A 27-year-old female presented to our clinic with the complaints of glare and intolerance to light in her left eye (LE) after an ICL (STAAR V4C model) implantation in both eyes (BE) done 3 months back, elsewhere. The preoperative refractive error was -5 D in BE. The preoperative reports showed that BE had a similar white-to-white (WTW) measurement of 11.8 mm and anterior chamber depth (ACD) of 3.1 mm in BE. Hence, a similar-sized nontoric ICL of 13.2 mm size was implanted in BE by the referring primary surgeon. At presentation, uncorrected visual acuity (UCVA) in her right eye (RE) was 20/20, N6 and that of (LE) was 20/30, N6. Slit-lamp evaluation of RE showed clear cornea with peripheral anterior chamber depth (PACD) of ½ corneal thickness (CT). Pupil was 3 mm, round, regular and reactive []. ICL was in place with a slit lamp vault of 1 CT. In the LE, cornea was clear, AC was quiet with PACD of ¼ CT. Pupil was 8 mm dilated and fixed []. ICL was in place with optic capture at the pupillary border at 4 o'clock []. Slit lamp vault of the ICL was approximately 2 times CT. Lens was clear with 16 mm Hg IOP. At presentation, patient was on topical Pilocarpine Hydrochloride 2%, Brimonidine tartarate 0.2%, Timolol maleate 0.5% combination in LE. Gonioscopy showed open angles up to scleral spur in the RE and LE showed 2700 peripheral anterior synechiae. Anterior segment optical coherence tomography (AS-OCT, Optovue) showed ICL vault of 675μ in the RE and 998μ in the LE []. Fundus evaluation showed a healthy disc with cup disc ratio of 0.3:1 in BE.
A diagnosis of high ICL vault in LE with secondary angle closure and anisocoria was made. Under peribulbar anesthesia, after forming the AC with viscoelastic, the ICL was gently manipulated by ICL manipulator from the side port incision and rotated from horizontal to vertical meridian under the iris, without getting it into the AC. After relieving the pupillary capture, intracameral pilocarpine was injected to constrict the pupil. As the pupil did not constrict, a pupilloplasty was performed. The previous temporal clear corneal incision was opened with a sharp keratome. A needle of the 10-0 prolene suture was passed from superior side port. A microforceps was passed from the main temporal incision to grasp the superior iris through which the needle was passed. A 26-G needle was passed through the inferior side port into the AC and then pierced through the inferior part of the iris. The needle of the prolene suture was then passed into the barrel of the 26 G needle and the needle was pulled out of the AC through the inferior side port []. The suture at the inferior side was brought out through the superior sideport as a loop using an IOL dialer. A single-pass four throw technique was used to create a helical loop. Later, the superior and inferior ends of the suture were pulled to create a knot at the iris plane, in the AC approximating the iris []. A similar procedure was repeated on the other side. At the end of the procedure the pupil size was reduced to 4 mm. After thorough viscoelastic removal, the eye was patched.
On postoperative day 1, UCVA was 20/25, cornea was clear with IOP 12 mm Hg in the LE. The pupil size was around 4 mm []. The ICL vault reduced to 204 microns on AS-OCT []. She was prescribed topical prednisolone acetate 1%, moxifloxacin 0.5% every 2 hourly.
At the last follow up of 12 months, the patient was asymptomatic the UCVA in LE remained at 20/25 and near vision of N6 with an IOP of 11 mm Hg and a ICL vault of 270 microns.


An 80-year-old man was injured in a head-on collision with an oncoming vehicle. He was transported to our hospital by doctor car. During the whole-body evaluation, we diagnosed him with traumatic gastric perforation, right femoral trochanteric fracture (AO 31-A3), right femoral shaft fracture (32-A3), right patellar open fracture (91.1-A1), right tibial plateau open fracture (41-C1), right tibial shaft open fracture (42-A3), right lower leg severe crush wound, right fibula fracture (42-B2), and left distal radius fracture(23-A2) (, ). Hemorrhage from his right lower leg wound could not be controlled with compression, and his vital signs indicated that he was in shock. The mangled extremity severity score [] was 8 points. Taking into consideration the abdominal trauma, his age, and the severity of the lower leg wound, we performed right above-the-knee amputation for lifesaving purposes and to decrease the treatment period. Following amputation, we performed laparoscopic gastrorrhaphy. Considering the patient’s general condition, we decided to perform the femoral trochanteric osteosynthesis operation in two stages. His whole-body management was completed in the intensive care unit. Because he experienced severe hip pain during body movements, after ensuring that his general condition was stable, we performed internal fixation for the right femoral trochanteric fracture on the 5th day after the injury.
While the patient was under general anesthesia, we first inserted a 2.4 mm Kirschner wire under fluoroscopic guidance 3 cm proximal to the femoral cut end and attached a horseshoe and traction rope to it (). Then, we tightened the rope to the foot piece of the traction table and secured it (). Since there is a risk of injury to the femoral arteriovenous vein when inserting the Kirschner wire, the position of the blood vessel was confirmed in advance by ultrasonography. Although shortening of the bone fracture was reduced by traction, rotation control was impossible; therefore, the horseshoe was manually controlled through clean sheets during surgery to reduce rotational displacement (). We performed internal fixation surgery using a trochanteric femoral nail in the usual manner (). The patient began transfer to a wheelchair with pain relief the day after surgery, and he started walker walking 2 days after surgery.


Case 1: A 58-year-old woman with a diagnosis of bronchiectasis presented with recent hemoptysis and was admitted to our hospital, in which TAE was performed (). The left angiogram of the left bronchial artery showed that it had a co-trunk with the esophageal arteries, a giant saccular cast at the origin of the left bronchial artery (somewhere between the fourth and fifth ribs), and several tortuous bronchial arteries. Subsequently, a microcatheter was advanced to a tortuous artery under fluoroscopic guidance, and we injected the gel foam to distally embolize the bronchiectatic arteries. Then, 29 steel coils (2/3 mm*20 mm, 2 mm/4 mm*40 mm, and 3 mm*30 mm) were used to occlude the BAA and arteries. The right bronchial arteriography also showed several engorged and tortuous arteries; thus, we used the same method, injecting three steel coils and the gel foam to occlude the afferent artery to stop the bleeding. The post-artery angiography showed no definite enhancement of the aneurysm, and the patient’s hemoptysis disappeared.


The first patient was a 66-year-old man with unremarkable general health, having a history of right eye gradual visual deterioration, and on dilated fundus examination presenting an inferior exudative retinal detachment which extended up to the inferior vascular arcades. The B-scan ultrasound showed an elevated diffuse sessile lesion of 2.7 mm in thickness and 23 mm in longitudinal base, with low-to-medium internal echogenicity. Due to the extensive retinal detachment and the poor visualization of the lesion, diffuse CM, intraocular lymphoma, and choroidal metastasis were included in the differential diagnosis. The systemic screening denied any primary malignancies elsewhere or metastatic deposits from the primary intraocular tumor; therefore, vitrectomy with choroidal biopsy and injection of silicone oil was performed. The histopathological examination confirmed the diagnosis of CM, and due to the large tumor size, the patient underwent primary enucleation. The pathological examination of the enucleated globe disclosed extramedullary hematopoiesis within the iris []. The iris on clinical examination before surgery was described as normal.


The second patient was a 56-year-old male in good general health and with a family history for CM; he presented with a visual field defect in the right eye and fundal examination revealed a choroidal mass nasal to the optic disc with associated exudative retinal detachment; the B-scan ultrasound showed that the lesion had a thickness of 5.2 mm and low-to-medium internal reflectivity. The tumor was treated with Ruthenium plaque brachytherapy followed by two sessions of diode laser thermotherapy; unfortunately, 5 years later, the patient developed recurrent vitreous hemorrhages that rendered necessary vitrectomy, later complicated by intractable neovascular glaucoma and hyphema, which led to secondary enucleation. The pathology disclosed spindle cell-type CM and the iris showed focal EMH [Figure and ].


The third patient was a 75-year-old male referred to our service for an unexplained vitreous hemorrhage. Initially, he underwent vitrectomy and injection of silicone oil followed by silicone oil and cataract removal that was subsequently complicated by hyphema with blood dispersion in the anterior chamber precluding iris and fundal view; the B-scan ultrasound detected a lesion of 5.1 mm in elevation and 12.4 mm and 12.1 mm of longitudinal and transverse base, with low-to-medium internal echogenicity and intrinsic blood flow highly suggestive of CM. Three months after, the patient underwent enucleation as the absent view of the tumor did not allow any globe-saving treatments. The histopathological examination confirmed the diagnosis of spindle cell-type CM and EMH in the iris stroma [].
In all three cases, no vortex vein invasion or extrascleral extension was observed. In all patients, at the time of diagnosis, the systemic investigations denied primary malignancies elsewhere or metastatic deposits from the primary intraocular malignancy. To date, all patients are alive and none had developed metastatic disease.


