A thirty-five year old male presented with complaints of headache radiating to his face for about six months and impaired vision. He presented to an outpatient of Ear, Nose and Throat clinic in April 2012. The Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) images (Figure
) shows a tumor extending to the sphenoidal sinus from the anterior segment of the sphenoid bone. The tumor invades the ethmoid bone, sellar and supra-sellar regions, bilateral retro-orbital areas, almost completely invading the left maxillary sinus and extending to the nasal cavity. The mass was observed to displace optic nerves bilaterally. The tumor size was measured at 57 × 56 × 63 mm. Post-contrast series demonstrated intense and heterogeneous contrast enhancement. Based on the biopsy findings, the patient was diagnosed with ameloblastic carcinoma with basaloid appearance (Figure
). The patient underwent surgery in the Neurosurgery Clinic in May 2012. Due to the size of the mass and proximity to critical organs, only R2 (macroscopic residual tumor) resection could be performed. The patient developed post-operative infection, and was treated with appropriate antibiotic therapy, which failed to treat the infection. The patient was operated again in June 2012. After the recovery from infection, due to the recurrent and residual mass, the multi-disciplinary oncology council decided to consult with the Radiation Oncology Clinic for post-operative external radiotherapy. The visual field examination The visual assessment conducted by the Eye Diseases Clinic before the initiation of external radiotherapy revealed bilateral visual impairment and diplopia. Serial tomographic sections were taken for the purpose of contouring in radiation therapy plan. The sections were transmitted to the contouring work station through Digital Imaging and Communications in Medicine (DICOM), and Reconstructive Digital Radiography (DRR) was obtained. The DRR contouring of the patient was performed using a Tomocon (TetramedTM, Slovak republic) contouring workstation. The patient’s eyes, optic nerves, lenses, brain stem, optic chiasm, parotid glands, spinal cord, cochleae, vestibules and skin were contoured as critical organs. Prior to the radiotherapy for ameloblastic carcinoma, two separate clinical target volumes (CTV) were defined. CTV1 was defined by adding a 5 mm margin to the gross tumor volume, while planning target volume (PTV) 1 was obtained by adding a 3 mm margin to the CTV1 volume, and then administration of 60 Gy total dose was planned using simultaneous integrated boost (SIB) technique. PTV2 was defined by adding a 15 mm margin to CTV1 volume, and the prescription dose was 50 Gy to PTV2 (Table
). The patient’s treatment plan was designed with the Tomotherapy planning system (Accuray Inc., Madison, USA). With this planning system, the appropriate prescription doses for organs at risk (OAR) were defined, and routine quality assurance for the prescribed doses was conducted to prepare the patient for the treatment. Related to metastases and close proximity of OAR’s to PTV’s, some of the OAR dose objectives were slightly exceeded Quantec recommendations. The patient was informed about the treatment related adverse effects and informed consent was signed before the start of the treatment session. Prior to each session of treatment, daily Mega Voltage Computerized Tomography (MVCT) scans were performed, and these were compared with the images of treatment planning to achieve set-up accuracy.
The MR images taken at 2 months after radiotherapy showed partial regression in lesion size. Complete clinical remission was achieved in patient’s bilateral visual impairment and diplopia during follow-up. The PET scan taken at 12 months after radiotherapy demonstrated regression of the tumor in the left maxillary sinus, which reduced to 3 × 3.5 × 3 cm, and 18F-fluoro-2-deoxy-D-glucose (FDG) uptake decreased (Previous SUD: 25.36; Current SUD 5.33), while a complete response was achieved in the lesion intracranial extensions (Figure
). The brain MRI detected no pathological contrast involvement in this area. The patient is under ongoing follow-up. He has not reported any complaints in the check-up conducted in January 2014.


An 83-year-old Caucasian man of European descent presented to a community hospital
with a 2-day history of increasing pain and swelling in his left lower leg without a
previous history of trauma. His relevant past medical history included fasciotomy of
an atraumatic compartment syndrome of his left thigh 2 months ago, traumatic
hemarthrosis of his right knee half a year ago and a 2-year course of low-dose
steroid therapy for polymyalgia. Furthermore, he had hypertensive cardiomyopathy,
permanent atrial fibrillation, benign prostate hyperplasia, presbyacusis, and a
history of surgery for patellar tendon rupture 1 year ago. Aside from
prednisolone 5mg/day, he took nebivolol 2.5mg/day, torasemide 10mg/day and
tamsulosin 0.4mg/day. Warfarin had been stopped 2 months ago after his
compartment syndrome of the thigh.
During physical examination, he had pain at rest, to palpation and with passive
stretching of the foot (Numeric Rating Scale 4 to 5) at his left lower leg. Marked
swelling with emerging tension blisters was found at his proximal anterior tibia.
His peripheral pulses were palpable and his neurologic status was intact. There were
no systemic signs of disease. Ultrasound revealed a hematoma, 6×3×2cm, in
the anterior tibial compartment, but no evidence of vessel pathology or deep vein
thrombosis. Compartment pressure of the anterior tibial compartment was measured
with the help of a pressure monitoring device and was markedly elevated. Laboratory
findings included an elevated C-reactive protein of 94mg/L (normal <5mg/L),
decreased hemoglobin of 86g/L (normal 125 to 172g/L), decreased hematocrit of
0.28L/L (normal 0.37 to 0.49L/L) and prothrombin time (PT) of 87% (normal 70 to
100%). Activated partial thromboplastin time (aPTT; normal 24 to 36 seconds)
was not measured because it was falsely not deemed relevant or simply forgotten at
that time.
The diagnosis of compartment syndrome was made and the patient underwent immediate
lateral fasciotomy with a limited incision of approximately 5cm of the anterior
tibial compartment by a rather small skin incision and subcutaneous fascia release
as described by Mubarak and Owen [] (Table outlines the course of disease). The
anterior tibialis muscles protruded instantly and were still vital. The wound was
left open and covered with dressings. Two days later, secondary hemorrhage and foot
drop (M3, active movement against gravity) developed. Thus, he was taken to the
operating room again and a hematoma within the anterior tibial compartment was
evacuated. Postoperatively, his foot drop mildly improved. Again, 2 days later,
another secondary hematoma occurred and he was transferred to a larger regional
hospital in order to treat his condition, with its peculiar laboratory findings and
uncontrollable bleeding, in the realm of an interdisciplinary approach. The lateral
fasciotomy wound was lengthened []. Furthermore, his aPTT was measured and found to be elevated, which
prompted further hematologic evaluation. On the fifth postoperative day, diagnosis
of acquired hemophilia A was finally made by a hematology consultant. Due to massive
unstoppable bleeding of approximately 0.5L/hour accompanied by a fall in hematocrit
from 29% to 19.5%, despite the administration of four units of red blood cells,
recombinant factor VIIa (rFVIIa) was used as a single bleeding control agent and
corticosteroids (1mg/kg body weight) were increased for inhibitor eradication. Of
note, no other blood products or factor replacements were administered. In our
hospital, we also do not administer factor VIII inhibitor bypass activity (FEIBA)
routinely in acquired hemophilia A, but reserve this treatment for refractory
hereditary cases. With this drug therapy in place and the assumption that his
uncontrolled bleeding had been controlled, vacuum-assisted closure (VAC) therapy was
instigated. VAC therapy represents the regional standard therapy for most open
wounds and even though it may monitor the amount of bleeding, it does not provide
visual control. However, secondary hemorrhage occurred again and the patient was
transferred to a university hospital.
In order to halt the uncontrollable bleeding, the wound was covered with a special
dressing with polyvinyl alcohol (PVA) foam, a jetting hose through which the wound
was kept moist and a big bulky absorbable dressing (Figures a, b). On day 15, implementation of VAC therapy
failed again and uncontrollable bleeding led to further therapy with the special
dressing mentioned above (Figures a and ). By this time, the patient had received at least seven units of red
blood cells and almost 20 administrations of NovoSeven® (rFVIIa), usually in
the dose of 7mg each. No other blood products were used except for 1g of tranexamic
acid intraoperatively on his arrival at the university hospital. At that point his
factor VIII was still 3%. For the next 2 weeks, dressing changes were
undertaken at regular intervals of approximately 3 days. Administration of
rFVIIa at regular intervals, at least once a day just shortly before dressing
changes was continued. His factor VIII started to rise slowly, beginning on day 17
with 9%. After 4 weeks, his factor VIII had risen to 41% and VAC therapy could
be applied again in order to condition the wound for definite closure
(Figure b). After another VAC change, and rise of
factor VIII to 88%, a split-thickness skin graft was carried out 1.5 months
after the first fasciotomy. At this time, rFVIIa support was no longer necessary.
After leaving a VAC on top of the split-thickness skin graft for 5 days, mild
delayed wound healing was observed in the anterior middle and posterior distal parts
of the wound (Figure a). This was treated with
AQUACEL® (primary wound dressing) and Mepitel® (wound contact
layer), (wound contact layer), while the rest of the wound was dressed with dry
padding. In the meantime, factor VIII had increased >100% and corticosteroid
therapy could be reduced in a stepwise fashion approximately twice a month. After
discharging the patient into a rehabilitation clinic 2 months postoperatively,
he was frequently seen in our out-patient clinic (Figure b). After 3.5 months, small parts of the wound had still not
healed (Figure c), and a split-thickness skin graft was
carried out for a second time (Figure a to c) Afterward, wound healing went slowly, but finally succeeded
approximately 5 months after his initial presentation while his factor VIII
remained normal and prednisone was stopped 5 months after diagnosis
(Figure ). He had 5 out of 5 muscle strength
globally, but needed to ambulate with crutches after being confined to bed rest for
a long time.
Unfortunately, the patient was hospitalized again after 4.5 months. This time,
he had developed a spontaneous hematoma in his left iliopsoas muscle. It was not due
to a relapse of acquired anti-factor VIII deficiency, but rivaroxaban, which had
been administered for intermittent atrial fibrillation. From that point, oral
anticoagulants were stopped and he only received low-molecular-weight heparins daily
while immobilized. Unfortunately, he developed cholangitis, which was suspected due
to icterus and increased cholestasis/liver parameters followed by an ultrasound and
a computed tomography scan of the abdomen as well as a magnetic resonance
cholangiopancreatography and finally confirmed by a liver biopsy. He is scheduled
for a rehabilitation program in order to regain normal ambulation without crutches
upon his discharge from our hospital.


A 19-year-old female with acute developed abdominal pain of 7 hours duration was referred to our hospital from a local clinic. Abdominal contrast-enhanced computed tomography (CT) that was performed at the local clinic revealed jejunojejunal intussusception owing to a solitary polyp (). She had no specific past medical, surgical, or familial history. Her vital signs were stable. On examination, the abdomen was mildly distended, but rigidity and rebound tenderness were not clearly elicited. All laboratory findings were within the normal range. There was no evidence of definite bowel obstruction in the plain abdominal X-ray taken in our emergency department. Abdominal ultrasonography (US) was performed to evaluate the current status of intussusception. There was still long segmental small bowel intussusception with a target sign at the left periumbilical area (). We decided to perform an emergent operation.
We used a 12 mm supraumbilical port for the camera. 5 mm ports were placed in the right mid- and lower quadrants of the abdomen (). A jejunojejunal intussusception was found to be approximately 20 cm distal to the ligament of Treitz. The intussusceptional segment was approximately 50 cm in length. The involved bowel was dilated, but there was no evidence of bowel ischemia or perforation. Laparoscopic intracorporeal reduction with blunt graspers was performed cautiously. We palpated the remaining small bowels to the terminal ileum using laparoscopic instruments, showing no other masses or abnormalities. Afterwards, a 5 cm extension of the vertical incision was made along the supraumbilical port site, through which the small bowel was exteriorized. The large solitary luminal protruding polyp was located in the jejunum (). Approximately 10 cm of jejunum including the polyp was resected. An end-to-end anastomosis was created by the hand-sewn method. The anastomosed jejunum was placed back into the peritoneal cavity. The extensional incision site was closed. A drain was inserted near the anastomosis site in the pelvic cavity. The total operation time was 137 minutes.
The pathologic report indicated a solitary hamartomatous polyp, measuring 6 cm in maximum diameter (). Microscopically, the polyp showed cystic dilation and hyperplastic glands with inflammatory stroma, which were consistent with a juvenile polyp (). Since the anastomotic bowel was dilated and edematous during the operation, we advanced the patient's diet slowly. The patient was discharged on the seventh postoperative day (POD) without complications. Three weeks after the operation, the patient underwent gastroduodenoscopy, colonoscopy, and small bowel series with double-contrast barium. These examinations revealed no specific findings.


A 29-year-old female has had asymptomatic, slightly erythematous, and hypopigmented pityriasis versicolor-like lesions on her face, neck, trunk, and extremities since the age of five as well as multiple brownish-black, hyperkeratotic, papular plaque, wart-like lesions on the extremities. The lesions progressively increased in number and size with age (Figure A, B). No abnormalities were observed upon examination of the hair, nails, mucosal membranes, and other systems, including abdominal echography and chest X-ray. Histopathology of a flat wart-like lesion showed marked hyperkeratosis, mild acanthosis, and the presence of distinct homogeneous intracytoplasmic inclusion bodies in the large clear cells of the epidermis (Figure C). Additional systemic examinations and laboratory investigations, including an HIV test, were all normal. Topical 5-fluorouracil (5-FU) and imiquimod 5% cream were applied to the small pityriatic or flat wart-like lesions for three days per week at Jikei University School Hospital and Nippon Medical School Hospital. The lesions gradually decreased in size and number. She has been applying ultraviolet (UV) blocker most days and is being followed by Nippon Medical School Hospital.


The patient is a 60-year-old Caucasian male who underwent liver transplantation on 1/24/2011 for cirrhosis secondary to Hepatitis C virus (HCV) infection, with a biopsy proven Stage II HCC (3.2 cm single lesion). He underwent chemoembolization prior to transplant. Surgical pathology of the native liver explant demonstrated a residual 2 cm well-differentiated HCC with no lymphovascular invasion and negative margins.
The patient initially had good liver function but developed recurrent HCV liver disease about one year after transplant and was initiated on antiviral therapy with an interferon, ribavirin, and boceprevir protocol. In December 2013 the patient developed several violaceous, painful, firm, immobile skin lesions on his right anterior chest wall, several inches from his transplant incision (). These lesions were biopsied and demonstrated subcutaneous metastatic well-differentiated HCC (). Immunohistochemical staining was positive for HepPar-1 (). Interestingly, imaging did not reveal any evidence of intrahepatic or pulmonary HCC recurrence. The patient had undergone a percutaneous biopsy of his HCC pretransplant, but this had been done in October of 2010, more than three years earlier. His alpha-fetoprotein (AFP) levels were never elevated.
With clinically and radiographically localized disease, the patient underwent metastectomy with wide local excision and mesh reconstruction in January 2014. Surgical pathology revealed three nodules, the largest measuring 3.7 cm, with each revealing a moderately differentiated HCC. Lymphovascular invasion was also present. After resection, the patient's immunosuppression was changed from a tacrolimus-based to an everolimus-based regimen, due to its potential antitumor properties, and sorafenib therapy was initiated.


The second patient is a 55-year-old Caucasian male who underwent orthotopic liver transplantation on 4/7/2012 for HCV-associated cirrhosis and biopsy proven well-differentiated Stage II HCC (4.9 cm single lesion). He underwent chemoembolization of this mass prior to transplant. Posttransplant surgical pathology of the native liver explant revealed a minimal focus (0.5 cm) of residual HCC at the previous chemoembolization site, as well as another 2.5 cm adenocarcinoma in the perihilar region of the liver, which was suggestive by morphologic appearance and immunophenotypic profiling (positive for CK7, CK20, and mCEA) to be consistent with a mixed HCC/cholangiocarcinoma. This tumor demonstrated microscopic lymphatic, vascular, and perineural invasion with bile duct dysplasia. The lesion had not been seen on pretransplant imaging studies or during his hepatic angiogram during chemoembolization. Because of this, he was maintained with a low-dose immunosuppression regimen and closely monitored for recurrence.
In December 2013, eighteen months following transplant, the patient developed numerous painful skin nodules on his abdomen along the lateral and superior aspects of his previous incision site, chest wall, and scalp (). A biopsy and histopathologic examination of one of the skin lesions revealed tumor cells which were positive for CK7 and EMA immunostains and which were morphologically compatible with metastatic cholangiocarcinoma/HCC (Figures and ). Again, imaging did not reveal any evidence of intrahepatic tumor recurrence, or any other site of metastasis. His AFP levels remained normal as they had been before transplant, but his CA19-9 level in January 2014 was markedly elevated at 5600 U/mL (not done before transplant).
This patient's immunosuppression was also changed from a tacrolimus- to an everolimus-based regimen. He was treated with palliative electron beam radiation therapy to the skin lesions (250 cGy/d given as 14 fractions to 3500 cGy) and was initiated on a systemic chemotherapy regimen of gemcitabine (1000 mg/m2 IV on days 1 and 8) and cisplatin (25 mg/m2 IV on days 1 and 8) every 21 days with the goal of completing six cycles in total. In March 2014, he developed a large pleural effusion, which thoracentesis confirmed as malignant. Due to a rapidly deteriorating performance status, chemotherapy was discontinued and hospice services were initiated.


A 51-year-old man suffered from progressive dysphagia to solids for over about 6 months and slow weight loss of 5 kg was referred to our institution with the presumptive diagnosis of achalasia. Preoperative workup consisted in a careful clinical history, correct interpretation of anamnesis, and symptoms; then esophagogastroduodenoscopy was performed and showed a dilated esophagus without evident mucosal lesion, and the passage through the cardia was more difficult: “crossing snap” passage. Manometry revealed absence of peristalsis and impaired swallow-induced LES relaxation with classic manometric pattern (). The barium swallow showed an emptying defect with “bird beak” sign and narrowing at esophageal junction (). We made a diagnosis of esophageal achalasia and performed a laparoscopic Heller's myotomy with Dor fundoplication (Figures and ). We use the laparoscopic approach to perform this kind of surgery. Several studies demonstrate that this is the best way to treat this pathology. We use Veres' needle placed in Palmer's point to create pneumoperitoneum and then we place five trocars: the first 10–12 mm trocar is placed in supraumbilical region, two 10–12 mm trocars in right and left side, and two 5 mm trocars in paraxiphoid region and left iliac region []. The surgical exploration of peritoneal cavity does not reveal any anatomic abnormality or suspect neoplastic lesions or secondary localizations. Two months after surgery, the patient complained of worsening dysphagia. We repeated several esophagogastroduodenoscopies with numerous biopsies that showed only cardia inflammation and were negative for malignancy. Tumor markers were negative too. Balloon dilatation was performed to improve symptoms. Persisting dysphagia, one month after we performed EUS with biopsies, showed infiltrating gastric adenocarcinoma of the cardia (T3 WHO, Siewert II) (). After staging CT scan, total gastroesophagectomy was performed, with D2 lymph-node resection and Roux-en-Y reconstruction. The surgical specimen contained a thick, hard tumor 3,6 × 2,5 × 1,3 cms located in the gastroesophageal junction (Siewert II), extensively infiltrating the wall and reaching in some areas the subserosal layer (Figures and ). Histological finding was “poorly differentiated adenocarcinoma (WHO: G3)” (Figures and ).


A 50-year-old male presented with dysphagia and progressive painless swelling in the left submandibular region of 4-month duration. As the mass mimicking peritonsillar abscess, it had been drained in the previous Ear Nose Throat clinic and was given narrow antibiotics for a week.
On intraoral examination of the patient, there was a firm bulging of the left soft palate and left lateral pharyngeal wall crossing the midline and pushing the uvula to right side along with a smooth overlying mucosa. Digital palpation of the left tonsil was felt to be firm as well. Although the nontender lesion of the patient caused a considerable degree of dysphagia, no major complaints were reported. He had no fever and denied soreness of his throat. The mass pushing the left tonsil towards the midline of the oropharynx was extended from the left side of nasopharynx to the oropharynx. Externally, there was a swelling in the left submandibular region. Clinical examination did not reveal involvement of any of the cranial nerves. With a clinical diagnosis of parapharyngeal space tumour CT and MRI scan were taken which showed homogenously enhancing tumour measuring 5 × 4 cm in the left parapharyngeal space (). Fine needle aspiration cytology of the mass in the neck was consistent with benign mixed tumour. A transcervical approach was used to gain access to the left parapharyngeal space without any mandible osteotomy. The tumour was completely excised. On gross examination the lesion was 9 × 6 × 2.5 cm (). Histopathological examination showed a neoplasm having an admixture of epithelial and stromal components ().


A 47-year-old female was referred to our clinic with a complaint of swelling being around 3 × 4 cm in diameter, of solid consistency, nonmobile, and not painful when palpated in the lower pole of the right parotid gland. Confirmed by FNAC showing admixed epithelial, myoepithelial, and mesenchymal components consistent with pleomorphic adenoma, the lesion was found to be well defined and encapsulated at magnetic resonance imaging (Figures and ). The lesion was surgically removed by total parotidectomy via a classic transparotid nerve-sparing technique. No complications were observed four years of follow-up after surgery.


A 56-year-old male presented with fullness in the left side of his throat for a year. Intraoral examination showed occupying the left soft palate and left lateral pharyngeal wall crossing the midline and pushing the uvula to right side along with a smooth overlying mucosa. FNAC confirmed the diagnosis pleomorphic adenoma. CT and MRI showed tumour measuring 3 × 4 cm in the left parapharyngeal space (). A transcervical approach was used to gain entry into parapharyngeal space without any osteotomy of the mandible; the tumour was excised. Postoperative period was uneventful.


A previously healthy 23-year-old man presented with ten days of sore throat, myalgias, and night sweats. On admission, the patient was febrile and tachycardic. Physical examination revealed posterior oropharyngeal erythema and shotty cervical lymphadenopathy. Chest radiograph revealed multiple patchy diffuse infiltrates (). Ultrasound of the neck showed nonocclusive thrombus of the left internal jugular vein extending into the proximal subclavian vein. Given these findings, the diagnosis of Lemierre's Syndrome was suspected. Computed tomography (CT) of the chest confirmed the presence of patchy bilateral cavitary lung nodules and pleural effusions.
Blood cultures later were positive for Fusobacterium necrophorum and confirmed the diagnosis. The patient's respiratory status rapidly decompensated five days into the patient's hospital course despite supportive care and prompt initiation of antimicrobial therapy. Repeat chest radiograph demonstrated worsening bilateral pulmonary infiltrates and pleural effusions (). Radiographic evidence, PaO2/FiO2 ratio of 88 mmHg, and the timeline of decompensation were consistent with diagnosis of severe ARDS. The patient was intubated and remained on mechanical ventilation for eight days after a seven-day weaning period (). The highest positive end-expiratory pressure (PEEP) and FiO2 required to maintain oxygenation were 5 cmH2O and 40% respectively, and albuterol/ipratropium bromide was given throughout ventilation. In addition, the patient required chest tube drainage of bilateral empyemas. The patient was started on unfractioned heparin to treat the internal jugular vein thrombus. However, he later developed an acute anemia requiring premature discontinuation of anticoagulation.
The patient's hospital course was further complicated by the development of pyomyositis of the right deltoid requiring surgical debridement and drainage. Abdominal imaging revealed a splenic infarct and transthoracic echocardiogram demonstrated a tricuspid valve vegetation consistent with endocarditis. The patient was discharged 23 days after admission and completed four weeks of outpatient treatment with metronidazole and aztreonam.


A 23-year-old man presented to his primary care physician with complaints of four days of fevers, chills, and sore throat. The patient was sent home on azithromycin for suspected bacterial pharyngitis. The patient presented to the emergency room three days later with worsening symptoms. Physical examination revealed fullness and exquisite tenderness to palpation along the left neck as well as tonsillar exudates.
Laboratory evaluation was notable for leukocytosis with bandemia, acute renal failure, and elevated liver enzymes. CT of the chest demonstrated multiple peripheral nodules suspicious for septic emboli and bilateral pleural effusions. CT of the neck demonstrated thrombus and suppurative phlebitis of the left internal jugular vein. The diagnosis of Lemierre's syndrome was confirmed when blood cultures grew out Fusobacterium necrophorum. The patient was started on broad-spectrum antibiotic therapy and initiated on unfractioned heparin for treatment of the internal jugular vein thrombus.
The patient developed acute hypoxemic respiratory failure and septic shock requiring vasopressor support three days into his hospitalization. He was emergently intubated on a PEEP of 10 cmH2O and an FiO2 of 50% and was given albuterol and ipratropium bromide throughout intubation (). PaO2/FiO2 ratio of 89 mmHg, radiographic evidence of bilateral pulmonary infiltrates, and chronological disease progression were consistent with diagnosis of severe ARDS. Repeat CT scan of the chest showed heterogeneous fluid collections of the thorax requiring decortications and chest tube placement. Laboratory evaluation of the pleural fluid was consistent with empyema and hemothorax, at which point anticoagulation therapy was discontinued. The patient required blood product transfusion for acute blood loss anemia. The patient's respiratory status eventually improved and after a weaning period of five days he was extubated fourteen days later.
Twenty-eight days after presentation, the patient was discharged. He completed four weeks of antibiotic therapy of piperacillin/tazobactam and metronidazole. Interestingly, the patient represented to the hospital two years later with streptococcal pharyngitis. Repeat ultrasound of the neck demonstrated stable, chronic DVT in left internal jugular vein. Given that there was no extension of the original thrombus, the patient was discharged home without further anticoagulation.


A 57 year-old Caucasian female was referred to our department complaining of a pain in her right knee for the last six months. Imaging showed a non-homogeneous sclerotic lesion located in the medial aspect of the distal femur without cortical erosion resembling a benign chondroma (Figure ). Due to local pain, aggravated by local tapping, a CT guided core biopsy was performed by medial access. The histology suggested a diagnosis of low-grade chondrosarcoma.Total-body CT-scan and PET-scan evidenced the absence of distant metastases. A distal femur resection and prosthesis reconstruction was proposed to the patient as curettage but, considering advantages and disadvantage and given that the tumour did not compromise the joint surface, we decided to program a complex osteotomy to preserve joint stability. Computerized tomography (CT) was used to plan the cutting planes to facilitate minimal wide resection (Figure ).The day before surgery, under general anaesthesia, six K-wires were inserted, respecting 3-4 mm of margin, to delimit the tumour defining the resections planes, sparing joint surface and intra-articular space (Figure ). The K-wires were then cut under the skin.The next day, in the operating theatre, the patient was placed in the supine position; to access the surgical area, the medial approach was used; the residual K-wires were identified and isolated externally until the bone surface (Figure ). The scalpels were put externally to K-wires and used as a guide to perform four osteotomies, delimiting a wedge shape resection; the biopsy track was removed en-bloc with the mass (Figure ). Reconstruction was performed by morcellized bone allograft. Histology, performed on the resection specimen, confirmed low grade chondrosarcoma and demonstrated wide resection with a minimum margin of four millimetres evidenced at the posterior osteotomy.At two year follow-up the X-ray shows a quite complete osteointegration (Figure ), the patient is free from disease and able to walk normally with a modest patellar lateral instability. The Musculoskeletal Tumor Society score is 25; the patient is particularly satisfied to have maintained joint integrity.
The main objective in oncological surgical orthopaedics is to achieve a wide surgical margin; it is one of the most important prognostic factors []. Wide surgery can cause important loss of function due to ligaments, muscles, tendons and neurovascular bundles that can be involved in resection.
In low grade tumours obtaining minimal wide resection can allow the patient to maintain a satisfying quality of life. Computed assisted resections can be considered the most advantageous technique to reach the best surgical outcome; unfortunately, navigation systems are only available in specialized centres.
The reported case shows how it is possible to perform a multiplanar complex resection also when navigation systems are not available. This technique allowed resection of the mass, sparing the joint and collateral ligaments, sacrificing just medial patellar retinaculum and can be applied in low-grade tumours where a minimal wide margin can be considered sufficient.
The surgical treatment of low-grade chondrosarcoma of the appendicular skeleton remains controversial. Some authors prefer wide resection margins, while others consider intralesional curettage sufficient for adequate local control [,]. This discordance is probably caused by inter-observer variability in the histological diagnosis of cartilaginous tumours. Etchebehere et al. reported that biopsies yielded the correct diagnosis in 96% of chondrosarcoma cases; In actually, the correct grade was identified in only 46% of the time. This suggests that some chondrosarcomas may be undertreated using intralesional methods based on biopsy grading [].
Our group sustains the use of wide resection for low-grade chondrosarcoma to minimize risk of local recurrence. We also maintain that to reduce the risk of undertreating a lesion that could be more aggressive than expected at definitive histology.


Case 1 is a 32-year-old Italian female pilot of the Italian Air Force (ItAF). At the time of the study she had 680 hours of flight experience. She was assessed with reaching and walking distance memory tests twice in the second trimester of pregnancy and one year after delivery. Circulating levels of estradiol, progesterone and testosterone were measured on three different occasions during the second trimester of pregnancy and one year after delivery in the follicular phase of three different menstrual cycles. Estradiol levels were significantly different (p < .05), that is 798 ± 126 pMol/L and 181 ± 121 pMol/L. Progesterone was 151.6 ± 18.2 nMol/L during the second trimester and dropped to 1.9 ± 0.5 nMol/L (p < .05) during the follicular phase of the normal menstrual cycle. Finally, testosterone remained almost stable throughout the entire observation period: 2.2 ± 0.6 nMol/L during pregnancy vs. 2.9 ± 0.3 nMol/L postpartum (p = n.s.).
Her performance on the memory tests was compared with the performances of 10 women ItAF pilots (mean age 28.9 ± 2.8 years; mean education 18 ± 0) and with the validated normative data reported for the WalCT and CBT in Piccardi et al. []. Both groups (pilots and normative sample) were matched with Case 1 for age, gender and education.
The study was approved by the local ethical committee of the Experimental Flight Center, Aerospace Medicine Department, “M. de Bernardi ” Air Base (prot. n. 2012/09/24 RMAS), Italy. Written informed consent to participate in to the study was provided by Case 1 and by the control groups (both pilots and normative sample).
The CBT [] is a widely used visuo-spatial memory task in which nine blocks (4.5 × 4.5 cm) are fixed on a baseboard (30 × 25 cm) in a scattered array. It tests both working memory and long-term memory. To test working memory (WM), the examiner taps a number of blocks at a rate of one block per 2 s, after which the subject has to tap the block sequence in the same order. The block sequences gradually increase in length (starting from a 2-block sequence); the score is the number of blocks in the longest sequence remembered correctly (block span).
We assessed two aspects of visuo-spatial long-term memory: learning (L) and delayed recall (DR). In the L part of the test, she had to learn an eight-block sequence (following the procedure described in [, ]) demonstrated by the examiner. The learning criterion was reached if she reproduced the correct sequence three times in a row (maximum number of trials: 18). The learning score was calculated by attributing one point for each block correctly tapped until the criterion was reached; then it was added to the score corresponding to correct performance of the remaining trials (up to the 18th; maximum score: 144). Five minutes later, the DR part of the test was administered. The examiner asked Case 1 to reproduce the previously learned eight-block sequence. The score was the number of blocks correctly reproduced (maximum score: 8). She was tested individually in a quiet room with artificial lighting. She sat facing the examiner on a height-adjustable office chair in front of the CBT baseboard. Case 1’s performance on WM and the L and DR tests of the CBT was severely impaired when compared with the performances of the other women pilots and the women in the normative group (see Results section).
To assess her ability to learn and remember spatial locations during navigation we used the Walking Corsi Test (WalCT: 16, 26). In the WalCT, she had to reproduce a walked sequence (previously demonstrated by the examiner) and to stop at different locations. The WalCT is a larger version of the CBT (3 × 2.5 m; scale 1:10 of the CBT), which is set up in an empty room. It consists of nine squares placed on a carpet in the same positions as in the standard CBT. The examiner shows the sequence by walking on the carpet and stopping on each square for 2 s. In this study, she had to repeat the exact sequence by walking and stopping on the squares included in the sequence. Also in the WalCT, she had to perform three different tasks: topographical working memory (TWM), in which a square span was obtained; topographical learning (TL), in which she had to learn an eight-square sequence following the same procedure and adopting the same learning criterion as in the CBT; and topographical delayed recall (TDR), in which Case 1 had to perform the eight-square sequence after five minutes had elapsed.
Results showed that Case 1’s TWM did not differ from that of controls (i.e., women pilots and nonpilots). Case 1’s performance on the TL and TDR after five minutes was comparable to that of controls (see Table and Results section).


A 52-year-old man was diagnosed as being a hepatitis C virus (HCV, Genotype 1) carrier in 1997, but he was not treated. He sought medical advice in regard to hepatitis at a hospital. Combination therapy with weekly subcutaneous injection of pegylated IFN-α-2b (PEG-IFN-α-2b) 100 mg/body and oral administration of ribavirin 800 mg/day were initiated in June 2011. Erythema involving the cervical and dorsal regions appeared, and weight loss was noted 3 months after the initiation of therapy. In January 2012, exacerbation of the erythema, general malaise, muscular pain, and a severe increase in the level of creatine kinase (CK) 23–36,500 U/l were observed. Therefore, PEG-IFN-α-2b and ribavirin were discontinued, and the patient was admitted to our hospital. Heliotrope rash on the eyelids, shawl sign, and protruding and purple-red erythema (Fig. ) were present on the posterior cervical to dorsal and anterior cervical to thoracic regions. Proximal upper limb-dominant muscular weakness of the cervical flexors and deltoid muscle and decreased grip strength were also observed. The blood examination showed increased levels of CK (29,333 U/l), aldolase (288.8 U/l), C-reactive protein (3.94 mg/dl), aspartate aminotransferase (1,106 U/l), alanine aminotransferase (1,171 U/l), and lactate dehydrogenase (1,709 U/l). The thyroid function was normal. Positive levels of antinuclear antibody (1:640, speckled pattern) were detected. Anti-aminoacyl tRNA synthetase (ARS), anti-signal recognition particle, anti-Mi-2 antibody, anti-PM/SCL antibody, anti-MDA5 antibody, anti-ribonucleoprotein antibody, anti-double stranded DNA antibody, and other disease-specific autoantibodies were negative. Complement level was normal. Electromyography showed proximal muscle-predominant myogenic changes. Magnetic resonance imaging of upper limbs showed diffuse myopathy. A skin biopsy showed infiltration of monocytes and CD4+-dominant lymphocytes around blood vessels in the superficial corium layer and in the middle to deep layers of the corium (Fig. ). Although a muscle biopsy was not performed because of the patient’s non-consent, based on these findings, a diagnosis of DM was made [, ], and prednisolone 80 mg/day and IVIG (400 mg/kg/day × 5 days) were initiated. Because a sufficient decrease in the levels of muscle enzymes was not achieved, administration of tacrolimus (3 mg/day) was initiated 13 days after admission, and IVIG was performed twice more. The serum levels of muscle enzymes decreased to the reference range without the reactivation of HCV.


A 15-year-old male patient reported with the chief complaint of swelling on the left side of lower jaw since 9-10 months. He noticed a swelling in the lower jaw in the posterior region, which was initially small in size and gradually increased to the present size. It was initially painless, but the patient now complains of mild intermittent pain, occasionally. The patient was prescribed antibiotics and analgesics by a general practitioner 3-4 times in the last 9 months.
Extraoral examination revealed a solitary swelling in the left mandibular ramus area. The swelling was roughly oval in shape with approximate size of 2 cm × 3 cm. The margins of the swelling were diffuse. The skin overlying the swelling was smooth and normal in color ().
On palpation, temperature of overlying skin of swelling was slightly elevated. The consistency of the swelling was bony hard. Medio-lateral expansion of the cortical plates was noted at angle of mandible. A single left submandibular lymph node of size approximately 1 to 1.5 cm was noted, which was slightly tender and mobile.
Intraoral examination revealed a single small swelling in retromolar area, slightly obliterating the pterygopalatine raphe. Expansion of buccal and lingual cortical plate was noted. A deep periodontal pocket was noted distal to 37 ().
Provisional diagnosis on clinical examination was made as benign odontogenic lesion. Differential diagnosis of ameloblastoma, odontogenic keratocyst, dentigerous cyst associated with 38, calcifying odontogenic cyst, calcifying epithelial odontogenic tumor, and ameloblastic fibroma was considered.
Radiographic examination of the lesion showed a well-defined unilocular radiolucency involving the left side of the mandible which extended anteroposteriorly from the distal surface of the left mandibular second molar to the posterior border of ramus of mandible and superoinferiorly from coronoid notch to the inferior border of mandible. It showed well corticated borders. Resorption of the distal surface of root of the mandibular second molar was also noted ().
CT and 3D CT scan of the lesion showed a unilocular osteolytic lesion in the posterior part of body and ramus of the mandible. Bilateral cortical plate expansion was noted. Perforation of the lingual cortical plate was also revealed (Figures and ). Radiologic examination showed that mandibular left third molar was absent. So the possibility of “dentigerous cyst associated with 38” which was considered in the provisional diagnosis was ruled out.
Routine hemogram was performed and all the blood indices were within normal limits. An incisional biopsy was then performed, which on histopathologic examination revealed a cystic cavity lined by odontogenic epithelium and a connective tissue capsule. Epithelium shows palisaded basal layer resembling ameloblast-like cells and a superficial layer showing stellate reticulum-like cells. The connective tissue was dense, fibrous with collagen fibers arranged haphazardly. Numerous engorged and dilated blood vessels were seen ().
From the above clinicopathological features, a diagnosis of unicystic ameloblastoma was made. The patient then underwent a mandibular segmental resection involving condyle and reconstruction was done with 2.7 mm titanium reconstruction plate and iliac crest graft, under general anesthesia. Healing was uneventful. Patient was followed up after 1 month with radiographic evaluation which showed complete healing of wounds and well maintained graft ().
We received a segmental resected specimen involving condyle, coronoid process, upto ascending ramus, which showed perforation in the anterior border of ascending ramus. Histopathological examination of the excisional biopsy specimen showed lesional tissue that consisted of a cystic cavity lined by odontogenic epithelium and connective tissue capsule. The epithelium showed cuboidal or columnar basal cells with hyperchromatic nuclei, nuclear palisading with polarization, cytoplasmic vacuolization with intercellular spacing, and subepithelial hyalinization and superficial layer showing stellate reticulum-like cells. There was also proliferation of these cells in cystic lumen in a plexiform pattern. The cells are arranged in interconnecting strands and cords with peripheral palisaded layer and central stellate reticulum-like cells (). Tissue material resembling an odontogenic keratocyst lining was not observed, even with serial sections of tissue. So possibility of ameloblastic transformation of odontogenic keratocyst was also excluded.
According to the classification suggested by Ackermann et al. [], it was classified as unicystic ameloblastoma subgroup 1.2 which is also known as plexiform unicystic ameloblastoma.


An 11-year-old male child reported to the Department of Pedodontics and Preventive Dentistry, with a chief complaint of an extra tooth. The intraoral examination confirmed the patient's chief complaint and an erupted supernumerary tooth, located palatally, tuberculate in shape was located (). Radiographic examination revealed the presence of two supernumerary teeth, one erupted and one impacted, both in normal vertical alignment (). The medical history of the child was nonsignificant and he was born to non- consanguineous parents. The treatment plan involved surgical removal of both the mesiodentes after taking parent consent. Prior to surgical procedure, complete hematological investigations were performed to rule out any possible complications. The child was administered local anesthesia (greater palatine and nasopalatine nerve block). The palatally erupted mesiodens was extracted first () and a full thickness palatal flap was raised using a mucoperiosteal elevator. The impacted tooth was exposed, luxated out of its socket and removed (). Hemostasis was achieved and the flap was replaced back and sutured with nonresorbable black silk suture. Postsurgical instructions were explained to the patient and he was kept on analgesic and antibiotic coverage. Patient was instructed to maintain a good oral hygiene using a soft bristle toothbrush and chlorhexidine mouthwash twice daily. The recall visits was scheduled for 1 week for suture removal and evaluation of healing followed by a 6 monthly recall pattern for continued observation. The patient is on follow-up for the last 1 year.


A 9-year-old female patient presented at the Department of Pedodontics and Preventive Dentistry, with a chief complaint of a sharp pointed tooth inside oral cavity which irritated her tongue. Intraoral examination revealed an erupted conical mesiodens in the anterior palate (). Radiographic examination revealed two mesiodentes, one erupted and one impacted, both conical in shape (). Treatment plan involving surgical removal of both mesiodentes was explained to the parents. Complete hemogram and parental consent was obtained prior to initiation of the surgical procedure. The case demonstrated the possibility of occurrence of the impacted mesiodens in a more vestibular location, as detected by SLOB technique. The palatally erupted mesiodens was first removed and labial approach for surgical removal of impacted mesiodens was planned. For this, a labial apically repositioned flap was raised using a mucoperiosteal elevator (). The bone overlying the crown of the tooth was removed using carbide bur and saline spray. The tooth was exposed and removed from its socket (). The flap was replaced and sutured with black silk suture and postoperative instructions were given to the patient. The patient is on follow-up and healing is uneventful ().


A 7-year-old female child reported to the Department of Pedodontics and Preventive Dentistry, accompanied with her parents, who were anxious about delay in eruption of an upper front tooth. Intraoral examination revealed missing permanent left maxillary central incisor. Intraoral periapical radiograph revealed an impacted conical mesiodens with inverted alignment (). Root apices of the permanent central incisors were not closed. The surgical intervention was delayed till the completion of root closure of central incisors. The patient was on follow-up for 1 year following which the supernumerary was extracted surgically after central incisor had obtained root closure. The healing is uneventful and the central incisors have now erupted in the oral cavity.


A 10-year-old boy sustained periorbital injuries from road traffic accident (RTA), and had left orbital floor fracture. CT confirmed the fracture # and the left orbital floor was explored and repaired with titanium mesh via transconjunctival approach and his pre-operative problems of diplopia and restriction of gaze was resolved ( to ).


A 12-year-old boy sustained a fracture in left parasymphyseal region, which was treated in a different center with reduction followed by circum-mandibular wiring and maxillomandibular fixation. The patient presented 6 months later, with a history of extraoral discharging sinus from the lower border of mandible fractured site, which started after 1 month of the initial operation. The orthopantomogram (OPG) revealed an unerupted left lower 1st premolar which was pushed to the lower border fracture site due to wiring. The area was reoperated with, curettage and removal of the displaced tooth, to restore normal function and occlusion ( to ).


A 3-year-old boy sustained a hairline crack in the body of the mandible, following a fall. X-rays revealed an undisplaced hairline crack in the left mandible which was treated conservatively ( and ).


A 12-year-old boy sustained an undisplaced fracture in the left parasymphyseal region of mandible, following an RTA, and 3D CT scan revealed the same. The patient was treated conservatively and the patient’s 6-month follow-up pictures reveal normal occlusion and mouth opening ( to ).


A 3-year-old boy sustained head injury and left periorbital trauma, following a fall from 2 storey open terrace. The CT scan confirmed a left maxillary fracture, which was treated conservatively. The 5 weeks postoperative picture revealed minimal swelling, and normal functionality of mouth opening, occlusion and vision ().


An 8-year-old boy sustained left zygomatic-maxilla fracture, following a fall from height (tree) and reported to OPD, 3 weeks later, with a firm left cheek hematoma, X-ray revealed a fractured maxilla, with little displacement. The late presentation made the case a conservative management, with slow and subsequent recovery and function ( and ).


A 4-year-old boy sustained head injury with a huge periorbital swelling of right eye, following a fall from height. The 3D CT revealed a fracture nasal bone and frontal bone fracture. The treatment was conservative due to his head injury ( and ).
with no obvious deformity


In June 2012, a 12-year-old female presented to the Department of Breast Cancer Surgery, Tangshan People’s Hospital (Tangshan, China) with a painless lump close to the left breast areola. The patient had first noticed the lump two months prior to presentation, during which time there had been no significant increase in the sixe of the lump. There was no history of local trauma, and no family history of relevant malignancy. Examination revealed a 4.0×3.0-cm, firm, well-circumscribed, mobile mass located eccentrically beside the areola at the 3 o’clock position. No nipple discharge or inversion were observed, and no clinical alterations were found in the ipsi- or contralateral lymph nodes. Ultrasound examination of the breast showed a well-defined hypoechoic nodule measuring 4.0×3.9×2.5 cm in size, without calcification or evidence of invasion (). The mass was considered as benign in appearance and diagnosed as a fibroadenoma of the breast.
Not only for this reason, but also at the patient’s request, core biopsy of the tumor was not performed and the patient therefore immediately underwent surgical removal of the nodule under local anesthetic. The macroscopic examination of breast operative specimens revealed the presence of a nodule measuring 4.0×4.0×2.9 cm, and the lesion was void of an intact capsule. The cut surface appeared solid and gray-white. Microscopic analysis of hematoxylin and eosin-stained sections showed tumor cells arranged in lobules separated by dense fibrous septa (). The lobules showed a tubuloalveolar and glandular pattern with abundant secretion, which is usually pale pink (). A honeycomb pattern was also observed. The tumor consisted of cells with minimal to middle nuclear atypia with abundant slightly basophil cytoplasm, as well as intracytoplasmic vacuoles. The presence of secretions which are strongly periodic acid-Schiff-positive are a hallmark of SBC () (). No nuclear division was observed in the present case. Immunohistochemistry was also performed, revealing that the tumor cells were negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2, and showed positive staining for S100 (). A diagnosis of secretory breast cancer was then established. