In February 2009 a 53-year-old female patient was admitted to the University Hospital in Freiburg, Germany for further evaluation. The patient was initially diagnosed with autoimmune hepatitis/primary biliary cholangitis (AIH/PBC) overlap syndrome (positive for anti-nuclear antibodies, antibodies to smooth muscle cells, antibodies to pyruvate decarboxylase E2 subunit, and to soluble liver antigen) in 1989. Since histology and clinical chemistry showed that the AIH component was predominant without cholestasis, the prescribed therapy was a combination of corticosteroids and azathioprine.
In 2006 the patient was previously admitted in the Hospital of Norden, Germany with the first episode of acute variceal bleeding with hemodynamic instability. Banding of varices was performed. Sonography of the abdominal organs showed signs of liver cirrhosis including enlarged spleen. No other abnormalities were found. Within the following 3 years she bled three times per year from these varices. In 2008 she had two episodes of bleeding from rectal varices which were treated with rubber band ligation. Medical therapy of portal hypertension with propranolol was initiated but had to be stopped even at the low dose of 20 mg twice daily due to intolerable cardiovascular side effects (i.e., bradycardia and hypotension). The patient was regularly monitored in the liver transplant center of the University Hospital in Hannover (Medizinische Hochschule Hannover). She was waitlisted for liver transplantation and the implantation of TIPS was scheduled. She was referred to our hepatological unit in order to check whether the application of an inhibitor of the enzyme phosphodiesterase-5 could be an option to lower portal pressure and reduce the risk for bleeding from esophageal varices.
The patient was in a good clinical condition upon admission. The physical examination findings were normal except for the palpable liver and minor bilateral varicose veins of the lower extremities. Examination of heart and lungs was unremarkable. No bipedal edema was present. There were no signs of hepatic encephalopathy. Blood pressure was 154/86 mmHg and the heart rate was 78/min. ECG and echocardiography findings were normal except for a slight tricuspid valve insufficiency. Systolic pulmonary artery pressure was not increased (26 mmHg). Laboratory results showed no pathological values except a slight increase in total bilirubin (1.6 mg/dL) and thrombocytopenia of 105.000/μL, establishing the case as Child A cirrhosis (i.e., normal bilirubin, normal serum albumin, normal INR, no ascites, no hepatic encephalopathy). In esophago-gastro-duodenoscopy scarring transformation of two ligated varices was observed. Three small varices of grade 1-2 were visible. At this point, the daily medication consisted of azathioprine 75 mg, prednisolone 5 mg, pantoprazole 20 mg, and calcium 500 mg.
To test the effect of a PDE-5-inhibitor on portal hemodynamics in February 2009 10 mg of Vardenafil were administered orally. Wedged hepatic vein pressure (WHVP) and free hepatic vein pressure (FHVP) were measured in triplicate before and one hour after the drug administration. The HVPG, defined as WHVP - FHVP, decreased by 14% from 10.5 to 9.0 mmHg. Duplex sonography showed an increase in portal flow by 28% (0.97 L/min to 1.24 L/min) 60 min after drug intake. Systemic blood pressure changed from 130/87 to 121/75 mmHg one hour after drug administration, while heart rate changed from 65 to 61/min. Portal flow monitored by flow-sensitive 3D magnetic resonance imaging increased by 16 % (0.85 L/min to 0.99 L/min). Maximal flow velocity remained constant, at 24 cm/s in duplex sonography and 17 cm/s in 3D MRI. No relevant effect was observed on systemic blood pressure. Visualization of the portal venous system by MRI (Figure ) confirmed the duplex sonographic findings of a prograde blood flow in the portal vein and the two main intrahepatic branches and a recanalized umbilical vein originating from the left main branch of the portal vein.
We discussed an experimental therapeutic approach of the application of a PDE-5-inhibitor with the patient. The patient was informed that this was an off-label use and gave written informed consent. After having verified that the PDE-5-inhibitor Vardenafil decreased HVPG and that it led to an increase of portal venous blood flow confirmed by two independent methods we decided to start a long-term therapy with 5 mg Tadalafil/day, as this PDE-5-inhibitor has a longer half-life than Vardenafil. In June 2009 an HVPG one hour after oral administration of 5 mg Tadalafil of 10.5 mm Hg was measured. Portal venous blood flow remained elevated at 1.21 L/min. Systemic blood pressure showed no clinically relevant changes (124/79 mmHg, heart rate 88/min to 127/77 mmHg, heart rate 64/min) in the acute setting. The next evaluation was performed in October 2009 wherein after 10 mg Tadalafil the HVPG decreased by 15% from 12.0 to 10.0 mm Hg. Portal venous blood flow remained markedly elevated (1.28 L/min in Duplex sonography and 0.99 L/min as measured by MRI). In March 2010 HVPG was 10.5 mm Hg, while portal venous blood flow remained about 30% higher than the initial reading as verified by the two methods. Notably, the flow in the umbilical vein was not influenced by the PDE-5-inhibitor. The results of the measurements are shown in Table . No relevant changes in heart rate or blood pressure occurred. In April 2010 a second-grade esophageal varix was injected with acryl-glue prophylactically. In March 2011 the last measurement of portal blood flow using duplex sonography and the MRI method was performed. It showed that the portal venous blood flow remained constant at a level above than at the start of treatment. Further invasive portal pressure measurements were not performed.
The clinical course of the patient remained stable. The portal venous blood flow determined by duplex sonography was constant within the range of 1.2 and 1.4 L/min. Endoscopic monitoring every six months showed scarring in the distal esophagus and with no signs of new esophageal varices. The varices remained closed by thrombosis. Two episodes of upper gastrointestinal bleeding occurred in 02/2016 and 04/2016. Upper endoscopy excluded bleeding from varices or portal hypertensive gastropathy. The bleeding from the small visible erosions in the duodenum was attributed to NSAID use which the patient had taken due to headache. After administration of a proton pump inhibitor no further bleeding occurred. In 12/2016 portal flow was quantified to be 1.06 L/min. However, this was measured with a different sonographic device. The next sonographic examination in 09/2017 with the original device revealed a constant portal blood flow of 1.29 L/min.
Figure shows the distal aspect of the esophagus with visible scars caused by sclerosing and banding, with the old varices remained thrombosed. Figure shows an abdominal computer tomographic angiography. The portal vein (solid arrow) was perfused in a prograde direction, the diameter was enlarged. There were collateral veins at the splenic hilus and an enlarged left ovarian vein (dashed arrows).
The patient continued the daily intake of 5 mg Tadalafil. Other medications consisted of 75 mg Azathioprine per day and 2.5 mg Prednisone per day. Because of the stable clinical condition the patient is no longer on the list of liver transplant candidates. During the time of follow-up the number of varicose veins of the lower extremities increased and a local therapy was suggested.


A 46-year-old female underwent decompressive craniectomy due to recurrent seizures resulting from an anaplastic oligodendroglioma in the left temporal lobe. She had postoperative left temporal hollowing for 7 years and came to our outpatient clinic. After consultation, she decided to undergo autogenous fat grafting in the depressed temporal area. A 32-mL lipoaspirate was harvested from both medial thighs and 8 mL was injected into the left temporal area. The remaining 24-mL lipoaspirate was stored frozen. A second touch-up session was done after the 1-month follow-up due to a remnant depression resulting from fat reabsorption. An additional 4.8 mL of fat was transferred at that session. She was very satisfied with the result, reporting a score of 5 on the Likert scale after the 1-month follow-up visit. The 1-year follow-up score was 4. No donor or recipient site complications such as seroma, hematoma, infection or surface irregularity were reported ().


A 12-year-old female child presented with complaints of constipation and bleeding per rectum since one and half month and abdominal distention since ten days. She had been treated earlier for anal fissures with serial dilatation elsewhere. Family history was non-contributory. At admission, she was cachectic with a grossly distended abdomen. Per rectal examination revealed tight anal stenosis (). Abdominal X-ray suggested intestinal obstruction.
Under anaesthesia, severe anorectal stenosis was confirmed and biopsied. In view of the massive abdominal distension, a transverse colostomy was done. The biopsy revealed inflammatory lesion. Carcinoembryonic antigen (CEA) and CA 19-9 were within normal limits. Contrast computed tomography (CT) abdomen showed circumferential thickening of rectum with preserved peri-rectal fat planes suggestive of inflammatory pathology. Colonoscopic evaluation revealed linear ulcers in distal colon. Biopsy from these lesions was also non-specific. Patient was taken home at persistence of parents.
After three months, she was admitted with rectal bleeding. Tumor markers were (CEA and CA 19-9) were raised. CT abdomen showed circumferential thickened rectum with frozen pelvis suggestive of malignancy (). Repeat colonoscopic biopsy from the rectum revealed highly undifferentiated mucinous adenocarcinoma of rectum (). Patient was referred to the oncology team. She was advised radiotherapy in view of inoperability of the lesion. She succumbed within 6 months.


