 2016, the thoracic CT scan revealed four new infracentimetric lung nodules that were confirmed to be hypermetabolic mild positive on PET scan (standardized uptake values from 2.2 to 5.5). There was no evidence of other extrapulmonary metastatic spreads (Figure A).
The patient was healthy with Eastern Cooperative Oncology Group 0 and no weight loss. As conventional chemotherapies are mostly inefficient, and based on encouraging results regarding patients with mucosal melanoma enrolled in first line therapy PD-1 inhibitor trials, a tumor board council validated a treatment course of pembrolizumab. The patient was given pembrolizumab 200 mg IV, over 30 min, every 3 weeks (D1 = D21) from February to April 2017 (3 injections), with no specific side effects except for fatigue grade 1. However, in May 2017, the patient newly presented a right chest pain and a rapid deterioration of the general status. A PET scan revealed the emergence of multiple new centimetric hypermetabolic lung spots along with increased size and glycolic activity in the previously identified nodules that were associated with multiple new hypermetabolic liver, subcutaneous tissues, and peritoneal lesions (Figure B), and showed a rapidly progressive disease over 2 months.
We performed blood tests to biologically document this hyperprogressive (HP) patient, but he refused new tumor biopsy. Immunophenotyping analyses by flow cytometry (BD Fortessa®/FlowJo software®) were performed from peripheral blood mononuclear cells (PBMC) based on a Ficoll density gradient after the third injection of pembrolizumab. As no other patient samples were available, we compared the sample to healthy donors (HD).
In the myeloid cells analysis presented in Figure , the HP patient had a higher proportion of monocytes (HLADR+ CD33+, CD14+) and CD16+ monocytes (HLADR+ CD33+, CD14+ CD16+) compared to the HD (Figure A). Furthermore, the patient’s monocytes and CD16+ monocytes had an increased median fluorescence intensity of PDL1 compared to HD. Additionally, between the live PBMC samples, the percentage of the immunosuppressive population of granulocytic myeloid-derived suppressor cells (Gr-MDSC), defined as CD33+/HLADR−/CD15+/CD14−, was increased in the HP patient (Figure B).
In the lymphoid cell analysis presented in Figure , the HP patient presented a shift in CD4 and CD8 differentiation, with an increased proportion of CD4/CD8 naïve and CD4 terminally differentiated cells (TEMRA: Effector Memory CD45RA+), and a decrease in memory cells (central memory/effector memory). Among natural killer cells (NK cells), the HP patient had an over-expression of NK bright (CD56+ high) cells and an under-expression of the receptors NKp30 and NKp46 (Figure ).
After three cycles of pembrolizumab, one cycle of salvage dacarbazine was given, but it did not bring any clinical improvement. The patient was then treated with best supportive care on a palliative basis. He unfortunately passed away in July 2017.


In November 2012, a 49-year-old Korean woman was referred to the Department of Endocrine Surgery due to a right adrenal mass, identified by abdominal sonography during a routine healthcare checkup. She had been suffering from headache, tachycardia, palpitations, and cold sweats for 5 years but had not previously undergone adrenal disease related diagnostic tests. Her mother and two sisters had a history of thyroidectomy as treatment for papillary thyroid cancer. Twenty-four-hour urine collection revealed elevated vanillyl mandelic acid (VMA; 11.7 mg/day, reference: 2–7 mg/day), metanephrine (1625.6 μg/day, reference: 52–341 μg/day), normetanephrine (5459.5 μg/day, reference: 88–444 μg/day), epinephrine (256.4 μg/day, reference: 0.20 μg/day), and norepinephrine (153.2 μg/day, reference: 15–80 μg/day). An abdominal computed tomography (CT) scan revealed a heterogeneous right adrenal mass of approximately 4.7 × 3.5 cm (). Metaiodobenzylguanidine scintigraphy and single-photon emission CT showed increased uptake in the right adrenal gland (). The patient underwent right adrenalectomy using the posterior retroperitoneoscopic approach. The final pathologic diagnosis was a PCC with a size of 6.0 × 4.0 × 3.0 cm and a high risk of malignancy with a “PCC of the adrenal gland scaled score” of 13.
During the 65-month follow-up after adrenalectomy, the levels of urine VMA, catecholamine, serum calcitonin, calcium, carcinoembryonic antigen, and parathyroid hormone remained within normal ranges. There was no evidence of malignant thyroid nodules on neck ultrasound examination. Genetic counseling was performed by a specialist nurse. Due to the family history of thyroid cancer, we suggested germline mutation screening of the RET gene to the patient and her family members. The index patient and her two sons, two younger brothers, one younger sister, and mother agreed to the germline mutation test and provided informed consent. The informed consent statement contained a statement concerning the sharing of results as follows: “The research, which was conducted for your information or human tissue samples, can be shared with other researchers through congress. We can publish the results so that other interested people can learn from this study.”


Patient one was a 52-month old male with bilateral RB at the time of infarct diagnosis in his right eye. He was homozygous for the C677T polymorphism, and experienced choroidal ischemia after his seventh dose of OAC (carboplatin, topotecan, and melphalan) to the right eye only. His prior six OAC doses were unremarkable except for vasospasm of the ophthalmic artery during the fifth dose, which limited the ability for simultaneous bilateral chemotherapy infusion. The seventh dose, however, was his first administration of nitrous oxide during the procedure; he received 24 min of nitrous oxide induction anesthesia with a maximum end tidal nitrous oxide (ET N2O) of 60.2% (higher ET N2O percentage correlates to higher nitrous oxide concentration in the blood). He experienced no intra-procedural complications. One month later, new choroidal ischemia was identified in the right eye, presumed to be due to an infarction.


Patient two was a 13-month old female with bilateral RB when she experienced ischemia of her left choroid. She was heterozygous for the A1298C polymorphism and experienced an infarction after her third cycle of carboplatin OAC to the left eye only, anesthetically induced by nitrous oxide. Two prior OAC infusions were done with sevoflurane induction alone. She received 47 min of nitrous oxide, with 65.6% max ET N2O, and the procedure was without acute complications. Follow-up 1 month later revealed infarction of the lateral half of the posterior choroid.


Patient three was a 25-month old male with unilateral RB when he experienced choroidal infarction in the treated eye. His infarction was diagnosed at the one-month follow-up appointment after his second dose of OAC with melphalan and carboplatin. He was heterozygous for two polymorphisms: C677T and A1298C. While he did not receive nitrous oxide during his first OAC session, he did receive 58 min of nitrous oxide with max ET N2O 31.9% during this second session of OAC.


Patient four was a 58-month old female when her right eye experienced a choroidal infarction following OAC for her bilateral RB. Her genetic testing showed heterozygosity for the C677T polymorphisim. The infarct occurred after her eighth dose of OAC with carboplatin, topotecan, and melphalan to the right eye (tenth treatment of OAC for this patient, two treatments only to left eye). This was her first time receiving nitrous oxide (duration 21 min, max ET N2O 60.5%) during OAC for the right eye. This patient’s choroidal ischemia was identified by RetCam images at her one-month follow-up appointment.
There were no systemic thrombotic events in these patients following OAC. Post-OAC cerebral angiograms performed in each patient (standard of care) showed no evidence of vasospasm in the ipsilateral arteries. In each patient, these angiograms confirmed anterograde flow in the internal carotid artery, anterior cerebral artery, and middle cerebral artery, as well as patent ophthalmic arteries. In all four patients, indirect ophthalmoscopy and fundus photography 1 month after OAC showed marked disturbance of the retinal pigment epithelium and OCT confirmed distinct thinning of the choroid. In all four patients, the choroidal damage covered the lateral 180° from the central pole to the periphery. See Fig. for a representative RetCam fundus photographs and OCT images from patients 2 and 3. Post-infarct brain magnetic resonance images were performed in patients with bilateral RB (1, 2, and 4) to monitor for pinealoblastoma, and no past cerebrovascular events were identified.


