A 38-year-old Portuguese, Caucasian man working in the viticulture and forestry industry was referred to a pulmonary clinic following complaints of progressive right side pleuritic chest pain, non-productive cough, low-grade fever, and general fatigue.
He was a former smoker (10 packs a year) and had asymptomatic Swyer-James-MacLeod Syndrome (SJMS) that was diagnosed at the age of 28 after a routine chest X-ray. He also had arterial hypertension that was controlled with atenolol and amiloride plus hydrochlorothiazide. He also reported frequent exposure to organic dust during work.
A physical examination of our patient revealed normal body temperature, pulse rate, respiratory rate, blood pressure and oxygen saturation. His chest examination revealed crackles in his lower right hemithorax. The rest of his physical exam was unremarkable.
Blood sample analysis showed that he had no abnormalities except for an elevated erythrocyte sedimentation rate (ESR) (72 mm/h, normal: <20 mm/h) and C-reactive protein (CRP) (25.95 mg/dL, normal: <1 mg/dL). His lung function tests and arterial blood gas levels were normal.
A plain chest X-ray disclosed a large infiltrate in the right inferior lung field of our patient and a chest computed tomography (CT) scan confirmed the presence of a consolidation and/or a mass of 35 × 64 × 37 mm in diameter located in the upper segment of the right lower lobe and posterior segment of his right upper lobe. The mass had direct contact with the contiguous pleura and was associated with a small pleural effusion, and there was also no mediastinal lymphadenopathy (Figure ).
We initiated a therapy of levofloxacin 500 mg/day for one week. However, our patient showed no clinical response to this treatment.
Bronchoscopy was subsequently performed on our patient. His bronchoalveolar lavage (BAL) fluid revealed negative cytological, bacteriological, mycobacteriological and mycological exams. Bronchial brushing and transbronchial biopsies were also obtained and were negative for neoplastic cells.
A transthoracic CT-guided fine needle aspiration of the lesion was negative for neoplastic cells, but revealed fungal elements.
Finally, surgical lung biopsies were performed, which showed evidence of tissue invasion by fungal organisms and Sabouraud glucose agar cultures isolated multiple Aspergillus glaucus colonies. Serological tests did not reveal elevated titres of Aspergillus antibody or antigen (Platelia™ Aspergillus EIA, Bio-Rad).
Human immunodeficiency virus 1 and 2 tests, as well as differential cell counts for lymphocyte subpopulations, were performed on our patient and excluded underlying immunosuppression.
Our final diagnosis was semi-invasive pulmonary aspergillosis and we started him on itraconazole (400 mg orally per day) for one year. During follow-up examination he had remained asymptomatic and repeated chest CT revealed partial regression of the mass volume and resolution of the pleural effusion (Figure ). His recent BAL fluid examination presented positive galactomannan and negative mycological exam. Blood analysis showed normalization of his ESR and CRP level.
He maintains treatment with itraconazol and is under deliberation for surgical resection of the residual lesion.


A 45-year-old man was admitted with a painful pelvic palpable mass and weight loss in November 2006. Pelvic CT scan revealed a 12 × 11 × 12 cm pelvic mass () and several peritoneal lesions. Ultrasound-guided biopsy was performed and cytologic analysis revealed a high-grade mesenchymal neoplasia with small round blue cells. Immunohistochemistry was positive for CD99, enolase, EMA, vimentin, and desmin and negative for 35βH11 and AE1/AE3 cytokeratins, chromogranin, synaptophysin, WT1, CD3, CD20, CD30, CD34, S-100, myogenin, and Myo-D1 (). These findings were consistent with a pelvic DSRCT with extensive peritoneal involvement. Systemic chemotherapy based on vincristine, doxorubicin, and cyclophosphamide, alternating with ifosfamide and etoposide, was initiated. Disease progression was observed after four cycles. Six months after diagnosis, the patient developed severe hypoglycemia, presenting with seizures. Liver function was normal, and adrenal insufficiency was excluded. He received intravenous glucose infusion and hydrocortisone with poor glycemic control. A glucagon stimulation test, as previously described in [], was performed with partial response (). To better evaluate the etiology of hypoglycemia, the glucose infusion was interrupted for 10 minutes to enable measurements of glucose, cortisol, GH, insulin, C-peptide, IGF-I, and IGF-II (). With a glucose level of 7 mg/dL, there was appropriate release of cortisol and growth hormone (GH) excluding adrenal and GH deficiency. While C-peptide, insulin levels, and IGF-1 were adequately suppressed, IGF-2 was slightly elevated with increased IGF-II and IGF-I ratio (IGF-II/IGF-I = 22.94) () which suggested a paraneoplastic non-islet cell tumor hypoglycemia related to IGF-II overproduction by DSRCT []. Despite the attempt to control tumor mass and the hypoglycemia, the patient died nine months after diagnosis.


A 59-year-old male presented to the emergency room with sudden, sharp, left-sided chest pain without radiation. He has a long-standing history of hypertension, hyperlipidemia, and coronary artery disease. He had a previous myocardial infarction approximately 10 years prior for which he had a bare-metal stent placed in his right coronary artery. The patient has a 50-pack-year history of smoking, but he quit 10 years ago after his first myocardial infarction. He does not drink alcohol or use illicit drugs. His family history is only positive for hypertension. He was compliant with his medications which were lisinopril, amlodipine, simvastatin, metoprolol, omeprazole, and a 325 mg aspirin.
He was found to have a normal complete blood count, with a hemoglobin of 13.8 g/dL, hematocrit of 40%, white blood cell count of 6,700/mm3, and platelet count of 266,000/mm3. His coagulation studies revealed a partial thromboplastin time (PTT) of 27 sec (normal 22.1–37.6 sec) and an initial prothrombin time (PT) of 15.7 sec (normal 11.9–14.9 sec) with an INR of 1.22. The results of a complete electrolyte panel, liver function studies, and lipid panel were all within normal limits except for an HDL of 26 mg/dL (normal 40–60 mg/dL). Cardiac enzymes were initially normal but continued to increase to a CK-MB Index of 8.6 (>4 consistent with myocardial infarction), CPK of 971 U/L (30–200 U/L), and Troponin-I of 17.49 ng/mL (normal <1.5 ng/mL).
The patient underwent cardiac catheterization and had 60–75% restenosis of the mid right coronary artery (RCA) and 75% stenosis of the left circumflex artery. There was placement of a 2.75 × 32 mm and a 2.75 × 12 mm Taxus drug-eluting stent (Boston Scientific Corporation) in the RCA and a 2.75 × 24 mm Taxus drug-eluting stent in the left circumflex. Excellent flow was noted and 0% residual stenosis remained after the stenting. The patient received 600 mg clopidogrel after the procedure.
Approximately 90 minutes later, the patient developed severe chest pain and ST-segment elevation in the inferior leads on a 12-lead EKG. He was immediately moved to the catheterization suite for repeat cardiac catheterization. There were occlusions of both the RCA and left circumflex artery stents. After thrombectomy, the patient received heparin and eptifibatide. Another 2.5 × 24 mm Taxus drug-eluting stent was placed in the left circumflex in addition to previous stent. The ST-segment returned to baseline and the patient was without chest pain. The patient was continued on clopidogrel, aspirin, and eptifibatide for the following four days and then discharged home.
The patient returned to the emergency room the same day as discharge complaining of severe chest pain. He again had ST-segment elevation and underwent cardiac catheterization. There was 100% restenosis of the left circumflex artery (), but good inflow of the RCA. Thrombectomy was performed, and a 2.5 × 24 mm Taxus stent was deployed in the left circumflex. Hypercoagulable laboratory studies were drawn and thromboelastograph demonstrated clopidogrel resistance in the patient, with platelet inhibition of 4%. Therapy was started with eptifibatide, clopidogrel, aspirin, warfarin, and a heparin drip. After four days, the INR was 2.41 and the heparin drip was discontinued. Soon afterwards, the patient developed recurrent chest pain () and was taken back to the cardiac catheterization lab. Both the left circumflex artery and RCA stents were re-stenosed. He was referred to surgery for emergent coronary bypass graft. The patient was stabilized and discharged home on low-molecular-weight-heparin, aspirin, and clopidogrel. A complete timeline of events is shown in .
After an extensive hypercoagulable work-up, the patient tested negative for antinuclear antibody (ANA), IgA/IgM anticardiolipin antibody, homocysteine, IgG/IgA/IgM β2 glycoprotein, Protein C deficiency, Protein S deficiency, anti-thrombin III deficiency, Factor V Leiden, and Prothrombin 20210A. A dilute Russell Viper venom time was 35 sec (normal <43 sec). The only abnormal laboratory values were an IgG anticardiolipin antibody of 12 (normal <10) and a dilute prothrombin time (dPT) of 63.60 (normal 0–56.6 sec), with no lupus anticoagulant detected.
In follow-up with the patient, he has remained on low-molecular-weight heparin, aspirin, and clopidogrel for 6 weeks. He has had no chest pain or other known thrombosis. His repeated laboratory studies show an undetectable level of IgG anticardiolipin antibody as well as undetectable levels of IgA/IgM anticardiolipin antibody or lupus anticoagulant.