A 44-year-old male presented as a critical trauma after his head and chest were pinned against a loading dock by a semi-truck traveling at 5 miles per hour. Upon arrival, the patient was in severe hypovolemic shock mainly from active large volume hemorrhage from the oropharynx. He required nasal and oropharyngeal packing, as well as aggressive fluid resuscitation with over two dozen units of blood products. In addition to numerous noncranial injuries, he suffered multiple skull fractures including bilateral fractures traversing the carotid canals.
Computed tomography (CT) of the head revealed hemorrhage throughout the basal cisterns, trace hemorrhage within the fourth ventricle, and a thin retroclival hematoma. On CT angiography (CTA), there was suspicion of a focal tear in the cavernous right ICA and faint contrast blush at the left cavernous sinus suspicious for CCF. The angiogram revealed bilateral CCFs, left worse than right. There was no evidence of retrograde venous drainage into the right superior ophthalmic vein (SOV) or the right inferior petrosal sinus at this time []. The left ICA drained into both the cavernous sinus and the bony venous channels within the petrous bone and clivus with retrograde flow into the left SOV. There was no evidence of retrograde cortical venous drainage on either side. There was evidence of vasospasm of the A1 segment of the left anterior cerebral artery (ACA) []. Transarterial coil embolization of the larger left CCF was attempted once the catheter was directed across the tear in the ICA; however, after 3 coils were deployed, subsequent coil deployment resulted in the stretching and herniation of the coil into the carotid artery necessitating retrieval. The procedure was aborted. Given the presence of vasospasm in the left A1 segment, thought to be a hypoplastic A1 at the time, left ICA sacrifice was deemed unsafe. The patient was then transferred to the ICU for management of intracranial pressure (ICP); a follow-up CT later that evening showed a right epidural hematoma which required evacuation [].
The patient was monitored closely in the ICU, and he needed medical management of his ICP. He had bilateral movement to central pain by day 4, and we had no indication that he was symptomatic from vasospasm. He was kept normotensive and normovolemic and was monitored closely.
On day 12, after his ICP was well-controlled, he was taken back to the angiography suite where transvenous embolization of the left SOV was performed via left internal jugular vein access to protect the left eye. An attempt was made to embolize the right SOV as well via the right internal jugular vein. However, despite multiple attempts, the microcatheter could not be navigated anteriorly into the right SOV. Although postprocedural arteriograms revealed successful embolization of the left SOV, there was retrograde filling of the right SOV which was not previously observed []. There was evidence of mild-to-moderate vasospasm involving the left ICA, M1, and A1 [], whereas the vasospasm involving the right was less severe []. There was retrograde corticovenous drainage from the left ICA CCF but not from the right.
The patient was returned to the angiography suite on day 13 for attempted transvenous embolization of the left cavernous sinus and CCF. Multiple attempts to protect the cavernous left ICA using a Scepter C balloon were unsuccessful as the catheter and balloon could not be navigated beyond the fistula site. Because the left ICA could not be protected, transvenous embolization of the CCF was aborted. Sacrifice of the left ICA was not a viable option at the time due to poor collateral supply from the right anterior circulation to the left anterior circulation.
The right SOV was embolized via direct SOV cut-down access on day 19. Cerebral angiogram showed resolution of the vasospasm in the left A1 segment and improved collateral flow from the left anterior circulation to the right across the anterior communicating artery (Acomm). The amount of arteriovenous shunting on the right ICA was significantly reduced. On the left, anterograde flow into the anterior circulation was significantly reduced likely because of the improved collateral supply. There was still evidence of retrograde corticovenous drainage into the left superficial middle cerebral vein.
Given the new evidence of collateral flow from the left ICA to the right anterior circulation via the Acomm, at this point the plan became to sacrifice the left ICA because it was the main contributor to the CCF. A balloon occlusion test of the left ICA showed that the venous phase of the left anterior circulation delayed by 1.75 s compared to the right side. Therefore, it was determined that sacrifice of the left ICA was feasible. Because the left ICA distal to the fistula could not be easily accessed, the left cavernous sinus was aggressively embolized through a transvenous route using coils. After transcavernous embolization, there was significant reduction of the arteriovenous flow but a channel remained patent to the distal left anterior circulation. There was concern that coils from the tranvenous embolization could be a source for emboli to the left MCA circulation. Therefore, the proximal left ICA was occluded using amplatzer vascular plugs. Postprocedural angiogram revealed adequate perfusion of the left anterior circulation from the right ICA. Although there was no longer any evidence of retrograde corticovenous drainage on the left, the right superficial middle cerebral vein filled retrograde from the right ICA injection [].
A remaining concern at this point was the retrograde cortical venous drainage to the right superficial middle cerebral vein. The site of the fistula could not be accessed from the right inferior petrosal sinus, and although coils were deployed in the cavernous sinus during the cut-down access of the left SOV, it did not cure the fistula. Viable treatment options for treating the residual fistula directly included accessing the cavernous sinus directly via needle puncture through the orbit or surgically accessing of the right superficial middle cerebral vein. Because treatment of the fistula site could result in coils herniating into the right carotid artery or stenosis of the carotid artery from external pressure caused by the coil mass, we elected not to attempt to treat the fistula site directly. Instead, we performed a right craniotomy and ligated the arterialized right superficial middle cerebral vein at the fistula site [Figure and ] to protect the brain from potential venous infarction. The patient tolerated the procedures well and was discharged to a rehabilitation facility. On follow-up, the patient lost vision in his right eye likely from venous infarction but maintained vision in the left eye. He also had a left 6th nerve palsy likely secondary to the coil pack in the cavernous sinus. He was otherwise neurologically intact and completely independent.
Follow-up cerebral angiogram at 6 months revealed interval healing of the residual right CCF. There continued to be adequate collateral flow into the left anterior circulation from the right via the Acomm. However, there was residual filling of the left CCF via retrograde flow from the right anterior circulation across the Acomm []. There was retrograde cortical venous drainage on the left side. An attempt to access the fistula site transvenously through the inferior petrosal sinus was unsuccessful; therefore, the right ICA was used to access the distal left ICA via the Acomm, and the ophthalmic portion of the left ICA was embolized using coils and onyx. No residual left CCF was seen but there remained slight filling of the right CCF which drained directly into the right inferior petrosal sinus. A subsequent follow-up angiogram 6 months later showed healing of this residual fistula.


A 49-year-old woman presented with acute coronary syndrome for which she received aspirin, clopidogrel, atorvastatin, enoxaparin, and tenecteplase at another facility. She was then transferred to our institute for further management. She underwent coronary angiography which was suggestive of triple vessel disease. As the patient was in acute congestive heart failure (Killip IV) with pulmonary edema, she was intubated and mechanically ventilated. She underwent coronary artery bypass grafting surgery the following day where she received 20,000U of unfractionated heparin.
On postoperative day (POD) 6, the patient developed right pedal edema with cyanosis. Bilateral lower limbs Arterial Doppler was normal. Venous Doppler of the right lower limb was suggestive of thrombosis of the right Common Femoral, Superficial Femoral, Popliteal, and Great Saphenous Veins. She also had progressively worsening thrombocytopenia in which the platelet count dropped from 297 × 109/L on day 1 of postenoxaparin exposure to a nadir of 20 × 109/L on day 8. With a suspicion of HIT and thrombosis (HITT), enoxaparin was replaced with fondaparinux on POD 7. She tested positive for HIT type 2 antibodies on day 10. Her platelets started improving by POD 11 [].
On POD 13, two-dimensional echocardiography done was suggestive of a left ventricular thrombus (with an ejection fraction of 25%) which resolved completely by POD 44 with anticoagulation. Fondaparinux was bridged with oral Vitamin K Antagonist-Acenocoumarol for HITT and PCD. Once there was a line of demarcation for gangrene, she underwent a right forefoot amputation on POD 34.
The patient was discharged on POD 47 with medications for cardiac failure along with acenocoumarol.


A 55-year-old woman underwent cataract surgery with intraocular lens (IOL) in her right eye (RE) elsewhere. The first postoperative period was uneventful, after which she complained of ocular pain, discharge, and gradual decrease of vision in the same eye for which she reported to our institute. Her best-corrected visual acuity (BCVA) in the RE was light perception. On slit lamp examination, the patient had conjunctival congestion, chemosis, marked corneal edema, grade 4 anterior chamber (AC) reaction with a hypopyon of 3 mm, and a thickened inflammatory fibrous membrane within the AC. There was no view of the fundus. No evidence of corneal, scleral, or orbital involvement was seen. Applanation tonometry reading was 19 mmHg and 12 mmHg in RE and left eye, respectively. The left eye had BCVA of 20/200 with immature cataract and normal fundus. B-scan ultrasonogram revealed dense membranous echoes in vitreous cavity suggesting endophthalmitis []. Aqueous humor and vitreous aspirate were inoculated in chocolate agar, blood agar (BA), thioglycolate broth, Sabaroud's dextrose agar, brain heart infusion broth (BHIB) and sent for Gram and KOH stain. Then, the patient underwent standard 20 g pars plana vitrectomy along with intravitreal injections of vancomycin (1 mg/0.1 ml), ceftazidime (2.25 mg/0.1 ml), and dexamethasone (400 μg/0.1 ml) at the end of the procedure. Direct mount showed Gram-negative rods on Gram's stain. Turbidity was found only in BHIB. Gram-staining from BHIB revealed Gram-negative rods. The subcultured colonies on BA were translucent simulating Pseudomonas aeruginosa. The next day, size of colonies became larger and color turned golden yellow and the isolate was identified as A. salmonicida by VITEK 2 (version 5.02) system (BioMerieux, USA). Antibiotic sensitivity was determined by Kirby-Bauer disc diffusion method, and the isolate was found to be sensitive for amikacin, gentamycin, and colistin. We repeated intravitreal antibiotics (amikacin [125 μg/0.1 ml][] and dexamethasone) after 48 h and it responded well to the treatment. Six weeks after the surgery, her right eye BCVA was 20/400 with a quiet AC and posterior segment. There was a fibrous membrane anterior to the IOL obscuring the view of posterior segment (vitreous haze 2+). The patient was advised neodymium-doped yttrium aluminium garnet membranectomy for the same which she underwent without improving the visual acuity.


A 40-year-old woman on treatment for bipolar depression attended the psychiatry outpatient department on May 10, 2014. She complained of excessive tiredness for the past few days and was admitted for evaluation in view of her multiple admissions in the past. She was afebrile with normal vitals and Glasgow Coma Scale of 15. Her psychiatric history revealed bipolar depression for the past 5 years with an episode of depression in 2013. She was on tablet quetiapine 400 mg and tablet valproate 500 mg for July 15, 2013. There was no medical history of diabetes in her or her first-degree relatives. Ten months after the initiation of medication, her weight was 231 lbs (105 kg) with body mass index of 40.92 kg/m2 (height 5 feet 3 inches) indicating class III obesity.
Laboratory investigations revealed an elevated random blood sugar (RBS) value of 443 mg/dl. Urine acetone was positive (+++). Arterial blood gas analysis revealed pH 7.1 and bicarbonate 10.54 mEq/L (normal 22–26 mEq/L) and PaCO230 (normal 35–45) revealing a picture of uncompensated metabolic acidosis. Next day fasting lipid profile was done which showed elevated total cholesterol 509 mg/dl (normal <190 mg%) and triglyceride 2871 mg/dl (normal <150 mg/dl). Glycated hemoglobin was 9.2% (normal 4–6.4%) indicating poor glycemic control. Serum pancreatic amylase was 104 U/L (normal 0–137 U/L), and lipase was 114U/L (normal 0–160 U/L). Other investigations such as hemoglobin, total and differential count, platelet count, erythrocyte sedimentation, renal and liver function tests, lipid profile, serum sodium, and potassium were within the normal limits.
Diagnosis of DKA was made. After consultation with the physician, the patient was aggressively managed with 10 units regular insulin as bolus injection followed by 15 units plain insulin in 500 ml of 0.9% saline given as intravenous infusion at the rate of 15 drops per minute. She was also given intensive fluid management with normal saline and dextrose normal saline. When her blood glucose became 261 mg/dl, the insulin infusion was stopped, and plain insulin 8 units was given eighth hourly subcutaneously. Her fasting and postprandial blood sugars remained high on the consecutive days, and the insulin therapy was stepped up to 14 units in morning, 14 units in afternoon and 10 units at night(14-14-10) on May 17, 2014. Tablet atorvastatin 20 mg once daily was initiated in view of her deranged lipid profile. The dose of quetiapine was stepped down (18th - 300 mg, 20th - 250 mg, and 21st - 100 mg) and stopped on May 22, 2014. The RBS values on 22nd and 23rd were 76 and 90 mg%, respectively, and the patient was discharged with tablet amisulpride 200 mg twice daily and tablet metformin 1000 mg once daily.