We describe a 40-year-old woman complaining of a progressive painless enlargement of the anterior neck, dyspnea, dysphagia, odynophagia, and weight loss of 7 Kg in 4 months. The thyroid gland was hard and the ultrasound exam calculated a volume of 70 g. The patient had hypothyroidism and was undergoing hormonal replacement. Fine needle aspiration was suggestive of Riedel's thyroiditis. The CT scan confirmed a large thyroid lesion with esophageal invasion and decreased tracheal lumen of about 50% (). Bilateral vocal fold paresis was verified by means of a laryngoscopy. The dysphagia and dyspnea worsened progressively and the weight loss reached 21 Kg in 6 months after the first symptoms, so she needed a surgical approach for diagnosis and treatment ().
The patient underwent surgical decompression of the airway (), protection tracheotomy, and gastrostomy for nutritional intake. An extremely fibrotic and hard gland with tracheal infiltration was found. The intraoperative frozen section exam confirmed the diagnosis of Riedel's thyroiditis.
The follow-up was satisfactory using prednisolone 40 mg/day. Her symptoms improved 5 months after surgery and the feeding intake was exclusively oral. Her weight recovered and the tracheal cannula was removed 5 months after the tracheotomy due to the improvement of the vocal folds motion. The prednisolone was discontinued after 2 years and the evolution has been excellent, nowadays only using levothyroxine ().
We were unable to perform the blood dosage of IgG4 and IgG at the time of the active disease. The hematoxylin and eosin staining of the thyroid lesions revealed lymphoplasmacytic infiltration, severe fibrosis, and phlebitis (). The IgG4 immunostaining revealed the total number of IgG4-positive plasma cells 12/HPF (), and the IgG4/IgG ratio was 25%.


A 67-year-old male patient with highly symptomatic PVCs (ambulatory Holter monitor: 31.562 PVCs/112.680 total beat; PVC burden: 28%) was referred to our clinic for catheter ablation. He reportedly underwent a coronary bypass grafting surgery 5 years ago, and his coronary angiography which was performed recently revealed no significant stenosis with completely patent 2 vascular grafts. His echocardiogram was unremarkable with normal biventricular size and function. PVCs were reported to be completely refractory to beta blockers and non-DHP calcium channel blockers for the last 2 years. His physical examination was again unremarkable except for very frequent extrasystoles. An electrocardiogram (ECG) revealed frequent, mostly bigeminy, monomorphic PVCs with LBBB pattern, monophasic R wave in DI, DII, and aVL, and precordial transition between V2 and V3.
The electrophysiologic study was performed using a electroanatomic mapping system (Carto 3 Mapping System, BioSense Webster, Diamond Bar, CA, USA) and one quadripolar atrial mapping catheter and one irrigated mapping and ablation catheter (ThermoCool, BioSense Webster, Diamond Bar, CA, USA) inside a steerable sheath. Initial activation mapping did not yield a “sufficiently early activation” after the mapping of middle cardiac vein, proximal right ventricular outflow tract (RVOT), right paraseptal, and supravalvular and infravalvular left ventricular outflow tracts (LVOT). The earliest site was located on the tricuspid annulus (−12 msec), adjacent to the His bundle anterosuperiorly with a wide-area simultaneous activation with a small His potential on the proximal bipole during sinus beats.
After informing the patient of potential hazards and risk of complications, several power-titrated Rf ablations were delivered at right and left parahisian regions (supravalvular and infravalvular), starting at sites away from His potential recording regions with Rf levels starting from 5Watts up to 35 Watts (Fig. ). During the Rf delivery, the PVCs vanished transiently but consistently persisted later. Afterward, the earliest ventricular sites were targeted avoiding large but small His potentials, but early occurrence of very rapid junctional beats at power levels as low as 5 watts precluded this approach and PVCs persisted.
We suspected a subvalvular focus and approached the earliest right parahisian site retrogradely with inverted ablation catheter. The ablation catheter was advanced until it contacted the right ventricular apex. Then, it was progressively flexed while it was advanced under continuous clockwise torque through a steerable sheath held at the level of tricuspid annulus so that its tip finally faced the subvalvular region. We subsequently mapped the subtricuspid region and reached a previously unreachable new site which was actually just under the previously supravalvular “the earliest” region. The local electrogram was preceding the surface QRS by 24 msec and demonstrated QS on unipolar recording without any visible His-like potential in none of the bipoles (Fig. ). Again, Rf ablation was delivered to this site starting from 5 W and was cautiously increased to 35Watts for a total ablation time of 3 min (temperature limit 44°C) while monitoring for rapid junctional rhythm. PVCs were eliminated after 5 sec with no junctional rhythm or AV conduction injury. PVC elimination was tested with isoproterenol infusion with rapid pacing and programmed extrastimulation, but no PVCs were observed during the waiting period of 30 min. We also did not observe any atrioventricular conduction disturbance with similar AH and HV intervals. He remained completely asymptomatic afterward, and an ambulatory 24-h Holter monitor performed after 2 months revealed 28 multiform PVCs.


