A 30-year-old man with an extragonadal GCT of mediastinal origin complained of right homonymous hemianopia and was referred to Shinshu University Hospital for the treatment of the brain metastasis. About 4 months earlier, the patient had received induction chemotherapy with three courses of BEP (bleomycin, etoposide, and cisplatin) for multiple lung metastases in another hospital. The brain lesion had grown rapidly (), and serum tumor markers were elevated, including lactate dehydrogenase (LDH) at 447 U/l (normal, 118–236), αfetoprotein (AFP) at 480 ng/ml (normal ≦10), and human chorionic gonadotropin (HCG) at 629 IU/l (normal ≦1.0). The patient had immediate neurosurgery to remove the tumor. On pathology, the tumor was diagnosed as metastatic embryonal carcinoma and yolk sac tumor (). The patient also received whole brain radiation therapy (WBRT) (total 30 Gy/10 fractions) and adjuvant chemotherapy consisting of two courses of VIP therapy (etoposide, ifosfamide, and cisplatin). All tumor markers normalized. The residual lung tumors were resected, and no tumor remnant was seen on pathology.
One month after lung surgery, the patient developed lumbago and a gait disturbance. On magnetic resonance imaging (MRI), multiple leptomeningeal metastases with no brain recurrence were seen (). Salvage chemotherapy, consisting of combination irinotecan and nedaplatin therapy, was given. After four courses of therapy, the leptomeningeal lesions disappeared (). However, the serum HCG elevated again, and recurrent cerebral ventricular and meningeal lesions appeared within a short period of time. Despite the use of additional salvage chemotherapy involving three courses of TIN therapy (paclitaxel, ifosfamide, and nedaplatin), in combination with the peripheral blood stem cell transplantation, the patient died due to disease progression 12 months after the initial brain surgery.


The patient was a right-handed Native Chinese, male and 80 years old, with 16 years of education. He had a stroke with a sudden onset of a blurred vision and light numbness over his left limbs in July of 2003. At that time he also complained about reading difficulties. Common therapies for stroke patients were administered following the first month of his stroke onset. Thereafter, he stayed in a sanitarium and regularly took oral medicines. In February of 2007, he was admitted to the 1st affiliated hospital of Nanjing Medical University and complained of reading problem for about three years post-onset. Neurological examination revealed a right homonyous hemianopsia. The MRIs (January, 2004) showed that he had lesions involving the left occipitotemporal cortex and the left splenium of the corpus callosum (for details, see Lesion Analysis below). Neuropsychological assessments showed that the patient was unable to identify the left component of Chinese characters, a symptom similar to the cases reported by Binder et al. in alphabetic readers (the authors labeled this symptom as left hemiparalexia). The patient often misread Chinese character as another one that shares the same right component as the target. For example, he misread (/deng 1/, lamp) as (/da 3/, beat), and (/zhi 4/, order) as (/tie 3/, iron). Visual perimetry confirmed a right homonymous hemianopia but with 1.5° of foveal sparing. The Line Bisection Test and Albert Cancellation Test showed no sign of visual hemineglect. According to the assessments with the Chinese version of Western Aphasia Battery, the patient was not aphasic; his Aphasia Quotient was 97.8 (cutoff: 93.8). He scored 27 on mini-mental state examination (MMSE, cutoff: 24).
Two healthy men (both were 80 years old and with approximately the same educational experience with KY) served as normal controls in the behavioral experiments.
The study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University. The patient and the normal controls gave written informed consent prior to their participation in the study according to the Declaration of Helsinki, and they also provided written informed consent (as outlined in the PLoS consent form) to publication of their case details.


An ultrasound scan was performed at 8th gestational week in a 28-year-old primigravida which revealed an 8 × 6 × 7 cm smooth-walled, mixed echogenic mass with irregular inner contents in the left ovary () and a viable singleton intrauterine pregnancy. A repeat scan four weeks later, showed an increase in the size of the mass. Its largest diameter was 9.85 cm and three-dimensional Power Doppler with the use of minimum-maximum mode revealed a hyperechoic solid part and speckled appearance of sebaceous contents suggesting a dermoid cyst (). Power Doppler didnot detect any vascularization neither at the periphery nor in the central region of the cyst. A magnetic resonance at 15th gestational week imaging MRI showed signal intensity consistent with fat allowing characterization of the mass as a mature cystic teratoma (). Tumor marker Ca125 was negative (31 u/mL). Differential diagnosis included serous and mucinous cystadenoma, endometrioma, and malignant tumors such as mucinous cystadenocarcinoma, serous cystadenocarcinoma, and embryonal carcinoma. Following extensive discussion about the risks and benefits the patient opted for surgical removal. It was decided to proceed with exploratory laparotomy at 16 weeks gestation under general anesthesia with resection of the left adnexal mass and preservation of as much ovarian tissue as possible. The fetus tolerated the operation well. The final pathological diagnosis was “mature cystic teratoma.”


A 57-year-old woman, with a history of hypertension, was admitted to the emergency department of a rural non-PCI-capable Hospital due to an atypical, non-compressing, non-excruciating chest pain of recent origin (30 minutes) with radiation to the back. The patient was hemodynamically stable, with no peripheral pulse deficit. Auscultation of the heart revealed a 2/6 systolic murmur at the right base and apex and an early diastolic murmur at the right base without pericardial friction. The electrocardiogram (ECG) (Figure ) was compatible with the diagnosis of a STEMI of the inferior wall. The doctor in charge decided to administer thrombolytic treatment with tenecteplase (TNK) (Metalyse®) without further delay. The patient's symptoms were partially relieved, while the pre-existing ST elevation did not seem to be completely normalized in the following 60 minutes. For this reason, she was referred to our hospital for rescue angioplasty []. When the patient arrived had a remission both of the initial thoracic pain and of ST-elevation in the ECG (Figure ), remaining hemodynamically stable without obvious perceivable peripheral artery pulse deficit, but was clearly uncomfortable and she was complaining for a diffuse abdominal pain without any sign of peritoneal irritation. In addition, she was anuric during the whole time of her transport, namely about 3 hours. Blood sample analysis showed: Hct 37%, WBC 14,600/μL, PMN 86%, Ur 70 mg/dl, Cr 1.3 mg/dl, SGOT 63 U/L, CPK 483 U/L, TNI 2.1 ng/ml. A bedside chest x-ray was not diagnostic, while a quick bedside transthoracic echocardiography (TTE) revealed severe hypokinesia of the posterior and the inferior wall and a dilated aorta with a high suspicion of an intimal dissection flap (Figure ). Color flow Doppler showed moderate aortic and mild mitral regurgitation (Figure ). AAD complicated with an inferior AMI was highly suspected. The following Multidetector Computed Tomography Angiography (MDCTA) confirmed the extended dissection from the ascending aorta to the iliac arteries (Figure and ). Cardiac surgeons were immediately informed and an emergent replacement of the aortic root and ascending aorta was decided. The patient was transported in the operating room in a critical state. The right axillary artery was cannulated before sternotomy. Then, a median sternotomy was performed and the pericardium was opened. A dilated ascending aorta, clots in the pericardium, dilatation of the right cardiac chambers due to infarction and a sub-epicardial hematoma along the right coronary artery in the atrio-ventricular groove were found. The right atrium was cannulated, the distal aorta was cross clamped and cold blood-crystalloid (4/1) cardioplegia was administrated initially retrograde via the coronary sinus and then anterograde via the left main coronary artery. The procedure took place under systematic hypothermia (25°C).. After the opening of the aorta the diagnosis of a type A aortic dissection was confirmed with the implication of the right coronary artery for its first 5 mm (Figure ). A rare finding was the real transection-disruption of the right coronary artery; the cause of the acute myocardial infarction (Figure ). A Bentall procedure was performed with the implantation of a valved-graft. A coronary artery bypass grafting with a saphenous vein graft anastomosed in the right coronary artery at the level of the crux was also done. The patient was rewarmed and weaned successfully from the cardiopulmonary bypass. Unfortunately, the patient died 48 hours after the operation because of multiple organ failure.


A 70-year-old Caucasian man with a history of right hemi-colectomy one year earlier (due to adenocarcinoma of the right colon) was admitted to our hospital with abdominal pain and unexplained weight loss. His laboratory values, X-rays, and computed tomography (CT) were not indicative of any distinctive pathology. Therefore, the general surgeons decided to proceed with an exploratory laparotomy, based on the patient's recent hemi-colectomy and the high clinical suspicion of a metachronous metastatic insult of the pancreas.
A metastatic tumor was identified in the uncinate process of the pancreas. During the dissection and preparation, the SMV involvement was identified on its anterior surface superiorly to the confluence of the middle colic vein at the level of the transverse mesocolon. No involvement of the superior mesenteric artery was identified. When it was decided that the tumor could be resected with a sufficient macroscopic margin, a duodenopancreatectomy was performed. Sufficient resection with healthy margins was documented by intra-operative histology. The tumor adhered only to the SMV, with the latter caudally divided at the point where the SMV emerged.
Accordingly, a right mid-thigh incision was performed, and an adequate SFV segment up to the junction with the profunda femoris vein was harvested. The duration from the vein preparation and harvest to skin closure was 15 to 20 minutes. During the venous reconstruction, a solution of 5000 U of heparin was delivered locally through the SMV. No valvulotomy was performed. The pancreatic head resection was immediately followed by the construction of a proximal anastomosis between a non-reversed SFV segment 3 cm to 4 cm in length and the central stump of the SMV in an end-to-end fashion (Figure ). The peripheral anastomosis was created in a similar fashion. The duration of the creation of each anastomosis was 10 minutes. Intra-operatively, the patency of the reconstruction was confirmed by a continuous wave Doppler signal. The operation was completed with the creation of pancreatojejunostomy and a new ileotransversostomy.
The patient's post-operative instructions included the administration of a prophylactic dose of low-molecular-weight heparin, limb elevation, and application of compression stockings (class II). During the immediate post-operative and follow-up phase (six months), only mild edema of the leg was marked. The SFV inter-position graft showed good patency (Figure ) on color duplex ultrasonography.