A 9-year-old boy was admitted to our hospital with a history of headache and vomiting for 2 days, accompanied by a single episode of transient weakness in his legs, and altered consciousness for half a day. Ten days before admission, he hit his head against an ice surface in a fall. He experienced no neurological symptoms after hitting his head and did not go to the hospital. Upon arrival, he was conscious, his muscle strength was symmetrical, and deep tendon reflexes were normal and symmetrical. His neck was stiff, but he had no other neurological deficits. His weight was 52 kg; height: 145 cm; body mass index: 24.7 kg/m2 (>P97). Magnetic resonance imaging (MRI) of vascular plaque in the patient’s head and neck revealed right internal jugular vein, transverse sinus, and sigmoid sinus thrombosis (). MRI of the head showed right temporal-parietal lobe hemorrhage (). The results of a comprehensive thrombophilia workup constituting protein C activity, protein S activity, antithrombin III, antiphospholipid syndrome antibody, and homocysteine concentration were normal. A thrombophilia workup was performed routinely to evaluate acute thrombosis of unknown cause. The D-dimer level was 90.65 nmol/L (range: 0–16.13 nmol/L), and routine blood laboratory evaluation revealed hemoglobin: 120 g/L, platelets: 182 × 109/L, and leukocytes: 13.2 × 109/L with neutrophilia. Tumor marker concentrations were within normal ranges and constituted free prostate-specific antigen, alpha-fetoprotein, prostate-specific antigen, non-small cell lung cancer-associated antigen, neuron-specific enolase, carbohydrate antigen 199, carbohydrate antigen 72-4, and carcinoembryonic antigen. He was treated with glycerol fructose. Thrombectomy was not performed owing to his stable condition and mild symptoms, and because of the intracranial hemorrhage, anticoagulant therapy was not started. His neurological symptoms resolved, and he was discharged. One month after discharge, repeat brain MRI showed that the thrombus had not disappeared, although the signal intensity was lower than in the first scan. MRI also showed that the intracranial hemorrhage was smaller; therefore, we did not initiate anticoagulation.
He returned to our hospital with an intermittent fever, 3.5 months after discharge. In the outpatient department, the attending doctor considered infection and performed routine blood evaluation, which showed hemocytopenia. Therefore, leukemia was suspected, and the patient was admitted to the hospital. Bone marrow aspiration and immunophenotyping revealed ALL with intermediate risk owing to central nervous system leukemia. Brain magnetic resonance venography (MRV) revealed right transverse sinus and sigmoid sinus thrombosis (), which was noted previously. The child had no neurological symptoms; therefore, we did not initiate anticoagulation. He was started on induction therapy comprising vincristine, daunorubicin, L-asparaginase, and corticosteroids. Cerebrospinal fluid pressure was within normal limits, and flow cytometry of the cerebrospinal fluid analysis revealed 27.32% abnormal immature B cells and only 5 white blood cells. After chemotherapy, bone marrow analysis demonstrated that the leukemia was in remission. The patient presented with severe vomiting 22 days after chemotherapy. The fibrinogen concentration had decreased to 0.72 g/L (range: 1.8–4.0 g/L), and cerebral MRV showed right sigmoid sinus, transverse sinus, and sagittal sinus thrombosis (). Computed tomography (CT) of the head revealed hemorrhage alongside the cerebral falx (). L-asparaginase was stopped, and owing to the intracranial hemorrhage, we did not start anticoagulation. Four days after developing the new CVST, the patient presented with persistent seizures and left-sided weakness. CT of the head showed right frontal lobar hemorrhage (). Because he was receiving anti-epileptic drugs, mannitol, and glycerin fructose, he showed remarkable improvement in the left-sided hemiplegia with only residual grade II weakness in his upper left extremity and focal seizures. However, the parenchymal hemorrhage worsened (). He continued to receive dehydrating therapy and antiepileptic drugs, and eventually, his neurological symptoms resolved completely. Brain CT showed that the hemorrhage had been absorbed, and he received L-asparaginase again 50 days after L-asparaginase cessation.


An Italian Caucasian 28-year-old woman was transported by ambulance to the emergency room (ER) on 27 July 2019, due to sudden and progressive dyspnoea, epigastric pain, and palpitations occurring while she was at the beach. The patient denied relevant pathological medical history except for short-lasting episodes of palpitations. She was on no regular medication and denied substance abuse.
Early medical examination in the ER revealed paleness, cold sweat, epistaxis, and signs of pulmonary oedema due to a new-onset atrial fibrillation with rapid ventricular response (170 b.p.m.); blood pressure (BP) was 230/110 mmHg and SpO2 was 96%.
Blood tests revealed leucocytosis, hyperglycaemia (309 mg/dL—normal range 70–110 mg/dL) and troponin T elevation (151 ng/L—normal range 0–14 ng/L). Blood gas analysis showed metabolic acidosis. Electrocardiogram revealed ST-segment depression in the lower lateral leads. Transthoracic echocardiogram (TTE) was performed too, showing 33% left ventricular ejection fraction (LVEF) with diffuse akinesia.
The patient was sedated, intubated and mechanically ventilated. Polypharmacological therapy, including amiodarone, bisoprolol, nitroglycerine, furosemide, ticagrelor, acetylsalicylic acid, heparin, ceftriaxone, and pantoprazole was started.
The patient was subsequently transferred to a II level emergency department. At her arrival, she presented with anisocoria, BP was 220/100 mmHg, heart rate was 160, and SpO2 was 74%. Blood gas analysis showed persistent severe metabolic acidosis with elevated lactate levels (5.8 mmol/L—normal value <2 mmol/L). A new TTE was performed, showing 20–30% LVEF. Chest X-ray revealed bilateral symmetrical and diffuse alveolar opacities ().
Given the sustained hypertension (mean arterial pressure 140 mmHg), despite sedation and maximal pharmacological therapy, resulting in progressive haemodynamic impairment with low ejection fraction, severe pulmonary oedema, and metabolic acidosis, the patient underwent urgent venoarterial extracorporeal membrane oxygenation (VA ECMO) in the cath lab. Coronary angiography did not show any coronary artery stenosis. A percutaneous left ventricular assist device (IMPELLA) was implanted. Three endomyocardial biopsies were obtained, subsequently turning out to be negative for myocarditis but suggestive of catecholamine-induced cardiomyopathy. The patient was then admitted to the cardiothoracic intensive care unit.
In the following day, she developed thrombocytopenia (platelet count of 33000 plt/mm3—normal range 150 000–450 000 plt/mm3) and acute kidney injury requiring renal replacement therapy (RRT).
On 29 July, sedation was transiently stopped. Neurological evaluation revealed right hemiplegia. Cerebral computed tomography (CT) scan showed hypodense (ischaemic) bilateral parieto-occipital areas and a hypodense subcortical area in the left frontal lobe (). Abdominal CT scan revealed a 5 cm tumour of the left adrenal gland compatible with pheochromocytoma ().
On 30 and 31 July, ECMO and IMPELLA were respectively removed, due to a gradually recovery of the LVEF. Hypertensive crisis and episodes of atrial fibrillation were treated with urapidil, esmolol, and amiodarone. CT scan was repeated confirming the previous findings.
As it was not possible to determine urinary metanephrines due to the ongoing RRT, on 1 August, plasmatic catecholamines were dosed, showing increased adrenaline and noradrenaline levels and therefore confirming pheochromocytoma diagnosis.
On 2 August, magnetic resonance imaging of the brain confirmed the presence of bilateral parieto-occipital ischaemic lesions of recent onset. Ischaemic lesions of the right cerebellum, right centrum semiovale and left frontal subcortical region where also found. Intense vasogenic oedema accompanied these lesions (), thus suggesting the diagnosis of posterior reversible encephalopathy syndrome (PRES).
On 5 August, the patient was transferred from the cardiothoracic intensive care unit to the Department of Shock and Trauma of the same hospital. Neurological evaluation showed persistence of the right hemiplegia. She was still sedated, intubated and mechanically ventilated. Sedation with sufentanil, propofol, and dexmedetomidine improved BP control. Moreover, antihypertensive therapy with doxazosin 16 mg/day and labetalol by continuous intravenous infusion was started, leading to rapid BP and heart rate control. Due to persistent oligo anuria, RRT was continued.
The following days, haemodynamic stability was reached: labetalol infusion was stopped and doxazosin administration was reduced up to 4 mg × 2/day.
On 13 August, left videolaparoscopic adrenalectomy was performed. Histological analysis confirmed the diagnosis of pheochromocytoma. The same day, doxazosin treatment was stopped. On 14 August, the patient was extubated. She was discharged from our department on 22 August. She was conscious; no residual focal deficit could be detected at neurological examination. She was breathing spontaneously. RRT had been stopped due to autonomous diuresis.
On 25 August, she was discharged from hospital. TTE was repeated before discharge, revealing complete recovery of left ventricular systolic function (LVEF 58%). Grade I diastolic dysfunction persisted, as suggested by E/A reversal (ratio < 1.0).


A 66-year-old female with gait disturbance slipped and fell off her wheelchair at home. She was right-handed and needed a wheelchair in everyday life due to leg weakness of unknown origin. She did not take any medications. She presented to the orthopaedic department of a local hospital complaining of right shoulder pain. Physical examination revealed marked swelling around the right shoulder joint. Additionally, pulsations of the right radial and ulnar arteries were weak but palpable. She also had radial nerve palsy; however, this paralysis gradually ameliorated during physical examination. Right shoulder radiograph showed a proximal humerus fracture with medial displacement of the humeral shaft (), for which closed reduction was attempted under intravenous anaesthesia. Although the humeral shaft displacement was improved after the attempt (), radial and ulnar pulsations were no longer palpable. Therefore, she urgently transferred to our hospital by helicopter. At the time of arrival, her vital signs were stable. Laboratory tests showed the abnormal values in C-reactive protein levels (6.7 mg/L, reference range <1.4 mg/L), creatinine phosphokinase levels (291 IU/L, reference range 41–153 IU/L), and extended activated partial thromboplastin time (41.7 s, reference range 24.0–39.0 s). Haemoglobin (12.3 g/L, reference range 11.6–14.8 g/L), creatinine (0.67 mg/dL, reference range 0.46–0.79 mg/dL), platelets (262 × 109/L, reference range 158–348 × 109/L), prothrombin time (12.8 s, reference range 10.7–12.9 s), and fibrinogen (400 mg/dL, reference range 200–400 mg/dL) were within reference range. Computed tomography (CT) angiography revealed disruption of the right axillary artery () along with contrast medium extravasation and a large haematoma (). Emergency angiography via the right common femoral artery was attempted to confirm the site of injury of the axillary artery after intravenous administration of heparin. However, the prominent meandering of the abdominal aorta and brachiocephalic artery hindered manipulation of the various catheters. Finally, right subclavian angiography was performed using a 4-Fr internal mammary artery catheter, which revealed disruption of the axillary artery distal to the origin of the subscapular artery () and presence of a collateral artery supplying blood to the right brachial artery (, ). In consultation with vascular surgeons, we decided to attempt performing endovascular treatment via the right femoral artery; however, it was impossible due to the pronounced meandering of the abdominal aorta and brachiocephalic artery. Therefore, we attempted to puncture the pulseless right brachial artery under ultrasound guidance, but we were unsuccessful. Fortunately, we were able to cross the breach in the axillary artery using a 0.014-inch guidewire (Cruise®, ASAHI INTECC, Japan) supported by a microcatheter through the 4-Fr internal mammary artery catheter via right femoral artery (, ), and subsequent contrast injection via the microcatheter showed flow in the right brachial artery (). We subsequently successfully punctured the right brachial artery using the guidewire inserted into the right brachial artery across the disrupted axillary artery as a marker (, ). Then, a 6-Fr sheath was inserted into the right brachial artery, and the guidewire which was advanced via right femoral artery was extracted through the 6-Fr sheath in the right brachial artery using a snare catheter (, ). Next, the site of thrombotic occlusion of the axillary artery was observed using an intravascular ultrasound probe (AltaView®, Terumo, Japan) inserted via the brachial artery (), which demonstrated thrombosis and dissection of the axillary artery () and the vessel diameter ranges from 4.5- to 5.0-mm at the occluded lesion and proximal normal axillary artery. We expanded the occluded lesion using a 3.5 mm × 40 mm sized balloon and placed a 5.0 mm × 50 mm Viabahn stent graft (Gore, Flagstaff, AZ, USA) across the lesion via a brachial artery (). Furthermore, the stent graft was dilated with a 5.0 mm × 40 mm sized balloon. The final subclavian injection ensured that distal flow to the brachial artery was preserved and that there was no leakage of contrast medium from the axillary artery (, ). Intravascular ultrasonography images revealed adequate expansion of the stent graft (). After the procedures, the right brachial, radial, and ulnar arteries were well palpable. Computed tomography angiography performed the day after the procedure showed good patency and no dye leakage from the right axillary artery. The patient received dual antiplatelet therapy with aspirin and clopidogrel after the procedure. The shoulder replacement surgery was needed and scheduled, and the patient was then discharged 24 days after the procedure. At 12 months after discharge, the patient had no neurological symptoms, and the radial and ulnar arteries were well palpable. There were no abnormal findings suspecting restenosis or occlusion of the axillary artery.