A 68-year-old gentleman presented to the Emergency Department (ED) with a six-month history of shortness of breath, which had worsened over the previous five days. He had a past medical history of mild Parkinson's disease, insulin-dependent type II diabetes mellitus, hypertension, and angina. He had recently commenced diuretics in the community for possible cardiac failure. He was a minimal drinker and ex-smoker.
Upon arrival in ED, he was in extremis with a respiratory rate of 30, SpO2 0.54 on air, improving to 0.72 with the application of 15 L oxygen via a non-rebreathe mask. His blood pressure and heart rate were normal. An arterial blood gas on oxygen showed pH 7.37, PaO2 5.3 kPa, PaCO2 6.4 kPa, BE −2.7 mEq/L, and lactate 4.4 mmol/L. There were fine bibasal inspiratory crepitations on auscultation of the chest with chest X-ray (CXR) findings consistent with pulmonary oedema. Laboratory investigations showed a significantly raised troponin T of 141 ng/L on admission, later rising to 1118 ng/L (normal range: <28 ng/L). Other than a mildly elevated CRP of 20 mg/L (normal range: <7 mg/L), blood tests were unremarkable including a normal neutrophil count. His initial ECG showed sinus rhythm with mild lateral ST depression but normal T-waves.
In addition to anticoagulation with aspirin, clopidogrel, and fondaparinux, the patient received glyceryl trinitrate and furosemide infusions in ED. This led to a good diuresis but persistent hypoxia; PaO2 improved only to 6.5 kPa despite CPAP of 7 cmH2O. He was, therefore, transferred to the Intensive Care Unit (ICU) for respiratory and circulatory support for a likely non-ST-elevation myocardial infarction (NSTEMI) with hypoxia from presumed cardiogenic pulmonary oedema +/− cardiogenic shock. Lactate had risen to 5.2 mmol/L and base excess deteriorated to −3.2 mEq/L. Noninvasive respiratory support was ineffective and the gentleman required intubation shortly after arrival. A preintubation CXR is shown ().
A transthoracic echocardiogram (TTE) showed regional wall motion abnormalities (RWMAs) not present six months earlier, but with normal biventricular size and preserved systolic function. Mild to moderate diastolic dysfunction was found (consistent with chronic hypertension). This suggested the recent myocardial infarction had not resulted in sufficient left ventricular impairment to explain the ongoing hypoxia. Cardiac output monitoring (via LiDCO®) showed a high cardiac output of 8-9 L/min with low vascular resistance; this was also inconsistent with cardiogenic pulmonary oedema and cardiogenic shock.
Despite radiological and clinical resolution of pulmonary oedema the oxygen requirements were largely static; one week after admission he was still requiring FiO2 0.6 to maintain PaO2 9-10 kPa; a later CXR is shown (). The possibility of a pulmonary embolus was investigated via CT pulmonary angiogram (CTPA). No emboli were visualised in the major pulmonary arteries or their immediate branches; however, poor contrast timing affected imaging of peripheral vessels. The lung parenchyma appeared normal and no pulmonary arteriovenous malformations (AVMs) were seen. Incidental imaging of the upper abdominal viscera showed a nodular and cirrhotic liver with ascites around both the liver and spleen (). Subsequent liver ultrasound showed an irregular outline with coarse texture consistent with micronodular cirrhosis. Hepatic vascular flows were normal. Mild finger clubbing was noted during his ICU admission, but no other stigmata of liver disease were present. Of note, this gentleman's liver function tests (LFTs) were largely normal until day seventeen of his admission, except for a stable but mildly raised bilirubin of <35 μmol/L (normal range: 5–17 μmol/L).
In light of the high cardiac output, persistent hypoxia unexplained by cardiac pathology, and a newly noted cirrhotic liver, the possibility of hepatopulmonary syndrome (HPS) was raised. Marked orthodeoxia was demonstrated; the FiO2 required to achieve fixed SpO2 rapidly fell from 0.66 to 0.46 upon moving from a semirecumbent to supine posture (); however, a test-dose of methylene blue did not improve oxygenation.
A contrast echocardiogram was performed specifically looking for HPS. This showed extensive opacification of the left heart within four to five cardiac cycles, consistent with an intrapulmonary shunt ( & supplementary material ()); this confirmed the diagnosis.
The ALT first became elevated at 66 IU/L (normal range: <45 IU/L) on day 17 of the patient's admission, progressively rising to 126 IU/L over the next three days. ALP was 213 IU/L on day 20 (normal range: 40–120 IU/L), having also been normal until three days earlier. His bilirubin remained stable at <35 μmol/L. An ammonia level was measured on day 19 in view of deterioration in LFTs and a failed sedation hold; the level was 205 μmol/L (normal range: 16–60 μmol/L). Admission INR was not recorded as the patient was not warfarinised; also our institution does not routinely record aspartate aminotransferase (AST); we cannot therefore retrospectively calculate a baseline Bonacini score to assess the likelihood of cirrhosis on admission. Platelet count on admission was 196 × 109/L with ALT 17 IU/L at that time. The INR was later measured at 1.5 when liver disease was suspected; however cirrhosis had already been demonstrated via CT and US imaging.
This gentleman's case was discussed with a tertiary hepatology centre—unfortunately there was no medical therapy that could be offered, and he was not a suitable candidate for liver transplantation given his comorbidities. Following discussion with this gentleman's family, the decision was made to withdraw care.


A 45-year-old housewife presented to the emergency department with complaints of pain and swelling in the right wrist and right elbow. She gave a history of fall from a bike on the outstretched hand in a high-velocity road traffic accident. There was no history of head injury or injury to any other part of the body. On examination, there was swelling and deformity in the right wrist as well as the right elbow. The right wrist joint was tender and the range of movement was painful. Similarly, there was tenderness in the right elbow and range of movement could not be assessed due to the pain. Crepitus could be felt at the right wrist joint suggesting a fracture, whereas there was no crepitation in the elbow. The distal neurovascular status was normal. Plain radiographs revealed severely-comminuted distal radius fracture with dorsal angulation with intra-articular extension, along with concomitant ipsilateral postero-lateral elbow dislocation (Figure ).
Closed reduction of the right elbow was done first in the emergency room under sedation with longitudinal traction and flexion of the elbow. The distal radius fracture was then reduced by giving longitudinal traction followed by initial dorsal tilt to dis-impact the fracture and then volar and ulnar tilt. The distal neurovascular status was again checked immediately after closed reduction and was found to be intact. The check films showed a congruent reduction of the elbow joint along with an acceptable reduction of the distal radius fracture (Figure ).
However, the patient was counselled for pinning of distal radius fracture in view of severe comminution and intra-articular extension to prevent a longitudinal collapse of the distal fragment. Due to financial constraints, the patient refused any operative intervention and hence was managed with an above-elbow posterior slab for one week followed by an above-elbow cast for three weeks. She was given a below-elbow cast for further two weeks. Active elbow and wrist range-of-motion exercises were started after six weeks of trauma. At the follow-up of one year, she had a good functional outcome with painless, full extension and flexion movements of the wrist and the elbow joint as well as full range of pronation and supination. She could resume her household work without any functional deficit.


A 53-year-old married Taiwanese woman was brought to our emergency unit with the chief complaint of shortness of breath and chest tightness for 1 day in July 2016. Her breathing sound was diminished over the right lung field but there was no fever, jugular vein engorgement, superficial lymphadenopathy, heart murmur, or peripheral edema. She was not a cigarette smoker and denied alcohol abuse. Her type 2 diabetes mellitus and hyperlipidemia had been under regular medical control for 2 years. Her surgical history included removal of an intracranial aneurysm in 2003 and uvulopalatopharyngoplasty for relieving obstructive sleep apnea syndrome in 2005. Malignancy had never been diagnosed either in our patient or her family members in the past. There was no evidence of myocardial ischemia by electrocardiogram and cardiac enzyme examination.
A routine chest X-ray film revealed massive right-side pleural effusion pushing her mediastinum and heart shadow leftward. After admission to a ward, a pigtail catheter was inserted for effusion drainage. A laboratory study disclosed an exudate nature without signs of bacterial infection. A cytology investigation reported a metastatic adenocarcinoma. A DNA study did not discover gene mutations of epidermal growth factor receptor. Positive findings of serum tumor makers included cancer antigen 125 (CA 125) 89.6 IU/ml and cancer antigen 15–3 (CA 15–3) 43 IU/ml, respectively. A computed tomography (CT) scan of her chest and abdomen, however, did not detect any suspicious primary site of her malignancy. Since her respiratory distress had been relieved by therapeutic thoracentesis, she was discharged without any other treatment on her own terms.
A mammogram was arranged for her at an out-patient clinic in August 2016. The result was also negative while her pleural effusion began to recur as revealed on chest films. She was lost to follow up in the following 4 months and similar difficult breathing struck again eventually in December 2016. During her second hospitalization, her respiratory discomfort was rapidly eliminated by a second thoracentesis. The obtained pleural effusion was sent for cytologic examination and made into a paraffin-embedded cell block for subsequent immunohistochemical study. The cytomorphology under microscope was an adenocarcinoma that showed a gland-like structure or tight clusters composed of tumor cells with highly pleomorphic nuclei and markedly vacuolated cytoplasm (Fig. ). Extensive immunohistochemistry staining of the cell block prepared from the pleural effusion sediment in an attempt to find out tumor origin showed that the metastatic adenocarcinoma was positive for cytokeratin 7 (CK7) and negative for cytokeratin 20 (CK20). Other positive markers included paired-box gene 8 (PAX8; scattered), estrogen receptor (ER; mild, 50%), progesterone receptor (PR; moderate, 10%), Wilms tumor 1 (WT1; strong, 100%), p53 (moderate, 30%), and CA 125 (strong, 100%; Figs. and ). While human epidermal growth factor receptor 2 (HER-2), thyroid transcription factor 1 (TTF-1), napsin A, GATA binding protein 3 (GATA3), and gross cystic disease fluid protein 15 (GCDFP-15) turned out to be negative. These results led to a conclusion that our patient’s pleural metastasis came from an occult primary site in her female genital organs, such as ovary, fallopian tube, peritoneum, or endometrium according to published guidelines and diagnostic flow charts [, ]. Her serum CA 125 and CA 15–3 levels rechecked at the second admission were 58.1 and 81.9 IU/ml, respectively. A sonogram of her breast did not reveal any suspicious lesions.
Because she insisted that she did not want to receive any kind of intravenous chemotherapy, we let her take tamoxifen as the first step of treatment. Unfortunately, her disease was proven resistant to tamoxifen 2 months later and a third pigtail catheter drainage for massive pleural effusion had to be performed in February 2017. Orally administered melphalan (2 mg/tablet, Alkeran™; Excella GmbH; Feucht, Germany), 7 mg/m2 daily for 5 consecutive days, was substituted for rescue. The drainage catheter had to be removed due to an accidental rupture of the collecting bag 11 days after starting melphalan treatment and a carbuncle developed around the insertion site of the catheter a few days later. However, surprisingly, her serum tumor markers declined quickly, and the effusion disappeared in a short period of time. Although a CT scan from chest downward to pelvis once again failed to locate a definite primary site as before, she tolerated the therapy very well and remained disease free for 3 months after completing six courses of a 28-day cycle of melphalan treatment totally with the second course delayed for 4 weeks due to her own choice (Figs. and ). A CT scan performed in September 2017, 1 month after the sixth cycle of melphalan treatment, disclosed no evidence of recurrence.
Based on our curiosity and interest, we searched for BRCA1 and BRCA2 gene mutations in the DNA extracted from paraffin-embedded cell block of effusion by NGS analysis. The specimen was sent to Yourgene Genomics Core Laboratory (Yourgene Bioscience; Taiwan), which has Ion AmpliSeq™ Exome Certified Service, for targeted genome sequencing. Tumor genomic DNA was extracted and purified by RecoverAll™ Total Nucleic Acid Isolation Kit for formalin-fixed paraffin-embedded (FFPE; AM1975; Thermo Fisher Scientific). A targeted capture library was constructed according to the protocol QIAseq Targeted DNA panels for human BRCA1 and BRCA2 (DHS-102Z, QIAGEN). Template preparation and Ion 540™ Chip were performed on Ion Chef™ (4484177, Thermo Fisher Scientific) using respectively 120 pM of equimolar pooled libraries. The samples were sequenced on an Ion S5 XL System (A27214, Thermo Fisher Scientific) using 500 flows. Sequencing data were analyzed by Torrent Suite 5.2.1 (Thermo Fisher Scientific). Variant identification was performed using QIAGEN’s QIAseq targeted sequencing data analysis portal (). Accordingly, two significant homozygous complementary DNA (cDNA) mutations were detected: c.3214delC of BRCA1 and c.5164_5165delAG of BRCA2. Our patient’s saliva was subsequently sent to a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (CurieMed Clinical Laboratory, a Taiwan agent of Veritas Genetics, USA) available for sequencing of germline BRCA1 and BRCA2. We collected and preserved 2 ml of saliva using SD-2000-DX collection kit (Samplify Bio, Massachusetts, United States of America). Genomic DNA extraction and purification, and targeted capture library DNA construction were performed by Veritas Genetics proprietary hybrid capture-based assay. The sample was sequenced on an Illumina NextSeq 500 platform. A heterozygous c.5164_5165delAG mutation of BRCA2 was detected.