A 50-year-old male patient was admitted to the hospital with complaints of myalgias of the upper and lower limb muscles for about 2–3 months and progressive difficulty in rising from a chair, walking, and combing hair. There was no fever, arthralgias, paraesthesias, skin lesions, rash, shortness of breath, cough, abdominal pain, or other symptoms. His physical examination was also unremarkable except for reduced muscle strength (3/5). Laboratory investigations showed elevated plasma creatine kinase (CK). Anti-nuclear antibodies were negative. A magnetic resonance imaging (MRI) of the upper and lower limb muscles was performed and revealed an increase in bulk with increased signal intensity on T2 sequencing of multiple upper and lower limb muscles with sparing of the posterior compartment muscles of the lower limb, suggestive of acute myositis. Electroneuromyography (ENMG) showed features consistent with myoneuropathy. As inflammatory polymyositis (PM) is a well-known paraneoplastic syndrome (PNS), screening positron emission tomography-computed tomography (PET-CT) was done at our center which showed focal areas of heterogeneous attenuation and mild diffuse 18F-fluorodeoxyglucose (18F-FDG) tracer uptake in the upper limb muscles and medial, anterior, and lateral compartment muscles of both lower limbs []. In addition to the muscle findings, PET/CT showed a 18F-FDG avid (maximum SUV 11.7) irregular lobulated heterogeneously enhancing mass arising from the dome of urinary bladder with intraluminal polypoid and extraluminal exophytic soft tissue component [Figures and ]. Biopsy of the bladder mass revealed small cell cancer.


A single breast amputation was performed on a 45-year-old woman with unifocal, unicentric breast cancer without affection of lymph nodes breast cancer and without any signs of disease generalization. Postoperative pathology revealed a poorly differentiated, grade 3 tumor with highly proliferative cells. Following tumor parameters were additionally determined – estrogen receptors were positive, Herceptin test was negative. No data exist about estimation of progesterone receptors and Ki-67 antigen. The patient received six courses of doxorubicin and cyclophosphamide chemotherapy, followed by local radiotherapy. No hormonal treatment was used. At 12 months after the breast amputation, radical hysterectomy and adnexectomy were performed. At 2 and 3 years after breast amputation, tumor markers were within the reference range for healthy individuals.
At 4 years after mastectomy, the patient began to complain of pain in the right ilium. Anteroposterior pelvic X-ray revealed an osteolytic lesion in the right iliac bone localized above the acetabular roof. Carcinoma Antigen 15-3 and Carcinoembryonic antigen tumor markers in the blood were increased significantly. Bone scans confirmed that the lesion was active and probably metastatic; however, similar abnormalities were not detected in the remaining skeleton. The right ilium was irradiated with 20 Gy radiotherapy. After 3 months, computed tomography (CT) was performed and a bone scan of the pelvis repeated. CT revealed a closed osteolytic lesion in the right iliac bone, ~15 cm3 in volume without cortex penetration (). The bone scans demonstrated increased osteoblastic activity with high metastatic potential despite the radiotherapy.
Based on the clinical state of the patient and the results of imaging, the interdisciplinary team, consisting of an orthopedic surgeon, pathomorphology specialist and oncology specialist, devised the therapeutic strategy, presented it to the patient and obtained written consent. The therapy was based on an open biopsy of the lesion, with the expectation of tumor-positive intraoperative pathology and planned administration of doxorubicin into the bone.
The patient underwent surgery in the supine position; the highest and most anterior possible site of bone penetration in the supraacetabular region was chosen, allowing the drug to be administered precisely without contact with surrounding tissues or the possibility of leakage from the administration site (). Fluoroscopy was used to identify the operated area []. The diameter of the osteotomy site was 1 cm and the roof of the bone was preserved for closure of the resected area. The intracystic material was removed. Pathomorphology analysis confirmed the presence of tumor cells and 5 mg doxorubicin liquid (2.5 ml; suspended in a solution of sodium chloride and hydrochloric acid) was applied to the defect (). The cavity was closed with the piece of bone cortex obtained during osteotomy (). The tightness of the cavity was checked intraoperatively using contrast liquid (). Drainage was applied.
Postoperative CT was performed during the hospitalization period (). During the postoperative period, no local or general complications occurred. The sutures were removed and the patient was discharged 10 days after the surgery. Tumor markers decreased to normal levels 3 months after the surgery.
During the following 6-month observation period, the patient had no signs of recurrence. No pain was reported, only mild discomfort within the first 6 weeks after the surgery, and her gait was normal. After 6 months, a second operation was performed on the same area of the bone and intraoperative pathological analysis for the presence of tumor cells was negative. The defect was reconstructed using bone allografts. The metastatic region was radiologically evaluated by CT at 4 and 14 months after the second operation, revealing complete healing of the bone allografts ( and ).


A 26-year-old woman with schizophrenia was admitted to our hospital for a left adrenal mass found when she had her gynecologic examination for secondary amenorrhea.
The patient was a hepatitis B positive female with a history of schizophrenia for more than 10 years, who exhibited male characteristics (including hirsutism and menoxenia) but with no lumbago. At the age of 13 years, the patient began to menstruate, but the cycles were rather irregular. Six years ago, her menstruation cycle became normal because she was consuming ethinylestradiol and cyproterone acetate tablets. In addition, she has been taking antipsychotic drugs for more than 10 years.
On a through laboratory examination, the patient had a high level of plasma testosterone (328.79 ng/mL). Complete blood count revealed increasing leukocytes (47.00/µL), thrombocytocrit (0.41%), and epithelia (33.5/µL). The level of plasma cortisol aldosterone, basal plasma renin activity, and angiotensin II showed no obvious abnormality. Abdominal sonography showed that there was a well-defined hyperechoic heterogeneous mass of 11.0×10.1×10.1 between the left adrenal gland and spleen. Computerized tomography scan of the abdomen with oral and intravenous contrast showed a big nonhomogeneous mass pushing the left kidney down in the left upper quadrant. It measured approximately 11.6×10.0 cm with multiple septa which showed slight enhancement in arterial phase and moderate enhancement in venous phase, so did the solid component of the tumor. This mass also had a vaguely defined border with the tail of the pancreas and spleen. Besides, a low-density lesion could be seen in the left lobe of the liver ( and ).
The left adrenal mass specimen measured 13.5×10.5×6.5 cm. A mixture of mature adipose tissue and bone marrow elements could be seen in the low-power histological picture (). Immunohistochemical staining was performed for Syn, Ck, Hmb45, Melan-A, Hmb45, and cgA ().
The patient was referred for a left adrenal laparoscopic excision, and the postoperative hospital course was uneventful. She recovered quickly, and the level of plasma testosterone was 0.68 ng/mL (). Her menstruation soon became regular and endocrine examinations returned to normal.
The patient’s family gave their written informed consent for all or any part of this material to appear in this paper and all editions of Cancer Management and Research, and any other works or products, in any form or medium.


A 43-year-old female had received both local and oral corticosteroid treatment for facial acne 1 month before presenting with neck/pharyngeal pain and progressive dysphagia. Magnetic resonance imaging (MRI) showed a T2-hyperintense signal involving the dens (C2), accompanied by an extensive inflammatory reaction involving the retropharyngeal space []. Computed tomography (CT) scan also documented early dens erosion [Figure and ]. Although blood cultures were negative, the C-reactive protein (CRP) level was elevated (29.3 mg/dl), and erythrocyte sedimentation rate (ESR) was 120 mm/h. The patient was afebrile on steroids, but was not on any antibiotics.
A biopsy was performed of the C1-C2 level through the posterior oral pharynx. Although the histological finding was consistent with inflammation, cultures remained negative (e.g., for common aerobic and anaerobic pathogens). Ten days later, however, the cultures grew P. acnes, sensitive to linezolid. A second confirmatory biopsy confirmed this diagnosis.
The patient was treated for 20 days with linezolid 600 mg, and was placed in a Halo-vest for atlantoaxial instability. Three months later, although laboratory tests documented resolution of the infection, both the MRI [] and CT scans [Figure and ] confirmed marked erosion of left C1-C2 joint/dens that required a transarticular C1-C2 posterior arthrodesis (Magerl's technique in combination with Gallie fixation with heterologous bone graft, Organizzazione Toscana Trapianti OTT). Three and 6 months later, the CT scan showed fusion [], the patient was clinically improved, and both CRP and ESR laboratory studies were normal.


A.D., a 21-year-old single female, a graduate, currently pursuing degree in education, staying with parents, hailing from a semi-urban background, belonging to middle socioeconomic status, presented with the complaints of fear of interacting with others – since early childhood, preoccupied about her appearance, figure, nose, hair, and complexion – for the past 8 years and excessive use of mobile phone for Facebook, WhatsApp, and taking selfies for the past 3 years. The symptoms had an insidious mode of onset, with continuous course and fluctuating progress. There was no specific precipitating factor. The client was apparently doing well till 2008, when she was 14 years old and was studying in high school. Though she was always a below-average student, she became extremely sensitive to her teacher's comments in tuition classes regarding her studies. She compared herself with other students and felt inferior.
There was a decline in academic performance because she found mathematics and science difficult. She used to cry a lot at home and told her parents that she did not want to study. She stopped going to tuition classes and school. A psychiatrist counselled her in the nearby city, and prescribed medication. With this, she somehow managed to pass high school. There was not much improvement in the symptoms for the next few years as she became preoccupied with her appearance that her nose was not sharp, she was not fair, and had a lot of pimples. This led to a number of consultations with dermatologists, repeated mirror gazing, reassurance seeking, mood fluctuations and attempts at self harm. They sought consultation from us at NIMHANS in May 2013 and was diagnosed as BDD and social anxiety disorder. She was treated with clomipramine 150 mg/day with lithium, sertraline, and risperidone being tapered off. Therapy sessions focused on psychoeducation, cognitive restructuring, mirror retraining, exposure, and response prevention. They returned to their hometown so that she could appear for her examinations. She visited us again in October 2013, as the symptoms worsened. There was again excessive preoccupation with her looks, repeated mirror gazing, reassurance seeking, handwashing, face washing, and demanding behavior. Clomipramine was increased to 200 mg. Therapy was initiated again mainly focusing on cognitive restructuring, mirror retraining, and exposure and response prevention. There was improvement in 2 months’ time. Subsequently, the patient was followed up every 6 months for reviewing the medication.
On subsequent follow ups it was seen that she continued her preoccupation with her appearance (figure, nose, complexion, and hair), leading to checking the mirror every hour of the day. She avoided seeing mirrors in shops, restaurants, etc., with the fear that she might look bad in it and also avoided going out in day time. She was very particular about her clothes and wanted it to be the perfect fit. She used to spend a lot of time on changing her hairstyle throughout the day. She wanted to look good in order to gain social acceptance and also be liked on Facebook and WhatsApp (ends up using her phone most time of the day). She avoided social interactions and giving presentations as she feared negative evaluation by others over what she said. She started using Facebook when she was Class XI, but on reaching college 1st year, there was excessive use of Facebook and WhatsApp. She had been preoccupied since then, whether others like her photograph on Facebook and whether others chat with her. She also had made a group of unknown friends. She checked her phone every 10 min for any messages or notifications on a usual day. She keeps clicking selfies every 15–20 min, till she was satisfied with a photograph, and if not she changed her hairstyle and clicks again. She clicked more selfies at night, because according to her, she looked better at night time, rather than day time, as it magnified her flaws. Whenever her net balance was over, she demanded her mother to get it recharged immediately. She preferred chatting and being with others online, rather than interacting in the real world. She avoided face-to-face conversations, giving presentations, purchasing things from a shop, eating, talking on a phone in a public place with the fear of negative evaluation by others, and being subject to the scrutiny of others. Premorbid temperament revealed that she had a lot of demands and temper tantrums as a child. She was overactive and would spend more time in extracurricular activities than academics. She had always been a below-average student in school and had difficulty in making friends. Family history revealed that the client's father had frequent anger outbursts and used to hit the client whenever she became demanding. Mother on the other hand was permissive. Assessment revealed the presence of problematic use of internet (score of 60 on Internet Addiction Test[]), excessive use of mobile and Facebook on Problematic Mobile Phone Use Questionnaire[] and Facebook Intensity Questionnaire,[] moderate social phobia on Liebowitz Social Anxiety Scale[] indicating moderate social phobia (score 58), and the patient got moderate score in the domains of anxiety (score 14) and stress (score-20) on Depression, Anxiety and Stress Scale.[]
Therapy components in the initial phase included psychoeducation about BDD and the cognitive-behavioral aspects, tracking mirror and mobile use, monitoring her negative automatic thoughts, triggers, and identifying the cognitive errors. In the middle phase of therapy, the cognitive errors and dysfunctional negative thoughts were challenged and her beliefs about the importance of appearance were identified. She was also encouraged to participate in other recreational activities such as yoga, walking, drawing, and going to the library. Specific contract was made regarding her mirror and mobile use on a typical day. Initial goal was to delay the frequency of use. Mirror retraining was also done. Exposure and behavioral experiments were used to modify the underlying beliefs of importance of appearance and social acceptance.
The outcome of the therapy was positive. Fifteen sessions were carried out with the client. Mirror usage had reduced to 5–6 times/day though she still avoided seeing mirrors of shopping malls, vehicles, etc. Mobile use was also reduced to 2–3 h every day. The craving for the mobile phone/internet was still there, and whenever the mobile balance would get over, she wanted to recharge it immediately. She was able to challenge certain negative automatic thoughts, but practice was needed in developing more realistic alternative thoughts. She would have benefitted from exposure to various social situations which she avoids, but due to lack of time, only one or two situations could be practiced.