A 46-year-old Japanese man was referred to our hospital with intrahepatic cholangiocellular carcinoma. The tumor was 3 cm in diameter and located at segment 8, between the root of the middle and right hepatic veins. Preoperative liver function tests were normal, and preoperative blood work was negative for hepatitis virus markers. The patient underwent an extended right hepatectomy without resection of the extrahepatic bile duct. The patient's middle hepatic vein was divided approximately 2 cm upstream from the root of the middle and left hepatic veins.
The patient's postoperative course was uneventful until day 10, when a gradual increase in serum bilirubin levels and ascites formation were noted. Although obstructive jaundice and portal thrombosis were excluded by ultrasound and computed tomography (CT) scans, the patients continued to deteriorate, displaying hyperbilirubinemia, coagulopathy and refractory ascites (Table ). Neither circulatory disturbance nor hepatic encephalopathy were seen during this period. The patient's Model for End-Stage Liver Disease (MELD) score also increased gradually, and reached 23 seven months after the initial hepatic surgery. MELD scores between 20 and 29 are associated with 3-month mortality rates of over 75%. Repeated abdominal paracentesis were necessary to treat his refractory ascites, which amounted to more than 10,000 ml per week.
In order to rule out an insufficient hepatic regeneration, the patient's liver volume was assessed by CT-volumetry using previously described methods []. Seven months after surger, his liver volume was 1290 ml, almost identical to the standard liver volume (1222 ml) which was calculated using Urata's formula []. Nevertheless, serum levels of hepatocyte growth factor were elevated to 1.61 ng/ml, signifying that the liver was still being stimulated to regenerate. Serum hyaluronic acid levels were also elevated to 3030 ng/ml, suggesting that sinusoidal endothelial cell function was severely disturbed []. An assessment of the patient's hepatic circulation by spectral Doppler ultrasound revealed a good hepatic arterial flow, but a relatively weak intrahepatic portal signal with no diastolic flow. The Doppler waveform of hepatic venous flow was monophasic, suggesting the presence of hepatic venous stenosis (Figure ). Because axial CT images only were not conclusive regarding the presence of hepatic vein stenosis, multiplanar reconstruction (MPR) images and three-dimensional CT images were also assessed, and the stenosis at the root of the left hepatic vein was clearly visualized (Figure ).
To further confirm the presence of hepatic venous stenosis, the pressure gradient between the left hepatic vein and right atrium was measured. Hepatic venous catheterization was performed through the jugular vein. The mean hepatic venous pressure was 15.6 mmHg, and the pressure abruptly decreased when the catheter was pulled through the assumed stenotic point into the right atrium. The pressure gradient between the left hepatic vein right atrium was 13.2 mmHg. The normal hepatic venous pressure gradient lies between 1 and 2 mmHg []. Thus, we confirmed the presence of hepatic venous stenosis morphologically and functionally.
Written informed consent was obtained from the patient for endovascular treatment. As an initial treatment option, hepatic venous balloon dilation was performed eight months after surgery. A transluminal angioplasty catheter (Synergy Balloon Catheter, Boston Scientific, Tokyo) with a balloon diameter of 10 mm and a length of 40 mm was used for venous dilatation. Although the pressure gradient across the left hepatic vein and right atrium decreased from 13 to 4 mmHg immediately after intervention, the effect was temporary. Ten minutes after balloon dilatation, the pressure gradient had increased to 10 mmHg. Although serum bilirubin levels decreased unexpectedly to near the normal range, refractory ascites remained. Therefore, the patient underwent endovascular stent placement therapy seven weeks later.
A self-expandable metallic stent (Luminexx, BARD, Covington, GA) with a diameter of 8 mm and a length of 40 mm was placed into the left hepatic vein via the internal jugular vein. Because the large umbilical fissure vein was bifurcated just behind the stenosis, another metallic stent with a diameter of 8 mm and a length of 2 mm was inserted into it using a stent-in-stent technique (Figure ). At the same time, in order to relieve the symptom of lower leg edema, the retrohepatic inferior vena cava was also dilated with a metallic stent (Spiral Z stent, Wilson-Cook Inc., Winston-Salem, MA) with a diameter of 20 mm and a length of 60 mm. The pressure gradient across the left hepatic vein and right atrium decreased to 3 mmHg just after stent placement, which was maintained even after 10 minutes. A Doppler ultrasound study three weeks after stent placement showed an increased hepatic venous flow velocity and a pulsatile venous waveform (Figure ). Along with the normalized bilirubin level, the patient's ascitic fluid volume also decreased favorably after the stent placement. Thus, the patient had recovered from his PLF.


A 53-year-old Canadian Caucasian woman, who was a clerical worker, presented to her family doctor with a five week history of progressive pain and black discoloration of the distal right third finger. She was initiated on acetylsalicylic acid and warfarin and referred to a regional tertiary care hospital.
Her past medical history included depression and a diagnosis of Wolfe Parkinson White (WPW) syndrome, treated since childhood with verapamil. She was taking no other medications. She has never smoked and denied a history of Raynaud's type changes in her digits. Her connective tissue disease review of systems was also otherwise unremarkable.
On examination in the emergency room, there was obvious digital necrosis of the distal right third finger with an adjacent area of pale swollen tissue with ulceration (Figure ). Allen's test was abnormal with poor refill bilaterally. Capillaroscopic examination of the periungal regions did not reveal dilated capillary loops. No peripheral bruits were audible. A teleangiectasia lesion was evident on the fifth digit. No other skin changes, specifically sclerodactyly, were present. She was admitted to hospital for further investigations and consultation with vascular specialists.
An angiogram revealed evidence of a bilateral obliterative vasculopathic process (Figures and ). Radiographs of the hands did not reveal any bony abnormality. Further investigations revealed a positive antinuclear antibody with titer > 1280 and anticentromere specificity. ACA were confirmed by enzyme-linked immunosorbent assay (ELISA) at greater than 100 U/mL. Anti-double stranded DNA, anti-Sjogrens Syndrome A, anti-Sjogrens Syndrome B and anti-ribonucleoprotein antibodies (anti-SSA, anti-SSB, anti-RNP), anti-Sm, anti-Scl-70, antineutrophil cytoplasmic antibodies, anticardiolipin antibodies, cryoglobulins, C3, C4, C-reactive protein, complete blood count, electrolytes, creatinine, hepatic transaminases, alkaline phosphatase and urinalysis were all normal or negative. Associated underlying pathology including cardiopulmonary, gastrointestinal and renal involvement were excluded through cardiology consultation, chest radiograph, echocardiogram, pulmonary function testing, high-resolution computerized tomography (CT) of the chest, 24 hour urine for creatinine clearance, serum chemistry and urinalysis, barium swallow, and CT abdomen and pelvis.
In hospital she was initiated on clopidogrel bisulfate, pentoxifylline, topical nitropaste, a two week trial of prednisone, a seven day course of clindamycin and morphine for pain control. Nifedipine was later initiated as an out-patient. Gradually over the next two months the necrosis resolved with minimal tissue loss at the digit tip. She continues to be followed in the rheumatology out-patient clinic with periodic evaluations for potential evolution of connective tissue disease and in cardiology clinic for follow-up of her WPW.


A 44-year-old Afro-Caribbean woman missionary worker with homozygous sickle cell disease (HbSS), originally from Grenada, was admitted to hospital with a three-day history of worsening shortness of breath, productive cough with yellow sputum, and pain in her lower back and both lower limbs. She denied any gastrointestinal symptoms.
In terms of her sickle cell anemia, the patient reported two previous sickle cell crises. The first in Grenada, in 2002, when she was plasma exchanged and the second, five months previously in Barbados, when she was transfused one unit of blood. She also had a history of pigmented gallstones. She was taking regular folic acid. Her vaccinations were not up-to-date and no prophylactic penicillin was being taken.
On examination, the patient was dehydrated, febrile at 38.5°C, tachycardic and desaturating on room air. She was clinically jaundiced. A systolic flow murmur was noted on examination of her cardiovascular system. On auscultation of her chest, there was reduced air entry and crepitations at the right base. Her abdominal examination revealed a mildly tender, enlarged liver. Her lower back and both thighs were tender on palpation.
Laboratory results showed a hemoglobin of 6.7 g/dL (her baseline hemoglobin was 7 g/dL); mean cell volume 87.8 fl; white cell count 18.7 × 109/L; neutrophils 13.6 × 109/L; platelets 81.0 × 109/L; C-reactive protein > 250 mg/L; creatinine kinase 10 U/L. Chest radiography showed a globular heart, moderate bilateral effusions, sickle cell bony changes but no focal consolidation.
Our patient's chest crisis was managed with analgesia, hydration, and continuous positive airway pressure (CPAP). Intravenous amoxicillin (500 mg every eight hours) and clarithromycin (500 mg every 12 hours) were prescribed to cover a possible chest infection. Despite this, her clinical condition continued to deteriorate and her hemoglobin dropped to 5.4 g/dL. It was then decided to perform an exchange transfusion.
On the second hospital day, Salmonella agbeni was grown from blood cultures and intravenous ceftriaxone (2 g every 24 hours) commenced. The patient continued to have persistent temperature spikes of > 38.5°C despite a two-week course of ceftriaxone. For enhanced intra-cellular penetration, ceftriaxone was then changed to oral ciprofloxacin (500 mg every 12 hours), to which the organism was also sensitive. Repeat blood cultures and stool cultures to assess carrier status were negative.
After seven days of ciprofloxacin our patient developed limited hip extension on the right with persistently raised inflammatory markers: C-reactive protein 237 mg/L; white cell count 16.2 × 109/L; neutrophils 12.3 × 109/L. In order to ascertain a focus of infection, plain radiography and a bone scan of her hips and pelvis were performed. The former demonstrated chronic avascular necrosis and the latter increased vascularity around the right hip. It was suggested this may represent infection and a magnetic resonance imaging (MRI) scan of the hips and pelvis was performed. This revealed the diagnosis of pyomyositis, with particular involvement of the left obturator externus and adductor brevis muscles (yellow arrow), and the right obturator externus, iliacus and iliopsoas muscles (red arrow) (Figure ).
Both orthopedic and radiology teams were consulted and it was decided there was no collection that could be drained either surgically or radiologically. As the source of infection was most likely to be gastrointestinal, a combination of intravenous ceftriaxone (2 g every 24 hours) and metronidazole (400 mg every eight hours) was prescribed to cover the possibility of a polymicrobial infection. Our patient was examined after a total of six weeks of intravenous antibiotic therapy and was found to have no residual functional limitations, her C-reactive protein had normalized and resolution was noted on repeat MRI (Figure ).


A 21-year-old male presented with a 2-year history of progressive shortness of breath on exertion and dry cough. At physical examination, auscultation of the lungs has revealed random wheezes and coarse crackles. Cardiac auscultation was normal, and no cyanosis or peripheral edema was observed. There was no history of smoking or previous known pulmonary disease. On routine blood examination, blood counts and serum chemistries were found to be normal. Arterial blood gas analysis and echocardiography showed no important abnormalities.
Pulmonary function tests (PFT) showed a mild restrictive ventilatory defect, with a reduced total lung capacity of 79% (5.94 L), forced vital capacity of 80% (4.18 L) and a forced expiratory volume in one second of 83% (3.72 L). The sputum was negative for acid-alcohol resistant bacillus and human immunodeficiency virus testing was negative as well. The chest plain films revealed a diffuse symmetric dense bilateral micronodular pattern (). Based on this finding, HRCT scan was obtained, revealing diffuse ground glass attenuation and septal thickening, more pronounced in lower pulmonary regions, with calcifications along the interlobar septa and subpleural regions. Subpleural cysts were also noticed (). The patient underwent a fiberoptic bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy. The lavage fluid was negative for tuberculosis or fungi. Microliths were not found. Histology revealed round, concentrically laminated microliths in the alveoli associated with slightly thickened interstitial septa, consistent with the diagnosis of PAM.