A 62-year-old female patient presented to our unit with complaints of double vision. She stated that her double vision had started approximately one month earlier. Neuroophthalmologic examination revealed bilateral light responses with no afferent pupil defect. Color vision test with Ishihara (14 card print) was 14/14 in both eyes. The patient exhibited abnormal head posture (face turn to right) and hypertropia of the left eye (10 prism diopters). Slight restriction of left eye movement was noted in down/right gaze. There were no obvious limitations in the other positions of gaze. In the Bielschowsky head tilt test, hypertropia increased when the head was tilted to the left. Best corrected visual acuity on Snellen chart was 10/10 in both eyes. Anterior segment and fundus examinations were normal in both eyes. The patient was diagnosed with left fourth cranial nerve palsy and cranial imaging was requested to establish etiology; however, the patient did not return for follow-up. Approximately 2 months later, our unit was consulted again regarding the patient due to complaints of reduced vision and pain in the left eye. She also had complaints of progressive swelling in the left half of her face and enlargement of her left eye for about one month. On neuroophthalmologic examination, light response was normal in the right eye and weak in the left eye. Relative afferent pupil defect was noted in the left eye. Right eye movements were unrestricted in all directions, while left eye movements were restricted in all directions with minimal upward gaze (). Proptosis was noted in the left eye, and Hertel exophthalmometer measurements were 18 mm for the right eye and 24 mm for the left eye. Best corrected visual acuity on Snellen chart was 9/10 in the right eye and counting fingers from 2 m in the left eye. Color vision score was 14/14 in the right and 0/14 in the left eye. Chemosis and upper lid edema were observed in the left eye on slit-lamp examination. The anterior segment appeared normal. Intraocular pressure measured by Goldmann applanation tonometry was 15 mmHg in both eyes. Fundus examination was normal in the right eye, while optic disc hyperemia and increased tortuosity and caliber of the retinal vessels were observed in the left eye (). Reliable results could not be obtained in visual field and visual evoked potential tests. Computed tomography scans revealed a mass filling the left nasal cavity and anterior/posterior ethmoid sinuses, extending beyond the medial rectus muscle into the cone and compressing the optic nerve. Orbital magnetic resonance imaging revealed a soft tissue mass with homogeneous enhancement, hypointense in T1-weighted sequences and hyperintense in T2-weighted sequences, which appeared to be displacing the optic nerve inferiorly (). Based on the results of histopathological examination of a punch biopsy obtained from the nasal passage, the patient was diagnosed with olfactory neuroblastoma (Hyams grade III). Immunohistochemical staining for differential diagnosis of the round cell tumor was negative for CD2, CD3, CD20, CD38, cytokeratin, CD99, HMB45 and GFAP. A small number of cells were positive for CD56, chromogranin, and synaptophysin, while very few cells were positive for BCL2, NF, and S100. Ki-67 labeling index was 25% ().


History
A 73-year-old lady with severe anal pain and rectal bleeding was submitted to colonoscopy in March 2017. She previously suffered from glaucoma and depression. An outgrowing neoplasm of the anal canal was detected 3 cm from the anal margin; the pathologic report disclosed a squamous carcinoma. At the first oncologic assessment, the patient's general conditions were considered stable and the performance status was scored as Eastern Cooperative Oncology Group (ECOG) 1 for depression, local pain, and rectal bleeding.
Staging radiological findings
The staging CT imaging acquired in April 2017 confirmed the presence of a known neoplasm, which measured 5.5 cm in the axial diameter and 8 cm in the cranial-caudal extension. The primary lesion infiltrated the presacral space, the left piriformis muscle, and the perirectal space. The rectovaginal septum and vagina were involved too, and several perirectal nodal lesions were described as radiologically suspect or clearly positive. No secondary lesions were detected in the lungs, while three liver metastases were observed: one in segment VIII (maximum diameter 31 mm) and two in segment V (maximum diameters 13 and 5 mm, respectively). According to the radiological findings, the disease was staged as cT4 cN1 cM1 (liver), stage IV. The case was discussed in the institutional multidisciplinary tumor board for lower gastrointestinal malignancies, and it was decided not to perform further radiological investigations, promptly referring the patient to a protection colostomy and concurrent, long-course chemoradiotherapy. See Figure for computed tomography (CT) hepatic findings.
Chemoradiotherapy on the primary site
Colostomy was performed in May 2017 and chemoradiotherapy was started in June 2017 with the following schedule: 55 Gy in 2.2 Gy fractions to the primary lesion with infiltrated surrounding tissue, infiltrated presacral space, left piriformis muscle, rectovaginal septum, and vagina (CTV1); 55 Gy in 2 Gy fractions to the positive per-rectal nodal lesions (CTV2); 45 Gy in 1.8 Gy fractions to the pelvic, mesorectal, and inguinal nodes (CTV3). The radiation dose has been delivered through the simultaneous integrated boost (SIB) protocol. Concomitant chemotherapy with 5-fluorouracil (1000 mg/m2 on days 1-4 and 22-25) and mitomycin C (10 mg/m2 on days 1 and 22) was administered during the first and last weeks of radiotherapy. The aforementioned treatment was performed using the volumetric arc therapy (VMAT) delivery technique (RapidArc, Varian, Palo Alto, CA, USA) on a standard X10 MV linear particle accelerator (Linac) and ended on July 18, 2017. The first clinical revaluation was performed 10 days after treatment; the patient suffered from severe tenesmus, mucorrhea, and moderate fatigue. Her ECOG PS score was 2.
Restaging radiological findings after chemoradiotherapy on the primary site
A restaging CT of the thorax and an abdominal MRI were performed in August 2017. The CT scan confirmed the absence of secondary lesions in the lungs. The abdominal and pelvic MRIs showed a significant reduction in the primary lesion (the cranial-caudal extension was reduced from 8 cm to 2.5 cm); neoplastic infiltration of the left pararectal space, left piriformis muscle, and rectovaginal septum was still present as a consequence of a limited local response to chemoradiotherapy. The secondary lesion described in the VIII hepatic segment showed a significant dimensional reduction (15x7 mm versus 31x18 mm), while only one lesion was still detectable in segment V (9 mm versus 13 mm). See Figure .
Magnetic Resonance-guided Radiotherapy (MRgRT) SBRT for hepatic lesions
Considering the partial response on both the primary and secondary lesions, it was decided to refer the patient to SBRT treatment for the residual hepatic lesions. In consideration of the patient’s general condition and PS (ECOG 2), a total dose of 3500 cGy in five fractions (to be delivered every other day) was prescribed on both lesions. A significant respiratory movement was expected in relation to their location (V and VIII hepatic segments) and, therefore, the patient was referred to MR-guided respiratory-gated tri-60-Cobalt radiotherapy (MRIdian, ViewRay Inc., Mountain View, California, USA) []. Specific informed consent for MRgRT was acquired from the patient during a dedicated, extensive clinical interview during which the procedures were described in full detail in order to ensure the patient’s active collaboration during SBRT, as well as the necessary training for the use of the visual feedback system. Complete blood count and hepatic function panel were performed before radiotherapy. The patient received specific training on breath control, free breathing (FB), deep inspiration breath-hold (DIBH), and deep expiration breath-hold (DEBH). A simulation MRI was acquired with 175, 25, and 25 seconds (s) sequences, respectively. CT simulation imaging was then acquired according to the breathing phase on a helical CT scanner (GE HiSpeed DX/i Spiral, Boston, MA, USA); the slice thickness was 3 mm and no intravenous contrast agent was administered, following the simulation protocol of our institution. The patient was immobilized in the supine position with both arms up, using the Fluxboard device (FluxBoard, MacroMedics, The Netherlands) in an appropriate and comfortable configuration (U-grip 11, elbow position Q, black leg support in position 73, feet fix 29). DIBH MR and CT were chosen as the planning imaging, as the patient showed an acceptable attitude to maintain this condition.
Therapy volumes contouring
The restaging diagnostic CT and MR imaging were fused with the simulation MR and utilized for target identification. Lesions were not visible on simulation CT imaging (see Figure ).
The identification of target volumes proved to be challenging on simulation MRI too, due to the good response to chemotherapy. A radiologist expert in liver lesion diagnosis was involved in target contouring and margin definition. An anisotropic margin of 0.5 cm was added to the V hepatic segment lesion’s gross tumor volume (GTV) (2.8 cc) in the cranial-caudal direction and of 0.2 cm in the lateral one, obtaining the PTV V segment (12.5 cc). An isotropic margin of 0.6 cm was added to the VIII hepatic segment lesion’s GTV (1.8 cc) in all directions, except for the left side facing the adjacent cystic lesion, obtaining the planning target volume (PTV) VIII segment (7.2 cc). Two cystic lesions were identified very close to both PTV volumes and contoured as cyst V (3.0 cc) and cyst VIII (1.5 cc). The upper abdominal organs at risk (OaR) were contoured according to the usual internal protocols: bowel loops, right and left kidneys, aorta, inferior cava vein, lung, and healthy liver were considered.
MRgRT planning and delivery
Both target volumes (PTV V segment and VIII segment) were not clearly visible on the cine MR during the simulation imaging acquisition: an indirect target gating protocol was therefore adopted, using cyst V and cyst VIII as the target gating volumes. An isotropic boundary of 0.3 cm was set for both volumes.
A. Lesion of the V hepatic segment: Treatment parameters were set as ROI 5%; delay time: 0 s; and wait time: 120 s. Visual feedback for gating purposes was used: the beam on time resulted to be 4.12 minutes, while the average irradiation time was 21 minutes per fraction.
B. Lesion of the VIII hepatic segment: Treatment parameters were set as ROI 5%; delay time: 0 s; and wait time: 120 s. Visual feedback for gating purposes was used: beam on time resulted to be nine minutes, while the average irradiation time was 14 minutes per fraction.
Two different plans were calculated in the same DIBH conditions for sequential delivery, one for each lesion. See Figure .
Restaging after hepatic SBRT and tolerance assessment
The patient showed optimal treatment compliance. The result of the complete blood count and hepatic function panel was always in range during and after treatment. Restaging imaging showed a complete response in the irradiated lesions. See Figure .


A 42-year-old woman, presented with a history of hemoptysis for 1 month. She attended the First Affiliated Hospital of Wenzhou Medical University with a 10-day history of chest pain. There was no history of malignant thromboembolic, hematologic, or inflammatory disease. Physical examination showed her blood pressure was 126/79 mmHg, her pulse was regular with a rate of 72/min, and her breathing rate was 20/min. A systolic rumble at the apex area was noted. Arterial blood gas analysis showed pH of 7.39, PO2 of 176.7 mmHg, PCO2 of 39.1 mmHg, and oxygen saturation of 99.5% under a reserved O2 mask. Transthoracic echocardiography demonstrated a large, immobile, ovoid mass attached to the wall of the left atrium (LA); the mitral valve was involved. Echocardiography revealed moderate, mitral insufficiency, and an abnormal echoic mass in the left atrium. A diagnosis of primary cardiac tumor without metastases was considered in the clinic. Intraoperatively, a mass was found originating from the ostium of the left inferior pulmonary vein in the left atrium, extending to the mitral orifice. Wide surgical excision of the mass was performed. Macroscopically, the specimen measured 5.5 cm × 5 cm × 4 cm. The tumor was grey, solid, and firm.
Histologically, the tumor contained variable amounts of spindle cells and osseous differentiation in different areas. Primary, cardiac fibroblastic osteosarcoma had the typical appearance of interlacing hyperchromatic spindle-shaped stromal cells associated with osseous matrix (Fig. A). Osteoclastic-like, giant cells were scattered throughout without foci of hemorrhage and necrosis (Fig. B). Tumor cells were pleomorphic with spindle-shaped nuclei and hyperchromatin (Fig. C). Immunohistochemical examination showed that tumor cells were positive for vimentin, S-100 protein, and Bcl-2, but negative for cytokeratin, epithelial membrane antigen (EMA), smooth muscle actin, CD99, and CD34. The proliferative index (Ki-67) was approximately 60%. The genetic profile of this tumor by fluorescence in situ hybridization (FISH) showed the amplification of mdm-2 genes. These findings were compatible with a histological diagnosis of fibroblastic osteosarcoma. She was asymptomatic in the immediate postoperative phase. However, 3 months after the operation, her condition worsened and transthoracic echocardiography demonstrated a 3.2 cm × 2 cm recurrent mass in the wall of the left atrium (LA). She died shortly afterwards as a result of the local disease recurrence.


A sixty five-year-old Japanese woman with cirrhosis, hepatocellular carcinoma, chronic heart failure, pulmonary hypertension and diabetes mellitus presented with fatigue and diarrhea. Three weeks prior to admission she had developed diarrhea and general fatigue. She visited another hospital and computed tomography (CT) revealed a ruptured aneurysm of the descending aorta. For further surgical work up and treatment, she was transferred to our hospital. Physical examination was unremarkable except for a low grade fever of 37.9 °C. Laboratory examination detected an elevated white blood cell count and C-reactive protein. Her Child–Pugh score was 9 points out of 15 (Child–Pugh: B). Chest CT revealed a ruptured aneurysm of the descending aorta of 58 × 47 mm in size (Fig. ). Based on the imaging study and presence of inflammation, we made a diagnosis of mycotic aneurysm.
Although the principal treatment for mycotic aneurysm is surgical resection and debridement with antibiotics, thoracic endovascular aortic repair (TEVAR) was performed, due to her high risk of perioperative death. We treated her with ampicillin/sulbactam 3 g every 6 h. 3 days after admission, E. tarda grew from her blood cultures (Fig. ). E. tarda was identified using MicroScan WalkAway and Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI TOFMS). Despite treatment with antibiotics, the fever persisted and the organism continued to grow from blood cultures. We switched antibiotics to vancomycin and meropenem because of clinical deterioration and persistent bacteremia. E. tarda turned out to be susceptible to amoxicillin, cephalosporin, aminoglycosides, and quinolones. On day 8, we changed antibiotics to ampicillin 2 g every 4 h as de-escalation. On day 9, we added gentamicin because the blood culture taken on day 7 was again positive, which finally led to negative blood cultures on day 11. We conducted two weeks of dual therapy with ampicillin and gentamicin, followed by 4 weeks of monotherapy with ampicillin (Fig. ). After a total of 6 weeks of intravenous antibiotic therapy, we switched to oral amoxicillin as suppressive therapy. She was transferred to another hospital 58 days after TEVAR.
Four months later, the patient inadvertently discontinued her antibiotic therapy for a week, which led to recurrence of fever again. She was admitted to another hospital, and E. tarda was confirmed again from blood cultures. She was treated with intravenous ampicillin for another 6 weeks and restarted on suppressive therapy with oral amoxicillin. The antibiotic susceptibility of E. tarda did not change from the first strain. Two months later, she visited our hospital with hemoptysis. A broncho-aortic fistula was confirmed and we performed another stent graft treatment. Blood cultures, which were taken at this time, were sterile. We started treatment with ampicillin/sulbactam 3 g every 6 h, and after 6 weeks of intravenous therapy, changed to oral amoxcillin/clavulanate. 3 years after this episode as of this writing, there has been no recurrence of symptoms after the second stent insertion.


A 37-year-old female from Spain presented to our center in August of 2017 with complaints of chronic intractable pain in the coccyx. The patient suffered from this pain since 2009 when she sustained a coccyx fracture in a work-related slip and fall injury while working as an airline stewardess in Europe. At the time of presentation, the patient endorsed 10/10 coccyx pain on visual analog scale. She described the pain as sharp, stinging, shooting, and radiating throughout her bilateral lower extremities. Due to the injury, she was forced to quit when her pain prevented her from performing her duties. At the time of presentation, she could not sit or walk for more than 10 minutes consecutively and required special cushioning to be brought with her at all times.
Prior to presenting to our center, she had been evaluated and treated by pain management physicians, orthopedic surgeons, and multiple urgent care clinicians in both Spain and the UK. Her past treatments in Europe included multiple coccygeal blocks, trigger point injections, epidural steroid injections, and a conventional spinal cord stimulator in 2011. The spinal cord stimulation therapy consisted of an ANS Genesis (company acquired in 2005 by St. Jude Medical, which was subsequently purchased by Abbot) spinal cord stimulator with one octode lead placed through the sacrococcygeal hiatus. This stimulator was placed in Spain in 2011 and the patient continued to use the stimulator at presentation. Stimulator treatment was previously complicated by an infection, which was treated with IV antibiotics and surgical debridement. The patient reported pain relief from the stimulator, but she was experiencing diminished relief from the stimulator over the last several years and also had inadequate coverage in her most painful region, which was the coccyx itself. She continued to have the stimulator turned on as it provided some relief, but she was still incapacitated from the pain. She was maintained on a pain medication regiment consisting of oxycodone 10 mg PO BID, dexketoprofen 25 mg PO QID, duloxetine 60 mg PO QD, trazodone 100 mg PO QD, and pregabalin 75 mg PO BID. Despite this intensive medical treatment, the patient experienced poor symptom control in addition to side effects from these medications, including constipation and drowsiness.
The patient presented to us seeking other potential options for pain relief, in particular a conventional radiofrequency ablation of the nerves innervating the coccyx or an endoscopic radiofrequency ablation of those nerves. Considering the patient's persistent severe coccydynia and failure of extensive conservative and interventional treatments and the chronicity of her pain, we proposed a DRG stimulator trial in September of 2017. The use of DRG stimulation for coccydynia is an off-label use; the reason we considered DRG stimulation was secondary to our highly successful experiences with DRG stimulation for both complex pelvic and rectal pain, as well as low back and SI joint pain. Our rationale for proceeding with the trial was the potential for better regional coverage versus conventional sacral nerve stimulation, similar to our experience in those cases.
Our proposed approach was a bilateral L1 and S2 DRG stimulator trial. The patient decided to proceed with the DRG stimulator trial and underwent psychological clearance prior to the procedure. During the 7-day trial, the patient rated her pain less than 1/10 on visual analog score, improved sleep hygiene, functioned better in general, and was actually able to ambulate for approximately four miles without limitations. Prior to the trial she could not walk more than a city block without severe pain. She was able to function better in almost all her daily activities and she was able to position herself with minimal limitations and without the aid of her cushion, which she previously carried with her at all times, and claimed to have close to 100% coverage of her pain. After the trial, the patient decided to proceed with permanent lead implantation. She understood she had the option to have the procedure performed in Europe or to have it performed at our institute. After consideration, she decided to proceed with the implantation at our center. We then decided to leave her current spinal cord stimulator system in place rather than to explant the system.
A board-certified anesthesiologist monitored the patient throughout the implant procedure. Thirty minutes prior to the procedure the patient received 2 grams of cefazolin. The patient was placed in the prone position with bolsters under the lumbar/lower thoracic region. After positioning was deemed adequate, the patient received propofol sedation. The lumbar spine and buttocks were prepped and draped in normal sterile fashion with betadine followed by DuraPrep. The L1 vertebral body was then aligned on fluoroscopy and 1.0% lidocaine mixed with 0.5% bupivacaine was used for local anesthesia. A Tuohy needle was inserted at the right side one level below the left L1 target foramen at the level of the pedicle and was then guided toward the midline at the interspace of the target level. Loss of resistance to air was achieved close to the midline. At this point, the 4-contact DRG lead (Axium™, St. Jude/Abbot, Lake Bluff, IL) was loaded into the introducer catheter with the lead tip approximately 2-3 mm outside of the introducer. The loaded introducer was then passed into the Tuohy needle. The introducer then accessed the epidural space and was directed toward the foramen. The introducer was passed through the target foramen until the middle two contacts were under the level of the pedicle. The introducer was then withdrawn to approximately 5 mm after the proximal contact while applying counterforce on the lead. A strain relief loop was created in the usual fashion []. Subsequently, the introducer was removed from the Tuohy needle and the lead was left in place. Fluoroscopy was performed to confirm no displacement of the lead had occurred. The same procedure was performed to place a lead on the right L1 DRG. Figures and depict the position of bilateral leads on the L1 level.
At this point the right S2 foramen was aligned under fluoroscopy. A Tuohy needle was directed into the posterior S2 foramen and its position was confirmed on fluoroscopy. The lead loaded introducer was then passed through the anterior foramen and the electrodes were maneuvered such that the final position was with 1 contact anterior to the anterior wall of the sacral vertebral body (extraforaminal), 2 contacts intrasacral, and 1 contact in the sacral epidural space. A strain relief loop was created as previously described []. The introducer was then withdrawn into the Tuohy needle with the lead left in place. In withdrawing the Tuohy needle another small loop was placed subcutaneously for additional tensile strength. The lead position was checked again in the AP and lateral position. The same procedure was performed to place a lead on the left S2 DRG. Figures and depict the position of bilateral leads on the S2 level.
All 4 lead positions were then checked again and found to be in good position as well as their tension loops. The leads were then secured with Tegaderm. A marking was placed on the right buttock that was 4 cm transverse in the upper outer quadrant, since the patient's ANS Genesis stimulator was implanted on the left side. 10 cc of 1.0% lidocaine mixed with 0.5% bupivacaine was used to anesthetize the incision site. An incision was made and a pocket was created. The leads were tunneled to the pocket as previously described []. The leads were connected to the pulse generator and impedances were confirmed. The incisions were irrigated with Bacitracin solution and the generator was anchored with 2.0 Ethibond. The right buttock wound was closed in layers by using 2.0 Vicryl and the skin was closed with staples. All 4 lead puncture sites were small and the leads were not visualized with manipulation of the puncture site. The lead placement puncture sites and the buttock incision were covered with Steristrips followed by gauze and Tegaderm.
On four-month follow-up, the patient still reports >90% pain relief from the stimulator therapy with concomitant improvements in daily functioning. The improvement in pain control allowed her to discontinue her oxycodone, which was causing her to suffer from side effects before.


An 84-year-old Caucasian male with recent hospitalization for bleeding peptic ulcer disease and Helicobacter pylori–positive gastritis on amoxicillin, clarithromycin, and proton pump inhibitor presented to the hospital with fever, productive cough, and generalized fatigue for 5 days. He denied any sick contacts, recent travels, weight loss, night sweats, recent flu like illness, or exposure to marine sources, plant, or animal products. His other medical problems include chronic kidney disease, chronic obstructive pulmonary disease, stroke, prostate cancer treated with radiation therapy, and Paget’s disease. His vitals on admission include blood pressure of 110/75 mm Hg, temperature of 101.3°F, respiratory rate of 19 breaths per minute, pulse rate of 87 beats per minute, and pulse oximetry of 96% on 3 L nasal cannula. Physical examination was unremarkable other than decreased breath sounds more pronounced on the lower lobes with minimal expiratory rhonchi. Initial laboratory workup showed elevated white blood cell (WBC) count at 14.5 with neutrophilic predominance, stable hemoglobin of 13.5, and platelets of 488. Kidney function was normal with no electrolyte abnormalities noted on admission laboratory tests. Chest X-ray came back significant for bilateral lower lobe consolidation with left-sided pleural effusion (). Two sets of blood, sputum, and urine cultures were sent, and he was started empirically on intravenous vancomycin and piperacillin/tazobactam for possible health care–acquired pneumonia. The patient remained febrile, and WBC count remained elevated with continuous production of thick, brownish colored sputum. Eventually, 2 sets of blood culture from admission and respiratory cultures came back significant for S putrefaciens susceptible to antibiotics given (as shown in ). Therefore, antimicrobials were tailored to culture and sensitivity and he was started on cefepime. WBC count trended down to 10 000 and subsequent blood cultures became negative. Despite negative blood cultures he remained febrile and had continuous thick and brownish secretions. Repeat sputum culture showed upper respiratory flora. Computer tomography scan of the chest without contrast was done, which showed persistent bibasilar opacities with small to moderate right pleural effusion and small left pleural effusion ( and ). Possible thoracentesis and bronchoscopy were planned. The patient responded to cefepime to some extent with negative blood cultures and trending down WBC count but at this point coinfection with other antimicrobial could not be ruled out as the patient was still spiking fever and thick brownish sputum. The patient’s prognosis considering his old age and multiple comorbid conditions was discussed with the family and they decided to pursue no further medical interventions including thoracentesis and bronchoscopy. Comfort care measures were initiated and he was transferred to palliative medicine service.


We present the case of a 42-year-old female patient with no significant pathological history. She presented at the Department of Emergency Ophthalmology, claiming a drop of vision in the left eye (LE), which gradually installed during the last 48 hours before she presented at the Emergency Department. There was no history of ocular trauma or surgery.
The ophthalmic evaluation at the time of admission revealed a well-contoured and normally colored optic disc, retinal hemorrhage radiating from the inferotemporal optic disc margin with a flame shaped aspect, dot-spot retinal hemorrhages and low foveolar reflex, at the right eye (RE). At the left eye (LE), an elevated optic disc with moderate retinal oedema marked retinal hemorrhages, and preretinal hemorrhage with no foveolar reflex. The slit lamp examination of the anterior segment was normal for the RE and delayed RFM for the LE.
The visual acuity (VA) for the RE was 0.9 with correction and for the LE was counting fingers at 1 meter, not correctable.
In the first stage of biohumoral status assessment, we performed blood tests such as CBC, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, blood glucose test, lipid profile, total serum protein and thyroid markers. The results of blood test showed a severe pancytopenia with 1.43 X 10³/ µl leukocytes, 24 X 10³/ µl thrombocytes and severe low levels of Hb 5 g/ dl, inflammatory markers were high, erythrocyte sedimentation rate ESR 60 mm/ h, CPR 17.63 mg/ l, lower fibrinogen levels 94.77 mg/ dl. Given the analyses, we suspected disseminated intravascular coagulation and we performed D- Dimeri test with positive result.
Interdisciplinary medical evaluations were made by colleagues from internal medicine, cardiology and hematology departments. In the multidisciplinary team, we decided to complete the investigations with Hemostasis Analyzer Markers (Pts, Ptr, INR, and APTT), which suggested a hemostasis disorder. Lactate dehydrogenase test, Polymerase chain reaction (PCR) and ferritin were on high levels, serum iron was on low levels, negative serology for HIV, Hepatitis B and Hepatitis C, anti-thyroid peroxidase antibodies (anti-TPO antibodies) and the thyroid hormones within normal limits. At the time of admission, the CT for head segment did not indicate pathological changes.
A bone marrow aspiration and biopsy were made. Leukocyte concentrate, cytological blood smear test, and the cytological examination of the spinal cord were inconclusive because they showed a low percentage of promyelocytes of approximately 8% and blasts of approximately 6%. Due to the patient’s general condition changing with the onset of fever we decided to transfer her to the intensive care unit. Given the unfavorable evolution, we repeated the CT for head segment, which showed multiple supratentorial lesional processes predominantly in the white matter and calf body and a few isolated thalamic lesions that raised the suspicion of brain microabscesses in a septic context (). The head CT also revealed a modulation of signal diffusion in the left eye-viewable on the hemosiderin-susceptible sequence in moderate hyposignal, which almost totally interests the vitreous body, possibly hemorrhagic.
At the CT for thorax and abdomen, we found multiple pulmonary outbreaks spread in both lungs, parapneumonic pleurisy of 6 mm on the right and 5 mm on the left, pelvic ascites fluid with infiltrative appearance around the genitals. Blood culture test was negative; RT-PCR Sepsis test was negative for S. aureus, Enterococcus faecalis, Streptococcus agalactiae, Enterobacteriaceae, Candida spp and Pseudomonas aeruginosa.
The examination of the posterior pole revealed marked changes of the retina and optic disc with massive hemorrhages that practically covered a large part of the posterior pole for the LE and for the RE extensive retinal hemorrhage, marked papillary edema, both eyes with vitreous condensation (,). It was difficult to determine the patient’s VA given the general altered status.
The patient was transferred to the hematology department having an extended mucosal cutaneous hemorrhage syndrome (), hepatic cytolysis syndrome and started the specific treatment for LAM3 with Vesanoid 45 mg/ m2 - 80 mg/ day. The general status of the patient worsened, becoming confused, jaundice with haematological status in the collapse with WBC=55.76 X 10³/ µl, Neutrophils 0.00 X 10³/ µl, Lymphocytes 0.00 X 10³/ µl, Monocytes 0.00 X 10³/ µl, Eosinophils 0.00 X 10³/ µl, Basophils 0.02 X 10³/ µl, she had PLT=8 X 10³/ µl, Hb=7.7 g/ dl.
In the hematology department, the test battery was extended with flow cytometer, PML RAR alpha transcript t 15, 17, and immunohistochemistry. The result of PML RAR alpha screening transcript (15;17) was positive.
The patient received antibiotics, red blood cell transfusion, freshly frozen plasma platelets, cryoprecipitate, corticosteroid, and haemostatic. Due to severe coagulopathy and severe fibrinogenemia, she received treatment with Haemocomplettan fibrinogen concentrate.
Thirteen days after admission, the patient suffered a respiratory cardiac arrest and died. Later on, after the patient died, the result of Bone Marrow Biopsy revealed a hypercellularity with intertrabecular infiltration of blastic cells with cytoplasmic granulations and Auer rods, about 80-90% of the total cells.