One year and 6 months ago, a 49-year-old man with biopsy-proven prostate cancer (Gleason score 4 + 5), serum prostate-specific antigen (PSA) level of 15.0 ng/mL and clinical stage of T2N0M0 underwent maximum androgen blockade (MAB) therapy and high-dose brachytherapy (110 Gy) as initial treatments. One year and 2 months ago, he received external beam radiotherapy (39.6 Gy). The PSA value reached the nadir of 0.053 ng/mL; however, the PSA value gradually increased to 6.53 ng/mL and CRPC was diagnosed. He underwent fluorodeoxyglucose (FDG) PET/CT and 11C-choline PET/CT examination to evaluate the patient's current disease status for restaging. Although FDG PET/CT showed no abnormal FDG uptake in the whole body (Fig. ), 11C-choline PET/CT showed a tiny left obturator lymph node measuring 8 mm with abnormal 11C-choline uptake (maximum standardized uptake value of 6.28), suggesting one lymph node metastasis (Fig. ). Under the diagnosis of oligometastasis, he received intensity-modulated radiation therapy (IMRT) (Fig. ) and MAB (goserelin acetate and bicalutamide) was restarted. PSA value gradually decreased and reached nadir (0.091 ng/mL) after 6 months. However, the PSA value increased to 0.24 ng/mL at 10 months after the start of IMRT and new hormonal therapy (Abiraterone) was started, which improved the PSA level to 0.028 ng/mL after 7 months.


An 81-year-old man with a history of persistent non-valvular AF, heart failure with reduced ejection fraction (HFrEF), diabetes mellitus, and hypertension (CHADS2-VASc score 6 and HAS-BLED score 3) was deemed a poor candidate for anticoagulation because of recurrent falls and history of GI bleeding. He was selected for the WATCHMAN device. The initial procedure was aborted after significant resistance to device advancement was encountered in the right femoral vein. Bilateral lower extremity venography demonstrated totally occluded femoral and iliac veins bilaterally (. Given no transvenous access to the inferior vena cava, the decision was made to implant the device via a transhepatic approach.
Under general anaesthesia and fluoroscopic guidance, percutaneous transhepatic access to the right hepatic vein was achieved by an interventional radiologist under sterile condition (. First, a skin incision was made below the costal margin at the mid-axillary line. The trajectory of the needle was guided by the visualization of the hepatic vein. The needle was advanced with intermittent gentle aspiration until blood is obtained, and then the contrast was injected to visualize entry into the hepatic vein. Once the needle entered the hepatic vein, a 0.035-inch wire was advanced via the hepatic vein into the superior vena cava. A Cook Medical (Bloomington, IN, USA) 16 Fr Check-Flo Performer introducer was passed over the wire and situated at the inferior vena cava. A St. Jude Medical (St. Paul, MN, USA) SL1 long 8.5 Fr introducer (curve type SL1™, sheath usable length 63 cm and dilator usable length 67 cm) was passed over the wire to the superior vena cava. A standard shape Brockenbrough (BRK) extra sharp needle (St. Jude Medical, St. Paul, MN, USA), was advanced into the sheath. Under transoesophageal echocardiogram (TOE) and fluoroscopic guidance, the sheath was advanced to the interatrial septum. At the mid-level of the intact septum, a posterior puncture was performed and the SL1 was advanced into the left atrium. The patient was anticoagulated with heparin with an activated clotting time (ACT) goal of 200 s given transhepatic access. An Amplatz Super Stiff (Boston Scientific, Natick, MA, USA) 0.035-inch wire was advanced to the left superior pulmonary vein. The SL1 was exchanged for a Boston Scientific double curve WATCHMAN 14 Fr delivery sheath. A 6 Fr pigtail catheter was utilized to direct this sheath into the LAA. A 27-mm WATCHMAN device was chosen after the angiography of the LAA. Under apnoeic conditions, the device was deployed (Video 1) with angiography and TOE confirming the seal of the appendage. The 16-Fr delivery sheath was then utilized to perform final venograms. After device delivery, the vascular sheath was injected with contrast for hepatic venography. A 6-Fr Terumo destination sheath was then advanced into the lumen of the 16-Fr sheath and we sequentially deployed two 10-mm Amplatzer occluding plugs (AGA Medical, St. Paul, MN, USA) in the transhepatic tract. The plugs were sequentially forming a characteristic dog bone appearance (Video 2). Complete hemostasis was achieved. Final TOE demonstrated no significant pericardial effusion. Due to the manipulation of the vasculature in that area, he was monitored for 48 h to rule out any signs and symptoms of bleeding. After his vital signs, physical exam and labs remained stable for 48 h, oral anticoagulation with rivaroxaban and antiplatelet therapy (with aspirin) was started. He had an uneventful hospitalization and was discharged home after 3 days. No adverse events were reported at follow-up. He was instructed to continue rivaroxaban and aspirin for 6 weeks, switch to aspirin and clopidogrel until 6 months, and after that aspirin alone.


A 50-year-old female who had a history of positive hepatitis B surface antigen for more than 10 years presented to The Infectious Department of our hospital complaining of aggravating anorexia and fatigue. During her presentation in The Infectious Department, she had nausea and vomit symptoms.
The patient’s symptoms started a week ago with gradually increasing gastrointestinal symptoms including anorexia and nausea. Her liver function tests showed elevated transaminases.
She had a past medical history of being a carrier of HBV for more than 10 years without antiviral treatment. She had no cardiac function abnormalities, arterial hypertension or diabetes mellitus. She had no negative drug history, and no alcohol intake.
The patient reported that her four siblings were infected with HBV, her mother died from hepatocellular carcinoma, and her father was in good physical condition.
After admission, the patient’s temperature was 36.6 °C, heart rate was 91 bpm, respiratory rate was 20 breaths per minute, blood pressure was 145/104 mmHg and oxygen saturation in room air was 99%. The patient was 160 cm tall and weighed 53 kg. The clinical examination revealed light scleral icterus without any other pathological signs.
Laboratory values on admission and during hospitalization are shown in Table . A series of tests were performed after admission to The Infectious Disease Department. Blood analysis revealed the following: Alanine aminotransferase, 575 U/L; Aspartate aminotransferase, 593 U/L; Total bilirubin, 108.3 μmol/L; Alkaline phosphatase 116 IU/L; Positive hepatitis B surface antigen, anti-LKM-1 > 1:80; Positive anti-soluble liver antigen/liver-pancreas; Positive anti-mitochondrial antibody; and Positive anti-SSA antibody and anti-SSB antibody.
The hematoxylin and eosin staining of liver tissue: The structure of hepatic lobules is unclear. The hematoxylin and eosin staining showed varying degrees of hepatocyte edema with moderate to severe piecemeal necrosis and scattered eosinophilic bodies (Figure , arrows). Small bile duct in the portal area was accompanied by lymphocyte-predominant inflammation with a small amount of eosinophil infiltration (Figure , filled triangles).
Immunohistochemistry analysis of liver tissue: The proliferation of small bile ducts in the portal area were obvious (Figure , arrows), with more infiltration of lymphocytes and plasma cells and positive marker detection including hepatitis B surface antigen (+), HBcAg (+-), bile duct epithelium (CK19+), IgG (+), and IgG4 (-) combined hepatocellular and cholangiocarcinoma. Findings were consistent with mild chronic hepatitis compatible with HBV infection, without histological stigmata of autoimmunity (Figure ).
Mesh fiber staining of liver tissue: The reticular fiber staining showed that the hepatic lobular stent was significantly damaged (Figure , arrows). The characteristic floral ring structure of AIH was not seen (Figure ).
Masson staining of liver tissue: The portal area was enlarged with fibrosis, the formation of bridging fiber band was visible in the focal area, and collagen fiber proliferated in the portal area by Masson staining (Figure , arrows).


In January 2018, a 23-year-old man presented with left hip pain with no obvious cause. The pain was not linked to physical activities such as walking. The pain was not relieved after rest and showed no response to treatment.
Routine blood investigations, tumor markers, and erythrocyte sedimentation rate were within the normal reference range.
X-ray plain film showed bone destruction in the left femoral neck with peri-lesional sclerosis (Figure ). MRI examination of the pelvis showed bone destruction in the medullary cavity of the left femoral head and neck. The lesions showed low signal on T1-sequence and high signal on T2 sequence (Figure and ). Therefore, the preliminary diagnosis was malignant space occupying lesions.
In February 2018, 18F-FDG PET/CT imaging from the head to trunk was performed. The results showed bone destruction in the left ischium, left acetabulum, and left femoral head neck, accompanied by increased radioactive uptake (Figure ); the maximum standard uptake value (SUVmax) was 4.2. Soft tissue swelling was observed around the upper part of the left femur, which was accompanied by increased radioactive uptake (SUVmax: 3.5). CT examination revealed osteoblastic destruction in the left femoral head and neck, with hardened lesion edges; there was swelling of adjacent soft tissue, which showed slightly lower density than the surrounding muscle tissue with an unclear boundary (Figure ). As there were no abnormalities in other organs, a diagnosis of primary low-grade malignant bone lesion was suspected.


The patient, a 22-year-old gravida 1 para 0 woman, was referred to our centre at 24+4 weeks of gestation; her spouse was 26 years old. Both were of QingYuan, Guangdong, ancestry. Prenatal ultrasonography at 24 weeks of gestation indicated foetal hydrops with cardiomegaly (cardiothoracic ratio 0.73), pericardial effusion, a small amount of ascites, bilateral pleural effusion, echogenic bowel, bilateral choroid plexus cyst, thickened placenta, and elevated middle cerebral artery peak systolic velocity (50.22 cm/s, >1.55 multiples of the median) (), which was highly suspicious for a significant risk for severe anaemia.
The couple agreed to participate in our study and signed informed consent forms. The study was approved by the Ethics Committee of Guangdong Women and Children Hospital (IRB reference number: 201811179) and complies with the CARE case report guidelines. We have deidentified the details such that the identity of the patient cannot be ascertained in any way.
After pretest counselling, percutaneous umbilical blood sampling was offered to the parents. Umbilical cord blood test results of TORCH (toxoplasmosis, rubella cytomegalovirus, herpes simplex, and HIV) analysis, parvovirus B19 analysis, and glucose-6-phosphate dehydrogenase deficiency (G6PD) screening were normal. Routine foetal blood examination revealed severe foetal anaemia with an Hb level of 5.9 g/dL (reference range for 24-week foetus: >10 g/dL). Hb electrophoresis analysis showed significantly elevated Hb Bart’s (89.3%) and Hb Portland (5.9%) (), indicating Bart’s hydrops foetalis. The pregnant woman had a rhesus positive O blood type. Results of screening for red blood cell antibodies, TORCH analysis, G6PD deficiency screening, parvovirus infection, and foeto–maternal haemorrhage detection by the Kleihauer–Betke test were all negative. The haematological data and thalassaemia genotypes of the family are summarised in . The patient had a decreased MCV (70.7 fL) and MCH (25.1 pg), and her spouse’s MCV and MCH were normal.
The suspension-array system, which detects the 23 most frequent deletions and mutations in southern China, suggested that the mother had a –SEA/ deletion, the paternal sample was negative for both α-thal and β-thal, and the foetal sample had a homozygous (–SEA/) deletion, which was not in accordance with Mendelian inheritance. DNA sequencing of the α-globin gene of the paternal sample did not reveal any mutation. The results of gap-PCR, which detects uncommon deletional mutations (–FIL/, –THAI/, –11.1/, –27.6/, –21.9/), were negative. Other causes should be considered in the differential diagnosis of Bart’s hydrops foetalis, including uniparental disomy (UPD), nonpaternity, or a de novo deletion causing α0-thal. Nonpaternity was first excluded by quantitative fluorescence PCR (QF-PCR). The karyotype of the foetus was normal (46,XX). However, single nucleotide polymorphism (SNP) array testing of the foetus, which was performed on a commercial 750K microarray chip (Affymetrix CytoScan 750K Array; Affymetrix/Thermo Fisher Scientific, Santa Clara, CA, USA), indicated a loss of 196 kb in 16p13.3. The deletion region included HBA1 and HBA2, which would explain the clinical manifestation of Bart’s hydrops foetalis in the absence of both α-globin genes. This finding might also explain why the family samples were not consistent with Mendelian inheritance indicated by the suspension-array system. SNP array technology also excluded UPD through SNP allele pattern analysis. The 5′ deletion breakpoint was located upstream of the POLR3K gene, and the 3′ breakpoint was located downstream of the LUC7L gene. Compared with the references, the 5′ breakpoint of the deletion was located at 85,880, and the 3′ breakpoint was located between 282,157 and 293,265 (). To the best of our knowledge, this large deletion has not been reported before. Microdeletions were not detected in the pregnant woman or her spouse, indicating that the deletion was a de novo copy number variation.
After counselling, the decision was made to terminate the pregnancy. The aborted foetus had characteristics of hydrops along with an enlarged placenta (). Autopsy indicated foetal hydrops with cardiomegaly, pericardial effusion, ascites, bilateral pleural effusion, and bilateral choroid plexus cyst.


A 58-year-old male smoker presented to our hospital with one-month history of chest and back pain. The performance status (PS) value of the patient was 0. Systemic evaluation including brain magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT) scan showed a cavitary nodule on the inferior lobe of the right lung and the presence of malignant pleural effusion (). Histopathology review of the tissue biopsy sample suggested stage IV poorly differentiated carcinoma. Twelve days after admission, malignant pleural effusion was aggravated and a video-assisted thoracoscopic lobectomy and lymph node dissection was performed for symptom management. Pathological examination of tumor, visceral pleura, and lymph nodes confirmed the diagnosis of poorly differentiated adenosquamous carcinoma and the presence of tumor cells in the visceral pleura and lymph nodes. Amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) assay was performed using pleural effusion samples to profile the EGFR mutation status, which showed weak signals for L858R and T790M mutations (CT value: 43.83 and 40.67, respectively, ). The patient was administered with third-generation EGFR-TKI osimertinib (150 mg, orally thrice daily) combined with cisplatin (40 mg every ten days). After 5 days of osimertinib treatment, pleural effusion was reduced. Unfortunately, the patient showed a rapid disease progression and died of respiratory failure after 15 days of osimertinib plus cisplatin administration. To understand the underlying mechanism of treatment failure, both surgical and lymph node tissue samples were subjected to capture-based ultra-deep sequencing that target the exons and critical introns of 520 cancer-related genes (Oncoscreen PlusTM, Burning Rock Biotech, China). HRAS Q61L and NRAS Q61K were consistently found in the primary tumor and lymph nodes ( and ). However, EGFR mutations were not detected, indicating that the EGFR L858R and T790M detected by ARMS-PCR may be false-positive mutations.


A 66-year-old man presented to the department of internal medicine with history of fever, cough, and difficulty in breathing and exertional chest pain. He had past history of hypertension, diabetes (diabetic nephropathy, estimated glomerular filtration rate 45 mL/min), and smoking. On admission, he was febrile and breathless. The chest had bilateral rhonchi and basal crepts. His blood sugar was 465 mg/dL and the ketone levels were high in urine. Arterial blood gas estimation showed metabolic acidosis. Other blood tests are summarized in . Chest X-ray showed increased bronchovascular markings in both the lower lobes (). Computed tomography (CT) scan chest showed bilateral pneumonic consolidation in the lower lobes (). He was managed with insulin, antibiotics, intravenous fluids, and the ketoacidosis was corrected. Reverse transcription–polymerase chain reaction for COVID-19 was negative.
On Day 3 of admission, he had severe chest pain and breathlessness with hypotension and the electrocardiogram (EKG) showed junctional rhythm with ST-elevation in inferior and lateral leads (). He was noted to be in acute left ventricular failure and required mechanical ventilation to maintain oxygen levels. Bedside echocardiogram showed that the patient had moderate to severe mitral regurgitation and severe left ventricular systolic dysfunction. He was given ticagrelor 180 mg and aspirin 325 mg orally and started on inotropes and diuretics and shifted to cardiac cath lab for primary angioplasty. The procedure was performed through the right femoral route (6F artery and 7F vein accessed). Additional 5F arterial sheath was introduced through the left side in preparation for need of emergent left ventricular support device. Coronary angiogram revealed a chronic total occlusion of right coronary artery. There was 30–40% stenosis in distal left main and 80% stenosis of osteoproximal left circumflex artery (Video 1). The left anterior descending artery was free of significant disease. Percutaneous coronary intervention was done and a stent was implanted from left main to left circumflex artery with good result (Video 2). ST-elevation settled in the electrocardiogram (). A total of 7000 IU of unfractionated heparin was given to maintain an activated coagulation time between 250 and 300 s during the procedure. The procedure was complicated by sustained ventricular tachycardia and paroxysms of atrial fibrillation with fast ventricular rate requiring multiple DC shocks and intravenous cordarone (). The patient improved within a few hours and haemodynamics and arrhythmia settled down. Inotropes were discontinued.
Later in the evening, the patient started having hypotension (blood pressure 80–90/60 mmHg and heart rate -110/min, sinus rhythm). The EKG was unchanged. There was a small groin haematoma and no tenderness was noted in the flanks. Intravenous fluids and colloids were given and when the haemodynamics didn’t improve, inotropes were added. A bedside ultrasound showed a small haematoma in the groin but no blood was seen in the abdomen sufficient to explain the hypotension. Blood gases showed rising lactate levels and a 4.6 gm/dL fall in haemoglobin (11.7–7.1 g/dL). Six units of blood, four units of fresh frozen plasma were given over next 24 h. The abdominal girth increased gradually pointing towards retroperitoneal haemorrhage. After stabilization, CT scan of the abdomen was performed which revealed a massive retroperitoneal bleed into the left psoas and the left iliacus muscle (). A CT aortogram was also performed which failed to show any bleeder. A peripheral angiogram was also performed of the left iliac arteries and no bleeder was identified (Video 3). Antiplatelet drugs were discontinued. Laboratory results showed that the platelet count and prothrombin time were normal (196 000 cells/mm3 and 14.2 s, respectively). The activated partial thromboplastin time was marginally above normal (58.3 s; control 34.2 s). The surgeons ruled out any surgical intervention because there was no specific site of bleeding. We continued to replace blood and fresh frozen plasma. Despite best of efforts, the bleeding could not be controlled and the patient died.


A 47-year-old gentleman presented with a productive cough, pleuritic chest pain, and fever for 2 days. Physical examination revealed a febrile gentleman of Thai ethnicity. He had a regular pulse, S1/S2 as normal without murmurs or rub. Lung examinations revealed left basal crepitations. Vital signs were blood pressure (BP) 130/83 mmHg, heart rate 104 beats/min, oxygen saturation 97% on room air, respiratory rate 16/min, and temperature 38°C. Chest radiograph showed left lower zone retrocardiac opacities (), and he was transferred to the isolation ward. SARS-CoV-2 polymerase chain reaction (PCR) came back positive from his nasopharyngeal swab. The patient did not have any significant medical history. He denied travel, but he was in close contact with a colleague with COVID-19. He came from a TB endemic area.
On Day 3 of hospitalization, he deteriorated requiring 4 L nasal cannula to achieve SpO2 94%. His BP was 125/80 mmHg, his rate 110 beats/min, and he had tachypnoea 20/min. There was no evidence of heart failure or tamponade. Electrocardiogram (ECG) showed sinus tachycardia with normal QRS complexes (). High sensitive troponin I was 4 ng/mL (normal values: <14 ng/mL). There was absolute monocytosis (0.92 × 109/L, normal range 0.2–0.7 × 109/L) and elevated C-reactive protein at 134.7 mg/L (normal values < 5 mg/L). A repeat chest radiograph showed a marked increase in heart size (). He was started on active drug remdesivir (300 mg in total for 2 days) as a part of an ongoing trial.
Subsequent ECG revealed persistent sinus tachycardia and no evolution of ST-T wave changes. Labs were remarkable for monocytosis (1.02 × 109/L). Liver function tests and coagulation panel were normal. Arterial blood gas showed acute respiratory alkalosis with pH 7.48, pCO2 39, pO2 68, bicarbonate of 29 on 3 L nasal cannula. Lactate was raised at 2.7 mmol/L (normal value < 2 mmol/L). Transthoracic echocardiogram demonstrated a hyperdynamic left ventricle with left ventricular ejection fraction of 65%. There was the right atrial collapse, diastolic collapse of the right ventricle, 3.5 cm of pericardial effusion, and plethoric inferior vena cava of 2.2 cm with < 50% variation (Videos 1 and 2). The effusion was noted to be complex with fibrin deposits adhering to the myocardium (Video 3). The transmitral flow variation was 30%, and the transtricuspid variation was 50%.
The patient was transferred to the intensive care unit. The patient developed sinus tachycardia (range up to 130 beats/min) with concomitant febrile episodes of 39°C. Pericardiocentesis was performed in view of persistent tachycardia and rapid accumulation of pericardial effusion. The procedure was done under echocardiographic guidance. Pericardiocentesis yielded 900 mL of haemoserous fluid [fluid lactate dehydrogenase (LDH) 2253 IU/L, fluid/serum LDH > 0.6; normal value 270–550 IU/L]. Cytology was negative for malignancy. Adenovirus PCR, enterovirus PCR, and SARS-CoV-2 PCR were negative. Acid-fast bacilli were detected and TB PCR was positive. Fluid microscopy revealed predominantly nucleated cells (8513 cells/µL) with 91% lymphocytes. Adenosine deaminase for pericardial fluid was significantly elevated at 44 U/L (normal value < 20 U/L). The retroviral screen and autoimmune panel were negative. The immediate resolution of tachycardia (heart rate reduced to 80–90 beats/min) signifies the haemodynamic improvement gained from relieving the tamponade. The pericardial effusion was highly diagnostic of TB pericarditis in the absence of coagulopathy, malignancy, and autoimmune aetiologies. He was commenced on rifampicin, isoniazid, ethambutol, and pyrazinamide. Subsequent echocardiogram showed resolution of effusion with marked improvement of symptoms. A follow-up CT thorax revealed left lung lower lobe collapse-consolidation, small pleural effusion with a marked reduction in pericardial effusion ().
He was discharged after 2 weeks into anti-TB therapy. Subsequently, he was reviewed during follow-up (4 weeks post-discharge) with resolution of pericardial effusion and residual left retrocardiac consolidation on chest X-ray.


A 61-year-old man with a history of head and neck cancer underwent left lingual resection and left anterior cervical lymph node dissection followed by chemoradiotherapy. He has no history of syncope before cancer. Two months later, he was transferred to our hospital with loss of consciousness. Head MRI did not show any signs of cerebral infarction or tumour brain metastasis. Electroencephalograph findings were normal, and epilepsy was thoroughly ruled out from situation of syncope and neurological findings. The transthoracic echocardiogram was normal and did not reveal any evidence of structural heart disease. He was hospitalized, and he experienced hypotension and sinus bradycardia () resulting in the disturbance of consciousness for ∼30 min after walking and urination. Syncope occurred without premonitory symptoms, and it lasted long, which is not typical of vasovagal syncope or situational syncope. Sinus bradycardia continued ∼20 min after sinus arrest, and blood pressure lowered as well, causing loss of consciousness (). His consciousness recovered as the heart rate and blood pressure recovered. Shellong test performed to screen for orthostatic hypotension showed normal blood pressure reaction on orthostasis. There was no oral medication (beta-blockers, Ca channel blockers, and others) that induced bradycardia in this patient. Considering his previous head and neck cancer, the three potential causes of syncope were investigated: carotid sinus syndrome, glossopharyngeal neuralgia syndrome, and parapharyngeal space lesions syncope syndrome. Carotid artery massage and cervical rotation-extension examinations revealed no abnormalities, and glossopharyngeal neuralgia was not observed. Therefore, parapharyngeal space lesions syncope syndrome was suspected. Cervical CT revealed the recurrence of a tongue cancer infiltrating the para-nasopharyngeal space ().
Mixed neuroregulatory syncope is an indication for pacemaker implantation in case of recurring syncope according to the latest ESC guidelines and in the Japanese circulation society guideline. However, pacemaker implantation must be carefully considered because it entails risks of complications and requires informed consent. We were unable to implant even the temporary pacemaker, although we provided sufficient explanation to the patient and to his family; no further invasive treatment was desired. The patient died because of the original disease 3 months after the aforementioned hospital admission.


A 68-year-old Peruvian man had been suffering from lumbar pain for several days. His CT scan revealed a mass compressing his right ureter and iliac vessels. He underwent exploratory laparotomy with radical resection of a retroperitoneal tumor (10 cm × 8.3 cm × 8 cm), as well as ileocecectomy and ileocecal anastomosis. Pathological analysis () showed that the tumor was a DDL (T2 N0 M0, FNCLCC grade 2, stage IIIA, <50% necrosis, R0). This diagnosis was corroborated by immunohistochemistry markers (ie, the positivity of D33 and NSE and negativity of h-CD and S100). One month after the surgery (for details of the disease course, see ), his initial postoperative scan showed the absence of disease. However, 2 months later (3 months after the surgery), his new CT scan revealed a 1.6 cm × 2.3 cm mass anterior to the right iliac vessels (first recurrence). He received neoadjuvant chemotherapy with doxorubicin plus ifosfamide (6 cycles). Then he underwent resection of the retroperitoneal tumor (R0) and right ureterectomy. The patient further received 3 cycles of doxorubicin plus ifosfamide postoperatively. Eight months after chemotherapy (11 months after the second surgery), a control imaging revealed 2 anterior psoas masses measuring 1.5 cm × 1.5 cm and 1.3 cm × 1 cm (second recurrence). The biopsy of one of the lesions revealed a malignant spindle cell neoplasm compatible with DDL. Two months later, the CT scan showed that the masses had enlarged to 3.0 cm × 1.9 cm and 2.1 cm × 1.6 cm. However, CT scans and a chest x-ray revealed no evidence of metastatic disease. The patient underwent a third surgery wherein the 2 masses and a right pelvic mass were resected entirely (R0). At this point, the patient sought for different treatment options involving an integrative approach. Three months later, he came to the Centro Médico Antroposófico (CMA) and became our patient.
The recommended treatment was subcutaneous injections of VAE obtained from the host tree ash (AbnobaVISCUM® Fraxini); the injections were given thrice per week in increasing doses. The application of VAE Fraxini in the periumbilical area started at 0.2 mg; after 6 months, the dose was increased to 2 mg, which was then maintained for 7 months. The subcutaneous VAE injections occasionally induced self-limited local erythema and swelling of the skin around the application site, which could be tolerated by the patient. Nine months after the VAE treatment was initiated (12 months after the third surgery), a retroperitoneal mass measuring 4.1 cm × 3.0 cm was noticed (third recurrence). After 5 more months, the dose of VAE was increased to 20 mg thrice per week. Three months later, the patient underwent resection (fourth surgery) of a right iliac fossa tumor (a mass measuring 4.7 cm × 3.5 cm with a moderate amount of surrounding fibroadipose tissue) and a right juxtarenal psoas tumor (a well-encapsulated, focal fibro-fatty soft tissue measuring 8.7 cm × 6.5 cm with central areas of probable necrosis). Both tumors were DDLs (FNCLCC grade 3, pT2b). The patient had a negative margin resection (R0) for the larger sarcoma, and the other exhibited focal involvement by the tumor. A cholecystectomy (mild chronic cholecystitis and cholelithiasis) and appendectomy were also performed, and both organs were negative for tumor. Additionally, he received 12 cycles of three-dimensional conformal radiotherapy post-surgery.
As a result of the previous surgeries, which involved a partial right ureter resection with psoas bladder hitch, the patient developed obstructive renal failure as evidenced by the right ureteral obstruction and abnormal serum creatinine levels. The patient then underwent a right percutaneous nephrostomy with stent placement.
Throughout this time, the patient continued to receive VAE Fraxini. Follow-up magnetic resonance imaging was performed periodically post-surgery. Three-month breaks without VAE Fraxini application were set twice per year after obtaining the first negative follow-up magnetic resonance imaging result. The frequency of subcutaneous VAE Fraxini application was reduced to twice per week from month 54 on. The patient reached a recurrence-free interval of 69 months; however, the magnetic resonance imaging performed on month 86 of VAE Fraxini treatment showed a mass in the right iliac fossa. The tumor measuring 8.1 cm × 4.8 cm (FNCLCC grade 3, pT2b) was resected. The tumor showed areas of well-differentiated liposarcoma, which were mixed with areas of intermediate to highly dedifferentiated myxoid fibrosarcoma and high-grade undifferentiated pleomorphic sarcoma. The tumor was relatively well-circumscribed and mostly surrounded by fibroconnective and fibroadipose tissues of variable thickness. However, the resection margins were involved by the sarcoma. One month after the surgery, the VAE treatment was resumed. The patient started receiving intravenous infusion of 100 mg VAE obtained from pine as host tree (Helixor® P); the injections were administered in 500 mL of standard saline solution over 2 hours thrice a week. The dose was increased by 100 mg per application until 400 mg was reached which was maintained until 12 applications were completed. Then, the patient was subjected again to subcutaneous injection with 20 mg VAE Fraxini thrice per week. Five months after the surgery, multiple abdominal and retroperitoneal nodular tumor implants were detected, and their number and size increased within the following 9 months. For 2 weeks, the patient received intravenous infusion of VAE (Helixor® P, maximum dose: 400 mg) followed by subcutaneous infusion of 20 mg VAE Fraxini. One of the implants caused urinary tract obstruction, and the patient developed renal and abdominal pain, which was treated with buprenorphine 20 mg/25 cm2 transdermal patches and with anthroposophic remedies (Wala® Solum Inject, Wala® Plexus coeliacus D15, Wala® Bryonia/Stannum, Weleda® Formica comp injections, thrice per week). Weleda® Equisetum sulfuratum tostum D3 was applied (thrice a day) to support the urinary function. When the pain was relieved and controlled, intravenous infusions of VAE were resumed. He also received 1 cycle of eribulin (1.65 mg IV infusion). In month 103 of the VAE treatment, the patient underwent pleurodesis due to pleural effusion; however, he died 2 weeks later. Altogether, the patient received a total of 103 months (8.6 years) of VAE treatment and achieved 10.5 years of survival.
Within approximately 2 years during which the first 3 surgeries were performed, the patient’s weight decreased from 84 kg to 71 kg. Since the VAE treatment started, the patient’s quality of life progressively improved as seen in his increased appetite, resulting in weight gain (up to 77 kg) during the low-dose VAE treatment. After the fourth surgery, his weight was 70 kg to 74 kg. After the fifth surgery, his weight decreased to 66 kg and then increased again to 70 kg (). The ideal body weight based on his height (172 cm), gender, and age is 54.7 kg to 74.0 kg.
The patient was married and had 3 grown-up children. He had a history of tobacco use, but he quit after being diagnosed with DDL. He consumed alcoholic beverages occasionally. His medical history included diphtheria and hemorrhoidectomy. His father died of leukemia, and his paternal uncle had an unknown cancer of the lower extremity. Further medications included allopurinol tablets for high blood uric acid level and a combination preparation of hydrocodone 10 mg and bitartrate and acetaminophen 500 mg tablets for left lumbar region pain. The patient stopped taking these medications on month 18 of VAE treatment.


A 32-year-old Caucasian female with a history of recently diagnosed systemic lupus erythematosus (SLE) presented to the emergency department with sudden-onset left-sided flank pain. The pain was dull and constant in origin with a score of 10 out of 10. She reported nausea but denied dysuria, hematuria, fever, chills, chest pain, shortness of breath, or changes in bowel function.
Seven weeks prior to this admission, she was hospitalized for autoimmune hemolytic anemia with a nadir hemoglobin level of 4.6 g/dL. Her hematologic workups were remarkable for positive antiglobulin test (Coombs test), nuclear dense fine speckled pattern on antinuclear antibodies screening with 1:640 titer, and positive anti-double-stranded DNA antibody of 259 IU/mL. Her recent C3 and C4 levels were diminished at 27 and 4 mg/dL, respectively. She was treated with intravenous methylprednisolone followed by packed red cell transfusion. Her hospital course was complicated by acute kidney injury with a presenting serum creatinine level of 2.20 mg/dL. Urine analysis showed 3+ occult blood and 2+ protein with a urine protein-creatinine ratio of 1.95 g/g. CT of the abdomen and pelvis was notable for small pericardial effusion and normal renal morphology. She was started on intravenous fluid and her serum creatinine level gradually improved. Her anemia and acute kidney injury improved, thus she was discharged home. At that time her hemoglobin level was 8.9 g/dL and her serum creatinine level was 1.22 mg/dL. Kidney biopsy was arranged as an outpatient procedure.
One week after discharge (or 9 days prior to the recent admission), she underwent a CT-guided core needle biopsy of the left kidney. The cortex was obtained from the lower pole of the left kidney. There were no immediate complications and the patient was discharged on the same day. The kidney biopsy showed immune complex-mediated proliferative glomerulonephritis, 2/5 global glomerulosclerosis, and mild arteriolar hyalinosis. These findings were consistent with International Society of Nephrology/Renal Pathology Society class III or IV lupus nephritis. No structures similar to small arterial aneurysmal wall were identified from the obtained core tissue. Induction therapy was not initiated at that time.
In this recent admission, the patient presented with sudden-onset left-sided flank pain. Initial vital signs were a temperature of 36.4°C, a heart rate of 100/min, a respiratory rate of 20/min, a blood pressure of 151/108 mm Hg, and an oxygen saturation of 100% on room air. She appeared pale and her left flank was tender to palpation, without discoloration or abdominal distention. Other parts of physical examination were unremarkable.
Initial investigations demonstrated hemoglobin 7.1 g/dL, hematocrit 20.5%, platelets 183,000/μL, and international normalization ratio 1.1. Metabolic panel showed serum sodium 140 mEq/L, serum potassium 3.8 mEq/L, serum chloride 104 mEq/L, serum bicarbonate 28.1 mEq/L, serum creatinine 1.11 mg/dL, and blood urea nitrogen 24 mg/dL.
A CT scan of the abdomen and pelvis with intravenous contrast medium (Fig. ) revealed a large hyperdense left perinephric collection consistent with perinephric hematoma with a moderate amount of retroperitoneal stranding most prominent on the left side extending across the midline to the right side. The retroperitoneal stranding stems from the level of the left hemidiaphragm to the left lower pelvis. Contrast extravasation was suspected in the lower pole of the left kidney consistent with active bleeding site. Chronic stranding in the right perinephric space was also noted.
The patient underwent emergent selective left renal artery coil embolization. The procedure was successful without any complications. Left renal angiography showed an approximately 2 × 1 cm intraparenchymal pseudoaneurysm in the lower pole of the left kidney with active extravasation. The coils were placed in the medial and lateral branches supplying the pseudoaneurysm (Fig. ). Small microaneurysms were also noted on angiography.
The patient followed with her nephrologist and hematologist after hospital discharge. Her flank pain completely resolved, and she received an induction therapy followed by maintenance therapy for her lupus nephritis.


A 28-year old man, with no known previous medical history, was admitted to the emergency department with a 6-day history of pleuritic chest pain and gradual-onset shortness of breath. The patient also noted going through upper respiratory tract infection symptoms (fever, malaise and rhinorrhea) a couple of days before the onset of above-mentioned symptoms which had got better gradually without seeking medical advice. Moreover, he reported new onset anosmia from one week before admission. The patient’s history of smoking was remarkable in his record.
Upon admission, his blood pressure was measured at 95/60 mmHg and he had tachycardia with heart rate of 125 beats per minute.
He was afebrile (temperature: 36.8 degree centigrade) and in respiratory distress with oxygen saturation of 85% in room air.
On physical examination heart sounds were determined to be muffled, no gallop or heart murmurs were detected and only tachycardia was noticed. The Jugular Venous Pressure (JVP) was also prominent (10 cm H2o) and lung auscultation revealed normal vesicular breath sounds.


A 13-year-old girl child presented with chief complaints of generalized weakness, pain, and swelling over left lower limb for 5 days in pediatrics emergency of tertiary care hospital. The child was diagnosed with CD 1 month back by duodenum biopsy, tissue transglutaminase antibody IgA. On examination, the patient was thin built and emaciated. Her height was 144 cm and weight was 22 kg, vital parameters were stable, and child had pallor, generalized lymphadenopathy in the form of enlarged significant lymph nodes over cervical, axillary, and inguinal region. Left lower limb was swollen and showing dilated and tortuous vein. On systemic examination, there were no significant positive findings. Blood investigation showed following results: hemoglobin (Hb) = 7 gram%, total leukocyte counts (TLC) = 4000/cubic mm, differential leukocyte counts (DLC): neutrophils = 80%, lymphocytes = 15%, monocytes = 1%, eosinophils-1%. Blood urea = 27 mg%, serum creatinine = 0.7 mg%, serum uric acid = 3 mg%, serum aspartate aminotransferase (AST) = 157 IU, alanine aminotransferase (ALT) = 160 IU, serum protein = 4.9 gm%, prothrombin time (PT) = 23.7 s, partial thromboplastin time with Kaolin (PTTK) = 69.5, international normalized ratio (INR) = 2.03, serum Vitamin D3 = 12 ng/dl.(>30 ng/dl considered normal). On Doppler examination, an echogenic thrombus was present in left common femoral and left deep femoral vein making a diagnosis of left lower limb deep vein thrombosis. Furthermore, coagulation studies were done showing antithrombin (AT) III = 26% (normal range 17–30%), Protein C = 98.33% (normal range 70–150%), Protein S = 100.52% (normal range 70–150%), Prolactin = 6.35 ng/ml (normal range 2.8–29.2), Homocysteine = 5.63 umol/l (normal range 3.7–13.9), Factor V Leiden mutation < 220 copies/ml essentially a normal study. The patient was started on intravenous antibiotics and appropriate intravenous fluids in view of high grade fever and early signs of septic shock. During the hospital stay, patient continued to have high grade fever, although clinical condition apparently became stable. Work-up for fever came up with chest X-ray having multiple nodular opacities, ultrasonography of abdomen showed multiple enlarged paraaortic, pre-aortic peri-pancreatic, and inguinal lymph nodes. Remaining investigations like CBC was within normal range, Monteux skin test was negative, blood cultures were sterile, and sputum for Acid Fast Bacilli (AFB) was negative. Later on day 7 of admission, patient had an episode of seizure. On being evaluated, Serum Calcium = 7 mg%, ionized calcium = 3.22 mg%, and CSF examination was normal, magnetic resonance imaging (MRI) brain showed multiple granulomas, making presumptive diagnosis of TB or Lymphoma []. Contrast Enhanced Computed Tomography (CECT) Chest showed multiple opacities and enlarged hilar, mediastinal lymph nodes suggestive of TB or Lymphoma []. Bronchoalveolar lavage (BAL) fluid examination showed occasional 1–2 acid fast bacilli. Further cartridge-based nucleic acid amplification (CBNAAT) was run on BAL fluid which confirmed diagnosis of TB without any drug resistance. Abdomen CECT showed multiple enlarged lymph nodes. CT guided lymph node biopsy was taken suggestive of TB showing Acid Fast Bacilli on Zeil Neilson stain. Bone marrow examination showed tubercular granuloma and iron deficiency anaemia. The final diagnosis of CD with lower limb DVT with disseminated TB was made and the patient was put on anti-tubercular treatment (ATT) along with warfarin and low molecular weight heparin (LMWH, Enoxaparin) was started after 5 days of warfarin overlap in prescribed doses. Enoxaparin was continued for next 3 months. The patient is being regularly followed up in Out Patient Department and has maintained strict compliance with gluten-free diet. After 1 month, the patient was gaining weight, Hb improved to 11 gm%, and Doppler study of leg showed resolving stages of thrombus. The same treatment was continued and after 3 months, thrombus was completely resolved. The anticoagulant was stopped and ATT was continued for next 6 months. Now the patient is on regular follow-up and after 1 year has shown no signs of any residual illness. The ethical permission was obtained from Institutional Ethics Committee and a written informed consent was obtained from parents of the child for publication of this case report.


An 81-year-old Japanese woman was admitted to our hospital because of chest pain at rest over a month period. She had undergone surgical treatment for papillary thyroid carcinoma 30 years previously and regularly attended a local hospital for treatment of psychiatric problems and hypothyroidism. On admission, her vital signs were unremarkable (blood pressure 125/81 mm Hg, heart rate 78 beats/min, and oxygen saturation 95%). Physical examination showed no heart murmur and there was no jugular venous distention or pedal oedema.


A 38-year old woman, gravida 2 para 2, presented to an affiliated hospital in June 2012 with hypertension (blood pressure 155/90 mmHg), generalized edema, and an erythematous rash across the cheeks and bridge of the nose. Additional testing revealed proteinuria of 5.3 g/24 h without erythrocyturia and with a normal kidney function (serum creatinine 55 µmol/L, eGFR 107 ml/min/1.73 m2, calculated using the MDRD formula).
Antinuclear antibodies (ANA) were absent and the levels of C3 and C4 were within normal range. The patient had not menstruated for over a year, after years of irregular blood loss following her last pregnancy 12 years prior to presentation. Therefore, she was referred to a gynaecologist. Surprisingly, the β-HCG level was 60 IU/mL (reference 0–1 IU/mL) but an abdominal ultrasound showed no abnormalities. A kidney biopsy was performed, which showed mesangiocapillary glomerulonephritis with extensive PAS+ pseudothrombi and pseudo-fullhouse immunofluorescent subendothelial and mesangial immune complexes. Based on light, immunofluorescence and electron microscopy there was a high suspicion of the presence of cryoglobulins (). Serum cryoglobulins were tested three times over the disease course and were always absent. Upon suspicion of lupus nephritis, the patient was admitted for treatment with prednisone and mycofenolate mofetil (MMF) resulting in partial remission of proteinuria (hence 1.65 g/24h).
In October 2012, our patient reported abdominal discomfort which appeared to be secondary to ascites. Aspiration of ascites showed reactive fluid without signs of malignancy or infection. The nephrotic syndrome was still in remission (proteinuria of 0.8 g/24h), β-HCG had decreased to 36 IU/mL. The ascites progressed in the following years upon which the patient was referred to the Amsterdam University Medical Centers. Liver MRI and biopsy showed NRH with portal hypertension. A 99mTc human serum albumin scan and subsequent duodenoscopy with biopsy showed esophageal varices and a protein losing enteropathy (due to lymphangiectasia in the duodenum). The patient also had Raynaud’s phenomenon since the onset of the nephrotic syndrome in 2012; capillary microscopy revealed no morphological abnormalities. Despite the absence of ANA, the symptoms were explained as manifestations of systemic lupus erythematosus (SLE), because an alternative diagnosis was deemed unlikely.
Tumor markers were monitored and increased over time (β-HCG 172 IU/mL (), CA-125 1955 IU/mL in August 2014). Ultrasound, CT, and MRI showed no abnormalities of the uterus or ovaries, besides uterus myomatosus, so watchful waiting was continued. Meanwhile, the patient developed an uterovaginal prolapse due to high intra-abdominal pressure as a result of the persistent ascites, for which sacrospinal fixation was performed in December 2014. The surgery was complicated by an abdominal sepsis. The patient recovered after treatment with antibiotics.
In October 2014 MMF was discontinued due to drug-induced biopsy-proven liver damage. Several months later the nephrotic syndrome relapsed (proteinuria 8.51 g/24h) after which a second kidney biopsy was performed. This revealed similar findings compared to the biopsy of 2012, suggestive for either lupus nephritis or cryoglobulinemic glomerulonephritis (). Blood tests were negative for cryoglobulins, however ANA were present and also antibodies against Sm and RNP antigens, but not to dsDNA. Anti-cardiolipin IgG/IgM, anti-beta-2-glycoproteine IgG/IgM and lupus anticoagulant were negative. These serological findings in combination with the histological findings of the renal biopsies were supportive for the diagnosis of systemic lupus erythematosus. The question arose whether the PLE and NRH could also be part of the same disease entity, as described previously. MMF was reinstated without effect. Next, induction with cyclophosphamide (6 fortnightly pulses of 500 mg) and prednisone was administered in accordance with the Eurolupus regimen, followed by azathioprine.
Over the course of 2015 the patient had recurrent transient ischemic attacks and one minor stroke. Libman-Sacks endocarditis and antiphospholipid syndrome were considered unlikely based on a normal transthoracic cardiac ultrasound and the absence of antiphospholipid antibodies.
In July 2015, the patient was admitted to the intensive care unit with signs of shock due to intra-pelvic hemorrhage of unknown source. As there were no apparent signs of malignancy on MRI, an elective hysterectomy was performed. Pathological analysis revealed a partially removed 6.4 cm PSTT. Adjuvant chemotherapy was administered according to the etoposide and cisplatin with etoposide, methotrexate and actinomycin D (EP-EMA) schedule. After surgery, and subsequent chemotherapy, the nephrotic syndrome went into remission and remained so even after tapering prednisone and discontinuing azathioprine. The edema, ascites and Raynaud’s phenomenon disappeared and there were no further cerebrovascular events. Serological testing was repeated and ANA were absent. In retrospect, the PSTT appears to have been the cause of the nephrotic syndrome and lupus-like disease in this patient.


A 54-year-old woman presented to the outpatient ear, nose and throat neck lump clinic with a 2-week history of multiple bilateral neck lumps. These painless lumps had been progressively enlarging over a 2-week period. She had also been having episodes of night sweats but she felt these were related to her menopause. She had not noticed any other lumps around her body. She denied any weight loss and had no head and neck red flag symptoms or B-type symptoms. Additionally, she had no recent viral illness.
Thirteen years prior to presentation, she had bilateral breast augmentation with silicone-based implants. Three years following insertion, her silicone implants were recalled by the manufacturer and were replaced with saline-based implants. On removal, there was no evidence of implant rupture or leakage. She had no other relevant medical history. She was a non-smoker and consumed five units of alcohol per week.
On examination, she had multiple bilateral palpable lymph nodes in levels IV and Vb, more prominent on the left. A flexible nasoendoscopy and oral cavity examination were unremarkable. At this stage, the differential diagnosis included lymphoma, head and neck cancer, metastases and reactive lymphadenopathy secondary to infection.


A 24-year-old female patient presented to clinic with right shoulder pain and decreased range of motion (ROM). Her symptoms began 1 year before presentation, but significantly worsened over the last month. She used nonsteroidal anti-inflammatory drugs which alleviated the pain at the beginning but failed to do so in the last couple of months. Her history was negative for any traumatic events, fever, chills, and skin lesions. She did not report any other musculoskeletal symptoms. Her previous medical history and family history were noncontributory.
On physical examination, the patient’s active and passive right shoulder motion was markedly decreased with abduction to 45°, forward flexion to 45°, and abducted internal/external rotation each 30°. The joint was mildly tender on palpation, and the pain was mainly motion related. There was no swelling or erythema of the joint. Her distal pulses were palpable and neurological examination was normal. Detailed orthopedic examination of the axial and appendicular skeleton did not reveal any other findings.
Her initial right shoulder X-rays revealed joint space narrowing and marginal osteophytes, resembling primary glenohumeral osteoarthritis (). An MRI was ordered to reveal the cause of the significant loss of ROM and arthritic changes. Shoulder MRI (with i.v. gadolinium contrast) was reported as “extensive capsulitis and synovitis, synovial thickening/proliferation zones suggestive of PVNS, and a localized nodular component with a diameter of 12 mm. Glenoid cartilage erosion and marginal osteophyte formation” ().
The patient underwent arthroscopic debridement and synovial biopsy of the shoulder with PVNS as a pre-diagnosis. During the surgery, the extensive hypertrophied synovial tissue was debrided, and samples were taken from the nodular portion of the thickened synovium which was also clearly seen on the MRI (). Articular cartilage was also found to be injured, with delaminated areas on both humeral and glenoid surfaces. Early post-operative physical therapy was initiated, and the patient was kept in a sling for 3 weeks.
Histologic examination of the synovial tissue unexpectedly came back as non-LCH of the synovium (). Microscopic appearance was not suggestive of malignant behavior. The tumor had both lymphoid and histiocytic proliferations in a fibroadipose tissue, with the histiocytic component showing significant pleomorphism and occasional giant cells. Immunohistochemical staining of the neoplastic histiocytic cells was positive for CD163 and CD68 (); negative for CD1a, S100, Langerin, fascin, CD33, CD30, HMB45, pankeratin, and MPO. Following these results, the patient was worked up and staged by the hematology/oncology service. Further radiographic examinations including a PET scan and cranial MRI were normal. No further medical therapy was needed.
The patient’s post-operative clinical course was unremarkable. She was pain-free 1 month after surgery, with a significantly better ROM. On her post-operative 3rd month examination, she had pain-free abduction and flexion to 160, internal and external rotation to 75 (). Her latest follow-up visit was at the post-operative 26th month, and she remains symptom free without any sign of local recurrence.


A 27-year-old male was referred to our department in September 2017 with a chief complaint of a six-month progressive trismus and jaw pain. His medical history was unremarkable, and there was no report of recent trauma or infection. Clinical assessment showed limited mouth opening of 25 mm and pain affecting the right side of the TMJ area. There was no associated clicking or deviation on mouth opening.
An orthopantomograph did not reveal any significant abnormality of the jaw, and non-contrast computed tomography (CT) showed a well-defined round mass in the right infratemporal fossa with no cranial or TMJ bony extensions []. Magnetic resonance imaging (MRI) revealed a defined round soft tissue mass measuring 3.2 × 3.1 × 2.8 cm, medial to right TMJ head with minimal extension into the soft tissue component of the TMJ []. Both CT and MRI excluded the cranial extension and vascular nature of the lesion but highlighted close proximity to the internal carotid and internal maxillary arteries.
Based on the clinical findings and imaging modalities, a differential diagnosis of neurofibroma, trigeminal schwannoma, and giant cell tumor was proposed. As the lesion was located at a relatively inaccessible position and being close to critical anatomical structures, the preoperative diagnostic biopsy was neither feasible nor advisable. Therefore, the patient underwent total surgical excision of the lesion under general anesthesia via trans-oral anterior lateral mandibulotomy approach for direct access to the infratemporal fossa. The approach involved a midline lip split that was extended to the submandibular neck crease. The mandibular symphysis was then exposed, marked, and fixed with two mini bone plates before osteotomy. Subsequently, the mandible was laterally rotated, the lingual and inferior alveolar nerves were identified and protected, and the lateral pterygoid muscle was excised to closely approach the lesion, which was then visualized via endoscope and freed from all attachments ensuring total and complete excision. The maxillary artery branches were circulating the mass, and identified and clipped endoscopically [].
The histopathology result showed fibrohistiocytic cells with hemosiderophages, foamy macrophages and osteoclast-type multinucleated giant cells on a background of fibrocollagenous tissue with chondroid islands and osteoid formation. The cells appeared to form a lining giving a partly cystic appearance. There were large areas of coagulated necrosis, cholesterol clefts, hemorrhage, and scattered dystrophic calcifications []. The histopathological features were consistent with chondroid TGCT, a rare subset of localized TGCT that was completely excised.
At 18-months post-operative review, the patient showed remarkable recovery with improvement in mouth opening to 35 mm and resolution of the associated jaw pain. In addition, the 18-month post-operative MRI showed no evidence of recurrence [].


A systemically healthy, 55-year-old countryside female reported to the emergency department complaining about pain and swelling for 5 months with a history of dull aching, poorly localized, progressively intensifying pain of the lower left back region of the jaw radiating to the left preauricular, and temporal region. At the time of presentation, a single, large, tender, and diffuse swelling measuring 4 cm × 2 cm was noted along the left half of the mandible with intact overlying skin. Intra-oral examination revealed moderate gingival inflammation with a periodontal pocket of 4 mm in the left mandibular second molar without any history of pus discharge. An expansion of the buccal cortical plate over the molar region was noted []. The patient reported no former history of trauma, surgery, or infection at the same local site. Orthopantomograph and cone-beam computed tomography demonstrated multiple ill-defined radiolucencies from the symphyseal region extending posteriorly involving the condyle. The lower border of the mandible appeared intact with no root resorption or displacement of the tooth [Figure and ]. The differential diagnosis included malignancy, osteosarcoma, chronic relapsing multifocal osteomyelitis, and granulomatous diseases.
Fine-needle aspiration cytology and microbiology were demanded to ascertain the nature of the lesion that revealed necrotic granular material with extensive inflammatory infiltrate surrounding the bony spicules with capillary proliferation and fibrosis. Furthermore seen in smears were the cell debris, areas of bone necrosis, and actively phagocytizing macrophages. Abundant colonies of filamentous bacteria were suggestive of Actinomyces. The 40X view of microscopy identified the species as A. israelli [].
Empirically, amoxicillin + clavulanic acid 1.2 g intravenous 12 hourly was administered and the patient was scheduled for open debridement, curettage, and saucerization. Significant granulation tissue with lytic loculated lesions was seen underneath the periosteum from which frank purulent discharge was expressed. Curettage and saucerization were performed, preserving the inferior alveolar nerve. Several areas of significant decortication and rough osteomyelitic bone were debrided []. No postoperative complications occurred. The patient was discharged on the 5th postoperative day and further reviewed monthly for clinical and radiographic assessment for 6 months. Antibiotics continued for 4 weeks. The surgical site showed significant healing and remained well without any signs of infectious relapse [].


A 25-year-old man was diagnosed with stage IIA classical Hodgkin lymphoma (cHL) involving bilateral cervical nodes and mediastinum (bulky). A staging PET/CT scan revealed a 2 x 3.9 cm right cervical node, with a standardized uptake value (SUV) of 10.5, a 1.9 x 2.5 cm right paratracheal node with a SUV of 8.0, and a 10.3 x 5.7 cm bulky mediastinic involvement with a SUV of 12.6. The therapeutic program was ABVD regimen for 4 cycles with an interim PET scan evaluation and Involved-field radiotherapy (IFRT). PET/CT scan performed after 2 cycles of the ABVD regimen demonstrated a persistent positivity on mediastinum (Deauville score: 4), with decreased mediastinal mass at CT scan. Therefore, the treatment was shifted to the BEACOPP regimen. Two cycles of BEACOPP and RT were scheduled. After 2 cycles, the PET/CT scan was persistently positive, with a Deauville score of 4 in the residual mediastinal mass, which was further reduced at CT scan. A CT scan guided biopsy of the positive PET area did not show any evidence of lymphoma. The patient was treated with 4 cycles of therapy following the BeGEV scheme, with stem cell collection after the second cycle. Pre-transplantation PET/CT scan showed again a persistent mediastinal PET scan positivity; a new biopsy was performed, suggesting again fibrotic tissue, in absence of lymphoproliferative disease. The patient received a high dose chemotherapy and ASCT, followed by a consolidation RT on mediastinal bulk. A CT scan after 45 days showed a reduction of the residual mass (3.8 x 2 cm) and a PET/CT scan performed after 3 months showed a reduction of the SUVmax and a Deauville score of 3. A new CT scan was performed after 3 months and showed a further minimal reduction of the residual mediastinal mass. No signs of active disease were observed during the follow-up.
Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan is without any doubt the best currently available predictor for HL patients. However, it should be used carefully due to the well-known false positivity issues.
Our case clearly points out the wide variability of PET scan interpretation before and after stem cell transplantation, which could possibly lead to overtreat the patient or, by the contrary, underestimate a PET scan positive signal. According to the wide literature data, we probably overtreat some interim PET scan-positive patients (10-15%) or undertreat some interim PET scan-negative patients (5- 10%) (-).
The role of interim PET scan in advanced HL has been supported by several prospective studies, confirming that an early intensification in interim PET scan-positive patients significantly improves PFS (-). Moreover, with the interim FDG-PET scan evaluation, we avoid to use in all the patients a very intensive treatment such as the BEACOPP regimen.
In localized-stage HL patients, the role of FDG-PET scan is less consolidated and the literature data are conflicting (-). In particular, in bulky disease we can frequently observe a persistence of positivity either in interim PET scan or in end-of-treatment PET scan ().
Several papers and clinical trials tried to understand whether the PET scan results could be used to spare RT in HL patients. However, the chemotherapy in association with RT still remain the golden standard (,).
In uncertain cases, a CT scan-guided biopsy is mandatory in order to demonstrate the presence of residual disease. The possibility of PET scan false positivity is well known and reported in several studies, and every clinical decision should be supported whenever possible by a CT scan-guided biopsy. The possibility to overtreat patients should be considered in particular in localized-stage with bulky mass, due to the high frequency of false positive PET scans. Unfortunately, the persistence of positivity, even if intense, is usually very limited, the attempt to perform a biopsy to identify the cause very often fails, and in a CT scan-guided biopsy this result cannot be considered certain. The only reliable technique is the PET/CT scan-guided biopsy, but it is not applicable in all the centers (,).
Thus, a biopsy result suggesting the absence of lym- phoma should always be carefully discussed, in order to exclude a false negative specimen and not to lose or undertreat the patient.
Another issue about the PET-CT scan is its role in the peri-transplantation period. The literature has focused on pre-transplant PET scan, which is known to be important and predictive of good clinical outcomes: several authors reported a better PFS obtained with high dose chemotherapy with a negative PET scan (). The role of PET scans after transplantation is more controversial (,). Some studies reported that persistence of PET scan positivity is associated with lower PFS and OS (), however the data in this field are still limited. As a matter of fact, post-transplantation management, such as maintenance BV, is so far guided by pre-transplantation patient’s characteristics (). Therefore, PET scan interpretation is a really critical issue, because it is not known which patients could be treated with RT only, or could be rescued by new agents, or in which patients an allo-SCT would be indicated (,).
After an allo-SCT, the PET scan role is far more complicated, as false positivity has been described in case of graft versus host disease (GVHD) and other transplantation-associated complications (,). The case we described here is paradigmatic of all PET scan issues discussed above. The patient was probably overtreated. We should have continued with the scheduled therapy also with a PET scan positivity and with a Deauville score of 4 on bulky mass, considering that RT is curative in HL, omitting the high dose chemotherapy. In that moment, we had a persistent PET scan positivity on residual bulky disease, with a negative histological test, which however did not guarantee the absence of disease. However, considering the increasing SUVmax of the mediastinal mass, the young age and the very good conditions of the patient, and the global low therapeutic load as well, we proceeded to intensification. Clearly, the interim PET scan positivity could underlie a spread of the disease due to an insensitivity to chemotherapy, but this situation is much more likely with a Deauville score of 5 (-), when all the statements about PET scan false positivity are not applicable.
In the case we described, even the peri-transplantation PET scan was meaningful, in the era of post-transplantation maintenance with BV. Pre-transplantation PET scan was still positive, again with a negative biopsy. High dose chemotherapy was performed, but a softer approach, with strict clinical follow-up and PET scan, should have been another rational approach, as clearly demonstrated in the post-transplantation follow-up.
Post-transplantation PET scan showed a SUV reduction of the known lesion, which was treated with local RT on initial bulky mass, showing a progressive disappearance in the follow-up. It could be speculated that a follow-up-based approach could have led to the same result.
In summary, the answer to the starting question is that, in our opinion, we can trust in PET scan, even if not blindly, and we should have a good knowledge of PET imaging technique and of PET scan interpretation.
In a localized stage with bulky disease, an interim positive PET scan with a Deauville score of 4 suggests to proceed with the scheduled therapy with a new PET evaluation before the start of RT. In our opinion, in case of PET scan positivity, and regardless of biopsy result, the patient should be treated with RT at the end of the pharmacological treatment. In case of persistent positivity at the end of treatment, a CT or PET/CT scan guided biopsy is mandatory, and if positivity is confirmed, the patient should undergo a salvage treatment. If the biopsy is negative, without any other sign or symptom of active disease, it could be useful to repeat a PET/CT scan after 2 or 3 months.