A 34-year-old Caucasian woman, gravida 4, para 0, with a history of one spontaneous abortion in early pregnancy and two extrauterine tubal pregnancies treated by laparoscopic left and right salpingectomy, self-referred to our department due to painless vaginal bleeding. She was six weeks pregnant after a successful IVF-ET program, according to our institution's protocol. Two blastocysts were transferred. Her gynecological findings on admission were as follows: smaller vaginal blood coagulum, mild fresh uterine hemorrhage, livid cervix, the external cervical ostium was closed and our patient had a six-week-sized uterus with unremarkable adnexal findings. Our patient's abdomen was soft and not tender. The first color Doppler transvaginal ultrasound scan revealed an intra-uterine gestational sac and live embryo with a crown-rump length (CRL) of 4 mm. Physical examination of our patient, performed at admission, showed normal temperature, blood pressure and heart rate. The established diagnosis was a threatened abortion. A few days later our patient experienced heavy vaginal bleeding with clots. She was re-examined and a color Doppler transvaginal ultrasound revealed another gestational sac with a live embryo in the cervical region. The CRL was 3.8 m. Her estimated blood loss was more than 600 mL in 24 hours reducing her hemoglobin level from 131 g/L to 109 g/L. Liver and renal function tests were within normal limits. Four units of blood were cross-matched to her blood. Her serum β-human chorionic gonadotropin (β-HCG) concentration was 217,000 IU/L. Our patient was cautioned that conservative management could result in a hysterectomy and her written consent was obtained before the procedure. Under general anesthesia a Foley catheter balloon was inserted within the cervical canal, controlled by ultrasound guidance, inflated and fixed by cerclage sutures at the level of the external cervical os, followed by ligation of the descending cervical branches of the uterine arteries. Hemorrhage from the implantation site was controlled immediately. Our patient was counseled again regarding the continuation of her intra-uterine pregnancy, but she decided to start with methotrexate treatment being fully aware that she would lose the other embryo. Systemic methotrexate application was started at 1.5 mg/kg with folic acid because of the adverse effects of this therapy. The Foley catheter was removed 3 days later and evacuation of the intra-uterine gestational sac was performed. Our patient recovered well and her progress was observed by regular transvaginal ultrasound scans and measurements of β-HCG concentrations. A transvaginal color Doppler examination showed a 3 mm thin hyperechogenic endometrium and anechogenic zone in the cervical canal (28 × 12 mm) with no detectable blood flow. At six months after the procedure, our patient resumed her regular menstrual cycles and one year later she underwent another IVF-ET procedure with an unknown outcome.


A 72-year-old man was admitted in a first hospital for diffuse abdominal pain and diarrhea. This patient had no history of malignancy, HIV, diabetes or other chronic disease, and was never treated by immunosuppressive drugs. He was chronically treated for Parkinson disease, asbestosis, paroxystic atrial fibrillation, hyperuricemia and hypercholesterolemia. His current medications were allopurinol, amiodarone, levodopa and simvastatin. He was not under antiplatelet or anticoagulant therapy prior to admission. On physical examination, the patient was apyretic, with supple abdomen and no rebound tenderness. Peripheral oedema was noted. Routine laboratory investigations revealed: C-reactive protein (CRP) 16.4 mg/dL, white blood cell count 18,900/mm3, platelet count 530,000/mm3, INR 1.15, fibrinogen 396 mg/dL, proteins 3.8 g/dL, albumin 1.9 g/dL, urea 70 mg/dL, creatinine 0.80 mg/dL. A moderate proteinuria was noted (1.267 g/24 hr) without urinary casts.
The patient was investigated by abdomen computed tomodensitometry (CT) and upper and lower endoscopy. The abdomen CT with intravenous contrast disclosed a significant thickening of the wall of the third, fourth duodenum, and of the proximal part of the jejunum with infiltration of the loco-regional fat ().
Esogastroscopy revealed a proliferative aspect in the duodenum. Duodenal biopsy showed an infiltration of the mucosa by polynucleated cells, but no ulceration was evident. The lower endoscopy was negative.
A few days later, ecchymotic lesions appeared on the limbs and the patient started also to complain from diffuse arthralgias and weakness in the upper and lower limbs. Electromyography was consistent with an acute sensorimotor polyneuropathy.
Serological investigations revealed: rheumatoid factor (-), anti-nuclear antibodies (-), anti-neutrophilic cytoplasmic antibodies (-), cryoglobulin (-), low C3 and C4 fractions of complement. Serological tests were negative for hepatitis B and C, EBV and HIV.
Due to the possibility of a systemic inflammatory disease combining skin lesions, arthralgia, polyneuropathy, proteinuria, high CRP with low complement fractions, a pulse steroid therapy was proposed on day 14 for a presumptive diagnosis of vasculitis, either microscopic polyangiitis (MPA) or polyarteritis nodosa (PAN). However, no skin or sural nerve biopsies were performed. The steroids loading dose was 1 g methylprednisolone, followed by 2 mg/kg/day for one week, and then 4 mg/day.
The patient was referred to the intensive care unit (ICU) of our university hospital on day 15 for gastrointestinal bleeding with melena. Despite blood and platelets transfusions, he remained with a low arterial blood pressure at 90/65 mmHg and hemoglobin concentration remained below 0.4 g/dL. Urgent gastroscopy failed to reveal any lesion. Angiography demonstrated that the bleeding originated from a jejunal branch and microcatheter embolization was successful initially (). However, two major episodes of lower intestinal bleeding occurred again within 48 hours after the procedure. On day 19, conventional enteroscopy revealed proximal jejunal ulcer with visible vessel and endoscopic clipping was performed. During the ICU stay, the patient was fed by intravenous parenteral nutrition and received daily intravenous vitamin K1 supplements. Despite optimization of the coagulation, rebleeding was noted on day 26 (hemoglobin 0.37 g/dL), but abdomen CT and angiography with direct intra-arterial provocative papaverine administration were not able to identify the origin. Scintigraphy with 99mTc labeled erythrocytes suggested that the origin was proximal small bowel. After a recurrence of hemorrhagic shock on day 28, the patient underwent urgent laparotomy. Active jejunal bleeding was found leading to segmental resection. Lower intestinal bleeding was definitely stopped after surgery.
Histology of the jejunal resection showed a severe mucosal necrosis with loss of villi (). High-power examination revealed thrombosis and fibrinoid necrosis suggestive of vasculitis. Some of the endothelial cells presented the characteristic cytopathogenic aspect of CMV infection ().
CMV antigenemia determined by real-time PCR in blood was weakly positive (5200 DNA copies/mL).
Multiple skin biopsies (hands, arms, legs) had also been performed on day 20. The histological picture was consistent with a diagnosis of leukocytoclastic vasculitis, but was not specific. No CMV inclusion was noted. Direct immunofluorescence showed deposits of IgG, IgA, IgM and C3 fraction of complement.
There was no evidence of CMV-related retinitis, pneumonia, hepatitis or bone marrow depression; the gastrointestinal involvement was restricted to the small bowel.
Ganciclovir (200 mg every 12 h) was given intravenously for 14 days to treat CMV disease. CMV antigenemia was negative at the end of the treatment. The patient had been maintained on low doses of oral methylprednisolone (4 mg/day); steroids were discontinued after 2 months. Other complications, mainly bacterial pneumonia and sepsis, occurred during hospital stay. After a significant recovery, the patient was discharged from the ICU on day 58, but died on day 159 from unrelated cardiorespiratory complications. Postmortem examination was not obtained.


A 26-year-old woman born with Tetralogy of Fallot initially underwent a left Blalock-Taussig shunt followed by a complete repair with a transannular patch at 2 years of age. She complained of non-sustained short episodes of palpitations. Her Holter monitor showed episodes of six beat run of non-sustained ventricular tachycardia. She was scheduled to undergo surgical pulmonary valve replacement. In view of her symptoms and Holter results she underwent an electrophysiology study to map any substrate of ventricular tachycardia for intra-operative ablation. Her baseline electrocardiogram demonstrated complete right bundle branch block pattern (RBBB) with QRS duration of 174 msec secondary to surgical interruption of the right bundle branch. During the electrophysiology study she was noted to have intermittent narrow QRS complexes ().The QRS complexes had a duration of 98 msec with no change in the PR interval and AH interval. What is the mechanism of narrow QRS complexes in this patient with baseline right bundle branch block (RBBB) pattern?


A 48-year-old Caucasian man presented to the Accident and Emergency Department of our hospital with symptoms of extreme asthenia, but showed no evidence of Raynaud's syndrome. In the past few months, he had complained about a productive cough and post-prandial vomiting. At admission, he was evidently dehydrated and undernourished, very pale, dyspnoeic and tachycardiac (110 bpm) at rest. Heart sounds were soft but no other pathologic sign concerning his lungs and abdomen was noted. His blood pressure was 80 over 50 mmHg.
A blood cell count showed severe anaemia (haemoglobin = 3.8gr/dl) and the patient was prescribed an emergency transfusion of RBCs (0 Rh-positive), owing to the severe anaemia associated with dyspnoea and tachycardia at rest, and hypotension. Blood samples were also sent to our Blood Transfusion Service at this time. Previous data relating to our patient was not found in our records.
After centrifugation, samples showed low hematocrit and normal plasma appearance. The direct blood group test resulted in unequivocally A with Rh phenotype Ccddee, while the indirect test revealed agglutination of B cells and a strong agglutination of 0 cells. Antibody screening also showed strong agglutination (4+) of all panel cells.
The above-mentioned Accident and Emergency Department was immediately alerted to our patient's immunohaematological situation, and we advised urgent cessation of the transfusion of RBCs (0 Rh-positive), which the physician had already initiated as prescribed by the emergency guidelines in force. We also recommended our patient's transferral to the Haematology Department in Ferrara City Hospital, where he arrived in a state of severe cardiovascular shock.
Blood samples taken from him at this time showed dramatic haemolysis, which led to his death within a few hours.
Subsequent blood tests revealed the presence of cold agglutinin syndrome with very high levels of anti-H (1:65.600). He showed positive (3+) results for the direct antiglobulin test for complement fractions, which caused the intravascular haemolysis and consequent cardiovascular shock.
His death prevented further attempts to define the aetiology of his condition. However, an emergency ultrasonography had shown several enlarged lymph nodes (average diameter, 5 cm) along the iliac vessels and the thoracic and abdominal aorta, suggesting a lymphomatous pathology.


The patient was a 65-year-old male with a history of radical prostatectomy for prostate cancer. Following a positive faecal occult blood test, a total colonoscopy was performed at a previous hospital in 1996 and a sigmoid colon lesion was identified. He was referred to our hospital for more precise examination and treatment. Colonoscopy revealed a 12 mm type 0-Is lesion in the sigmoid colon. We diagnosed the lesion as an adenoma or an intramucosal cancer and tried to remove this lesion by en bloc EMR. However, as a result the lesion was removed by piecemeal resection (2-pieces). The post-resection defect was closed using metallic endoclips.
Histopathological examination revealed a well differentiated adenocarcinoma with low grade atypia, and the depth of invasion was intramucosa without lymphovascular invasion, cut end margin negative (Figure ). We considered the treatment to be a curative resection. Follow up colonoscopy was performed 1 and 3 years after endoscopic resection. The EPMR scar was recognized without any residual or recurrent lesion in the follow up (Figure ). Follow up colonoscopy was scheduled at 5 years after treatment, but cancelled for personal reasons.
In 2007, the third follow up colonoscopy revealed a protruding submucosal tumor (SMT), 20 mm in size at the site of the 1996 EPMR (Figure and ). The biopsy specimen from the colonic mucosa did not demonstrate any malignancy. Therefore, we planned a follow up colonoscopy 6 months later. The follow up colonoscopy revealed that the SMT-like lesion had grown to a large size, with a reddish surface pitted with crater-like irregularities (Figure and ). Histopathological diagnosis confirmed an adenocarcinoma, and a laparoscopic-assisted sigmoidectomy with D3 lymph node resection was performed in 2007. Histopathological analysis of the resected lesion revealed a moderately differentiated adenocarcinoma, and the depth of invasion was subserosa with lymph node metastasis, lymphovascular invasion, venous invasion and perineural invasion (Figure ).