A 61-year-old male presented to our clinic with worsening pain and numbness in both lower legs for 4 weeks. The symptoms started 1 year ago, and difficulty in walking appeared 6 months ago. He denied having fever, chills, nausea, vomiting, cough, difficulty breathing, or arthritis. The patient had a 2-year history of syphilis and had been treated with penicillin for 14 months. The patient was sexually active but did not has a stable sexual partner. No history of other infections or malignancy was reported.
Physical examination revealed normal vital signs. No rashes, papules, or ulcers were found and there was no generalized lymphadenopathy. The patient had a VAS score of 7 of both lower extremities. Motor power (left/right) was graded as follows: quadriceps (4/4), tibialis anterior (3/3), and dorsal thumb extensor (1/1). No bowel dysfunction was detected. There were no oral or genital lesions. Laboratory investigations on admission showed mild anemia (hemoglobin 11.7 g/dL; reference value: 12–16 g/dL), increased white blood cell count (13.8 × 109/L; reference value: 4.00–10.00 × 109/L), elevated C-reactive protein (77.43 mg/L; reference value: 0.00–10.00 mg/mL), procalcitonin (1.18 μg/L; reference value: 0.00–0.05 μg/L), and ESR (73 mm; reference value: 0–15 mm). Serological tests for hepatitis B virus and hepatitis C virus were negative. Syphilis test results were as follows: RPR (+) and RPR 1:2 (+) HIV and Mantoux tuberculin skin test were negative.
Lumbar spine x-ray revealed loss of disc height and abnormal high density of the vertebral body at L4 and L5 (Fig. ). Whole spine magnetic resonance imaging (MRI) identified severe narrowing of the disc space at L4–5 and a mass of 4.3 mm × 1.8 mm × 1.6 mm in size, which was located immediately behind the vertebral body at L4 (Fig. ). The mass had a sharp boundary. A lumbar CT scan showed extensive wormy appearance throughout the lumbar spine, which was the most noticeable at L4 and L5 (Fig. ).
Posterior decompression of the vertebral canal at L4–5 was performed after pedicle screw fixation (L3-S1) (Fig. ). The dural sac was pulled to the left side and the mass was found under the posterior longitudinal ligament and tenaciously attached to adjacent tissues. The mass was white–gray, rubbery, and resembled a tumor mass. Nucleus pulposus clamp and bone curets were used to remove the mass from the vertebral body at L4. There was no massive bleeding during the procedure and the mass appeared white–gray and was rubber (Fig. ). The postoperative VAS score of both lower extremities was 2. Dorsal thumb extensor motor power (left/right) at day 7 postoperatively was 3/3. Laboratory examinations showed normal white blood cell count and decline in C-reactive protein (20.35 mg/L) and ESR (58 mm). Pathological slices showed degenerative necrotic tissues and fibrous connective tissues with occasional perivascular infiltration by lymphocytes (Fig. ).


A previously healthy 24-year-old male presented to the Emergency Department in our hospital with 1-day history of altered conscious level. He had suffered from headache and difficulty walking for 3 weeks before his presentation. The headache was continued and progressive in nature, located in the occipital region, and was associated with nausea, vomiting, and diplopia. On examination, his Glasgow Coma Scale was 12/15. He had left sixth cranial nerve palsy with no papilledema, facial paralysis, or other neurological deficits. Computerized topography of the brain showed a large posterior fossa nonenhancing fourth ventricular lesion containing hemorrhage and calcification and causing obstructive hydrocephalus []. The patient's conscious level deteriorated rapidly necessitating the insertion of the emergency cerebrospinal fluid external ventricular drain (EVD) as the first procedure. Magnetic resonance imaging (MRI) of the brain showed a midline posterior fossa cystic lesion measuring 7.2 cm in the craniocaudal plane and 5.5 cm × 4.1 cm in the axial plane [Figure and ]. The lesion appeared to have two components; an anterior portion located within the fourth ventricle and a posterior portion adjacent to the vermis extending downward through the foramen magnum reaching the level of C1. The lesion was purely intraventricular and causing a significant mass effect on the medulla and pons. Following the EVD, the patient regained consciousness and his condition stabilized. On the following day, he underwent posterior fossa craniectomy and total excision of the tumor. The posterior cystic component of the lesion contained yellowish turbid fluid. It had a thin wall which extended down to the level of the C1 but was easily removable. The anterior portion was partly calcified and partly solid containing muddy-like material. Although its wall was slightly adherent to the floor of the fourth ventricle, it was excised completely.
Histopathology showed a cystic lesion lined by squamous epithelium (varies from flat, simple to stratified) with focal peripheral palisading. The wall shows extensive fibrosis, chronic inflammation, cholesterol clefts, and cystic changes, with calcification and focal osteoid formation. Wet keratin was identified. Focal cerebellar tissues with reactive gliosis were seen. These features were diagnostic of adamantinomatous type craniopharyngioma [Figure –]. Postoperatively, the patient made a good recovery with no neurological focal deficits apart from the left sixth nerve palsy which recovered only partially. The EVD was removed and no permanent shunting was required. Postoperative MRI showed no evidence of tumor residual and no hydrocephalus. At 2-year follow-up, the patient remains asymptomatic with no evidence of a recurrence.


A 28 year old male patient presented with a chief complaint of a small growth on the palate that had been slowly enlarging over the previous 7–8 years with no pain. Clinical examination showed 1 cm × 1 cm sized, firm swelling with normal overlying mucosa []. The swelling was nontender, nonfluctuant, sessile in appearance with well-defined margins. The patient had no significant medical history. On general and systemic examinations, the patient was apparently healthy. There was no regional lymphadenopathy. The adjacent teeth 25, 26 were carious. Radiological findings revealed localized osteolytic lesion on the left palate. Based on the clinical findings, a provisional diagnosis of palatal fibroma was made with a differential diagnosis of PA and lipoma.
Excisional biopsy was performed under local anesthesia, under aseptic condition and the specimen was sent for histopathological examination. Gross specimen comprised of an encapsulated soft tissue mass, measuring 1.5 cm × 1.5 cm × 1 cm, round, gray-white, and firm. Cut surface was firm and gray-white with no areas of hemorrhage, necrosis or cystic change [].
Under low magnification, hematoxylin and eosin-stained sections revealed, a well-circumscribed lesion composed of superficial and deep-seated keratin-filled multicystic spaces of variable size and shape []. On higher magnification, the epithelium enclosing the fibrous mass was parakeratinized stratified squamous epithelium. Within the stroma, a large number of cystic spaces, gland-like tubular structures, tumor islands and mucous cells could be seen [Figures and ]. Cystic spaces were of variable size and shape and were dispersed throughout the stroma. Cystic spaces were lined by squamous cells. Most of the cystic spaces contained keratotic lamellae, some contained eosinophilic material and some were empty []. The tumor islands were composed of basaloid cells. The tumor cells, dispersed throughout the stroma, were pleomorphic with shapes being basaloid, plasmacytoid, angular or elongated []. Periodic acid-Schiff staining revealed the presence of mucin in some cystic areas []. The connective tissue stroma was composed of dense collagen fibers, fibroblasts, endothelial-lined blood vessels with extravasated red blood cells and inflammatory infiltrate mainly comprising of lymphocytes. A histopathological diagnosis of PA, with extensive squamous metaplasia was made.


A 35-year-old male reported to Government Dental College, Indore, before 3 years, with a soft, non-tender compressible diffuse swelling involving the left parotid gland for the last 9–10 months. The swelling was noted to have gradually increased in size and was measuring 3.5 cm × 2.5 cm × 4.5 cm at the time of presentation []. It was a well-defined smooth-walled cystic lesion seen in the superficial lobe of the left parotid gland. The patient denied any history of trauma to the parotid area. The overlying skin was normal in color and freely moveable over the mass. The function of facial nerve was normal. There was no associated regional lymphadenopathy or thyroid enlargement. Intraoral examination revealed a free flow of saliva from the left parotid (Stensen's duct) opening.
The preoperative diagnosis of this case remained uncertain as the nature and clinical symptoms resembled the other cystic lesions of the parotid gland such as retention cysts, extravasation cysts, or cystic degenerative salivary gland tumor.
Further investigations were done including orthopantomographic radiograph and lateral skull radiograph however, both revealed normal conditions.
ELISA-based HIV was nonreactive. In addition, the patient did not belong to the HIV high-risk group based on social and family histories Biochemical investigation revealed high protein content A simple magnetic resonance imaging (MRI) was done which showed “A well-defined, thin, smooth-walled cystic lesion within the superficial part of the left parotid gland measuring about 3.7 cm × 2.6 cm × 4.2 cm. The fluid content of the lesion appeared hypertense on T1 as well as T2-weighted imaging (WI), suggestive of high proteinaceous or hemorrhagic content with no solid component. MRI picture was, therefore, indicative of a benign cystic lesion of the left parotid gland with a differential diagnosis of branchial cleft cyst [] Fine-needle aspiration cytology (FNAC): FNA of the mass yielded a chocolate brown, hemorrhagic fluid which on cytological examination revealed sparsely cellular smear consisting of inflammatory infiltrate predominantly with neutrophils, lymphocytes and cystic macrophages against a proteinaceous background suggestive of an infected cyst of the left parotid gland.
Hence, based on clinical presentation, aspiration and MRI, a final diagnosis of infected cyst of the left parotid gland was given.
The finding was explained and the patient agreed for the surgical excision of superficial parotid gland tissue under general anesthesia.
After skin preparation with povidone solution, access to the cyst was made through the lower neck incision at the deepest neck crest which is found to be posteroinferior to the cyst. This helps to minimize the postoperative scarring and avoid from puncturing the cyst. The incision was then extended to the mastoid, posterior and inferior auricles. The incision was then performed layer by layer until it reached the platysma muscle. This muscle was dissected to expose the underneath cyst capsule. Once the plane between cyst capsule and platysma muscle was identified, the blunt dissection was carried out carefully separating the cyst from the sternocleidomastoid muscle posteriorly and the posterior belly of digastric muscle underneath with the preservation of facial nerve. However, the upper part of the cyst was found embedded in the parotid tissue, so part of the superficial lobe of the left parotid gland was excised together with the cyst. The specimen was then sent for histopathological examination (HPE).
Patient recovery was nonincidental with no evidence of facial nerve palsy and wound infection.
The HPE showed a collapsed cyst wall with adjacent salivary gland and small reactive lymphoid tissue. The cyst was lined by thin ciliated columnar epithelium in some areas, cuboidal in other areas and flat squamous cells in still other areas. However, no nuclear atypia was seen. The appearance was that of a Lymphoepithelial cyst (LEC). The lymphoid tissue was of both diffuse and follicular nature [Figures –].


We report a case of a 40-year-old ASA I lady who presented with ongoing bilateral severe tinnitus for 6 days after a lumbar puncture. The patient also suffered from a headache that resolved by Day 6; however, her tinnitus had persisted. She described the tinnitus as severe and had caused great emotional distress. In addition, she reported subjective minor hearing losses in both ears, which were not fluctuating. There were no visual or balance problems – no vertigo, dizziness, ear fullness or migraines. Cranial nerve and otoscopic examinations were both normal. Audiogram revealed a normal hearing in the right ear and a low-frequency mild sensorineural hearing loss in the left ear (). Tympanograms were normal.
She had been involved in an early Alzheimer’s randomised controlled trial for the last 3 years and had been getting a trial medication or placebo every 3 months. She was otherwise well and not on any other medications. As part of the trial, she was required to have a lumbar puncture yearly. She reported no long-lasting neurological sequela after the previous two lumbar punctures, usually only reporting mild headache that would eventually subside. However, this time, she presented with refractory bilateral tinnitus persisting for 6 days.
In view of her ongoing symptoms, a decision was made to perform a blood patch. The patient had not received any medical therapy prior to this. For the procedure, 20 mL of venous blood was extracted from the patient’s right antecubital fossa and 18 mL of blood were injected into the epidural space with a 16G epidural needle. She reported immediate resolution of the tinnitus in her right ear, and by 24 h, the tinnitus in her left ear had also resolved. The patient completed a Tinnitus Handicap Inventory Severity Scale before and after the procedure. She scored 84 on the scale pre-procedure, which is classed as grade 5 or ‘catastrophic handicap’. She was discharged on the same day with questionnaires to complete. She was reviewed at 1 month in the otolaryngology clinic. A repeat audiogram revealed that her hearing was back to normal ().


A 67-year-old woman was admitted to our hospital in August 2016 for the treatment of ischemic gangrene of the right foot, with a Rutherford classification of R5. She had a history of end-stage kidney disease, hyperlipidemia, and hypertension. The ankle–brachial index (ABI) of her right foot was 0, and echocardiography of the right lower extremity revealed a high peak systolic velocity ratio (PSVR) of 20.9 at the right PA. Her right foot was treated using a 6-Fr sheath (Radifocus introducer, Terumo Medical Corporation, Tokyo, Japan). Pre-procedural angiography revealed subtotal occlusion with hard calcification in the PA (). After the lesion was crossed with a 0.014-inch guidewire (Agosal XS, St. Jude Medical, Tokyo, Japan), a second 0.014-inch guidewire (Treasure XS, St. Jude Medical) was placed in the CS (CROSSER, Medicon, Osaka, Japan) in an attempt to cross another lumen or create a crack (). When the second 0.014-inch guidewire (Treasure XS) had penetrated the calcification, the CS was used. The working time of CS was within 30 s. After repeatedly crossing a few lumens and creating cracks, a 5-mm balloon (Scoreflex PTA 5.0/40, Orbusneich Medical, Tokyo, Japan) was passed through the first 0.014-inch guidewire (Agosal XS), and it was inflated up to 10 atm for 60 s. After deflating the 5-mm balloon, the PA was checked via angiography and intravascular ultrasonography (IVUS)/catheterization (Eagle-Eye Platinum, Volcano, Tokyo, Japan), which revealed no major dissection or bleeding in the PA () with an improved blood flow and pulsation. The ABI had also improved to 0.92.


A 73-year-old man was admitted to our hospital in October 2016 for the treatment of ischemic gangrene of the right foot with a Rutherford classification of R5. He had a history of end-stage kidney disease, coronary artery bypass grafting, type 2 diabetes, hyperlipidemia, and hypertension. ABI of the right foot was 0, and echocardiography of the right lower extremity revealed a high PSVR of 16 in the right CFA. The right foot was treated using a 6-Fr sheath (Destination 45 cm, Terumo Medical Corporation) via an ipsilateral approach. Pre-procedural angiography revealed subtotal occlusion with hard calcification in the CFA (). After the lesion was crossed with Agosal XS (St. Jude Medical) (), Treasure XS (St. Jude Medical) and CS (CROSSER, Medicon) were used in an attempt to cross the lumen or create a crack (). The direction of Treasure XS was repeatedly changed to create another lumen or crack with the CS. After employing the CS, as in Case 1, a 3.5-mm balloon (NSE PTA 3.5/20, Goodman, Nagoya, Japan) was advanced through the Agosal XS and inflated up to 10 atm for 60 s. Next, the 3.5-mm balloon was advanced through the Treasure XS and inflated up to 10 atm for 60 s. After deflating the 3.5-mm balloon, a 7-mm balloon (Sterling Monorail 7.0/20, Boston Scientific Japan, Tokyo, Japan) was advanced through the Agosal XS and inflated up to 14 atm for 120 s. CFA was evaluated via angiography and IVUS/catheterization, which revealed no major dissection or bleeding in the CFA (), with a significant improvement in blood flow and pulsation. The ABI had also improved to 1.07.


We here present a case of an 81-year-old male patient who was referred to our outpatient clinic. His medical history describes an ischemic stroke, hypertension with a stable stage 3 nephropathy, and successfully treated multiple myeloma type IgA lambda. Two years before presentation, he suffered from symptomatic anemia, caused by a monoclonal gammaglobulinemia (29 g/L). He received treatment with melphalan 10 mg, prednisone 100 mg, and bortezomib 1.3 mg/m2 for 9 cycles, which resulted in a significant decrease of the paraproteinemia and a complete recovery of the anemia. Due to disease progression, he subsequently started with treatment consisting of lenalidomide 15 mg and dexamethasone 40 mg, which was poorly tolerated and stopped after 2 cycles. Subsequently, the patient was in a clinically stable condition with a low paraproteinemia (1–5 g/L) and mild anemia (hemoglobin 6.8 mmol/L).
In August 2015, the patient was admitted to the Department of Internal Medicine for complaints of dyspnea, general discomfort, and muscle weakness. Physical examination revealed a poor performance status (WHO 3–4), tachypnea (24/min) with a normal body temperature and blood pressure, and no clinical signs of pneumonia or cardiac decompensation. General blood tests, along with arterial blood gas analysis, were performed, which revealed a respiratory compensated metabolic acidosis (Table ; day 0). The anion gap, corrected for the hypoalbuminemia, was found to be increased (16.8) with an elevated arterial lactate level (9.5 mmol/L). We concluded that the patient's symptoms of dyspnea, muscle weakness, and general discomfort were most likely a consequence of the lactic acidosis.
In order to differentiate between a type A and B lactate acidosis and find a potential cause, more investigations were performed. Laboratory tests and CT scanning were conducted. No signs of ischemia were observed with normal vital parameters, a normal ECG, and contrast enhancement of all major abdominal and thoracic vessels. No signs of pulmonary embolism were present. General blood tests revealed a normal liver function, a stable kidney function (eGFR 41 mL/min) and an elevated PSA level (240 µg/L; normal <4.0 µg/L). Medication (metformin, salicylates) and food supplements were discussed with the patient and no toxic cause was identified. CT imaging of the thorax and abdomen revealed an enlarged prostate, hydronephrosis of the right kidney, 2 small nodules in the liver (segment 1 and 7), and enlarged mediastinal and paratracheal lymph nodes as well as sclerotic bone metastases. We concluded that the patient suffered from type B lactic acidosis most likely caused by metastatic prostate cancer. Treatment was started with cyproterone acetate 100 mg twice daily, prednisone 65 mg once daily, and thiamine 100 mg. Treatment with chemotherapy was considered, but impossible due to poor performance status, comorbidities, and age.
Soon after diagnosis, the patient clinically deteriorated. Arterial blood gas analysis showed increasing lactate levels up to 13.6 mmol/L and lowering pH levels to 7.23 (Table ; day 1–2). Since the patient became unconscious, he was admitted to the intensive care unit (ICU) and received 300 mmol NaHCO3 8.4%. Two days after admission to the ICU, the patient developed an adrenaline-resistant cardiac arrest. Since the patient signed a do not resuscitate (DNR) will, resuscitation did not take place.
Autopsy was performed, which revealed locally advanced and metastatic prostate cancer (Gleason score 5 + 5 = 10) with encasement of the right ureter. Histopathologic examination demonstrated metastases in the thoracic and lumbar spine, liver, lungs, and peritoneum. Furthermore, bilateral tumor thrombi were detected in the microcirculation of both lungs. No signs of activity of multiple myeloma or cardiac ischemia were noted.
On DNA isolated from the prostate carcinoma, targeted next-generation sequencing was performed aimed at a panel of genes including TP53, PIK3CA, PTEN, and IDH1 genes. A frameshift mutation was detected in exon 8 of the TP53 gene (c.887delA, p.H296Pfs*49) leading to a truncated gene product. Furthermore, an activating mutation was found in exon 10 of the PIK3CA gene (c.1634A>G, p.E545G). No mutations were observed in exon 1, 3, 5, 6, 7, and 8 of the PTEN gene and exon 4 of the IDH1 gene.


We report the case of a 59-year-old female patient of Southeast-Asian descent who underwent deceased donor renal transplantation at our institution in August 2016. At the time of initial referral for transplant evaluation in 2011, she had advanced chronic kidney disease but had not started dialysis. Medical records indicated that she had a slow rise in serum creatinine since 2006 but had never undergone a renal biopsy. No specific etiology had been ascribed to her kidney disease. Due to a history of 5 pregnancies that culminated in 3 live births and 2 miscarriages, she was broadly sensitized to human leukocyte antigens (HLA). Routine screening for anti-HLA antibodies with a Luminex-based solid-phase assay using single-antigen beads detected multiple class I and class II HLA antibodies in April 2016. Based on our institutional policy to denote HLA, to which antibodies of a strength greater than 4,000 mean fluorescence intensity (MFI) units are detected in the transplant candidate serum, as unacceptable, our patient's calculated panel reactive antibody (CPRA) level was 93%.
After an approximate wait-time of 5 years, she received an organ offer from a 46-year-old male deceased donor, who succumbed to a self-inflicted gunshot wound to the head. The deceased donor had a terminal creatinine of 1.2 mg/dL, and the organ offered was assigned a kidney donor profile index of 38%. Pre-implantation biopsy of the transplanted kidney demonstrated glomerulosclerosis in 4 out of 78 sampled glomeruli. Fibrosis affecting up to 10% of the tubule interstitium, mild arteriosclerosis, and patchy areas of acute tubular necrosis were also noted. Donor and recipient were blood type compatible (ABO type A). Complement-dependent cytotoxicity and flow cytometry-based cross-match testing of the current recipient's serum with donor T and B lymphocytes were negative. However, donor-specific antibodies (DSA) to class I antigen-HLA B45 (MFI 3,182) and class II antigen-DQ6 (MFI 3,802) were detected by Luminex-based solid-phase assay in the serum sample from April 2016. We consider antibody strength of MFI 2,000 or greater to be clinically significant. Since this suggested prior sensitization to donor HLA, the risk of early antibody-mediated rejection (AMR) due to a memory B-cell response was predicted to be high. Transplant surgery was uneventful with minimal intra-operative blood loss, and the organ incurred a cold-ischemia time of 15 h.
Immunosuppressive therapy for induction consisted of 6 mg/kg of intravenous (IV) antithymocyte globulin given in divided doses over 4 days; tapering doses of IV methylprednisolone given on postoperative days (PODs) 0–4. In addition, 375 mg/m2 of rituximab was administered on POD 1 to suppress humoral alloimmune response. For maintenance immunosuppressive therapy, the patient began receiving 1,000 mg of oral mycophenolate mofetil twice daily from POD 0. Excellent urine output of 1.3 L was noted in the first 12 h after transplant, and tacrolimus was initiated on POD 1. Tapering doses of oral prednisone were started on POD 5. The serum creatinine levels declined steadily from 7.9 mg/dL (pre-transplant) to 1.9 mg/dL by POD 5, and the patient did not require dialysis.
However, the hemoglobin trended down to 6.8 g/dL (baseline: 9.8 g/dL), and the platelet count gradually decreased to 61,000/µL (baseline: 302,000/µL) by POD 6. Alarmingly, the patient's creatinine rose to 2.9 mg/dL and then to 3.3 mg/dL in the 24-h period between POD 5 and POD 6. Lactate dehydrogenase was elevated at 1,016 U/L (reference range: 313–618 U/L), and haptoglobin was <10 mg/dL (reference range: 30–200 mg/dL). The corresponding tacrolimus trough level was 5 ng/mL. Renal allograft ultrasound demonstrated mildly heterogeneous echotexture of the transplant kidney, and Doppler evaluation of the intraparenchymal vessels showed resistive indices ranging from 0.80 to 0.83. One unit of apheresis platelets was transfused, and the patient underwent an urgent ultrasound-guided renal allograft biopsy. In the 6 h preceding the biopsy, the patient's recorded urine output was 100 mL. The patient's blood pressure remained stable with a systolic blood pressure of approximately 140 mm Hg throughout the hospitalization leading up to the biopsy.
An adequate biopsy sample consisting of 2 cores of cortical tissue exhibiting 26 glomeruli and 4 interlobular arteries was obtained. No immediate biopsy-related complications occurred. The most prominent finding on light microscopic examination was the demonstration of fibrin thrombi involving 1 arteriole and capillary loops in 2 glomeruli (Fig. ). Isometric cytoplasmic vacuolization of tubular epithelial cells and arteriolar myocytes was also apparent. There was no evidence of microvascular or tubulointerstitial inflammation. C4d was negative by immunofluorescence microscopy. Electron microscopy revealed diffuse swelling of glomerular capillary endothelial cells and cytoplasmic vacuolization of tubular epithelial cells. Histologic correlates of acute AMR were striking in their absence. DSA that were scored positive in the pretransplant serum sample were not detectable in the serum sample tested on the day of the biopsy (HLA B45: pretransplant MFI 3,182 vs. POD 6 MFI 1,438; DQ6: pretransplant MFI 3,082 vs. POD 6 MFI 640). Histopathologic features noted on the renal allograft biopsy, taken together with clinical and laboratory findings, suggested that CNI-induced de novo post-transplant HUS was the most proximate cause of acute oliguric renal failure in this case (Table ).
Tacrolimus was discontinued. A reversal of the upward trend in creatinine was immediately apparent after withholding the CNI. Creatinine improved to 2.4, 1.8, and 1 mg/dL in the 3 succeeding days. The patient received a transfusion of 1 unit of packed red blood cells after the kidney biopsy following which hemoglobin improved from 6.8 to 8.6 g/dL and steadily improved to 10.1 g/dL in the following 2 weeks. In the same period, a significant improvement in platelet count occurred (61,000–348,000/µL). Substitution of tacrolimus with another CNI, cyclosporine (CsA), was considered, but we favored the introduction of maintenance immunosuppression with a costimulatory blocker, belatacept, instead, given emerging evidence of its efficacy in highly sensitized renal transplant recipients. The first dose of IV belatacept (5 mg/kg) was administered on POD 9 (3 days after the diagnosis of TMA). The patient received 5 mg/kg of IV belatacept every 2 weeks thereafter for 2 months and was then transitioned to a 5 mg/kg once monthly dosing regimen. Twelve months after transplant, she continues to have excellent renal allograft function with a serum creatinine of 0.7 mg/dL and has had no recurrence of hematologic abnormalities. Her most recent hemoglobin and platelet count were 12.3 g/dL and 271,000/µL, respectively (Fig. ).


A 35-year-old woman with no past history of cancer presented to an outside hospital with severe headache and lower back pain in June 2016. Brain MRI showed hydrocephalus due to leptomeningeal metastases and a focal mass in the spinal cord adjacent to cerebellum. A large tumor was detected at the anterior thecal sac (T5/6 level) along with several enhanced plaques at the posterior (C2–5 level) and terminal sacs (S2 level).
The large spinal tumor causing the cord compression was excised, histopathological examination of which confirmed adenocarcinoma. The tumor was positive for CK7, CDX2, and PAX-8 and negative for TTF-1, CK20, ER/PR, and ALK rearrangements. In addition, immunohistochemical analysis of HER2 was equivocal (2+) which ultimately reflexed to FISH, demonstrating HER2 positivity on dual probe (HER2/CEP17 ratio 5.08). Furthermore, the tumor was wild type for EGFR and BRAF mutations, and microsatellite stable. Physical examination and series of imaging studies including thoracic and abdominal computed and positron emission tomography (PET/CT), esophagogastroduodenoscopy, and colonoscopy failed to identify the primary site of tumor origin, and a diagnosis of metastatic adenocarcinoma of unknown primary was made. To alleviate the symptoms, a ventriculo-peritoneal shunt was placed, and an Ommaya reservoir was implanted to deliver intrathecal chemotherapy with methotrexate, which ultimately yielded poor response after six cycles. In August 2016, the patient was referred to our hospital, where she was extensively evaluated and given several targeted and immunotherapeutic regimens including gefitinib, trastuzumab, lapatinib, ipilimumab, pembrolizumab, and chemotherapy drugs such as 5-fluorouracil, epirubicin, cyclophosphamide, docetaxel, carboplatin, and capecitabine. Despite myriads of regimens tried, only anti-HER2 therapy resulted in clinical benefit and alleviated lower extremity muscle spasticity and maintained adequate consciousness level. In September 2017, the spasticity in all four extremities worsened, and the patient started to manifest dysarthria and dysphagia. MRI demonstrated multiple enhanced lesions (Fig. ), and CSF cytology examination confirmed the presence of malignant cells (Fig. ). A portion (14 mL) of CSF was then spared for ctDNA analysis by CellMax SMSEQ liquid biopsy assay. SMSEQ next generation sequencing (NGS) revealed amplifications of HER2 and MPL, as well as mutations in the PIK3CA, CDKN2A and TP53 genes (Fig. ; Table ). Considering the CSF-ctDNA NGS results and recommendations, ado-trastuzumab emtansine was added to the combination regimen of intrathecal trastuzumab and oral lapatinib. Given the CDKN2A mutation, palbociclib was also tried for three weeks, but discontinued due to myelosuppressive side effects. Within two weeks from implementation of a new anti-HER2 regimen combination, the neurological signs of the patient dramatically improved and tumor markers such as CEA and CA19-9 decreased significantly. The following CSF cytology examinations confirmed an absence of malignant cells in three subsequent spinal taps. Currently the patient appears well.