An 18-year-old female was admitted to our hospital with chief complaints of acute onset vertigo and severe headache for the last 6 hours. Soon after hospitalization, she developed 2 episodes of generalized tonic-clonic seizures. There was past history of left hemiparesis 8 years back with recurrent episodes of vertigo and headache. There was no history of fever, head injury, ear discharge, and diplopia. There was no significant family history. On general examination, patient's blood pressure was 150/78 mmHg at the time of admission, and rest examination was unremarkable. Her sensorium was improved after 1 hour. Higher mental functions were normal. The functions of cranial nerves were intact. Motor, sensory examination was normal and deep tendon reflexes were well preserved. The patient was further evaluated with biochemical and haematological investigations. Complete blood count, electrolytes, and blood sugar level were normal. MRI brain was done which showed infarct in right gangliocapsular region (). We further evaluated the patient with cerebral angiography which showed occlusion of the right middle cerebral artery (M1) just distal to origin with the appearance of moyamoya collaterals (Figures , , and ). Right internal carotid artery showed reduced calibre in comparison to left, likely due to stenosis. Since our patient has a history of stroke, we further investigated the underlying cause. On subsequent investigation for thrombophilia profile, homocysteine level was moderately increased (42 micromole/litre) (), and rest coagulation profile was unremarkable. We treated the patient conservatively with cobalamin, B-6, folic acid, and aspirin. The patient was advised for neurosurgery consultation for revascularization and further follow-up.
The patient successfully underwent surgical revascularization and at 3-month follow-up, the patient was symptomatically better.


A 44-year-old G2P1011 female with no significant past medical history presented to the emergency department (ED) with a 2-week history of vaginal bleeding. The patient also complained of mild fatigue and dizziness along with left lower quadrant abdominal pain. Her last menstrual period was 8 weeks prior to the ED visit. The patient was tachycardic (heart rate 138 beats per minute) with otherwise normal vital signs. On physical examination, the patient had mild suprapubic tenderness, and the pelvic examination showed a closed external os with active vaginal bleeding. Her hemoglobin and hematocrit were 10.0 g/dL and 29.5%, respectively; serum beta-hCG was 71,964 mIU/mL. The preliminary transvaginal ultrasound report indicated an 8-week intrauterine pregnancy with cardiac activity, but the subsequent official report by a radiologist confirmed a cervical ectopic pregnancy (CEP) located at the posterior wall of the cervical canal (). The patient's tachycardia did not improve despite 2 L normal saline bolus, so she was given 2 units of packed red blood cells (PRBCs).
Due to the hypervascularity of the cervical ectopic pregnancy, the obstetrics consultant recommended uterine artery embolization (UAE) via interventional radiology. The pelvic angiogram revealed that the ectopic pregnancy was supplied mainly by the left uterine artery (); however the ascending components of both uterine arteries were selected with a microcatheter and embolized with Gelfoam (9 cc for right and 6 cc for left, resp.). Postembolization images showed satisfactory occlusion of blood flow ().
The patient was stable after BUAE and was transferred to the floor. In addition, intramuscular methotrexate (MTx) 1 mg/kg was given on day 1. Consequently, vaginal bleeding stopped, beta-HCG dropped to 16,086 mIU/mL, and her vital signs remained within normal limits. She was given folic acid on day 2 to neutralize the effects of methotrexate. Her remaining hospital course was uncomplicated and her beta-HCG trended down to 3,646 mIU/mL on day 3. She received a second dose of methotrexate 1 mg/kg IM on day 3 and was discharged home with no further vaginal bleeding. On follow-up day 35, the patient's beta-HCG was less than 1 mIU/ml. All symptoms had resolved and no further intervention was required. The patient was last seen in the clinic on day 51 for IUD placement. Her menstrual cycle was not reported.


An 83-year-old man on clopidogrel for coronary artery disease presented to the emergency department of our institution with symptoms of anaemia for the past 3 weeks (Table ) including increasing fatigue and increasing shortness of breath on exertion. He denied any per rectal bleeding or change in bowel habits and had no significant weight loss. He was noted to have a large partially reducible right inguinoscrotal hernia on examination containing bowel (Fig. ) which he stated had been present for more than 10 years, which had remained unchanged in size in the last few years.
His other significant background consisted of hypertension, three previous transient ischaemic attacks, type 2 diabetes mellitus and had a permanent pacemaker for sick sinus syndrome.
Colonoscopy demonstrated a large non-obstructing tumour located at the ascending colon. The tumour was confirmed as adenocarcinoma on histopathology.
Further investigations included a CEA level of 2 μg/L and computed tomography of the chest and abdomen which did not demonstrate metastatic disease but that the ascending colon tumour was located in his right inguinoscrotal hernia (Fig. ).
He underwent a laparoscopic right hemicolectomy. The caecal pole was adherent to the scrotal sac, and the adhesion was deemed to be inflammatory related rather than direct invasion from the tumour. Laparoscopic adhesiolysis was performed with a moderate degree of difficulty. A 30° laparoscope was used and inserted into the inguinoscrotal hernia for an angled view (Fig. ). Bowel manipulation was performed with atraumatic graspers, and adhesiolysis was achieved by an energy device (Olympus Thunderbeat™). Further mobilisation followed a standard lateral to medial approach, followed by inferior to superior mobilisation. The omentum was dissected off the transverse colon, lesser sac entered and hepatic flexure to transverse colon was mobilised. The ileocolic pedicle was isolated and stapled, and the diseased colon was delivered through the umbilical port site. A resection and a functional end-to-end anastomosis were performed with the GIA™ 80 mm stapler (Medtronic). Pneumoperitoneum was then re-established, and the deep ring was closed snugly around cord structures with 2-0 V-Loc™ (Medtronic) non-absorbable sutures laparoscopically.
He had an unremarkable post-op recovery and was discharged home after 7 days. There was no recurrence of the inguinoscrotal hernia at his 4-week post-operative review.
Histopathology confirmed that the ascending colon mucinous adenocarcinoma had invaded partially into serosa with clear resection margins. Four out of 15 lymph nodes were positive. TNM staging was T4aN2aM0 with an R0 resection.
Given the high-risk cancer and poor prognostic features, he is currently being planned for adjuvant capecitabine monotherapy.