A 21-year-old male, with androgenetic alopecia, generally healthy except for hypothyroidism treated with µg/d Eltroxin, developed bilateral gynecomastia four months after finasteride 1 mg/day initiation. Ten months after cessation of treatment, the patient still had enlarged breasts with no apparent improvement []. The second patient is a 65-year-old healthy male with androgenetic alopecia who developed unilateral left gynecomastia after two months of treatment. Stopping the treatment led to major improvement within two months, but at follow-up six years after this treatment, there is still slight residual swelling.


A 58-year-old woman, recipient of a mechanical aortic valve, suddenly lost vision 1 hour after being admitted to the hospital for evaluation of a 2-day history of fever up to 39.5°C. Although she was aware of being blind, she underestimated the seriousness of her condition and seemed unconcerned. The patient, who had undergone replacement of a stenotic aortic valve 7 years earlier, had a history of arterial hypertension and dyslipidaemia. Her family history was negative for valvular heart disease, rheumatismal diseases, stroke, or other neurologic disorders. The patient was a widow, retired accountant, living alone in Athens. She had not travelled outside the country and had not been exposed to contagious illnesses. She had never smoked and did not consume alcohol or use illegal drugs. Her daily medication regimen included acenocoumarol, metoprolol, and lisinopril. She had a history of allergy to β-lactam antimicrobials.
On physical examination, the patient appeared critically ill and had faintly icteric skin and sclerae. Her temperature was 37°C, blood pressure 100/60 mmHg, and heart rate 90 bpm. The second heart sound was consistent with a mechanical prosthetic valve. The pupillary responses to light were intact and the fundoscopy was normal. The remainder of the examination was normal.
A complete blood count showed 13,000 leukocytes/mm3, 97% granulocytes, and 2% lymphocytes. The hemoglobin was 14 g/dL, platelets 135,000/mm3, international normalized ratio 4.3, erythrocyte sedimentation rate 125 mm/h, C-reactive protein 38 mg/dL (normal < 0.5 mg/dL), fibrinogen 7.9 g/L, serum creatinine 3.2 mg/dL, blood urea nitrogen 82 mg/dL, aspartate aminotransferase 88 U/L, alanine aminotransferase 104 U/L, γ-glutamyltransferase 477 U/L, alkaline phosphatase 205 U/L, total serum bilirubin 5.2 mg/dL, direct bilirubin 3.5 mg/dL, and lactate dehydrogenase 430 U/L. The urine analysis revealed 2+ protein, and 5 to 8 erythrocytes, and 15 to 20 leukocytes per high-power field. The urinary sediment contained tubulo-epithelial cells and muddy-brown granular casts, no dysmorphic erythrocytes and no red-cell casts. The tests for hepatitis B surface antigen, hepatitis B core IgM antibody, hepatitis A IgM antibody, and hepatitis C antibody were negative. While the urine was sterile, 3 sets of blood cultures obtained at the time of admission grew methicillin-sensitive Staphylococcus aureus.
A few hours later, the patient became hypotensive and was admitted to the intensive care unit. Treatment with intravenous fluids, gentamicin, and vancomycin was begun, and anticoagulation was discontinued. A first computed tomography scan of the brain without contrast, obtained at the time of admission, was negative. A follow-up scan, performed 24 hours later, showed infarctions in both occipital lobes (). A transeosophageal echocardiogram showed the presence of a vegetation on the prosthetic aortic valve (Figures and ). Also see Videos 1 and 2 in Supplementary Material available online at doi: 10.1155/2010/408471.
Over the following 4 days, the patient became hemodynamically stable and her renal and liver function tests returned toward normal values. On the 20th hospital day, she was afebrile, and her vision was partially restored. On transesophageal echocardiographic examination, 1 month after admission, the vegetation had disappeared, and she suffered no further clinical manifestations of systemic embolisation.


A 69-year-old female, with a long history of poorly controlled diabetes and hypertension, presented to the emergency room with a one month history of toothaches that were treated conservatively by her dentist using broad spectrum antibiotics. In the emergency room, she was drowsy and lethargic but not disoriented, with a temperature of 38.6°C. Her pulse was 112, and her blood pressure was 136/79. She had submandibular swelling with complete trismus. On admission, she had leukocytosis (16 000) and normal chest radiographs. She underwent exploration under general anesthesia using nasotracheal intubation. Periapical infection of tooth 48 and a submandibular abscess were found. A maxillofacial surgeon extracted tooth 48 and incised and drained the submandibular dental abscess. Hydrogen peroxide was used intraoperatively and postoperatively through the drain. The patient showed marked improvement regarding her trismus post-op. However, she developed progressively more severe dysphagia post-op. Since she did not improve after two days, ENT and GI services were consulted.
We found that the patient had edema of the soft palate, deviation of the right tonsil to the midline and laceration in the posterior wall of the oropharynx. Because the patient had high creatinine levels at that time, neck computed tomography (CT) without contrast was performed. The CT showed massive soft tissue widening in the parapharyngeal area and dangerous space with free air and air bubbles []. This free air extended from the nasopharynx down to the mediastinum. The gastroenterologist performed gastroscopy and endoscopy, finding a duodenal ulcer, but nothing anatomical obstructing the upper gastrointestinal tract.
The patient was placed on amikacin, clindamycin and ceftazidime. The intraoperative culture was negative, but later Escherichia coli was cultured from the pus exuding from the drain and on the dressings. These E. coli were resistant to all antibiotics except ceftazidime. The patient was put on metronidazole and ceftazidime and showed some improvement. The maxillofacial surgeons decided to explore and clean the parapharyngeal space under general anesthesia. Intraoperatively, the patient had difficulty with the orotracheal intubation due to narrowing of the airway and copious amount of pus in the pharynx. The parapharyngeal space was drained externally and vigorous irrigation with hydrogen peroxide was performed. Postoperatively, the patient was admitted to the ICU and was found to have S–T segment elevation and multiple PVCs, which the cardiologist diagnosed as MI with LBBB. The echocardiogram showed concentric LVH with mild diastolic dysfunction as well as degenerative valvular disease (mild mitral, aortic and tricuspid regurgitation). Moreover, liver tests showed low albumin levels and elevated enzyme levels. The patient was kept intubated in the ICU, and copious amount of pus was suctioned through the mouth, but nothing drained through the parapharyngeal space drain. Her chest radiograph revealed a bilateral infiltrate suggesting aspiration pneumonia and bilateral pleural effusion.
We decided to evaluate the retropharyngeal area using MRI to exclude any neck collection. The MRI was also performed without contrast due to high creatinine levels, and it did not show any neck collection. However, air bubbles were found in the dangerous space []. The patient underwent tracheotomy and exploration of the dangerous space. Intraoperatively, the patient was found to have ulceration of the oropharyngeal wall with necrotic tissue in the sub-mucosa. External neck incision was performed, and the dangerous space was connected to the rest of the neck spaces. Thorough debridement of necrotic tissue was completed, followed by irrigation with hydrogen peroxide. A through-and-through drain was used at the end of surgery to irrigate and drain collection in the dangerous space postoperatively. Oral feeding was stopped, a nasogastric feeding tube was inserted and enteral feeding was started. The patient showed marked improvement post-op.
A week later, we performed suspension pharyngoscopy, which showed marked improvement of the posterior wall of the oro-pharynx and disappearance of the necrotic tissue. We repaired the pharyngeal opening of the fistulae with absorbable sutures and kept the drain in the external orifices to avoid re-accumulation of air and pus. The patient restarted with feeding and was discharged soon afterwards.


A 28-year-old man smoker and substance abuser (cocaine and circumstantial intravenous heroin) for the last 8 years, without known familiar history for CAD, presented to a local hospital with an antero-lateral ST segment elevation myocardial infarction (Figure ), associated with a low cardiac output syndrome. Heart ultrasound revealed severe hypokinesia of anterolatelar wall with ejection fraction of 30%. The patient was given immediately thrombolysis with tenecteplase (Metalyse) and his symptoms and ECG changes almost resolved. Few hours later he was transferred to our hospital for urgent catheterization due to recurrent ischemia and hemodynamic instability. At his admission the patient suffered from AMI complicated with cardiogenic shock and symptoms of congestive heart failure. Chest x-ray examination showed mild cardiomegaly, diffuse pulmonary congestion and perihilar infiltrates with the classic butterfly pattern, and Kerley B lines (Figure ). He was supported medically by combination of dobutamine, dopamine and furosemide. Coronary angiography revealed a huge thrombus formation of LM and suspicion of mobile parts to the rest of the left coronary system (Figures ). He stabilized hemodynamically using an intraaortic balloon pump (IABP), but due to a lot of episodes of angina and no clear-cut guidelines describing the best management approach for patients under this condition we decided to operate him under an estimated risk of 30% according to logistic EURO-score. Urgent CABG by using cardiopulmonary bypass at normothermia (37°C) with continuous warm blood cardioplegia was done. An organized thrombus was found in the opened left anterior descending artery and removed. Finally, the vessel was bypassed by the left internal thoracic artery. In addition, the first obtuse marginal branch was bypassed by a free left radial graft. After a successful bypass weaning, he was transferred in intensive care unit and extubated 12 hours later. The IABP was removed 24 hours later. Inotropes infusion was interrupted at 36 hours and he discharged from the hospital on the 8th postoperative day in a good condition.


A 49-year-old Caucasian woman presented with an acute deterioration in her allograft function seven years after she underwent a deceased-donor kidney transplant for end-stage kidney disease, secondary to autosomal dominant polycystic kidney disease. Her transplant was a three human leukocyte antigen (HLA) mismatch to an unsensitised recipient. The initial therapy was standard immunosuppression at that time (cyclosporin, mycophenolate mofetil and prednisolone). The transplantation was complicated by acute rejection after one year due to steroid withdrawal, which was treated with reinstitution of steroids and conversion to tacrolimus therapy one year later. This was some five years prior to her current presentation. Her serum creatinine concentration then stabilized at 125 μmol/L. She subsequently developed osteoporosis and was commenced on calcitriol and alendronate. She was prescribed HRT in the form of estradiol and norethisterone for both the symptoms of menopause and for protection of her bones. In 2002 after the publication of the WHI study [], she approached her general practitioner and requested to be withdrawn from HRT, which subsequently occurred over the next two months.
In early 2007, she presented to our transplant centre with lethargy, difficulty sleeping and anxiety over a period of one week. She had no recent illness. Her medications at this time included: tacrolimus 1.5 mg in the morning and 2 mg at night, prednisolone 4 mg daily, mycophenolate mofetil 500 mg twice daily, atorvastatin 20 mg daily, alendronate 70 mg weekly, omeprazole 20 mg daily, citalopram 20 mg daily, calcium carbonate 600 mg daily, calcitriol 0.25 μg daily and folic acid 5 mg daily. The only change to her medications had been the addition of tibolone therapy (2.5 mg per day) for the symptoms of menopause 10 days prior to presentation. On examination she was apyrexial, but was noted to be extremely tremulous and was newly hypertensive with a blood pressure of 144/96 mmHg (previous blood pressure: 118/74 mmHg). She was hyperglycemic with a blood sugar of 12.1 mmol/L, having not been diabetic previously (fasting glucose: 4.5 mmol/L). There was no abnormality found on examination of her cardiovascular, respiratory or gastrointestinal systems. She was found to have worsening graft function with a serum creatinine level of 177 μmol/L (previously 120 μmol/L) and to have tacrolimus toxicity with a level of 17.9 μg/L (liquid chromatography with tandem mass spectrometry (LC-MS/MS) performed at the transplant centre, see Figure ), having previously been 5.2 μg/L (enzyme immunoassay (MEIA) performed at a local pathology centre). She was serologically positive for BK virus but below the threshold of clinical significance (1 × 103 at our institution), with a quantitative polymerase chain reaction (PCR) level of 1.7 × 102, which had been noted for several months previously and had not changed.
Management included ceasing tibolone and reducing the tacrolimus dose to 0.5 mg in the morning and 1 mg at night until the concentration reduced to target level, which occurred over the next six days. Her creatinine level slowly returned to baseline over a period of three months, at which time her tacrolimus level was 4 μg/L at a dose of 2.5 mg per day; a similar dosage and drug level to where she had started.
The differential diagnosis of acute kidney injury included tacrolimus toxicity, BK nephropathy, acute rejection and chronic allograft nephropathy. Tacrolimus toxicity was consistent with the acute nature of the presentation, explained all of her symptoms and signs and was borne out by the resolution of her kidney injury as her tacrolimus level and allograft function returned to the previous baseline. It was noted that the baseline and recovery tacrolimus concentrations were measured by MEIA, compared to LC-MS/MS in our centre. However, previous studies have shown that MEIA overestimates tacrolimus concentration in the blood of kidney transplant recipients by 16 to 20 percent []. Therefore the different assay methodologies would be likely to underestimate the true size of the effect. BK nephropathy, acute rejection and chronic allograft nephropathy were all considered unlikely due to her clinical presentation and the investigations performed. Although a kidney transplant biopsy was not performed (due to her rapid improvement with reduction in tacrolimus dose and cessation of tibolone), none of these three possibilities would have resolved in this time-frame had they been the true cause of her kidney dysfunction.
The differential diagnosis of tacrolimus toxicity included interaction with new medications, overdose of tacrolimus tablets (either inadvertent or deliberate) and diarrhea. She had no history of a diarrheal illness or loose bowel motions. It was considered unlikely that she accidentally overdosed on the tablets as she was known to be adherent with very consistent blood levels of both tacrolimus and cyclosporin before that. There had been no recent dose changes to cause confusion. The only recent medication had been the tibolone, and although there are no reported drug interactions with tacrolimus and tibolone, we considered it possible that the initiation of tibolone had precipitated the tacrolimus toxicity by some unrecognised mechanism.


A 52-year-old Australian Caucasian male with cystic fibrosis was admitted to our hospital with an exacerbation of pulmonary sepsis accompanied by a vague abdominal pain. Abdominal X-ray revealed faecal loading in his caecum and ascending colon with proximal small bowel dilatation consistent with meconium ileus equivalent. His relevant medical history consisted of pancreatic insufficiency and bronchiectasis with moderately severe lung function impairment (FEV1 2.18 L/s; 53% predicted). He had multiple hospital admissions over the preceding two years with exacerbations of chronic airway sepsis.
The diagnosis of cystic fibrosis had been made during his early childhood when he presented with failure to thrive, and this had been confirmed with an elevated sweat test and genotyping that revealed him to be a heterozygote for G542X, with the other allele unidentified. G542X is a Class I mutation that results in the complete failure to synthesize functional cystic fibrosis transmembrane conductance regulator (CFTR) and is usually associated with pancreatic insufficiency. On this particular admission, his chest and abdominal symptoms resolved after a course of intravenous antibiotics, fluid replacement, and oral administration of N-acetyl cysteine. His 24-hour fecal fat levels were elevated at 41 grams and his pancreatic enzymes were thus increased.
He presented again after six weeks due to a recurrence of severe abdominal pain, anorexia and weight loss, but without any alteration to his bowel habit. Examination revealed epigastric tenderness and active bowel sounds, but no guarding. Results of respiratory examination were unchanged. On this occasion, abdominal X-ray was normal, as were his full blood count, urea and electrolytes, serum amylase (46 IU/L; NR < 100 IU/L), and liver function tests. However, he continued to complain of severe abdominal pain radiating through his back and lower chest. An abdominal ultrasound demonstrated an increased echogenicity consistent with inspissated secretions in the pancreatic duct and an 8 mm common bile duct with no other abnormalities.
Two days after admission, our patient became jaundiced. Repeat blood tests demonstrated a cholestatic picture: total protein 66 g/L, albumin 36 g/L, alkaline phosphates (ALP) 809IU/L, alanine transaminase (ALT) 543IU/L, glutamyl transaminase (GGT) 334IU/L, and bilirubin 23 mmol/L. His serum amylase (42IU/L) and lipase (4IU/L; NR: < 10IU/L), as well as urinary lipase (96IU/L, NR: < 500IU/L) levels remained normal. An abdominal computed tomography (CT) scan demonstrated that he had a heterogeneous mass measuring 5×5×5 cm and located at the head of the pancreas with biliary and pancreatic duct dilation (Figure ). Magnetic resonance cholangiopancreatography confirmed the enlargement of the head of his pancreas with dilated intrahepatic and extrahepatic biliary ducts. These findings were thought to be consistent with either acute pancreatitis or a pancreatic malignancy.
Results of his liver function tests remained abnormal (ALP 1085IU/L, ALT 249IU/L, GGT 383IU/L, and bilirubin 37 μmol/L) and the patient proceeded to endoscopic retrograde cholangiopancreatography, where a narrowing of the common bile duct at the head of the pancreas was identified with more distal anatomical distortion of the entire pancreatic ductal system. A biliary stent was consequently inserted. CT guided biopsy of the pancreatic mass demonstrated reactive pancreatic ductal epithelium with an infiltrate of macrophages and lymphocytes, but no evidence of malignancy was found.
The patient continued to experience abdominal pain and ursodeoxycholic acid was introduced to treat any potential contribution of biliary sludging to cholestasis and also to minimize the risk of stent occlusion. Following stent insertion and commencement of ursodeoxycholic acid, his symptoms and liver function tests slowly improved, and then returned to normal over the next 6 weeks. A repeat CT scan showed a resolution of biliary dilation, but no change in the pancreatic mass was noted. After 18 months he remains well with normal liver function tests and no abdominal pain. A repeat CT scan at this time demonstrated a complete resolution of the pancreatic mass (Figure ).


A 59-year-old Italian man presented with abdominal pain localized in the right upper quadrant, constipation and vomiting for longer than one week. The patient had inconstant symptoms including shortness of breath and dyspnea. His medical history included right-sided rib fractures in a motor vehicle crash seven years previously.
On physical examination, bowel sounds were present in the right hemithorax on auscultation. A chest X-ray showed elevation of the right hemidiaphragm elevation, with a portion of the colon and the small intestine transposed in the right hemithorax as a diaphragmatic rupture. A barium study showed small bowel and right colon herniation into the right hemithorax, passing behind the liver (Figure ). Computed tomography (CT) scan confirmed the diaphragmatic herniation (Figure ).
The patient underwent laparotomy, and herniation of the right colon and small intestine (40 mm in length) was seen. There were no ischemic changes or perforation, but the colon was slightly edematous. No resection of any part of the intestinal tract was necessary. The colon and the small intestine were reduced into the abdomen. As usual in traumatic lesions, there was absence of the hernial sack: the hernia opening was only 50 mm in length, (Figure ). The hernia opening was repaired with interrupted non-absorbable sutures; placement of a polymeric prosthetic mesh was not required at the time of the intervention. A drain was placed in the right side of the thorax. The operating time was 45 minutes. The thoracic drain was removed on the third post-operative day and the patient was discharged on the fifth postoperative day.


A 31-year-old Indian male patient, involved in a motor vehicle accident, suffered a grade IV spleenic and bowel injury. Computed tomography (CT) of the head was normal, Glasgow coma score was 15/15, and the patient did not have any significant past medical history. He underwent splenectomy and Hartman’s procedure; hemostasis was achieved by packing the abdominal cavity. He was transferred to the trauma intensive care unit (TICU) for further management.
In the TICU, the patient was sedated and supplemented with analgesia, resuscitated with blood, blood products, colloids, and crystalloids. Patient developed disseminated intravascular coagulopathy and hemorrhagic shock. Despite resuscitation, he remained hypotensive and he required adrenaline and noradrenalin. Tazocin® (piperacillin + tazobactam) was given prophylactically. But serum creatinine levels started to rise and on day 3 and the abdominal packs were removed. The patient was oliguric despite proper hydration and he developed anuria on day 4 [see ]. He was diagnosed as a case of ARF and daily HD was started. Intermittent daily dialysis was performed with Fresenius dialysis machine, through the right femoral vein using a double-lumen catheter, slow (5 h), flow rate (QB) 150–200 mL/min, QD 500 mL/min, dialytic fluid composition sodium 135 mmol/L, and potassium-free, low dose heparin, sodium bicarbonate 40 mmol.
The inotropes were weaned and discontinued on day 6. Enteral feeding was gradually increased to match the daily requirement. He was trying to obey simple commands, moving all limbs, pupils were equal, reacting to light, and CT of the brain was normal.
On day 8, the patient became febrile and a greenish discharge from the operative wound was observed. Following septic workup, his antibiotic management was changed to meropenem. The patient became acidotic (pH = 7.05), hypercarbic [see ], hypotensive, and highly febrile with leukocytosis (30,000) []. On day 13, he was diagnosed with septic shock and noradrenalin was started. The patient became stable with inotropic support and his oxygenation was within the normal range. He remained on daily HD. Percutaneous tracheostomy was performed on day 15. Posttracheostomy, his chest radiograph showed only a few hilar infiltrates and no other abnormality. On day 16, daily HD was performed with Fresenius dialysis machine, through right femoral vein double-lumen catheter, slow (4 h), flow rate (QB) 200 mL/min, QD 500 mL/min, dialystic fluid composition sodium 135 mmol/L, potassium 4 mmol/L, and low heparin, sodium bicarbonate 40 mmol. One hour after HD, the patient became unresponsive, with pupils dilated and fixed; he was hyperventilated immediately and intravenous mannitol was started. A CT scan of the brain showed severe brain edema and brain herniation []. His electroencephalograph (EEG) was flat and brain stem reflexes were absent. On day 18, he was confirmed as brain dead and he expired the same evening.


A 20-year-old female patient presented with complaints of pain in the abdomen in February 2008, with no other symptoms. Abdomen examination revealed a soft tender mass measuring 4 cm in the right lumbar region. No other clinical abnormalities were detected. Ultrasound abdomen showed a mass lesion in the right lumbar region. In February 2008, the patient underwent radical nephrectomy. The pathological diagnosis of pigmented renal cell carcinoma was made.
Pathological findings – The surgical radical nephrectomy specimen consisted of right kidney measuring 13 × 7 × 6.5 cm, ureter measuring 6.5 cm in length. Cross-section showed dark brown to tan tumor in the upper pole measuring 5 cm in diameter. Tumor was multilobulated and solid. The remaining renal parenchyma appeared normal including pelvicalyceal system []
Microscopically, the kidney tumor was predominantly composed of clear cells with focal granular cells. Tumor cells were arranged in acinar, solid and tubular patterns.
The tumor cells had clear cytoplasm, lacked significant pleomorphism and had low Fuhrman nuclear grade (II/IV). Tumor cells were separated by highly vascular and fibrous stroma. In the majority of tumor cells, dark brown pigment was observed in the cytoplasm of clear cells. The pigment was dark brown, granular, nonrefractile [].
Tumor capsule was free of tumor tissue. The renal vessels and ureter were free of disease. Special stain was performed on formalin-fixed and paraffin-embedded material. The pigment showed strongly black stain with Fontana Masson.


A 32-year-old woman who had low-grade pyrexia for 3 months was investigated elsewhere and referred to us with a diagnosis of a splenic abscess. Clinically, she had a mildly tender splenomegaly extending 4-cm below the costal margin. The investigations showed haemoglobin to be 9.8 gm% and ESR to be 100 mm/1st hour. All the biochemical parameters and chest x-ray were normal and she was HIV-negative. An echocardiogram was normal. Her computerized tomography (CT) scan showed a large, multilocular splenic abscess []. She had received two months of anti-tubercular chemotherapy (started elsewhere) but had responded poorly to it. She was administered pneumococcal and meningococcal vaccines in preparation of LS.
Surgery was performed under general endotracheal anaesthesia with the patient in left lateral decubitus position. A nasogastric tube and an indwelling urinary catheter were in situ. The first 10-mm port was placed midway between the left costal margin and the umbilicus by the open method. Another 10-mm and two 5-mm ports were positioned around the first port. Omentum adherent to the spleen was divided using an ultrasonic shears (Ethicon Endosurgery, Cincinnati, OH, USA). The lesser sac was entered and the splenic artery was dissected and divided after clipping. The short gastric vessels were divided using the ultrasonic shears. Two firings of a 45-mm endoscopic linear cutter device (Endo GIA, Ethicon Endosurgery) were used to resect the gastric fundus densely adherent to the spleen []. Dense adhesions at the splenic hilum precluded identification and dissection of the splenic vein. A 10-mm Ligasure vessel sealing device (Covidien, Boulder, Colorado, USA) was used for control of the hilum and for division of the posterior as well as diaphragmatic attachments of the spleen. The excised spleen was placed in an impervious retrieval bag and extracted after enlarging the site of the telescopic port. A tube drain was placed and the fascia at the extraction site was closed with non-absorbable suture. The skin was approximated with subcuticular suture. The total operative time was 230 min and blood loss 700 ml. Postoperatively, the drain yielded around 100 ml of amylase-rich fluid for the first 3 days. The patient was kept nil per oral and administered parenteral nutrition and subcutaneous octreotide. The drain was removed on the seventh day once the output reduced to 20 ml/24h and ultrasonography showed no residual collection. Histopathology of the spleen confirmed tuberculosis. She responded well to anti-tubercular chemotherapy and remained well 3 years later.


A 37-year-old afebrile male presented to the emergency department with swelling, change of skin color and evident pus discharge from the proximal penile shaft dorsally to the left side. The swelling complicated severe pain and penile detumescence but with no snap sound during sexual intercourse before 3 weeks. No more erections were reported thereafter. The patient denied any history of urethral discharge, intracorporeal therapy or instrumentation.
Physical examination revealed edema, redness, ulceration and discharge of thick, yellowish pus from the proximal penile shaft []. The external urethral meatus showed no urethral discharge. No rolling sign or corporal defects could be detected. Both testes and epididymides were palpably normal. Inguinal lymph nodes were not enlarged. Rectal examination was unremarkable.
Random blood sugar and white cell count were within normal. Urine analysis and culture showed no evidence of infection. HIV serology and urine culture for tuberculosis were negative.
Under spinal anesthesia the penile abscess was incised, pus was drained and a 4 × 5 cm area of necrotic skin was excised down to the intact cavernosal tunica albuginea []. Irrigation with saline and povidone iodine was carried out. Further debridement was required after 48 hours. The patient was kept on IV ciprofloxacine and daily dressing for 2 weeks when a full thickness skin graft was taken from the left thigh and applied to the penile shaft while artificially erected. The dressing was removed after 1 week and the patient was sent home with a viable graft. Follow up after 2 weeks revealed a viable graft [], normal voiding and normal morning erection with no deviation, pain or shortening.


A 35-year-old woman presented at 24+0 weeks of gestation of her fourth pregnancy. She had suffered two early pregnancy losses. The third pregnancy ended in the delivery of a healthy boy. Medical and family history of the proposita and her partner were unremarkable. First trimester-screening including ultrasound and maternal serum biochemistry had been normal (adjusted risks +21 = 1:1839; +18 = 1:610; +13 = 1:3515). In the 25th week, ultrasound revealed symmetric foetal retardation with cerebral ventriculomegaly, partial agenesis of the corpus callosum, short nasal bone and hyperechogenic bowel. Therefore, amniocentesis was performed and foetal karyotyping initiated. For rapid screening for aneuploidies, FISH was performed according to standard methods on uncultured amniotic cells using a commercially available probe set (Abbott, Wiesbaden). Signal patterns indicated a normal female gonosome constellation without evidence for aneuploidies detectable with the probes for chromosomes 13 and 18. Nevertheless, the approximately 200 kb-sized LSI21 probe for the DSCR1 containing the loci D21S529, D21S341 and D21S342 in 21q22 showed only one signal in 97 of 100 (97%) evaluated nuclei. To corroborate these findings by an independent probe, FISH was performed with a different commercial probe, PN21 (Kreatech, Berlin). This probe containing the markers D21S65, RH72110 and RH92717 and hybridising to DSCR4 and 8, revealed a normal pattern with two signals in the majority (86/100) of the nuclei, whereas a minority (14%) lacked one signal. Additional FISH analyses on uncultured amniotic cells with PAC probes for 21q11.2~21 (RP1-270M7 and RP1-152M24) as well as a commercial probe (Abbott, Wiesbaden) for the AML1 locus in 21q22 yielded a normal signal pattern. Mapping of both commercial probes indicated that they both hybridise approximately 3,3 Mb apart with the Abbott probe being located telomeric of the Kreatech probe (see Fig. ). Therefore, the FISH patterns were judged as indicative for a de novo deletion in 21q with the breakpoint between the regions the two probes hybridise to. This interpretation was confirmed by the results of chromosome banding analysis of 15 metaphases from two independent cultures. All metaphases analysed showed a terminal deletion of the long arm of chromosome 21 with the breakpoint in 21q22. Moreover, in all metaphases an additional small marker chromosome (sSMC) was detected, of which the origin could not be identified using DA/DAPI staining and various FISH probes. The karyotype was described as 47, XX, del(21)(q22),+mar[15]. Chromosome analysis in the parents including FISH with chromosome 21 specific probes revealed a normal female respectively male karyotype in 10 metaphases analysed.
The couple was extensively counselled on the results and the pregnancy was continued. The pregnancy was monitored regularly by ultrasound. Foetal growth restriction was obvious onward. By the end of the pregnancy the patient revealed clinical signs of preeclampsia so that birth was induced at 41+2 weeks of gestation.
The child was born at 41+3 weeks with a length of 46 cm (-2.74 SD), weight of 2240 g (-4.4 SD), and a head circumference of 31 cm (-3.16 SD). APGAR scores were 1/8/9. On examination a high nasal root, down-slanting palpebral fissures, retrogenia, posterior rotated, slightly low-set ears, a long philtrum, and a thin upper vermillion were noticed. The fingernails were small. A sacral dimple was observed. Ultrasound of the abdomen gave inconspicuous results. Echocardiography showed a patent ductus artiosus Botalli (PDA) and atrial septal defect (ASD) without hemodynamic consequence. Cerebral ultrasound showed a missing septum pellucidum. The infant had a good muscle tone. The major problem was the feeding, most probably due to sucking weakness and a lack of coordination so that a feeding tube had to be placed.
To confirm the prenatal findings and further characterise the chromosomal changes DNA was extracted from cord-blood taken at birth and subjected to molecular karyotyping using two different platforms. Array CGH was performed using the Human Genome CGH Microarray 244A platform (Agilent Technologies, Santa Clara, USA). Moreover, hybridization to Cyto2.7 arrays (Affymetrix, Santa Clara, CA, USA) was performed. Both array platforms confirmed the presence of a most likely telomeric deletion with the breakpoint in 21q22 at around chr21: 37,381,170 bp (Agilent 244A) and 37,302,549 bp (Cyto2.7 Affymetrix), both mapped according to NCBI Build 36. The molecular karyotyping results explained the discrepant results with the commercial FISH probes PN21 from Kreatech (~34,538,500-35,086,000 bp) and LSI 21 from Abbott (~38,353,445-38,553,733 bp) for 21q, which hybridise centromeric and telomeric of the breakpoint, respectively. Nevertheless, in addition both array platforms provide also evidence for a deletion of 21q11.2q22.13(14,319,839-37,381,170 bp) in a subset of cells as indicated by the decrease of the signal intensity to around -0.5 as typical for mosaicism of a loss. Therefore, we performed chromosome banding analysis on a peripheral blood sample of the child which indeed yielded evidence for the presence of four cell lines differing by the presence and absence of the del(21) and the sSMC. The karyotype was described as: mos 47, XX, del(21)(q22),+mar[22]/46, XX, del(21)(q22)[7]/46, XX, -21, +mar[5]/45, XX, -21[4]. The complete loss of chromosome 21 in 9 of 38 metaphases explains the decreased copy number in 21q11.2q22.13 in the array analyses and is also in line with the prenatal FISH analyses indicating loss of 21q21~22 including DSCR4/8 in 14% of nuclei. The lack of an imbalance at the very centromeric part of 21q in the array analyses along with the absence of larger copy number gains on other chromosomes suggests, that the sSMC is derived from chromosome 21 and represents a del(21)(q11.2). To confirm this view, FISH was performed with a probe (PAC 1174A5) for the rRNA gene cluster which yielded a signal on the sSMC []. A weak signal was observed with a whole chromosome painting probe for chromosome 21 (Kreatech, Berlin). Hybridization with a probe detecting the centromeres of chromosomes 13 and 21 (Kreatech, Berlin) showed a signal on the sSMC. In summary these findings render the interpretation that the sSMC, is a del(21)(q11.2) likely.


A 53-year-old male with generalized lymphadenopathy and fatigue, was diagnosed as MCL on inguinal lymph node biopsy. After 10 cycles of CHOP and 2 cycles of E-CHOP, lymph nodes bulged. Disease was still progressing after 2 cycles of R-ICE. Therefore, R-ICE was stopped. The patient was recruited in phase III study of temsirolimus (number: 3066K1-305-WW) on August 2006 but was randomized in investigator's choice group. According to the protocol, fludarabine 25 mg/m2 was infused daily for 5 days, and it was repeated every 28 days. After 8 cycles, fludarabine had to be stopped because of severe bone marrow inhibition on March 2007. One year later, enlarged iliac lymph-node compressed ureter, causing renal dysfunction with elevated blood creatinine. To confirm the diagnosis of recurrence, a biopsy of enlarged right cervical lymph node was performed and the place was noted on CT scan. After confirmation of the MCL recurrence, the patient was permitted to enter the temsirolimus treatment group on March 2008. He received temsirolimus 175 mg/week for 3 weeks, followed by weekly doses of 75 mg. Circulation blood count was monitored weekly, CT scan and serum chemistry every other month. Temsirolimus was suspended, when absolute neutrophil count <1000/μl, or hemoglobin <8 g/dl, or platelet <50000/μl. According to the response criteria for non-Hodgkin's lymphoma[] we use in our hospital, six of the largest dominant nodes or nodal masses were measured. The sum of dimensions of these six nodal masses was recorded before temsirolimus as well as every other month under temsirolimus treatment. Other lesions were recorded but not measured. After 2 months of temsirolimus treatment, a 33% regression of the sum of dimensions was observed by CT scan (Figure ). Meanwhile, renal function recovered and blood creatinine returned to normal level. However, lymph nodes enlargement was still present on CT scan after 6 months of temsirolimus. To assess the extent of the therapeutic effect, and to detect a possible early recurrence, a second biopsy of the same right cervical lymph node was performed but in a different direction. Informed consent was provided according to the Declaration of Helsinki. Disease remained stable until January 2009 when CT scan showed a cervical lymph node behind the right jugular vein bulged. Temsirolimus was then stopped. No further biopsy was taken. Patient then received arsenic combined with thalidomide and chlorambucil treatment. On March 2009, all lymph nodes enlarged, and disease still progressed after 3 cycles of bortezomib. The patient finally died of severe bone marrow inhibition and pulmonary infection after hyperCVAD treatment on October 2009.
During temsirolimus treatment, leukopenia and thrombocytopenia occasionally occurred, and disappeared after one week of treatment suspension. No sign of thrombosis was observed.
Cyclin D1, the hallmark of MCL, is the down stream target of mTOR. Its expression was assessed by immunohistochemical staining (Dako; Glostrup, Denmark; dilution 1:100) on the two successive biopsies. Tumor cell proliferation was assessed by Ki67 (Dako; dilution 1:100), apoptosis by cleaved caspase-3 (Cell signaling; MA, USA; dilution 1:50), microvessel density (MVD) by CD31 (Dako; dilution 1:50), and angiogenesis cytokine expression by VEGF-A (R&D system; MN, USA; dilution 1:200). Irrelevant isotypic antibodies and absence of primary antibodies were used as controls. Immunostained cells were counted on 5 different microscopic fields at ×400 magnification, out of fibrotic and necrotic areas, the count including a minimum of 1000 cells. Fibrotic areas were randomized photographed at ×200 magnification for five fields and analysed with Cell Software (Olympus, Tokyo). The ratio between fibrotic areas and tumor areas gave the relative fibrotic area. Differences between analyses before and after temsirolimus were assessed with Wilcoxon signed-rank test. Two-sided P < 0.05 was considered to be significant.
Comparison between the 2 biopsies, before and after temsirolimus, showed a significant decrease of cyclin D1 (P < 0.01), and Ki67 (P < 0.01). But there was no change in apoptotic cell counts (P = 0.15). VEGF-A expression (P <0.05) and microvessel density (P < 0.05) were also significantly decreased after temsirolimus therapy. Numerous patchy, well-limited fibrotic areas were observed within the tumor. Relative fibrotic area significantly increased after temsirolimus (P < 0.05) (Figure ).


A 65-year-old man, hypertensive with a history of percutaneous coronary intervention to left anterior descending artery and exertional dyspnea, was referred for AVR. Transthoracic echocardiography demonstrated a calcified aortic valve with peak and mean gradients of 80 and 45 mmHg, respectively. The left ventricular (LV) end-diastolic and systolic diameters were 44 and 25 mm, respectively, with an EF of 76%. There was severe concentric LV hypertrophy with no systolic anterior motion (SAM) of mitral valve and no dynamic LVOT obstruction. Basal septum measured 21 mm in diastole and 24 mm in systole, posterior wall measured 18 mm in diastole and 21 mm in systole, and LVOT measured 21 mm. E/A wave ratio in mitral inflow showed impaired relaxation pattern. The coronary stent was patent at angiography with tight ostial stenosis of second diagonal vessel. At surgery, left internal mammary artery was grafted to diagonal and his stenotic aortic valve was replaced with a 21-mm Carpentier-Edwards Perimount aortic heart valve under general anesthesia, normothermic cardiopulmonary bypass (CPB) and antegrade cold blood cardioplegia. CPB and aortic cross clamp times were 100 and 70 minutes, respectively. The patient had a body surface area of 1.58 m2 and the calculated indexed effective orifice area of prosthesis was 0.82 cm2/m2.
At the time of separation from CPB, the patient developed profound hypotension (systolic/diastolic blood pressure: 60/40 mmHg) which did not respond to incremental doses of vasopressors (epinephrine, norepinephrine) and to intraaortic balloon pump (IABP) counter pulsations. There were no ischemic changes noticed in the monitor. An emergency transesophageal echocardiogram was performed which showed a small hypercontractile LV and an abnormal turbulent flow velocity at the LVOT [, arrow heads] with peak and mean systolic gradients of 58 and 39 mmHg, respectively []. Peak and mean gradients across the prosthetic aortic valve were 17 and 8 mmHg, respectively. There was no SAM or midcavity obstruction noted but the basal septum was very thick and sigmoid shaped causing a turbulent flow at the LVOT [, arrow heads]. Mitral/aortic valve and right ventricle were normal. A diagnosis of dynamic LVOT obstruction was made and IABP was discontinued. A subaortic limited septal resection was performed as the thick septum was thought to be the cause for dynamic gradient. The hemodynamic readings were: mean systemic arterial pressure 50 mmHg; mean pulmonary artery pressure 20 mmHg; pulmonary capillary wedge pressure 15 mmHg; right atrial pressure 9 mmHg; cardiac index 2.0 L/min/m2; and systemic vascular resistance index 1638 dynes s/cm5m2. Phenylephrine boluses along with infusion were initiated to increase systemic vascular resistance, norepinephrine was continued, and the patient was separated from CPB after optimization of preload. A pulmonary capillary wedge pressure of 20–25 mmHg was aimed at. Atrioventricular synchrony was maintained with the help of atrioventricular pacing (DDD) at a heart rate of 60 beats per minute. The patient was shifted to the postcardiac surgical unit without sternal approximation with a systolic blood pressure of 80 mmHg. There was persistence of LVOT gradient. Despite resuscitative measures, patient went into refractory shock and finally developed pulseless electrical activity and expired.


A 9-year-old male child was admitted with a 3-year history of pica, recurrent constipation, abdominal pain, failure to thrive and painful defecation. Abdominal examination revealed moderate distention with multiple palpable intraluminal masses along the rectosigmoid, descending colon and the ascending colon up to the illeocaecal region, with no features of peritonitis. Anal inspection revealed stone pellets protruding through the anus. The rectal examination revealed hard, prickly masses filling the dilated rectum. It was impossible to negotiate and pass around the masses occluding the rectum.
A plain radiograph of the abdomen showed numerous opaque shadows of different sizes scattered throughout the colon []. Under general anesthesia, following anal dilatation, 1,025 pieces of stones were completely recovered manually, with a diameter ranging between 5 mm to 2.5 cm []. He had uneventful recovery. After evacuation, the patient was given laxatives as well as proctoclysis enema and he used to pass 40–60 pieces of stones a day for 7 days. On the 8th day, another radiograph of the abdomen revealed no residual stones. Mental health assessment by the pediatric psychiatrist did not reveal any gross abnormality. The patient was subsequently discharged on day 9 and was followed-up for a period of 6 months and was put under strict parental supervision. He had increased appetite and gained weight.


A 23-day-old full-term male weighing 2700 g, born by normal delivery to a second gravida mother with an uncomplicated perinatal history was brought to the pediatric emergency. The baby was apparently normal in the first 15 days of life, but when he refused to feed, he vomited and developed abdominal distension. After one week of treatment at a local hospital, the patient was referred to our center. On the eighth day of his illness, the patient had high fever, tachycardia, increasing abdominal distension, and increasing oxygen requirement. The physical examination revealed mild respiratory distress and a markedly distended, tender abdomen with no skin changes. The leukocyte count was 14,500/dL. The renal function tests were within normal limits. A diagnosis was made of peritonitis, possibly secondary to neonatal necrotizing enterocolitis (NNEC), and supportive treatment was started. On the 9th day, plain radiographs of the abdomen showed free air in the peritoneal cavity, dilated ileal loops, some air–fluid levels in the lower abdomen but no evidence of pneumatosis intestinalis. After placement of a left-sided flank drain, the baby’s respiration improved. However within 24 h, small bowel prolapsed through the drain site and the patient had to be taken up for emergency laparotomy. The peritoneal cavity was contaminated with fibrinopurulent debris especially in the right lower quadrant. The appendix, measuring 3.0 cm in length was perforated near the tip. There were no obvious signs of NNEC, Hirschsprung’s disease or other obvious anomalies in the intestine. An appendicectomy was performed and full-thickness biopsies taken from multiple sites from the large bowel. Histologic examination of the appendix showed that the lumen was filled with concretions with dense fibrinosuppurative infiltrate and transmural granulation at the site of perforation. Normal ganglia were found in all specimens of the large bowel. The postoperative period was uneventful. The child was thriving at six-month follow-up and his milestones were normal.