An 81-year-old man with a history of ESRD and hypertension presented to our hospital for profuse watery diarrhea, non-bloody emesis, abdominal pain, and subjective fever to 104.3°F of 1 day duration. At the time of admission, his physical exam was absence of pain or distention. Stool culture and polymerase chain reaction (PCR) for Clostridium difficile were collected, computed topography (CT) of abdomen/pelvis was performed, and rehydration with 2 L normal saline was given. Stool cultures and PCR were negative for C. difficile. CT revealed bowel wall thickening involving the duodenum and proximal jejunum consistent with duodenitis and enteritis. He improved after 4 days of conservative management of rehydration with a total of 5 L normal saline and antiemetic therapy with Zofran. He was discharged home with presumed viral gastroenteritis.
He returned to our hospital 4 days later for continued watery diarrhea and non-bloody emesis since time of discharge. An extended workup to include serum B12 (789 pg/mL), folate (>20.0 ng/mL), serum iron (36 μg/dL), transferrin (147 mg/dL), iron-binding capacity (210 μg/dL), iron saturation (17%), ferritin (497 ng/mL), serum gliadin Ab IgA (0.2 ELISA units/mL), tissue transglutaminase Ab IgA (0.2 ELISA units/mL), erythrocyte sedimentation rate (55 mm/h), C-reactive protein (9.1 mg/dL), and stool culture (heavy normal fecal flora; negative for Campylobacter, Salmonella, Shigella, Escherichia coli 0157, EHEC, Aeromonas, Vibrio, Yersinia, and Plesiomonas), ova and parasites (negative), leukocytes (positive), and fat (slightly increased) was performed to rule out malabsorption syndrome, inflammatory condition, or infectious etiology. With the exception of fecal leukocytes, all studies were within normal limits or at the patient's baseline values compared to 1 year prior. An upper endoscopy was performed showing multiple non-obstructing duodenal ulcers oozing blood located from the bulb to the 3rd/4th portion of the duodenum. Tissue samples of ulcers were taken and sent for pathologic evaluation. Of note, the patient had not been prescribed NSAIDs and denied taking over-the-counter products prior to admission. He was started on Nexium 40 mg twice daily and Carafate 1 mg four times daily. He improved with these interventions and was discharged home after a 5-day hospital stay.
The patient returned to our hospital for the third time, within 3 days of discharge, with similar complaints of nausea, vomiting, fever, and excessive diarrhea that had worsened since time of discharge. However, at this time, he endorsed some bright red blood in his stool. Fecal occult blood test was performed and positive. He was started on empiric antibiotics of Levofloxacin and Flagyl 500 mg for 5 days and received 2 units of packed red blood cells for an acute drop in his hemocrit from 31.6 at previous admission to 21.3 at current admission. Repeat upper endoscopy and colonoscopy were performed. Upper endoscopy was not significantly changed from prior, showing similar ulcers as above that had improved when compared to previous admission. Colonoscopy demonstrated patchy erythematous mucosa in the distal and terminal ileum. At this time, our initial pathology reports from the duodenal biopsies obtained during his previous stay resulted. Unfortunately, they were inconclusive but suggested an underlying inflammation of the intestinal mucosa. The samples were then sent to the Joint Pathology Center (JPC) for a second option. The patient was started on Prednisone 40 mg taken once daily to address his idiopathic colitis. He improved after steroid administration and was discharged from the hospital with a 2-week supply of Prednisone 40 mg. He was instructed to follow up in our gastroenterology clinic in 1 month.
After discharge, the JPC contacted our hospital with their findings. Review of his duodenal biopsies showed basophilic coral-like nonbirefringent material with an internal “fish-scale” pattern suggestive of sevelamer deposition (Fig. ). Given the patient was actively taking sevelamer carbonate for his ESRD, we concluded the patient most likely had sevelamer-induced duodenal ulceration. The patient's sevelamer prescription was discontinued and symptoms did not return after discontinuation. He continues to receive care at our facility. Repeat EGDs and colonoscopies since discharge have demonstrated complete resolution of all findings without new areas of inflammation.


A 40-year-old man, with unremarkable medical history and an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, was found to have abnormal chest X-ray findings at medical checkup and referred to our hospital. Chest X-ray at our hospital showed nodular opacity in the right upper lung field, reticular opacity in the entire right lung field, and right pleural effusion. Computed tomography (CT) of the chest showed a 38-mm nodule in the right upper lobe, increased bronchovascular markings and shaggy appearance in the entire right lung, and right pleural effusion (Fig. ). A bronchoscopic biopsy of the lung tumor tissue led to the diagnosis of lung adenocarcinoma with surrounding lymphangitic carcinomatosis. After detailed examination of the whole body, the disease was staged as cT4N3 (with metastases to the right supraclavicular and right mediastinal-hilar lymph nodes), M1c (BRA), stage IVB. Genetic testing of the cancer tissue specimens showed negative results for EGFR mutation and ALK translocation. The brain metastasis was initially treated with whole-brain irradiation, followed by systemic chemotherapy consisting of cisplatin (75 mg/m2) plus pemetrexed (500 mg/m2) every 3 weeks. However, before the second cycle of the chemotherapy, cough and dyspnea developed. CT showed no worsening of the primary lesion, but showed worsening of pulmonary lymphangitic carcinomatosis in the right lung and right pleural effusion (Fig. ). These findings were attributed to an inadequate effect of cisplatin and pemetrexed rather than complication by cardiac failure, because the patient had no decrease in cardiac function or any abnormal left lung findings. Thus, from the second cycle, cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (7.5 kg/m2) were to be given every 3 weeks, in the hope that bevacizumab, an angiogenesis inhibitor effective in controlling cancerous pleural effusion, would exert its efficacy on pulmonary lymphangitic carcinomatosis as well. After 1 cycle of the combined use of bevacizumab and chemotherapy, CT showed a marked improvement of pulmonary lymphangitic carcinomatosis and a reduction of pleural effusion (Fig. ). Then, stable disease was finally achieved after 4 cycles of the regimen of cisplatin and pemetrexed plus bevacizumab. Consequently, subsequent maintenance therapy consisting of pemetrexed and bevacizumab was continued up to 16 cycles, successfully leading to long-term progression-free survival.


A 13-year-old boy born out of a consanguineous marriage presented to the outpatient department with hyperpigmentation and hypertrichosis of lower extremities and trunk for last 4 years. The patient also had hearing loss for more than 5 years which was progressive and was using hearing aid for the same. There was no family history of similar skin changes.
On mucocutaneous examination well defined, bilaterally symmetrical hyperpigmented, indurated plaques with marked hypertrichosis were present over medial aspect of thighs and legs [Figure –]. Knees and feet were spared. Similar lesions were present over sacral area and lower back bilaterally []. General physical examinations showed mild hepatomegaly and pallor. He had short stature for his age (131 vs. 154 cm). Hallux valgus was also present [].
Routine laboratory investigations revealed haemoglobin to be 6.7 g/dl. Liver function tests, thyroid profile, serum cortisol (15.25 μg/dL), and blood sugar were normal. Chest X-ray was normal. Antinuclear antibody was negative. Growth hormone level was reduced to 0.77 ng/ml (normal range 1–14.4 ng/ml). Serum Vitamin D3 level (51.88 vs. 81–250 nmol/L) was found to be low. No “M” spike was seen in serum protein electrophoresis.
Ultrasonography (USG) abdomen revealed mild hepatomegaly. USG of scrotum was normal. Contrast enhanced computed tomography head, and orbit revealed bilateral mild axial proptosis.
Skin biopsy was taken from the hyperpigmented plaque on the thigh and revealed mild irregular acanthosis, and increased melanin deposition in basal keratinocytes. Significant thickening of collagen bundles in upper and mid-dermis was seen along with perivascular infiltrate of histiocytes. Immunohistochemistry was positive for CD68 and CD45 in dermal perivascular histiocytic infiltrate and for CD34+ in vessel endothelium [].
The final diagnosis of H syndrome was made based on the characteristic clinical and histopathological findings.


A 39-year-old never-smoker female without prior relevant medical history was admitted to the hospital with progressive symptoms of abdominal pain, dyspnea, and bilateral leg edema. A computed tomography scan revealed pericardial effusion; bilateral pleural effusion; a 3 cm mass in the right lung; hilar, mediastinal, and retroperitoneal lymphadenopa-thies; and ascitis (). Pericardial and pleural fluids were positive for adenocarcinoma cells, and the patient was diagnosed with lung adenocarcinoma stage IV.
A core biopsy of the lung mass was performed. Molecular analysis of the EGFR and the KRAS genes revealed absence of mutations. Immunostaining with IHC VENTANA clone DF53 identified overexpression of ALK, and fluorescence in situ hybridization using Vysis LSI ALK dual-color break-apart probe demonstrated an ALK rearrangement. When the sample was analyzed by nCounter, it showed a 3′/5′ imbalance indicative of an ALK rearrangement, but failed to give a positive signal for the EML4-ALK v1, v2, v3, or v5; TFG-ALK_T5:A20; KIF5B-ALK_K17:A20; or KIF5BALK_K24:A20 fusions. Finally, a band with a molecular weight higher than expected (239 bp) appeared after reverse transcriptase-polymerase chain reaction analysis (RT-PCR) with primers specific for EML4-ALK v1. No additional bands were apparent. The 239 bp band was submitted to Sanger sequencing revealing an atypical EML4-ALK fusion gene with a 129 bp insertion in the canonical junction of v1. A 115 bp segment of the insertion corresponded to an intronic region of LTBP1, a gene located in the short arm of chromosome 2, between the ALK and EML4 genes. The in silico translation of this new variant, which will be referred to as v1insLTBP1, showed an in-frame insertion of 43 aminoacids ().
The patient started crizotinib with good tolerance. The computed tomography scan performed a month later showed a reduction of the primary lesion, disappearance of hilary and reroperitoneal lymphadenopathies, and a reduction of the mediastinal lymph nodes. After 14 months, the patient continues to demonstrate partial response.
Written informed consent has been provided by the patient to have the case details and any accompanying images published.


A 20-year-old male presented to a major hospital with a history of intermittent severe abdominal pain which commenced at approximately 7 years of age. The pain was characterized by a diffuse cramping quality, with greatest severity in the supra-pubic region, and was relatively stable throughout its course. In the days prior to this presentation, the pain had increased in frequency and severity. The patient had been previously investigated with ultrasonography, which yielded no significant abnormality. There was no significant past medical or surgical history and he was on no regular medications.
The only notable clinical finding was tenderness in the supra-pubic region. There was no evidence of peritonism. Routine blood tests were normal. Abdomino-pelvic computed tomography (Fig. ) demonstrated a moderate amount of free fluid on the right side of the abdominal cavity and appendiceal thickening. A testicular ultrasound yielded no significant abnormality. Due largely to the unexplained CT findings, the patient was consented for a diagnostic laparoscopy.
Laparoscopy revealed an accessory intra-abdominal cyst encapsulating the entire length of small bowel (Fig. ) and the large bowel to the mid-transverse colon.
A large volume of ascites was also noted. The sac appeared morphologically similar to peritoneum. It enclosed the entirety of the small bowel from a point approximately 5 cm distal to the duodeno-jujenal flexure to the mid-transverse colon. The sac also encased the corresponding vascular supply, including the superior mesenteric artery (SMA) and its major branches. There was an orifice in the membrane close to the origin of the SMA to allow for entry of that vessel, at which point the membrane was found to be generating a band-like effect on the transverse colon (Fig. ).
After careful assessment, the decision was made to open the abdomen to allow for better visualization and complete resection of the sac. The membrane was dissected along its origin to the right iliac fossa. Numerous adhesions were noted inside the sac. The lateral boundary of the sac on the right side was noted to contain a vessel originating from the SMA trunk. This was followed down to the appendix and terminal ileum (TI). Its terminal branches were noted to end at the appendix. This vessel was clamped and ongoing strong pulsations were noted at the TI. The artery was subsequently divided and the sac released off the transverse colon. An appendicectomy was also performed. Specimens from the sac were sent for histopathological examination and the ascitic fluid was sent for cytology.
The post-operative period was uncomplicated and the patient was discharged on day 5. He remained symptomatically well at 1-month follow up.
Histopathological examination of the resected sac showed fibro-fatty tissue, with significant oedema and haemorrhage. Cytology of the intra-abdominal fluid demonstrated the presence of mesothelial cells and lymphocytes.


A 52-year-old woman diagnosed with PAH and anteroseptal MI was referred to our institute, where she presented with progressive dyspnea on exertion and peripheral edema. She had worked as a nurse without difficulty until she was 45 years old, when she began to experience increased general everyday fatigue. She had never smoked and she denied any illicit drug use.
In 2007, the patient had undergone cardiac catheterization at another hospital (pulmonary arterial pressure [PAP]: systolic/diastolic/mean = 72/27/45 mmHg, pulmonary artery wedge pressure [PAWP] = 14 mmHg, cardiac index = 2.16 L/min/m2, pulmonary vascular resistance [PVR] = 9.3 Wood units). Her left ventricular ejection fraction was 67%, left atrial dimension was 32 mm, and lung function was normal. She had subsequently begun combination therapy through that hospital with 125 mg bosentan twice daily and 20 mg sildenafil three times daily.
In 2009, the patient presented to her original hospital with prolonged chest pain and low blood pressure; she was considered to be in cardiogenic shock due to acute MI. Emergent coronary angiography revealed 99% stenosis of the left main coronary artery in an abnormally high position because of pressure from an aneurysm of the left coronary sinus of Valsalva (); consequently a Cypher stent (Cordis Corporation, Miami Lakes, FL, USA) was implanted at the patient’s original hospital during intra-aortic balloon pumping (). The aneurysm was not noted at the time during the procedure but was found retrospectively on review of the imaging findings at our hospital. For this reason, no additional examinations were conducted at the time of the procedure.
In April 2014, the patient was hospitalized with progressive heart failure and was then referred to our hospital for treatment and management of her pulmonary hypertension (PH). We promptly performed cardiac catheterization (mean PAP = 47 mmHg, PAWP = 21 mmHg, right atrial pressure = 12 mmHg, cardiac index = 2.36 L/min/m2 [Fick principle], PVR = 7.4 Wood units). Physical examination on admission revealed an increased P2 component of S2 and dilated jugular veins. No ascites was present, but the patient’s lower extremities were slightly edematous. An electrocardiogram revealed right ventricular hypertrophy with ST change. The plasma brain natriuretic peptide (BNP) concentration was 450 pg/mL. Transthoracic echocardiography showed that the anteroseptal wall was thin and akinetic and the left ventricular ejection fraction was 37% (); the inferior vena cava was dilated (27.7 mm) (). Pulmonary perfusion scintigraphy revealed no abnormalities. We performed echocardiography and magnetic resonance imaging. Multiple samples of whole blood were withdrawn during cardiac catheterization to measure O2 saturation to rule out other underlying heart diseases, such as primary left heart disease and congenital heart disease. There was no cardiac shunt, valvular disease, or lung disease. In addition, the results of both pulmonary function testing and high-resolution computed tomography (CT) were normal. Together, these findings supported the diagnosis of PH due to left heart disease (group 2 of the Dana Point 2008 classification). In addition, 64-slice multidetector CT at admission showed marked dilation of the main pulmonary artery (47.7 mm) (), no restenosis of the left main coronary artery, and aneurysm of the left coronary sinus of Valsalva (36.0 mm) (). The stent previously placed in the left main coronary trunk was located between the main pulmonary arterial trunk and the left coronary sinus of Valsalva ( and ).
Before the patient’s referral to our institution, her treatment had comprised oxygen therapy, bosentan (125 mg twice daily), sildenafil (20 mg three times daily), warfarin (4 mg daily), azosemide (60 mg daily), and spironolactone (25 mg daily); tolvaptan (7.5 mg daily) was added after referral. Thereafter, her pulmonary congestion decreased, as did her plasma BNP level (to 170 pg/mL) and mean PAP (to 38 mmHg). After one month of treatment with tolvaptan, the patient was discharged home. She has been followed through our outpatient clinic: at last review, her PH was in World Health Organization (WHO) functional class II and her plasma BNP level had remained unchanged since discharge.
The patient’s elder sister had also been diagnosed with PAH (mean PAP = 35 mmHg, PAWP = 11 mmHg, PVR = 4.8 Wood units). The chest radiographs of the two women were similar in regard to the degree of pulmonary artery dilatation ( and ). However, the sister had no left main trunk stenosis and no aneurysm of the left coronary sinus of Valsalva (), and the left ventricle was of normal size and had normal contractility. There were no signs of left heart disease, congenital heart disease, or lung disease. Because we suspected that these sisters had HPAH, we suggested professional genetic testing. Conventional Sanger sequencing and multiplex ligation-dependent probe amplification analysis of the genes encoding bone morphogenetic protein receptor type 2 (BMPR2) and activin A receptor type II–like kinase 1 (ACVRL1) failed to detect any pathogenic variants, but subsequent whole-exome sequencing revealed a novel heterozygous splicing mutation in the FLNA gene, namely IVS2-2A > G (c.374-2A > G in NM_001456) () in both sisters but not in their father (aged 89 years). This mutation changed the 3’ splice site consensus sequence from AG to GG and was expected to cause aberrant splicing. A four-generation pedigree of the family was generated from their responses to a questionnaire ().


A known to us 14-year-old girl with long-standing ES was admitted because of fatigue that got progressively worse over three days and new-onset petechiae. The patient was diagnosed with ES at the age of 3 years, when she presented with symptomatic thrombocytopenia without hemolysis and was found to have a strongly positive direct antiglobulin test (DAT) for non-specific warm IgG that persists to nowadays. Over the years, she had required therapy with corticosteroids and intravenous g globulin (IVIG) for symptomatic thrombocytopenia only, although she was treatment-free for almost four years. The patient’s last hemogram with reticulocyte count before this admission was three months ago and was normal.
On admission to us, she was pale, slightly tachycardic (heart rate of 108/min), had wet purpura, along with numerous petechiae and bruises on both lower extremities and a palpable spleen tip. Laboratory examinations on admission showed leukocytes 4,600/μL (53% neutrophils, 30% lymphocytes, 12% monocytes, 5% reactive lymphocytes), hemoglobin 8.4g/dL, hematocrit 24.4%, platelets 2,000/μL and reticulocytes 0.07%. DAT was 4+ positive for IgG alone. Biochemical studies revealed serum LDH 330U/L (reference range 120–246 U/L), total bilirubin 0.8mg/dL, direct bilirubin 0.2 mg/dL, alanine transaminase 14 U/L, aspartate transaminase 15 U/L, g-glutamyl transpeptidase 9 U/L, ferritin 208 ng/ml, haptoglobin 5.8mg/dL (reference range 30–140), vitamin B12 460pg/ml, and serum folate 2.87ng/ml (reference range 3–14). An abdominal ultrasonogram showed borderline splenomegaly, without focal lesions or gallstones. Serological studies were positive for HPV-B19 IgM (210 U/ml, positive >24U/ml by ELISA kit (RecomWell Mikrogen GmbH, Neuried, Germany), while real-time PCR of whole blood using the LightMix® Kit Parvovirus B19 (TIB MOLBIOL GmbH, Berlin, Germany) for the LightCycler 2.0 instrument (Roche GmbH, Mannheim, Germany) was positive for DNA of HPV-B19 (5.7×106 copies/ml). Additional real-time PCR of whole blood was negative for CMV, EBV, HSV-1, and HSV-2.
Due to laboratory evidence of hemolysis (very low serum haptoglobin) in a child with ES, she was started on intravenous methylprednisolone 80mg/day. The next day, a repeated hemogram showed hemoglobin 6.9g/dL, hematocrit 20.1%, platelets 14,000/μL and reticulocytes 0.09%, while indirect bilirubin picked at 1.8mg/dl. Due to worsening anemia with severe reticulocytopenia, a bone marrow aspirate was performed and showed a regular maturation of the myeloid precursors and abundant megakaryocytes. The erythroid series demonstrated severe decrease of erythroid precursors that were almost exclusively represented by pronormoblasts, frequently of giant size. On the 3rd hospital day, due to persistent anemia and thrombocytopenia, a single dose of IVIG was administered (40g or 830mg/kg). Treatment was well-tolerated. The next morning, hemoglobin was 8.1g/dL, hematocrit 23.4%, platelets 136,000/μL and reticulocytes 0.23%. Two days later, the hemoglobin was further increased to 9.6g/dL, hematocrit 28.4%, platelets 517,000/μL, and reticulocytes 4.05%. The patient was discharged home to continue a 4-week tapering of oral prednisolone along with daily oral folic acid 5mg/day. At the end of therapy, she had a normal full blood count (hemoglobin 12.2g/dL, platelets 277,000/μL) and serum haptoglobin (122 mg/dL). Eight months after the described events, she remains asymptomatic, off-therapy, with normal hemogram, but continues to have 4+ positive DAT for IgG.


A 21-year-old male with unremarkable past health except was allergic to cefuroxime and metronidazole presented with sore throat and shortness of breath. He was initially seen by otorhinolaryngologist for left tonsillitis in the Emergency Department. Flexible laryngoscopy showed mobile bilateral vocal cords with patent upper airway. He was in septic shock and transferred to the Intensive Care Unit for acute tonsillitis complicated with septic shock on October 7, 2016.
Detailed medical history reviewed a 4-day history of sore throat, fever, and poor oral intake. He was febrile with low-grade temperature of 37.6°C. Chest X-ray showed bilateral lower zone infiltrates. Ultrasound thorax showed bilateral pleural effusion around 4 cm without septation. He developed respiratory failure and intubated for respiratory support.
He was treated with doxycycline, clindamycin, and vancomycin empirically in view of the drug allergy history. Upon clinical deterioration, antibiotics were upgraded to meropenem and doxycycline.
Throat swab, urine, and sputum culture were negative. Endotracheal aspirates for influenza and other viruses were negative and bacterial culture was negative. Blood culture on day 2 yielded Fusobacterium necrophorum, sensitive to metronidazole and minimal inhibitory concentration of clindamycin 0.12 μg/mL. Microbiologists were consulted and suggested to keep meropenem alone.
In view of persistent leukocytosis and neck pain, computed tomography (CT) of neck and thorax was performed on October 13, 2016, which showed no obvious abscess, but left internal jugular thrombophlebitis [] and multiple cavitating lung nodules [] compatible with distal thromboembolism and supported the diagnosis of Lemierre's syndrome. Right internal jugular vein, left brachiocephalic vein, and superior vena cava were patent. Otorhinolaryngologist suggested to continue antibiotics and not for internal jugular vein ligation. He was shortly discharged to general ward to continue intravenous amoxicillin-clavulanate following the antibiotic desensitization protocol. He made satisfactory progress and was discharged home with oral amoxicillin-clavulanate. No anticoagulation was given. Subsequent follow-up with chest X-ray showed resolution of lung infiltrates, and antibiotic was stopped after 6 weeks.