We describe the case of a 40-year-old Berber man, originally from Morocco, who presented to our emergency room with self-inflicted testicular injuries. His medical history was marked by tuberculosis of the lung. His psychiatric history dated from 32 years of age, when he was treated due to alcohol and cannabis abuse. Many medical treatments and psychotherapy techniques were proposed for detoxification but they failed because of his poor compliance with therapy. At the time of admission, he had not consumed alcohol for several months, but he reported using cannabis, particularly a few hours before the act. No childhood trauma, personality or even borderline personality disorders (assessed as a lifetime diagnosis) were diagnosed. He reported no psychiatric or medical diseases among close relatives. He presented to our emergency room eight hours later with unilateral scrotal laceration (Figure ) and externalization of both testis (Figure ) using his long fingersnails (Figure ). This was associated with hemodynamic shock. Our patient underwent vascular filling and blood transfusion to achieve stabilization of his state. Upon examination of our patient's perineum, one wound was visible on the top of his right hemiscrotum measuring 4 cm with ecchymosis extended from his scrotum to the inguinal region. There was increase in scrotal volume due to the hematoma, with no active hemorrhage found (Figure ). Our patient was interviewed by our psychiatrist, who found appropriate orientation and good contact. His speech was normal, with emotional indifference. His mood was mildly depressed, following the events that led to his admission. He reported no suicidal ideation, suicidal behavior, or desire for self-injury, and had no psychotic ideation. Computed tomography with intravenous contrast was performed to localize his spermatic cord, which was fortunately not retracted into the inguinal or retroperitoneal region. After stabilization of his psychiatric state with a benzodiazepine drug (diazepam: 30 drops a day), our patient was admitted to the operating room and haemostasis was easily achieved after ligation of both spermatic cords (Figure ). The dartos and skin were then closed in two layers, with a good postoperative result. Our patient was discharged after his second day to a psychiatric department for supplement care and for substitution therapy for his cannabis use.


A 5.5-month-old female Brown Swiss calf was referred to our clinic because of a four-week history of prolonged periods of recumbency, difficulty in rising and a stiff gait in the hind limbs. There was progressive deterioration in the calf's condition during the first two weeks of the disease followed by stationary clinical signs up to the time of referral. The appetite was normal despite intermittent fever of up to 40°C. The calf had been treated with ketoprofen (Dolovet®, Dr. E. Graeub AG, Switzerland) for several days on two occasions.
At the time of admission to the large animal clinic, the calf was very quiet and its appetite was moderately reduced, but it presented with a normal mental status. The calf spent the majority of time lying in sternal recumbency when placed in a crate. When assisted, the calf stood with its hind limbs drawn forward under the abdomen, resulting in kyphosis of the back. It was reluctant to move and had a stiff and slightly ataxic gait with a shortened stride of the hind limbs. The musculature of the back and hind limbs was moderately atrophied.
Physical examination revealed abnormalities restricted to the musculoskeletal system. Palpation of the front and hind limbs, the pelvic region and tail, and cervical and thoracic vertebrae produced no abnormal findings, whereas palpation of the lumbosacral region elicited severe pain. Skin sensitivity of the entire body was normal. On transrectal examination, slight soft tissue swelling was palpated at the ventral aspect of the lumbosacral region.
Haematological analysis revealed leukocytosis (14.1 × 103 leukocytes/μL; normal, 4.0 to 8.8 × 103 cells/μL) and a mild increase in the activity of creatinine kinase (192 U/L; normal, 70 to 169 U/L). Cerebrospinal fluid collected via the lumbosacral space was within normal limits.
For radiographic examination, the calf was sedated with 0.2 mg/kg xylazine (Xylazin Streuli, Streuli Pharma AG, Switzerland) administered intramuscularly and anaesthetised using 2 mg/kg ketamine (Narketan® 10, Vétoquinol AG, Switzerland) and 0.02 mg/kg diazepam (Valium®, Roche Pharma AG, Switzerland) administered intravenously. The general anaesthesia allowed taking not only a laterolateral but also a ventrodorsal radiographic view. The radiographs showed narrowing of the intervertebral space between the 6th lumbar (L6) and the first sacral vertebra (S1). Lysis of the dorsal parts of the endplates of L6 and S1 with sclerosis of the adjacent bone could be seen (Figure ). According to these findings, a diagnosis of lumbosacral discospondylitis was made.
On transrectal ultrasonographic examination an irregular hyperechoic area at the ventral aspect of the junction of L6 and S1 could be detected. The hyperechoic specks were surrounded by a hypoechoic fluid accumulation and the ventral longitudinal ligament was displaced ventrally. These findings confirmed the radiological diagnosis.
Treatment was started because neurologic deficits were mild and the abnormalities of the stance could be explained by pain originating from osteolysis and soft tissue inflammation. The calf was kept in a small crate and was given 2 mg/kg cefquinom (Cobactan® 2.5%, Veterinaria AG, Switzerland) intramuscularly once daily for six weeks. In addition, during the first week the calf also received 3 mg/kg ketoprofen (Rifen 10%, Streuli Pharma AG, Switzerland) intravenously once daily, and during the first two weeks 4 mg/kg gentamicin (Vetagent®, Veterinaria AG, Switzerland) intravenously once daily.
As to be expected, clinical sings concerning the calf's gait and the kyphosis did not change significantly during the first four weeks of treatment. The calf spent most of the time lying and showed signs of pain when rising. The general condition and the calf's appetite improved slowly. The temperature fluctuated between 38.8°C and 39.4°C. After four weeks of treatment, the leukocyte count had decreased to 11.3 × 103/μL.
Radiographs taken of the standing calf after two weeks of treatment showed increased lysis of the endplates and adjacent bodies of L6 and S1 with further widening of the intervertebral space (Figure ). After four weeks of treatment, the size of the lytic area was unchanged and the margins of the adjacent endplate sclerosis had become more defined (Figure ). This became even more pronounced after six weeks of treatment.
Transrectal ultrasonographic examinations were carried out every ten days. Three weeks after beginning of treatment, the hyperechoic reactions became more organised and the fluid accumulation decreased, but the ventral longitudinal ligament was still displaced ventrally (Figure ).
Four weeks after the start of treatment, the calf began to rise on its own more frequently and with less effort, and the appetite returned to normal. Palpation of the lumbosacral area of the back still elicited pain but its severity was markedly reduced. When walking the calf for several meters in front of its crate, it moved more freely and the gait normalised. However, the calf still stood with the hind legs drawn under the body.
The calf was discharged after six weeks of treatment with the recommendation that exercise be limited to daily hand-walking for five minutes. The calf was kept in a small crate for another four months.
Clinical, radiographic and ultrasonographic examinations were repeated 3.5 months after discharge from the clinic. The general condition and demeanour were normal and the musculature of the back and hind limbs as well as the gait were the same as in other calves of the same age. The hind limbs were no longer drawn forward under the body and the palpation of the lumbosacral region of the back was not painful. During transrectal examination of the lumbosacral area, a discrete bony protuberance, 3 cm long and extending 1 cm ventrally, was felt at the junction between L6 and S1. Laterolateral radiographic views showed further remodelling of the vertebral endplates and spondylosis between L6 and S1. There was a small step in the vertebral canal (Figure ). The spondylosis was also seen on ultrasonograms, the fluid pocket in the surrounding tissues had disappeared.
The animal was discharged and kept on alpine pasture during the summer. According to the owner, the heifer was without any problems and was pregnant 1 year after the last examination.
Discospondylitis may occur via haematogenous spread of bacteria from primary infections of the umbilicus, lungs, urinary bladder or other organs [,,,,]. It may also occur secondary to back trauma [] or iatrogenic infections caused by epidural or paravertebral anaesthesia []. However, none of these risk factors could be identified in the calf described in this report.
Percutaneous aspiration of the intervertebral space for bacterial isolation was omitted because of its potential risks. Retrospectively, it could have been performed under fluoroscopic or ultrasonographic guidance while the calf was in general anaesthesia []. A bacterial blood culture - provided it had been positive - would have added useful etiological and therapeutic information and possibly would have allowed a specific and potentially cheaper antimicrobial treatment. A variety of organisms including Gram-negative and Gram-positive as well as aerobic and anaerobic bacteria have been associated with discospondylitis in animals. In a study of cattle suffering from cervical discospondylitis, Aspergillus fumigatus, Bacteroides nodosus, Clostridium perfringens, α-haemolytic streptococci and Staphylococcus epidermidis have been isolated from the affected vertebrae []. The calf did not have a history of urogenital tract infection nor did it show any signs of an infection. Whenever there is a suspicion of urinary tract infection in an animal with discospondylitis, a bacterial urinary culture should be performed prior to antimicrobial treatment [].
Aspirated or swallowed foreign bodies, such as grass awns, have been identified as a cause of discospondylitis in dogs. The foreign bodies migrate through the body and may reach an intervertebral space causing infection [,,]. A foreign body could not be ruled out as the cause of discospondylitis in this case, but it appeared unlikely.
Different animal species appear to have different predilection sites for discospondylitis. In cattle, the location may be cervical, thoracic or lumbosacral [-]. In dogs, the greater mobility of the lumbosacral space compared with other intervertebral spaces has been suggested as the cause for a predilection of disease at this site [,].
Animals with advanced lumbosacral discospondylitis often remain in a dog-sitting position for extended periods of time during attempts to rise. The further the changes of the lumbosacral discospondylitis progress, the more neurological deficits (e.g. loss of sensitivity and proprioception, posterior paresis or paralysis, cauda equina syndrome) and muscle atrophy [,,,] may occur. In our case, differential diagnoses such as meningitis, vertebral fracture or luxation, vertebral anomaly, spinal abscess, oedema, haemorrhage or neoplasia in the vertebral canal were less likely based on clinical, radiographic and cerebrospinal fluid examinations.
Advanced diagnostic techniques such as myelography, computed tomography, magnetic resonance imaging and scintigraphy are rarely used in cattle for economic reasons, because of the large body size of the patients and because of food safety considerations in the case of bone scintigraphy. They are described in literature in different species [,,,,] and may be very helpful in detecting multiple spinal lesions []. In the present case, computed tomography, although possible, was not an option because of financial restraints. Transrectal ultrasonography proved to be a useful ancillary diagnostic method, which also allowed to identify bony proliferation and involvement of adjacent soft tissues as well as to monitor healing []. Radiographic diagnosis was possible in the present heifer due to the small body size and the classical appearance of the radiographic findings.
In dogs, radiographic signs of discospondylitis are usually not apparent until two to three weeks after the onset of clinical signs []. Similar to the healing process described for dogs with discospondylitis [,], there was progressive osteolysis of the involved vertebrae after the start of treatment despite improvement of clinical signs in our calf. Sclerosis in the periphery of lytic lesions and bridging between the two affected vertebrae has also been seen during the healing process in cattle, dogs and horses with discospondylitis [-,,]. Complete fusion of the two affected vertebrae may occur at the end of the healing process [].
We assumed that the calf in this report was referred to us at a relatively early stage of the disease, which may have contributed to the successful outcome. Medical treatment is recommended in affected dogs that do not have clinical or radiographic signs of instability of the vertebral column or compression of the spinal cord. If these signs occur, decompression, curettage and/or surgical stabilisation are recommended in small animals [,,,]. At this stage of the disease, the prognosis is guarded to poor in horses and cattle [,,].
In dogs and horses, the administration of broad-spectrum bactericidal antibiotics for at least six weeks is considered the treatment of choice [,,,,]. The prognosis is improved considerably with early and long-term treatment.


A 59-year-old man was referred to the general surgery department of our hospital for a one-month history of progressive dysphagia for solids, which was not associated with malnutrition or significant weight loss. The patient had recently undergone esophagogastroduodenoscopy in another hospital, which revealed a bleeding, ulcerative lesion in the middle third of the esophagus, but no biopsy had been collected. The medical past history included COPD diagnosed in 1999 and a myocardial infarction in 2002. The patient had smoked approximately 25 cigarettes per day for several years.
Physical examination was unremarkable. Computed tomography (CT) of the chest and abdomen revealed stenosis involving a 5-cm segment of the middle third of the esophagus with no other lesions in the thoracic or abdominal organs. Barium studies disclosed a swelling in the esophageal wall 7 cm above the cardia with an ulcerative pattern, which reduced the diameter of the lumen to 5 mm. An endoscopic biopsy of the oesophageal mass demonstrated poorly differentiated (G3) squamous cell carcinoma.
Mid-distal esophagectomy was performed with oesophagogastric anastomosis and gastric tube reconstruction. Pathological examination of the surgical specimen confirmed the biopsy diagnosis of poorly differentiated (G3) SCC. The tumor, which measured 3 cm of length, had infiltrated the oesophageal wall and the surrounding paraesophageal fat. Surgical margins were tumor-free, as the seven perigastric limph-nodes dissected (pT3 N0). The postoperative period was quite unremarkable, and a contrast enhanced x-ray obtained on the 9th POD showed normal esophageal and gastric transit. On the 14th POD, the patient was discharged with an oncology referral for routine medical follow-up.
Nine months after the operation, CT and esophagogastroduodenoscopy were repeated. The imaging study revealed mild splenomegaly with multiple nonspecific nodules within the organ (Figure ). The patient was virtually asymptomatic with the exception of a vague sensation of mild discomfort in the left upper quadrant of the abdomen. FNAC of the spleen revealed a pattern of numerous inflammatory cells admixed with large cells displaying immunohistochemical positivity for several cytokeratins (Figure ). The specimen was Gram stain-negative. A bone-marrow biopsy was negative for metastatic involvement. The diagnosis was isolated metastases of the spleen with inflammatory and necrotic alterations.
The patient was referred to our centre for splenectomy, which was performed as a routine procedure to role out, also, a spontaneous rupture of the spleen. On 12th December 2007, the patient had transabdominal total splenectomy with splenic and celiac artery lymph node dissection.
The postoperative course was uneventful. On the 7th postoperative day, Doppler ultrasonography revealed portal-tree patency with no signs of thrombosis. Ten days later, the patient was discharged with a stable platelet count (780,000/mm3), Hb 10.9 g/dL, and a WBC count of 16,500/mm3.
Pathological examination of the spleen described multiple nodules containing medium to large-sized cells, some of which were keratinized. The nodules were mostly solid with areas of central necrosis (Figure ). The findings were consistent with metastases of SCC. Thereafter, the patient was referred to the oncology department of our hospital, where he received two 3-day cycles (separated by a 3-week interval) of systemic chemotherapy based on 5-fluorouracil (800 mg/day IV) and cisplatin (20 mg/day). Three months after the splenectomy, multiple liver metastases were seen on the CT scan, and cutaneous metastases were also present. The patient died 9 months later.


A 74-year-old man was admitted to our hospital complaining of irritant cough, shortness of breath, and intermittent fever for 3 months and had also recurrent episodes of pneumonia. Physical examination of the chest revealed dullness on percussion and decreased respiratory sounds in the right lung. Chest radiography showed total atelectasis of the right lung, and MSCT scan demonstrated an endoluminal mass in the right main bronchus, right upper lobe bronchus, and bronchus intermedius. The CT value of lesion ranged from −100 to −114 Hu, and no calcification was found within the tumor (Figures , , and ). There was also a minimal right pleural effusion. A well-circumscribed polypoid mass obstructing the right main bronchus was seen by fiberoptic bronchoscopy (), and biopsy was performed simultaneously. Biopsy specimens showed only acute inflammatory reactions associated with squamous metaplasia. Because of indeterminate biopsy specimen and total atelectasis complicated with postobstructive pneumonia, exploratory thoracotomy was done.
After opening the right main bronchus, an encapsulated yellow mass within the right main bronchus extending into right upper lobe and intermediate bronchus was seen, and the stalk of mass was found at the opening of right upper lobe. The mass measuring 1.5 cm × 4.5 cm was successfully excised. On microscopic examination, the tumor was made of groups of mature adipocytes. The postoperative course was uneventful, and the patient was discharged from hospital at 10th day and had been well at 24-month followup.


A 44-year-old woman was admitted to our hospital complaining of irritating cough for 1 month. All the laboratory values were in the normal range. She had normal chest radiographic findings, so MSCT scan was necessary for further investigation. MSCT revealed a low-attenuation endobronchial mass with CT value of −118 HU and 18 mm × 4 mm in size, obstructing the right inferior basal bronchus. Postobstructive partial atelectasis of the right lower lobe, and a minimal pleural effusion was also found (Figures , , and ). Flexible bronchoscopy revealed that a yellow smooth adipose lesion occluded right inferior lobe basal trunk bronchus, and the distal end of the lesion was invisible (). The result of biopsy was proved to be fatty tissue. The resection of right inferior lobe was done due to irreversible lung damage. The pathologic examination for endoluminal low-attenuation mass was definitely diagnosed as an endobronchial lipoma, and purulent infection was seen in the distal lung parenchyma. The patient had an uneventful postoperative period and was in good health at the followup of 2 years.


A 19-year-old Tanzanian primigravida at 32 weeks of gestation sought care at a tertiary hospital antenatal clinic. She presented with concerns of an insidious but progressive onset of an unusual darkening of her abdominal skin and both breasts. The darkening was not associated with itching or irritation of the skin.
She booked for antenatal care at a peripheral clinic and her progress had been unremarkable except for this unusual onset of abnormal skin color. She had no previous history of allergies or family history of skin condition. She was not on any medication except for prescribed iron and folic acid tablets given during antenatal consultations. Her past medical history was unremarkable with no history suggestive of goiter or hyperthyroidism.
On physical examination, her general condition was fair. She was not pale and had no lower limb edema. She had a pulse rate of 70 beats per minute that was regular. Her blood pressure was 120/70 mmHg. Her abdomen was distended with a uterine fundus of 34 weeks. A linea nigra was clearly seen, but in addition almost the entire abdominal skin had dark colored diffuse deep hyperpigmentation, extending from both iliac fossae to involve both breasts (nipples and areolae) to about 2-3 cm beyond the areolae circumferentially (Figure ). She had a fetus in longitudinal lie, cephalic presentation with a normal fetal heart rate of 140 beats per minute. Other system examination findings were unremarkable.
The impression at this stage was exaggerated pigmentation of pregnancy. No medications were prescribed, but she was reassured that the condition should have no effect on her pregnancy and its outcome. She continued attending antenatal care regularly. She had spontaneous onset of labor and normal delivery of a baby girl weighing 3200 g with an Apgar score of 9 and 10 at the first and fifth minutes respectively at 38 weeks gestation.
Our patient did not return for follow-up during her postpartum period. She was contacted by phone three months after delivery and she reported that her skin condition had not resolved. We lost contact with her thereafter.


A 67-year-old Caucasian woman with an unremarkable medical and breast history was referred to our breast unit with a screen-detected right breast mass. Mammography had revealed a fairly well-circumscribed 2 cm lesion located deep and in close proximity to the nipple and was graded as M3 on the Breast Imaging Reporting and Data System scale. Her physical examination and ultrasound showed no abnormalities. A subsequent diagnostic biopsy revealed an infiltrating ductal carcinoma with an adenoid cystic component. The patient was treated with simple mastectomy and sentinel node biopsy. The histologic examination revealed a lesion of 1.7 cm maximum diameter with mixed infiltrating NOS ductal carcinoma and ACC characteristics. The four sentinel nodes were all free of cancer. She had a good post-operative course and remained well with no evidence of recurrence 24 months later.
The tumor was whitish tan and was ill defined in appearance and firm in consistency. No nipple or skin involvement was present. Both the nuclear grade of the lesion and the Bloom-Richardson grade were two based on the overall appearance of the tumor. The lymph nodes were negative. The tumor was staged as T1N0M0 and was estrogen receptor (ER)- and progesterone receptor (PR)-negative. The proliferative activity was low as measured by the Ki-67 labeling method (12%). Immunohistochemically, overexpression of the proto-oncogene HER2/neu was found in 15% of the carcinomatous cells. In fluorescence in situ hybridization analysis, which was performed at a later stage, no protein amplification was ascertained.
Two histological patterns were blending into each other without a clear-cut boundary between them (Figure ). The dominant pattern, comprising more than 70%, was an ordinary, moderately differentiated ductal carcinoma NOS. It consisted of tubule islands and cribiform structures with epithelial cells exhibiting a high nuclear-to-cytoplasmic ratio, dark nuclear chromatin, and inconspicuous nucleoli. The mitotic index was low (< 2/10 hematopoietic tissue).
The rest of the histological pattern was limited and mainly consisted of well-defined nests and pseudo-glandular structures occasionally filled with homogeneous basophilic (periodic acid-Schiff stain-positive) material. Interestingly, the neoplasmic nests contained predominantly basaloid cells with sparse cytoplasm coexisting with epithelial cells with more abundant eosinophilic cytoplasm (Figures and ).


A 69-year-old woman who was diagnosed with a lung tumor was admitted to our hospital. The greatest diameter of the tumor was 12 mm, and it had increased over several months. Bronchoscopy did not yield a definitive diagnosis, so Thoracoscopic surgery for diagnosis and treatment was scheduled. Past medical history included mitral valve insufficiency treated with oral medication. Family history was unremarkable, and she had never been a smoker. The physical examination was normal. The results of the laboratory investigations, including a complete blood count, liver and renal function tests, coagulation studies and the serum cancer antigens, were within the normal range.
Pulmonary function tests showed that vital capacity (VC) was 2590 ml, percentage of predicted VC was 109.3%, forced expiratory volume in 1 s (FEV1) was 2120 ml and FEV percentage in 1 s was 81.9%. Chest computed tomography demonstrated a partilally serrated border 12-mm-diameter pulmonary nodule in anterior basal segment of the right lower lobe (RS8)(Figure ). To guide the surgeons in simulating the operation, preoperative three-dimensional (3D)-CT was performed. Using 3D volume rendering, a solid image was constructed from 0.65-mm data slices of the contrast-enhanced CT images. A colored map was used to highlight the blood vessels of the lung. The 3D rendered images were magnified, de-magnified, and rotated to examine these measurements (Figures , ). To secure an adequate margin from the tumor, preoperative needle marking was performed under CT guidance on the day before surgery. The needle marker (Guiding Marker System; Hakko Medical Products, Tokyo, Japan) was put around the tumor [].
VATS needle biopsy was then planned, with subsequent total thoracoscopic segmentectomy of anterior basal segment of the right lower lobe (RS8) if the diagnosis was malignancy. Our indication criteria for segmentectomy are clinical T1aN0M0 peripheral NSCLC. The segments for resection are determined based on tumor size and peripheral location in order to critically secure a segmental margin free of tumor cells. Segmentectomy is converted to lobectomy when the intraoperative node sampling shows node involvement. Under general anesthesia with single lung ventilation and thoracic epidural anesthesia, the patient was placed in the left decubitus position. The surgeon was positioned on the anterior side of the patient. Two thoracoports were placed in the sixth intercostal space (ICS) at the anterior axillary line and the seventh ICS at the posterior axillary line. The anterolateral 30-mm access port was placed in the fourth ICS. A Lap Protector Mini (Hakko Medical Co., Tokyo, Japan) was placed on the site of the access port. A 30-degree scope was used. The interlobular fissure was almost complete. Frozen section examination of the needle biopsy specimen confirmed the diagnosis of BAC, and VATS segmentectomy of RS8 with node dissection was performed. First, the intermediate pulmonary artery, the middle lobe pulmonary artery, A6, A7, and A8 were exposed in the interlobar site. Proximal A8 was ligated with 2-0 silk, and distal A8 was sealed and then divided with the VSS. The intersegmental plane was identified using the intersegmental veins as landmarks and the demarcation between the resected (inflated) and preserved (collapsed) lungs. This status of the lung was induced by the following three steps: temporarily re-inflating the whole lung, ligating the resected segmental bronchus (B8), and deflating preserved lung. After making the demarcation, ligated B8 was then stapled and divided with an endoscopic stapler. The intersegmental plane of the parenchyma was divided by electrocautery by 70 Watts from the pleural surface of the lung[,]. VSS was also used to dissect along the intersegmental veins. The intersegmental veins (V8a and V8b) that demark S8 and lateral basal segment (S9) were resected with RS8 after sealing and division with the VSS, while the intersegmental vein (V7) that demarks medial basal segment (S7) and S8 was preserved (Figure ). Finally, air leaks were repaired with several 4-0 PDS horizontal mattress sutures with absorbable pledgets (Medifit Felt, JMS Co., Hiroshima, Japan). Absorbable polyglycol acid sheets (NEOVEIL® sheet, Gunze, Ayabe, Japan) were applied to the intersegmental plane with fibrin glue to obviate further air leaks.
The operative time was 221 min, and blood loss was 30 ml. The chest drainage tube was removed on postoperative day 2. The patient was discharged from hospital on postoperative day 5 without any complications. Postoperative histopathological examination revealed that the tumor was T1aN0M0 BAC. The minimal distance between the surgical margin and the tumor edge was 15 mm, and the margin was free of malignancy.


An 81-year-old French man was admitted to our hospital for erysipelas of the right leg. The patient had suddenly developed this infection despite antibiotic treatment combining clindamycin and metronidazole for a chronic wound infection of the same leg with previous documentation of clindamycin-susceptible Staphylococcus aureus, Klebsiella oxytoca, Serratia marcescens, and Corynebacterium spp., but no anaerobe. His leukocyte count was 10.32 g/L with 72% polymorphonuclear cells, 18% lymphocytes, and 8% monocytes. Inflammatory syndrome was apparent with a C-reactive protein level of 119 mmol/L and a fibrinogen level of 8.6 g/L. Antibodies against streptolysin O and streptococcal DNase were not detectable in the patient's serum. Direct microscopic examination of a skin biopsy showed numerous polymorphonuclear cells and no bacteria. Culture remained sterile after a five-day inoculation on Columbia agar with 5% sheep blood (bioMérieux, Marcy-l'Etoile, France), Chocolate agar with PolyViteX agar (bioMérieux) and MacConkey agar (bioMérieux) at 37°C in 5% CO2. Three days later a subcutaneous swab yielded numerous polymorphonuclear cells, and semi-quantitative direct examination indicated an average of 15 to 30 organisms per microscopic field composed of an equal proportion of Gram-positive cocci, Gram-negative cocci, and Gram-positive rods. Culture under the same conditions described above yielded small, gray colonies after 48-hour inoculation on Columbia agar with 5% sheep blood. The Gram-positive rod was oxidase-negative and catalase-positive. Inoculation of an API Coryne system identification strip (bioMérieux), performed twice, yielded no reaction and thus no identifying profile. No other organism was isolated from this specimen. Antibiotic susceptibility assessed on Mueller-Hinton agar (bioMérieux) using the disc method (Mast Diagnostics, Amiens, France) and break points as previously reported [] yielded susceptibility to amoxicillin (minimum inhibitory concentration (MIC) ≤ 2 mg/L), rifampin (MIC ≤ 4 mg/L), doxycycline (MIC ≤ 4 mg/L), and vancomycin (MIC ≤ 4 mg/L) and resistance to co-trimoxazole, clindamycin, and metronidazole. The latter three antibiotics yielded no growth inhibition zone. To identify the isolate, we amplified (by polymerase chain reaction) and sequenced 1431 bases of the 16S rRNA gene [GenBank:] []. This sequence exhibited 99% sequence similarity with uncultured Pseudoclavibacter sp. [GenBank:] and 99% sequence similarity with uncultured Pseudoclavibacter sp. [GenBank:]. The third hit exhibited only 97% sequence similarity with Zimmermannella bifida [GenBank:]. The peptide profile of the isolate was determined by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry as previously described [] (Figure ). MALDI-TOF-based identification was achieved by comparing the isolate profile with the 3438 bacterial profiles deposited in the MALDI BioTyper database (Bruker Corp. Bremen, Germany), which includes 56 Arthrobacter, 17 Brevibacterium, three Pseudoclavibacter, and no Zimmermannella organism profiles (as of June 2010). The isolate was not identified with any of the species in the database, with the best identification score being 1.326 with Corynebacterium afermentans. The isolate has been deposited in the Collection de Souches de l'Unité des Rickettsies, Marseilles, France (CSUR P29). The clinical evolution was favorable under antibiotic treatment combining intravenous imipenem and vancomycin. Oral treatment with amoxicillin/clavulanate replaced intravenous antibiotics on day six.
Identification of the isolate was made possible only after 16S rRNA gene sequence analysis, as the isolate was not reactive on identification strips and did not exhibit any identifying phenotype. The 16S rRNA gene sequence comparison indicated that this isolate is representative of a previously uncultured organism. This case illustrates a new paradigm in using 16S rRNA gene sequence-based identification of organisms in clinical microbiology laboratories. Indeed, most of the emerging bacteria have been described previously on the basis of an original bacterial isolate exhibiting a 16S rRNA gene sequence with < 98.7% sequence similarity with any other sequence [,,]. In our case report, however, the 16S rRNA gene sequence was already available in GenBank before we recovered the isolate. Indeed, extensive genomic and metagenomic explorations of complex environmental and mucosa-associated flora yielded a tremendous amount of the original 16S rRNA gene sequence from as-yet-uncultured organisms [,]. In our case report, isolation of an organism exhibiting a 16S rRNA gene sequence identical to that of a previously uncultured organism underscores the uniqueness of this isolate.


While hospitalized, a 32-year old male patient diagnosed with Guillain Barre Syndrome had received flupirtine, ibuprofen, and metamizole as pain medication. Reported co-medications were: pregabalin, insulin, promethazine, enoxaparin and potassium citrate. After 3 days of flupirtine administration (600 mg/day) he displayed increased ALT (4×ULN) and AST levels (3×ULN). Treatment with flupirtine and pregabalin was discontinued. With a latency of 6 days he was re-exposed to pregabalin and responded with massively increases in ALT (28×ULN) and AST (24×ULN) levels. Drug-induced liver injury – induced by pregabalin was rated certain.
As described above the 226 cases also included cases, where co-medications rather than concomitant diseases (hepatitis) were more likely to be responsible for the hepatobiliary ADR. Specifically, in case no. 1 re-challenge with pregabalin led to a massive increase of serum transaminases. This case can therefore be rated as unlikely for flupirtine exposure to cause DILI. In contrast, in case no. 2 (see below) and due a positive re-challenge with flupirtine the reported ADR was rated to be “certain” (WHO/UMC system) or “possible” (CIOMS score). The difference in the score between both causality assessment systems is related to the lack of clinical information for case no. 2 (e.g. other than viral causes), which have a higher weight in the CIOMS score.


A 53-year-old female patient was admitted to the hospital and diagnosed with jaundice. Viral and autoimmune hepatitis were excluded. The patient had taken flupirtine on demand (unknown daily dose) for the treatment of pain related to cervical spine syndrome. The patient displayed increased transaminases (ALT: 31.0×ULN, AST: 19.8×ULN). Co-medications were estradiol+norethisterone and zolpidem on demand. After discontinuation of flupirtine the lab parameters decreased. Re-exposure (dose unknown) on day 5 of admission resulted in a recurrent increase of laboratory parameters (see below).
A systematic review of the 226 spontaneous individual reports of hepatobiliary ADRs associated with flupirtine intake defined 57 cases with elective liver biopsies. However, information on liver biopsies for 49 cases could be retrieved only and the findings are summarised in (note, for each case several diagnoses are listed). Essentially for 23 cases inflammatory hepatitis was confirmed by histopathology while histopathological features consistent with toxic liver damage were reported for 36 cases. Furthermore, in 29 out of the 36 cases (i.e. >80%) with toxic liver damage, co-medications with other drugs known to cause hepatobiliary ADRs were reported as well and in n = 6 cases autoimmune-related changes were excluded, but in 18 of the 226 patients positive titres for auto antibodies were noted.
Neither anti-nuclear antibodies (ANAs) nor anti-mitochondrial antibodies (AMAs) are sufficiently specific for the diagnosis of an autoimmune liver disease. Positive titres for these are also found in other conditions, such as collagenosis, rheumatoid arthritis, as well as primary biliary cirrhosis, which could however be excluded, based on the available histopathology findings. Furthermore, in one case the liver specific protein (LSP) was determined, but reported as negative.


A 41-year-old Caucasian man was sleeping when he suddenly experienced tonic movement of the right upper limb followed by loss of consciousness and clonic movements of his four extremities, all of which lasted approximately one minute and was self-limited. Our review of his symptoms was negative, including headaches and other neurologic symptoms or signs. His medical history included hypertension and Poland syndrome. His mother had had chronic obstructive pulmonary disease and had a heart attack at age 64, which caused her death. The rest of the patient's family history was negative for neurologic or vascular alterations.
A physical examination revealed the absence of his right breast and right pectoralis major muscles (Figure ) and right-handed symbrachydactyly, status post-multiple corrective surgeries (Figure ), corresponding to Poland syndrome. His neurological examination results were within normal limits. MRI studies showed multiple cerebral CMs, with the largest one, measuring 15.8 mm × 9.3 mm, located in the left frontal pole cortical region, with evidence of recent hemorrhage (Figure ). Two other CMs located in the right and left parietal lobes also showed evidence of bleeding (Figures and ). The majority of the CMs were located in the left hemisphere (Figure ). Multiple other cerebellar and brain stem CMs were also noted (Figures and ).
The patient presented to our hospital to discuss the possibility of undergoing stereotactic radiosurgery for treatment of the CMs. He had already been started on levetiracetam 75 mg twice daily, which led to good seizure control. Thus, electroencephalographic monitoring and/or telemetry to detect the seizure origin localization, continuing medical therapy, and observation were recommended at that point.


A 32-year-old male patient with no past medical history presented to the emergency room with abdominal pain, nausea, and vomiting. The patient had “normal” bowel movements and reported having these recurrent symptoms for the last 3 months. The patient was managed on an outpatient basis for nonspecific functional GI disorders and was treated as such with oral phloroglucinol and metoclopramide.
Initial assessment in the emergency room revealed a blood pressure at 70/40 mm Hg, a heart rate at 120 bpm, cold extremities and general pallor, mild pulmonary rales, abdominal bloating, and no lower leg edema. There was no signs of acute surgical abdomen. Electrocardiogram showed sinus tachycardia with narrow QRS and diffuse nonspecific ST/T changes, chest X rays showed cardiomegaly, and emergent cardiac echogram showed severe hypokinetic dilated cardiomyopathy () with ejection fraction at 25%, normal pericardium, and no significant intrinsic valvular disease.
The abdominal computed tomography (contrast-enhanced) scan showed nonspecific findings: no peritoneal effusion, no organic intraabdominal disease documented, and slow progression of contrast material attributed to the poor hemodynamic condition. Mesenteric angiography was not performed due to the unstable hemodynamic condition and the lack of consent.
Laboratory findings revealed negative troponin, mild leucocytosis, serum sodium at 120 mmol/L, creatinine at 1.7 mg/dL, brain natriuretic peptide (BNP) at 3535 pg/mL, glutamic oxaloacetic transaminase (GOT) at 52 U/L, glutamic pyruvic transaminase (GPT) at 73 U/L, lactate dehydrogenase (LDH) at 271 U/L, and serum lactate at 4.8 mmol/L. Amylase, lipase, cortisol level, and other routine laboratory results were all within normal limits.
In the evolution, abdominal pain was resistant to conventional analgesics and antispasmodics, and it was only relieved when the hemodynamic condition improved. Also, during the intensive care unit stay, there were paroxysms of recurrent abdominal pain concomittant with episodic worsening of the hemodynamic condition. Of note, the patient needed intravenous positive inotropic agents for 14 days before the hemodynamic condition stabilized.


Patient 4's parents separated when she was 4 years old, and a shared contact arrangement with both parents was agreed. After the separation of her parents, patient 4's behaviour became increasingly challenging. She found it difficult to settle in mainstream school and made little progress in her learning; she was, therefore, transferred to a special school for children with moderate learning disabilities. Patient 4's behaviour continued to deteriorate in the special school. She was very impulsive, defiant and constantly fidgety; she lashed out frequently at teachers and other children, and had a very poor concentration span. She had a structured behavioural management plan in school as well as a period of monitoring. However, although her behaviour improved slightly, she made no progress in her learning, as reflected by her poor school grades and her teachers' reports, and she continued to have problems with concentration and constant fidgeting.


A 51-year-old Asian woman diagnosed with a primary gastric GIST underwent wedge resection, achieving complete removal of the entire tumor with microscopic examination of the margins showing no tumor cells (R0 margins). She was considered at high risk for recurrence based on the tumor size (8 cm × 7 cm × 3 cm) and high mitotic rate (>50 mitoses per 50 high powered fields (HPF)) of the excised GIST [,]. In addition, mutation analysis showed that the tumor had KIT exon 11 deletions, a genotype shown to be associated with adverse outcomes after surgery []. As such, our patient was enrolled in the aforementioned Korean Phase II trial of adjuvant imatinib for patients with localized KIT exon 11-mutant GIST at high risk of relapse []. Our patient was started on imatinib adjuvant treatment 400 mg/day but developed a skin rash after three months; the rash was successfully managed with a temporary (three-week) dose interruption. Our patient was subsequently restarted on imatinib 300 mg/day and resumed taking standard-dose imatinib 400 mg/day after three months. She was maintained, generally tolerated this dose and completed the two-year adjuvant therapy regimen.
Ten months after stopping adjuvant imatinib treatment, recurrence was detected in this patient, as computed tomography (CT) scans revealed three gross peritoneal nodules in her upper abdomen (Figure and ). Our patient was rechallenged with imatinib 400 mg/day as first-line treatment for her recurrent or metastatic disease. After one month of treatment, a partial response (PR) by Response Evaluation Criteria In Solid Tumors was observed; the three peritoneal nodules had decreased in size from 31.4 mm, 15.3 mm and 22.1 mm (sum, 69 mm; Figure and ) to 17.1 mm, 9.2 mm and 12.4 mm, respectively (sum, 39 mm; Figure and ), representing a 43% decrease in size. Imatinib rechallenge was well tolerated, as the only adverse events experienced by our patient were grade 1 edema, anemia and fatigue. Our patient maintained a stable PR for over two and a half years after being rechallenged with imatinib treatment, as evidenced by repeated CT scans. However, progression was observed three months later; CT scans revealed that the sum of two peritoneal nodules had increased in size by 50% since the last tumor assessment. Disease progression was confronted through dose escalation to imatinib 800 mg/day. Our patient's response to dose escalation will be monitored closely during future follow-up visits.


We present the case of a 56-year-old Caucasian man with Forestier's disease also known as diffuse idiopathic skeletal hyperostosis (DISH). Forestier's disease is a common spinal enthesopathy that is mostly encountered in men older than 50 years []. A prevalence of 28% has been found in autopsy specimens []. DISH is more common in patients with diabetes and gout [].
Our patient sought the services of a local physical therapist while on vacation to obtain massages and other treatments for his aching and stiff neck. According to our patient, the physiotherapist (board certified per our patient's report), was more forceful in his manipulating than our patient was used to. He reports having had severe neck pain prior to a short period of unconsciousness. After the procedure, he was unable to mobilize himself off the table. Prior to this incidence the physiotherapist had reportedly not known about our patient's Forestier's disease. He supposedly had not asked about underlying diseases nor had our patient remembered to tell him.
Our patient was referred to a local hospital with a partial tetraparetic syndrome. MRI scans of the cervical spine showed a C 6/7 luxation fracture, as well as degenerative alterations with large spondylophytes bridging the vertebral bodies of the cervical spine extensively (consistent with Forestier's disease) (Figure ). Axial traction therapy was chosen for several days followed by a dorsal stabilization procedure using internal fixation. Twelve days after the initial trauma he was repatriated and referred to our division of spine surgery. Subjectively, the symptoms improved over time after the initial trauma. On admission to our institution our patient reported having electrifying pain in the whole left upper extremity. Finger abduction in the left hand was slightly reduced to grade M4 of five (according to British Medical Research Council grading, 1978). On the right side the active finger abduction was significantly reduced to grade M0-1/5 and elbow extension to M3/5.
A subsequent computed tomography (CT) scan showed an insufficient fracture reduction leaving the facet joints in a persistent subluxation, potentially continuing to compromise neural structures (Figure ). Our patient was also noted to have elevated inflammatory parameters. Due to his clinical presentation, revision surgery with posterior hardware removal, irrigation, debridement and decompressive laminectomy was undertaken. Our patient was then flipped into a supine position for a ventral approach. No obvious signs of infection were seen anteriorly and therefore a ventral inter-corporal fusion procedure was performed at level C6/7 and the cervical spine instrumented between the levels C5 to T1 using a plate (Vectra).
The results of cultures of the intra-operative biopsies taken from our patient's dorsal cervical spine were positive for a coagulase-negative Staphylococcus and Proteus mirabilis. An adequate antibiotic regime was established. Our patient was transferred to a neurological rehabilitation center eight days post-operatively in a stable condition.
At two-month follow-up, our patient reported satisfaction with the outcome. His inflammatory parameters had normalized and all the incisions looked well healed. He had an acceptable range of movement of his cervical spine. While his left upper extremity had full sensomotor function, on his right side function was still impaired. At six-month follow-up, persistent but slightly improving neurological deficits were recorded. Figure shows radiographic imaging results obtained at the six-month follow-up demonstrating no changes in alignment, intact hardware and osseous consolidation. Subsequent to the last follow-up, our patient was still undergoing ergotherapeutic and physiotherapeutic therapy addressing his right upper extremity limitations.


Patient V-1 (Fig. A) is an 8-year-old girl (part of a previously described large French Canadian consanguineous family, ) born at 41 weeks of gestation by spontaneous vaginal delivery and weighing 3320g (50th percentile). No limb deformities or other abnormalities were noted at birth and sclerae were white. She was able to sit independently at 6 months of age and had normal-appearing teeth. Her first fracture was a nondisplaced fracture in the proximal right femur at the age of 9 months. A skeletal survey revealed three vertebral compression fractures. The areal bone mineral density Z-score for lumbar vertebrae L1 to L4 on dual-energy X-ray absorptiometry was −0.1 at age 9 months. After pamidronate treatment was started at 9 months of age, no new vertebral compression fractures were observed. There were no radiographic signs of rickets at any time (Fig. B). However, she sustained 35 long-bone fractures, and underwent bilateral femoral intramedullary rodding (Fig. C, D). Iliac bone biopsy (at age 25 months) showed large amounts of unmineralized osteoid in bone. Biochemical parameters of mineral metabolism (serum calcium, phosphorus, 25-OH vitamin D, and parathyroid hormone), except for elevated alkaline phosphatase levels, were within normal limits at the time of biopsy and at all of the subsequent 6-monthly control examinations. The girl began walking independently at age 18 months but stopped ambulating at age 5 years because of frequent lower-extremity fractures. Growth was slow but height remained within the normal reference range (10th percentile at 8 years).


Patient IV-3 (Fig. A) is a 26-year-old man born at 40 weeks of gestation by spontaneous vaginal delivery, weighing 3520g (50th percentile). At birth, he had white sclera, normal facial features, no fractures, no limb deformities, and no joint hyperlaxity. He was able to walk independently at age 18 months, but beginning at age 6 years required a wheelchair because of recurrent fractures. His growth was severely restricted. At the age of 13 years, his height was equivalent to an average 3.5-year-old and areal bone mineral density at the lumbar spine was below that of an average newborn. He had severe scoliosis (72 degrees), bilateral coxa vara, acetabular protrusion, severe bowing of all long bones, and ‘popcorn epiphyses.’ Iliac bone biopsy showed a large quantity of unmineralized osteoid as well as absence of normal bone lamellation and evidence of a ‘fish-scale’ bone pattern (Fig. F-I). Serum calcium, phosphorus, and parathyroid hormone levels were within normal limits, but serum 25-OH vitamin D was slightly low (41 nmol/L; recommended range: 50-130 nmol/L) and alkaline phosphatase activity was slightly elevated (436U/L, normal: <300U/L). The urinary ratio between collagen type I N-telopeptide and creatinine, a marker of bone resorption, was elevated (three times the age- and sex-specific average value). Pamidronate treatment began at 13.7 years of age. Final height at 18 years of age was 110cm. Lower extremity X-rays at the age of 21 years showed significant widening of the metaphyses and epiphyses (Fig. E). He continued to have on average one long-bone fracture per year. Patient IV-3 has an affected brother (patient IV-4) who shares similar clinical features, and has been previously described.


The third patient in this series is a 14-year-old Italian boy. He was born at 41 weeks gestation by spontaneous vaginal delivery, weighing 2950g (<10th percentile). He had faintly blue sclera, no apparent fractures, and neither joint hyperlaxity nor skin hyperelasticity. The patient's parents are not consanguineous and an older brother is unaffected. The first fracture (humerus) at age 10 months was followed by fractures of femur and forearm. Pamidronate therapy began at age 2.3 years, but his growth remained very slow and he sustained multiple atraumatic fractures. Surgical corrections of long-bone deformities began at age 9 years. Severe kyphoscoliosis was treated by spinal fusion surgery at age 14 years. He was never able to stand or walk and is dependent upon an electric wheelchair for mobility. Serum calcium, phosphorus, parathyroid hormone, and 25-OH vitamin D levels were normal and urinary collagen type I N-telopeptide levels were in the upper part of the reference range. Iliac bone histology at age 10 years showed absence of normal spongiosa architecture and osteoid excess. Analysis of collagen type I protein from skin fibroblasts did not reveal any pathological findings. Sequencing of COL1A1, COL1A2, and CRTAP in genomic DNA revealed no mutations.


A 54-year-old male presented with a history of palpitation in the preceding 3 years, not controlled by oral metoprolol. During tachycardia (ventricular rate 125/min), the P wave morphology was negative in inferior leads and positive-negative in lead V1 ().
At the time of the invasive electrophysiological study, the patient was having a narrow QRS tachycardia with cycle length of 237ms and 2:1 A V conduction ( and ). The activation wavefront was propagating from proximal coronary sinus (CS) to distal CS; at the same time showing counterclockwise activation through the septum and upper lateral right atrium (RA). The lower lateral RA was activated earlier than upper lateral RA. The wave fronts were seen to collide in the high lateral RA while the tachycardia was supported by a circuit at the base of the RA. The activation pattern suggested the possibility of tachycardia wave front traversing the cavotricuspid isthmus (CTI) and posterior RA with early activation of lower lateral RA through transcristal conduction, and collision of the 2 resultant circumtricuspid wave fronts - counterclockwise and clockwise, along the septum and freewall in RA respectively - at the upper anterolateral RA region.
To confirm the proposed tachycardia mechanism, entrainment was performed from CTI, lower lateral RA, and posterior RA. This protocol showed concealed fusion with postpacing interval approximating tachycardia cycle length, suggesting a macroreentrant mechanism involving CTI, posterior RA and lower anterolateral RA. On pacing from the RA roof during tachycardia, at a pacing cycle length 20ms lower than that of tachycardia cycle length, neither concealed fusion nor similar post pacing interval could be demonstrated, excluding RA roof a part of this re-entrant circuit. Hence a lower loop re-entry involving CTI, lower lateral RA and low posterior RA, mediated by the breaks in conduction at lower cristae terminalis was considered.
Unlike to its original description where LLR intermittently converted to typical counterclockwise flutter, the reentry in this case was sustained and did not convert to typical flutter at any point during the study. Moreover, no other forms of CTI dependent flutters were inducible. The flutter terminated with linear ablation of CTI, and bidirectional block across the CTI was achieved with a few more burns. An aggressive pacing protocol after ablation failed to reinduce the tachycardia.


A 33-year-old woman with a long-standing history of insulin dependent diabetes complicated with diabetic retinopathy presented to Breast Clinic for evaluation of a new onset, painless, breast lump. She had incidentally discovered a lump in the upper outer quadrant of the left breast 3 months prior that had gradually increased in size in the interim. She denied breast pain, nipple discharge, or overlying skin changes. With regard to breast cancer risk factors, she was nulliparous, menopausal as she had a hysterectomy for dysfunctional uterine bleeding but ovaries were intact, had no previous history of breast biopsies, and was a nonsmoker. She had no personal or family history of breast or ovarian cancer. Her only medication was a NovoLog insulin pump.
Physical exam was remarkable for a dominant 3 × 1 centimeter hard, irregular, movable, painless mass palpable in the left upper outer quadrant and a smaller less defined lesion in the left lower quadrant of the breast. The differential diagnosis included fibroadenoma, fibrocystic change, malignancy (especially lobular carcinoma), PASH (pseudoangiomatous stromal hyperplasia), and diabetic mastopathy.
Imaging evaluations included a diagnostic mammogram that revealed extremely dense breasts. Ultrasound exam of the palpable area was also negative for abnormality. A bilateral MRI of the breast was performed () and demonstrated multiple regions of enhancement and a small incidental fibroadenoma of the left breast; no abnormality was detected at the area of palpable concern. A second look ultrasound and left diagnostic mammogram with magnification was obtained, and again while the fibroadenoma seen by MRI was detected by ultrasound this time, the area of the palpable abnormality showed normal tissue with no mass ().
In view of the size and clinically worrisome features of the palpable, yet radiographically occult mass, an excisional breast biopsy was performed to rule out malignancy. Pathology demonstrated benign breast parenchyma, dense stromal fibrosis, and periductal lymphocyte infiltrate suggestive of diabetic mastopathy (Figures and ).
At her three-month follow-up visit, the patient noted some fullness around her surgical scar that was palpable on clinical breast exam. Diagnostic left breast ultrasound demonstrated a surgical scar, dense breast tissue, but no abnormalities at the area of palpable concern. Continued observation of the breast was recommended with regular clinical follow-up.


A 49-year-old woman with a history of migraine presented to the emergency room with a thunderclap headache, initially without other symptoms but later followed by visual impairment. She remained conscious and had no complaints besides headache. She uses pantoprazole and had quit smoking 2 weeks earlier. She had been well until the development of the headache, and she had not experienced any trauma.
Her physical examination revealed that she had a pulse of 62 beats/minute and blood pressure of 219/100 mmHg. Her motor and sensory responses were normal. Cardiac and pulmonary sounds were normal. The ocular fundus appeared normal on the basis of ophthalmoscopy. Her electrocardiogram showed decreased T wave amplitude, ST segment depression and the presence of a marked U wave (Figure ), which were suggestive of severe hypokalemia []. The precordial leads matched the voltage criteria for left ventricular hypertrophy []. Laboratory analysis showed a low serum level of potassium at 2.7 mM/l. Her sodium and magnesium levels were normal. Arterial blood gas analysis showed a mixed metabolic and respiratory alkalosis, with an arterial pH of 7.64 and a bicarbonate level of 27.4 mM/l. However, within hours after presentation, the respiratory component resolved, leaving only metabolic alkalosis.


A 50-year-old Greek woman was referred to us with a history of reduced best-corrected visual acuity (BCVA) after blunt trauma to her right eye. Past medical and ocular history was unremarkable. Her BCVA one hour after the incident was hand movements at 10 cm. An anterior chamber examination revealed a round pupil with no signs of hyphema or iridodialysis. Fundoscopy revealed a full-thickness TMH with a minor sub-retinal hemorrhage and posterior vitreous detachment (PVD, Figure ). Cirrus optical coherence tomography (OCT) scans confirmed the funduscopic findings (Figure ).
Two days later, her BCVA was improved (counting fingers at 1.5 m), despite a foveal hemorrhage. Fluorescein angiography (FA) revealed masking in the fovea, progressive staining peripheral to the masking area and a central window defect (Figure ). OCT examination showed a marked decrease in retinal edema and a coagulum covering the TMH base (Figure ).
Seventeen days later, her BCVA had improved to 7 Early Treatment Diabetic Retinoapthy Study (ETDRS) letters at 4 m. Fundoscopy and OCT scans revealed TMH closure and adjacent pigment dispersion (Figures , ). Four months later, with a BCVA of 15 ETDRS letters at 4 m, our patient was fixating eccentrically, despite BCVA improvement. Fundoscopy showed hyper- and hypo-pigmentation in the TMH periphery and an OCT scan confirmed the TMH closure (Figures , ). FA revealed an absence of central window defect and mottled hyper-fluorescence consistent with diffuse retinal pigment epithelial (RPE) atrophy (Figure ).


A 37 year-old male without significant previous medical history, presented in June 2007 with a solitary soft tissue mass in the posterior side of the right elbow, with rapid growth that did not infiltrate the bone or the skin. The patient underwent a tumorectomy with wide margins. Following histological study, he received three cycles of chemotherapy (CTX+VCR+Doxorrubicin). One year after tumorectomy, a "de novo" intratesticular tumor appeared in the right testis, not previously detected. Orchiectomy was subsequently performed. A second line of chemotherapy (Ifosfamide) followed, but without positive response. Eight months following the orchiectomy, the patient died with multiple metastases in the left thigh, lung and mediastinum. No autopsy was performed (Figure )
The tumors were processed in molecular fixative solution for Tissue-Tek Xpress Rapid Tissue Processor® (Sakura), embedded in paraffin, cut in 4 μm thick sections and stained with hematoxylin and eosin for routine histological examination. Immunohistochemical analysis was done on the paraffin-embedded sections using standard protocol. Primary antibodies were: MyoD1 (Dako, diluted 1:50), Vimentin (Dako, diluted 1:100), Myogenin (Dako, diluted 1:50), SMA (specific muscle actin) (Dako, diluted 1:100), Desmin (Dako, diluted 1:100), EMA (Dako, Diluted 1:50), CD 99 (Signet Laboratories, Dehman, MA, USA, diluted 1:50), p57 (Dako, diluted 1:200), CD 56 (Dako, diluted 1:200), S100 protein (Dako, diluted 1:100), CEAp (Dako, diluted 1:400), CD31 (Dako, diluted 1:1000), CD34 (Dako, diluted 1:1000), MIB 1 (Dako, diluted 1:400), and pan-cytokeratin (AE1/AE3, Dako Glostrup, Denmark, diluted 1:50). Fluorescence in situ hybridization (FISH) and RT-PCR were carried out on the paraffin-embedded sections from the elbow and testicle tumors. For FISH we used the Poseidon Repeat Free FKHR (13q14) protocol (Kreatech Diagnostics, Amsterdam, the Netherlands). The probe used was FKHR (FOXO1A, 13q14) Break apart (POSEIDON). There are two critical regions: (i) critical region 1 (red), in which the distal FKHR gene region probe was directly labeled with Platinum Bright 550; and (ii) critical region 2 (green), in which the proximal FKHR gene region probe was directly labeled with Platinum Bright 495. Analysis was performed with a fluorescent microscope, and the software used for image interpretation was CW4000. RT-PCR was performed as previously reported [], using adequate primers to detect the chimeric transcriptional products PAX3-FKHR and PAX7-FKHR.
Grossly the surgical specimen from the elbow showed a 9 × 6 cms nodular solid tumor, white in color with a glistening surface, infiltrating the surrounding skeletal muscle.
Histologically, the tumor had abundant esosinophilic hyalinizing sclerotic matrix, containing predominant small round cells growing in small nests of fascicular, pseudovascular cord-like or single file. In some areas a predominant perivascular tumor growth was observed. No microalveolar pattern was seen. Wreath-like tumor cells and strap rhabdomyoblasts were not identified. Mitotic activity was up to 4 mitotic figures/10 HPF. Coagulative necrosis occupied 10% of the tumor mass. On hematoxylin and eosin findings an initial diagnosis of sclerosing sarcoma, most probably epitheloid sclerosing fibrosarcoma was reached (Figure ).
Immunohistochemically the tumor cells strongly expressed Vimentin, MyoD1, SMA and CD99, being negative for the remaining antibodies tested, including Myogenin and Desmin. The proliferation index measured with MIB 1 was about more than 25%-30% of tumor cells.
FISH hybridization did not show FOXO1A: 13q14 translocation and the chimeric transcriptional products PAX3-FKHR and PAX7-FKHR were also not found (Figure ).
On gross examination the orchiectomy specimen showed a peripheral subalbuginea intratesticular well-defined nodular tumor of 1.2 × 0.8 cms, grey to white with solid consistency, with central necrosis and delimited by a fibrous capsule from the normal testicular parenchyma. Histologically the tumor showed features of fusocellular rhabdomyosarcoma, composed of fascicles of spindle-shaped cells with small oval or elongated nuclei, vesicular chromatin and pale cytoplasm. Occasionally scattered in the tumor were a small number of spindled or polygonal cells with excentrically placed nuclei and abundant eosinophilic cytoplasm, resembling more mature rhabdomyoblasts, were also seen. Mitotic activity was more than 10 mitotic figures/10 HPF. The tumor infiltrated the surrounding testicular parenchyma and was centrally necrosed (30%). Immunohistochemically the cells stained positively for Vimentin, MyoD1, CD99, Myogenin, Desmin, SMA and WT-1. The proliferation index measured with MIB was about 20%. Again, FISH failed to show the FOXO1A: 13q14 translocation and the chimeric transcriptional products PAX3-FKHR and PAX7-FKHR were not found.
After the histological diagnosis of the surgical specimen from the testicular lesion, a complete sampling of the sclerosing rhabdomyosarcoma from the elbow treated one year before was performed. An extensive histological study of the new samples demonstrated new histological findings, such as the presence of two large endovascular (venous) emboli and 3 minute foci of tumor (measuring all together less than 3 mm) located in the non-tumoral soft tissue, next to the sclerosing rhabdomyosarcoma and apparently isolated from them by a fibrotic acellular band. Histologically, tumor cells from the emboli and extratumoral foci showed predominant fusocellular morphology. A few isolated round primitive cells without sclerosis and strap rhabdomyoblastic cells were also present. Immunohistochemically these cells expressed Vimentin, MyoD1, Myogenin, CD 99, SMA and Desmin, being histologically and immunohistologically identical to the testicular tumor studied one year later (Table and Figure ).


A 25-year-old athletic-body gentleman presented with significant pain in both shoulders and inability to do daily activities for 5 days after electrical shock. Immediately after electricity-induced trauma, he had been transferred to a major trauma center. Primary cares had been given. He had been visited by an emergency medicine physician. Routine anteroposterior radiograph of the shoulders () was misinterpreted. Then, he had been discharged with analgesic and arm sling. Five days later, he referred to the senior author with pain and restriction of bilateral shoulder movements. In physical exam, posterior positions of the humeral heads were not palpable due to his muscular body. The patient had fixed both upper limbs in adduction and internal rotation. Passive and active external rotation was blocked and very painful. Moreover, the patient did not permit passive abduction and forward flexion of more than 45 degrees. Neurovascular functions of both sides were normal. Bilateral shoulder posterior dislocation was suspected and CT scan was requested (). It showed bilateral posterior dislocation associated with articular surface defect of 50% in the right side and 30% in the left. He underwent closed reduction under general anesthesia after taking consent. Left side reduction was stable but the right was unstable in internal rotation. Bilateral shoulder spica cast was applied in 20 degrees of abduction and 15 degrees of external rotation.
After six weeks, the cast was discarded. Stability of joints was well. Rehabilitation program including active and passive range of motion and deltoid and rotator cuff strengthening exercises were begun. As he was a professional athlete in weight lifting, he continued exercises for one year. After one-year follow-up, he had bilateral stable joint with full range of motion without any history of dislocation. CT scan () showed bilateral small defect in anteromedial part of the humeral heads which is more in the left side.


A 24-year-old woman with a 3-year history of multiple sclerosis and a primary diagnosis of retrobulbar optic neuritis was referred to our department due to severe acute hepatitis. Three months earlier, she was admitted to the neurology department due to exacerbation of multiple sclerosis. Neurological treatment began with a 6-day course (0.5 g/d) of high-dose intravenous MT, resulting in full recovery of her left arm function. Routine laboratory examinations showed normal liver tests and no autoantibodies in the peripheral blood.
The patient was subsequently switched to beta-1b interferon (Betaferon) treatment and received 2 doses of this drug without any immediate or delayed adverse reactions. After 6 weeks, she developed a subsequent flare of MS, presenting as left-sided limb paralysis. A high-dose intravenous MT pulse (total dose 3.0 g) and 2 injections of Betaferon were given, effecting nearly a full recovery. Four weeks after the MT pulse and 1 week after her last Betaferon dose, the patient developed jaundice with elevated serum levels of aspartate aminotransferase (AST) 900 IU/L (n: 10-31 IU/L), serum alanine aminotransferase (ALT) l740 IU/L (n: 9-34 IU/L), serum alkaline phosphatase 186 IU/L (n: 38-126 IU/L), and serum GGTP 50 IU/L (n: -38 IU/L). The serum bilirubin level was 17.9 mg/dL (n: 0.3-1.2 mg/dL), the direct bilirubin was 16.1 mg/dL, and the prothrombin index was 35.1% (INR 2.52). The serum AFP level was 17.18 ng/mL (n: < 5 ng/mL). The patient had no history of hepatic disease and denied any use of alcohol. In the previous 6 months, the patient took acetaminophen (used only in a single dose before each Betaferon injection) and oral contraception, which was stopped immediately before the second MT pulse. Serological tests for hepatitis B (including antibodies to HBc), hepatitis C, hepatitis A, and infection with cytomegalovirus (CMV) were negative. Smooth muscle antibodies (SMA) were found in high titers (> 1:320), and autoantibodies against mitochondria and nuclei were undetected by direct immunofluorescence tests. Her copper urinary excretion was not elevated. An ultrasound abdominal examination showed an intact liver and a normal-sized spleen. No liver biopsy was done due to a low prothrombin level. With a MELD (model for end-stage liver disease) score of 26, the patient was a potential liver transplantation candidate. Fortunately, her liver function improved spontaneously, and the patient was discharged after 3 weeks with normal aminotransferase levels. Considering the potential hepatotoxicity of interferons, we cautiously suspected the Betaferon of inducing liver injury. Three months later, the patient developed a consecutive flare of multiple sclerosis, for which she received a 6-day intravenous MT pulse (total dose 3.0 g) without Betaferon. Her neurological symptoms resolved, but 4 weeks later, she was readmitted to our department with symptoms of acute hepatitis. The serum level of AST was 1488 IU/L, ALT was 1129 IU/L, alkaline phosphatase was 164 IU/L, GGTP was 168 IU/L, prothrombin index was 47% (INR 1.71), and serum bilirubin was 7.3 mg/dL. No drugs, as before, were used to treat the liver disease, and after several weeks, aminotransferases and bilirubin reached reference levels.


A 24-year-old southeast Asian woman was admitted with a history of a white spot on the right cornea and increasing discomfort. On examination, her vision was 6/36 on the right and 6/9 on the left. She had a corneal ulcer measuring 5.5 × 2 mm on her right cornea. A small localized area of scarring was present lateral to where the defect was present (Figure ). There was a +1 cell reaction in her right anterior chamber. She had a history of bilateral anterior uveitis. Corneal sensation was normal in both eyes. There were early bilateral posterior subcapsular cataracts.
In view of the findings, corneal scrapes were taken for microscopy, culture, and sensitivity. Virology assays inclusive of herpes simplex virus and varicella-zoster virus polymerase chain reaction were performed. Our patient had normal C-reactive protein, rheumatoid factor, anti-nuclear antibody, extractable nuclear antigen, syphilis, and hepatitis B and C serology. She was started on topical g. cephalothin 5% and g. gentamicin 0.9% hourly for 48 hours. She made a mild initial improvement and was changed to topical g. chloramphenicol 1% four times each day and g. prednisolone 0.5% four times each day once her microbiology and virology results were negative. A bandage contact lens was inserted to facilitate healing (Figure ).
In the third week of admission, she complained of a headache and was found to be mildly tachycardic. She was apyrexial with no reported malaise. A urinary dipstick analysis was performed, and her urinary glucose level was 21 mmol/L. Blood glucose was urgently requested and was found to be 23 mmol/L. A blood gas analysis showed a pH of 7.38, a partial pressure of carbon dioxide (pCO2) of 44.7 mmHg, and a partial pressure of oxygen (pO2) of 89.5 mmHg.
She was transferred to the care of the medical team and a diagnosis of type 1 diabetes was made. She was started on treatment with insulin. Her corneal ulcer persisted and punctal plugs were inserted to increase the tear film and facilitate healing. Autologous serum drops were started every two hours during waking hours. There was a rapid reduction of the epithelial defect as her blood glucose levels normalized (Figure ).
Four days after insulin treatment was started, her ulcer had healed and she was discharged from the hospital and follow-up was conducted at her local diabetes clinic. At a one-month review in the eye clinic, her ulcer remained healed, leaving a localized area of subepithelial scarring (Figure ).


A 35-year-old Caucasian man was admitted to our hospital with a symptomatic resistant gastric MALT NHL in July 2003. He had a history of stage IEA (Ann Arbour staging stage I for Lugano staging system for gastrointestinal lymphomas) [] gastric MALT NHL previously diagnosed in February 2001. At that time, due to the presence of HP infection, he received amoxicillin omeprazole and clarithromycin as eradication treatment. Two months later, an upper gastrointestinal endoscopy (UGE) with multiple gastric biopsies revealed a complete clinical and pathological response.
In February 2002, the patient experienced a local relapse without evidence of HP and was therefore treated with three cycles of standard cyclophosphamide, oncovin, doxorubicin, prednisone chemotherapy, achieving a minimal response with disappearance of all symptoms. Three additional cycles were performed but final evaluation revealed the persistence of microscopic disease. CT scans excluded distant disease. The patient was asymptomatic and declined further treatment for 14 months but, in May 2003, an additional course of antibiotics was suggested because of the onset of local symptoms. No clinical and pathological benefit was attained, and the patient was therefore considered for a total gastrectomy, which he declined.
In July 2003, he received the anti-CD20 monoclonal antibody rituximab in a four-week schedule as a part of a phase II study for patients affected by resistant or relapsing gastric MALT NHL. After two months, a UGE revealed microscopic persistence of lymphoma again with the disappearance of related symptoms. A maintenance treatment with four additional monthly doses of rituximab was delivered until December 2003, but the presence of MALT lymphoma was confirmed by multiple gastric biopsies. Due to asymptomatic disease, we decided to observe the patient with close follow-up.
In May 2004, the patient became newly symptomatic and the UGE documented a disease progression ().
Pathological evaluation showed gastric mucosa heavily infiltrated by a dense population of small and medium-sized lymphocytes immunoreactive for CD20, which formed lympho-epithelial lesions within the gastric glands (). Interphase FISH using the LSI® MALT1 Dual Color, Break Apart Probe (Vysis, Inc., Downers Grove, IL, USA) showed split signals in most of the nuclei analysed. This pattern was consistent with the occurrence of an 18q21 locus translocation, involving the MALT1 gene (), that was further characterized as at (1118)(q21q21) by using the LSI® API2/MALT1 Dual Fusion Translocation probe (Vysis, Inc., Downers Grove, IL, USA) [].
Endoscopic ultrasonography (EUS) showed hypoecogenic gastric wall pachynsis at the corresponding lesion, while total body CT scans and bone marrow biopsy excluded other disease localizations.
The patient was informed about the possibility of receiving RT on the stomach as a standard treatment after failure of the previous approaches, but he was concomitantly proposed to participate in a phase II study of RIT with Zevalin carried out in our institute for patients with resistant/refractory MALT NHL. Due to logistical problems and considering the possibility of performing RT even after Zevalin treatment, the patient signed the informed consent and was enrolled in the RIT study.
Before RIT administration, blood count was normal, hepatic renal and cardiac functions (evaluated by serum chemistry electrocardiography and echocardiography) showed no impairments.
Treatment with 90Y ibritumomab tiuxetan (Zevalin) was preceded by rituximab 250 mg/sqm on day 0 and 8. On day 8, Zevalin was administered at the dose of 0.4 mCi/kg (maximum dose 32 mCi) with a 10-minute intravenous injection for therapy. 111In ibritumomab tiuxetan imaging dosimetry was not performed since it is not mandatory.
Clinical and haematological evaluations were performed weekly for 12 weeks, then every two months for six months and thereafter once every six months. If the platelet level dropped below 30 × 109/L, then the platelet count was performed three times a week for as long as it was below this level. Serum chemistry was monitored monthly for six months and then every six months.
Zevalin treatment induced a transient and reversible haematological toxicity characterized by grade III thrombocytopenia, grade IV neutropenia and grade I anaemia (NCI scale). Neither platelet nor red blood cell transfusions were necessary. Platelet and neutrophil count nadirs were achieved after five and six weeks from Zevalin administration and recovered in one and two weeks, respectively. Other non-haematological toxicity was absent.
Four different endoscopic evaluations (UGE with multiple gastric biopsies and EUS) and total body CT scans were performed at two, four, six and 12 months from Zevalin administration, showing a clinical and pathological complete response (). In particular, gastric biopsies were characterized by small lymphocytes and plasma cells isolated in the lamina propria or forming small well-demarcated nodules (), with a normal pattern of the MALT1 and API-2 genes by interphase dual colour FISH ().


A 64-year-old female with a history of rheumatoid arthritis (RA) since 1985, treated in the past with a variety of agents, including methotrexate, steroids, gold, Imuran, Enbrel, and Humira. The dose and duration of treatments are not available. The patient had borderline leukopenia and neutropenia documented as early as 2001 but developed a more progressive severe neutropenia in 2007. There was no periodicity or cyclical neutropenia. She did not have splenomegaly. Her bone marrow revealed 20-30% cellularity with mild erythroid hyperplasia and mild myeloid and megakaryocyte hypoplasia. There was non-specific lymphocytosis and no dysplasia. The maturation was orderly, with 27% erythroblasts, 1% myeloblasts, and 30% neutrophils and precursors. She experienced numerous hospitalizations for sepsis as a consequence of her neutropenia, with white blood cell counts in the 2000-3000 range and neutrophils less than 5%, hemoglobin of 12.1 gm/dL, and platelet count of 186,000. Rheumatoid factor (RF) was 67 iu, and cyclic citrullinated peptide IgG antibody (CCP-IgG) was > 250 u. Anti-nuclear antibodies varied between negative and 1:160 with a homogeneous pattern. In the 6 months prior to starting G-CSF, her clinical status deteriorated, with multiple admissions to the hospital, fevers as high as 103.8°F, non-healing perineal ulcers, and decubitus ulcers requiring treatment with broad-spectrum intravenous antibiotics. Fevers frequently recurred within 4 days following cessation of parenteral antibiotics, necessitating their resumption. She also suffered from dysphagia and underwent gastrointestinal evaluation with endoscopies, which showed only non-specific gastritis.
She was found to have a small clone of T-gamma lymphocytes (0.8%) in the bone marrow and peripheral blood (confirmed by PCR), but did not respond to steroid pulses or cyclosporine. She had transient moderate renal dysfunction, with a creatinine rising to 3.2 before returning to normal in 4 weeks after cessation of cyclosporine. She was then treated with PEG-filgrastim without response and thereafter with G-CSF at doses as high as 600 mcg/day for 3 months. Following an initial response to G-CSF with some wound healing, her neutropenia became intermittently more severe. Two methylprednisolone dose packs were given during an arthritis flare one month before the study observation period. She was experiencing grade 4 neutropenia and agreed to participate in a phase 2 clinical trial of ezatiostat (Telintra, TLK199). Her median screening absolute neutrophil count (ANC) prior to entering the 2-month observation period was 0.18 × 109/L. The patient received RA treatment while on study, including fish oil, hydroxychloriquine at the start of cycle 7, and acetaminophen or ibuprofen as needed. She received ezatiostat at 2000 mg orally, daily for 21 days of a 28-day cycle, and has continued on ezatiostat therapy. Initially, G-CSF was continued along with the ezatiostat, but tapered and stopped by the end of cycle 2. Her ANC continued to respond after cessation of G-CSF for 8 months and continues.
Her post-ezatiostat treatment median ANC was 3.1 × 109/L. Figure shows the striking improvement in ANC counts beginning with ezatiostat treatment initiation and continuing to respond when G-CSF use was stopped. Figure shows the inadequate ANC response to G-CSF during the baseline run-in period (ANC of .1-.2 × 109/L), as well as post-ezatiostat improvement in ANC counts. Her complete blood counts have remained normal, with an ANC ranging between 1.60-3.75 × 109/L. After 11 months' participation in the study and 7 months of ezatiostat treatment, the T-gamma clone could no longer be identified by flow cytometry but persisted by PCR evaluation. RF had normalized (7 iu) but CCP-IgG remained > 250 u. She has shown remarkable clinical improvement with complete clearing of her arthritic symptoms and with an increase of her Karnofsky performance status from 50% to 90%, and she remains in complete remission from ICN. Accompanying the improvement in her ANC, she experienced a persistent infection-free period and has not required hospitalizations or antibiotic therapy since her ANC improvement. This patient has tolerated ezatiostat well, reporting only grade 1 nausea, abnormal urine and stool odor, and a metallic taste.


A 13-year-old boy presented at our outpatient clinic with longstanding discomfort in both groins and thighs. Pain was provoked by activity and he had therefore abandoned playing soccer. There was no history of trauma or relevant comorbidity. Posture and gait were normal. The legs were well-aligned. Spinal motion was normal. Complaints could not be provoked by physical examination of the hips: there was pain-free and full range of motion and the femoro-acetabular impingement test was negative.
The radiographic AP pelvis view showed coxae valgae with well-centered spherical femoral heads. On both sides, the acetabulum was slightly shallow; the epiphysis was continuous with the apophysis of the greater trochanter, the orientation of the growth zone of the femoral neck was horizontal (transversal), and the growth zones were closing. On the Lauenstein view, the projected epiphyseal height on both sides was less than normal, as was the radial expansion of the craniolateral and anterior part of the head. Magnetic resonance imaging confirmed a (pseudo-) coalescence between the epiphysis of the femoral head and the apophysis of the greater trochanter on the right side. On the left side, this was less marked


A 14-year-old boy presented with occasionally mild complaints of discomfort in his right groin and thigh. Complaints were provoked by activity, although he was able to continue physical education at school.
As in case 1, there was no history of trauma nor any relevant comorbidity. Physical examination of legs and spine was normal.
The AP pelvis view showed symmetrical coxae valgae with spherical heads well-centered in slightly shallow acetabula with an accessory bone at the cranio-lateral edge. On both sides, the epiphysis was continuous with the apophysis, with a horizontal orientation of the physes. On the Lauenstein view, the epiphyseal height seemed almost normal, but the craniolateral and anterior radial expansion of the head seemed to be reduced. No additional imaging was done.
In both cases, we were not able to relate the mild complaints to these abnormal radiological findings; nor could we otherwise objectify these complaints. At follow-up, complaints appeared to be self-limiting.


We report the case of an 86 year old British Caucasian lady with severe aortic stenosis (peak gradient 62 mmHg, mean gradient 32 mmHg, valve area 0.4 cm2) who described worsening dyspnoea and chest discomfort on minimal exertion. Her past medical history included coronary artery bypass grafting, hypertension and diabetes mellitus type 2.
She was deemed too high risk for conventional surgery and therefore underwent transapical approach TAVI with the implantation of a 23 mm Edwards Scientific Sapien XT valve prosthesis (a bovine tissue valve inserted on a cobalt chromium frame). Immediate transoephageal echocardiography and fluoroscopic imaging demonstrated excellent seating of the valve, subsequently confirmed angiographically.
Two days later the patient developed isolated electrocardiographic evidence of pericarditis with minimal associated chest pain. Transthoracic echocardiography demonstrated a well seated aortic prosthesis and a 0.8 cm pericardial effusion with no tamponade. The effusion was not drained and her electrocardiographic changes settled over the next few days. Three months later, transthoracic echocardiography showed an abnormal bidirectional signal at the apex (Additional File ). Peak velocity was 139.4 cm-1. Cardiovascular magnetic resonance (CMR) showed a discrete pseudoaneurysm with late gadolinium myocardial enhancement (Additional Files and ). The decision was made to treat her conservatively and keep her under regular surveillance.