An 80-year-old white man with a medical history of hypertension presented to the emergency department of an outside hospital after sustaining a fall. He had begun to drag his left leg at least one month prior to presentation, and over the preceding 5 days he had started to use a walker. The left-sided weakness was accompanied by progressive dysphagia, which occurred initially with fast eating and later with a regular eating rate. He had lost 35 lbs over the preceding 3 months. He had visited the emergency center monthly in the preceding 3 months because of falls. The patient was started on aspirin 25 mg/extended-release dipyridamole (Aggrenox®) 200 mg PO daily for suspected transient ischemic attacks.
At the time of presentation at Tyler County Hospital on May 16, 2008, a computed tomography (CT) of the patient's head demonstrated multiple cerebrovascular accidents. Cerebral atrophy and old infarcts in the right internal capsule, right cerebral peduncle, right thalamus, and left frontal lobe were identified. The patient was transferred from Tyler County Hospital in Woodville, Texas, to Christus St. Elizabeth Hospital in Beaumont, Texas, for a higher level of care.
Upon physical examination by the physicians at Christus St. Elizabeth Hospital, the patient's blood pressure was 158/81 mmHg, his respiratory rate 12 breaths per minute, heart rate 90 beats per minute, and temperature 37°Celsius. The patient was described as a cachectic Caucasian man, alert, awake, and oriented to person, time, and place. His speech was fluent; comprehension, naming, and repetition were intact. Examination of the cranial nerves showed mild drooping of the left angle of the mouth; all other cranial nerves were intact. Left hemiparesis was noted; motor strength was 4+/5 on the left symmetrically in the upper and lower extremities and 5-/5 in the right extremities. Deep tendon reflexes were hyperactive, but no extensor plantar responses were recorded. On admission to Christus St. Elizabeth Hospital, complete blood count and chemistry levels were normal, except for blood urea nitrogen and serum creatinine levels of 37 mg/dL and 2.4 mg/dL, respectively, indicating acute or chronic nephropathy. There was no history of renal insufficiency.
On his second hospital day, a magnetic resonance imaging (MRI) study of the brain without contrast demonstrated ill-defined white matter edema involving the right thalamus and left paramidline frontal lobe (sparing the cortex) and extending into the right cerebral peduncle. The lesions appeared bright on fluid-attenuated inversion recovery (FLAIR) sequences and diffusion images.
The findings raised concern about an underlying malignancy. Clinical findings and imaging studies (CT of the chest/abdomen/pelvis) did not, however, demonstrate any suspicious lesions. Immunofixation analysis was negative for antineuronal nuclear antibodies type 1 (anti-Hu) and 2 (anti-Ri). Renal and transrectal ultrasonography were conducted on the third inpatient day, prompted by the patient's newly diagnosed renal insufficiency, without contributory findings. A spinal tap yielded clear, colorless cerebrospinal fluid (CSF) with the following component levels: glucose 55 mg/dL (serum level, 88 mg/dL) and protein 31 mg/dL. Gram staining and culture were negative. On cytospin preparations, 10 cells were collected: 70% normal lymphocytes and 30% monocytes. A specimen was sent for polymerase chain reaction (PCR) analysis for JC virus and herpes simplex virus; both studies were negative. The CSF was also negative for the presence of Borrelia burgdorferi antigens. Myelin basic protein was elevated (12.63 ng/mL, reference < 4 ng/mL); no oligoclonal bands were identified. An electroencephalogram demonstrated mild bifrontal slowing, more prominent on the left than the right. A carotid Doppler ultrasound was normal. Serum and urine protein electrophoreses were consistent with proteinuria of glomerular pattern but negative for the presence of paraprotein.
On day 11, the patient experienced deterioration of his neurologic symptoms. On neurologic examination, the patient was awake but drowsy and oriented to time, place, and person. Mild left facial nerve palsy was again noted. Motor strength was 5/5 on the right, whereas on the left there was progressive weakness; motor strength was 2/5 on the left hand, 4-/5 on the left biceps, and 4-/5 over the left leg. Deep tendon reflexes were 2+, and no extensor plantar responses were reported. Coordination was normal on the right side, whereas some ataxia was recorded on the left. MRI without contrast of the cervical, thoracic, and lumbar spine on day 12 demonstrated no major stenosis or neural impingement. MRI of the brain on day 13 demonstrated two areas of abnormal signals on diffusion-weighted imaging (left frontal lobe measuring 2.7 × 2.7 cm and right thalamus and basal ganglion measuring 1.6 × 1.2 cm). FLAIR images were positive in these areas and in several other small areas elsewhere. No significant change was identified when this study was compared with the one obtained on the second inpatient day.
A brain biopsy was considered, and the patient was transferred to Memorial Hermann Hospital, Houston, Texas, on June 6, 2008. On admission, his vital signs were within normal limits. He was described as a cachectic Caucasian man with a poor performance status. His neurologic examination was remarkable for left facial drooping and left-sided weakness (1/5 in the left upper and 2/5 in the left lower extremity). Deep tendon reflexes were hyperactive on the left side and normal on the right side. In addition, pinprick, hot and cold, light touch, and vibratory sensation and proprioception were decreased on the left side. Gait could not be assessed due to his left motor weakness. His Folstein Mini Mental State Examination score was 23/30; orientation was intact, whereas registration (1/3) and recollection (0/3) were severely affected.
A repeat MRI at Memorial Hermann Hospital showed two prominent areas of signal abnormality: one in the subcortical white matter of the left frontal lobe and one in the right posterior limb of the internal capsule and thalamus extending along the corticospinal tract as far down as the pons. The lesions were hypointense on T1-weighted images and hyperintense on T2-weighted images. The cortex was spared (figure ).
Twenty-five days after his initial presentation, the patient underwent image-guided open brain biopsy through a left frontal craniotomy. Hematoxylin and eosin staining of the biopsy tissue revealed foamy macrophages infiltrating the brain tissue. Reactive gliosis with bizarre astrocytes was also seen. Stains for herpes simplex virus, cytomegalovirus, adenovirus, and Toxoplasma gondii were negative. Immunohistochemical staining with anti-simian virus 40 antibody was positive. The latter antibody stains positive for human polyomaviruses (JC virus, BK virus; KI polyomavirus, WU polyomavirus, and Merkel cell polyomavirus[]) (figure ). PCR of the CSF for JCV conducted in the same laboratory as previously was positive, establishing the diagnosis. The sensitivity level of the PCR was not available in the report but generally the sensitivity is 10-3 to 10-4.
This unexpected finding spawned a thorough investigation for an occult immunocompromising disorder. Testing for the human immunodeficiency virus (HIV) was negative by enzyme immunoassay (twice) and PCR. The patient's CD4 count was 332 cells/μl (normal range, 410-1590 cells/μl) and his CD8 count was 485 cells/μl (normal range, 190-1140 cells/μl), as measured by flow cytometry. Testing for other infectious causes (toxoplasmosis, hepatitides, Cryptococcus, human T-lymphotropic virus I and II) was also negative. His persistent lymphopenia (absolute lymphocyte count throughout the hospital course ranged between 120 and 1077 cells/μl) raised the suspicion for a rheumatologic disease. Athough his antinuclear antibody titer was high (1:1280), he did not meet any clinical criteria for lupus erythematosus. Testing for anti-Ro and anti-La autoantibodies was positive, but the absence of xerostomia/xerophthalmia and a negative biopsy of minor salivary glands did not substantiate the diagnosis of Sjögren syndrome. The rest of the rheumatologic testing (anti-double-stranded DNA, cyclic citrullinated peptide, anti-smooth muscle and anti-RNP antibodies; rapid plasma reagin; complement 3 and 4 levels) was unrevealing. A bone marrow biopsy revealed variable cellularity (10-30%), with trilineage hematopoiesis and increased iron stores. There was no morphologic evidence of malignancy. Stains and cultures for acid-fast bacilli and fungi and cultures for cytomegalovirus were negative. The chromosomal analysis was negative as well.
Throughout the rest of his hospital stay, the patient's neurologic condition continued to deteriorate. His course was marked by an episode of altered mental status, progressive dementia, motor weakness, declining visual acuity, and worsening performance status. He was discharged to a skilled nursing facility closer to home, where he died 3.5 months after the diagnosis of PML.


This case report presents a 74-year-old Hispanic male patient with a known history of high-grade carcinoma of urinary bladder and prostatic cancer, who came to the GU clinic complaining of a painful lump in the left groin for 2 weeks. Physical examination revealed a round, firm, mildly tender mass in the left upper groin. The overlying skin was intact and non-erythematous. After obtaining consent from the patient, a FNA of the mass was performed by cytopathologists using a 23-gauze needle attached to a 20-ml syringe following the standard aspiration procedure. The preliminary diagnosis was “neoplastic cells with giant cells present, final pending cellblock preparation.” The final diagnosis was “metastatic osteoclast-rich undifferentiated urothelial carcinoma.”


A 54 -year-old female presented with a slow growing 6 cm X 5 cm painless mass in the left pre-auricular region. The patient had been operated on 10 years back for a swelling at the same site, which was histopathologically proven to be PA. FNA was performed now, which showed cohesive clusters of ductal cells and fragments of myxoid stroma with a fine fibrillar structure. An air-dried preparation showed metachromatic stroma interdigitating intimately with small tumor cells with uniform nuclei with scanty cytoplasm. But, at places, these cells were arranged around small hyaline globules in a pattern suggestive of possible adenoid cystic carcinoma (ACC) []. Repeat aspiration was performed to document the third element of PA. A diligent search revealed plasmacytoid cells. A cytodiagnosis of PA was made based on the above findings. Histologic examination revealed tumor showing epithelial and myoepithelial elements. Squamoid areas were seen at places []. At one place, close association of epithelial element showing ductal differentiation with cartilaginous tissue was also seen []. But, some areas showing cribriform arrangement of small tumor cells was also evident []. A careful search revealed neural invasion in one area []. Hence, a final histodiagnosis of ACC ex PA, was rendered.


A 72 -year-old male presented with complaints of dysphagia and hoarseness of voice since 3 months. On examination, a growth was seen at the base of the tongue. A computed tomography scan showed a 4 cm × 4 cm mass arising from the posterior third base of the tongue in the midline, which was extending into the surrounding tissues. FNA of the lesion was performed, which revealed a dominant pattern of uniform small blue cells and metachromatic stroma very typical of cribriform ACC []. According to the protocol practiced at our laboratory, repeat aspiration was performed to rule out the remote possibility of PA and more air-dried preparations were made, which showed few chunks of metachromatic stroma interdigitating intimately with small tumor cells. A careful search showed plasmacytoid cells too. Therefore, a cytodiagnosis of PA was made. Pathological examination of biopsy tissue showed an encapsulated tumor beneath the normal squamous epithelium with extensive ACC-like cribriform areas []. But, one of the areas showed a cartilaginous area associated with epithelial elements showing ductal differentiation []. Immunohistochemistry was negative for CD- 117(c-kit). Therefore, a diagnosis of PA with extensive ACC-like cribriform areas was finalized.


A 64 -year-old male presented with a 10 cm × 10 cm painless swelling in the left parotid region since 6 months. It was diagnosed as PA on FNA performed outside. FNA was repeated at our place, which showed cohesive round to spindle cells embedded in an eosinophillic matrix []. Few areas showed reduced intercellular cohesion, with individual cells escaping from the surface of fragments []. Palisading was evident at places. Individual cells showed wavy nuclei with one end blunt and other one tapered with filamentous elongated cytoplasm. Ductal elements could not be demonstrated even on repeated aspirations. On this basis, cytodiagnosis of spindle cell sarcoma, possibly malignant peripheral nerve sheath tumor (MPNST), was considered []. Histopathological examination of the excised tumor revealed features consistent with spindle cell sarcoma.


A 56-year-old male presented with painless swelling of the left parotid area measuring 5 cm × 4cm. FNA smears were sparsely cellular, showing a background of fibrillary matrix material. Occasional plasmacytoid cells were seen. Cytodiagnosis of PA was finalized. The excised mass was grossly multicystic []. The histologic examination revealed a cyst wall lined by a single layer of columnar epithelium and fibrous tissue around the mucinous pool with little inflammation. Ciliated metaplasia was evident at places []. Final diagnosis of mucocoele was rendered. Cytology smears were reviewed again. Misinterpreting wispy mucus for chondromyxoid stroma was the reason for misdiagnosis [].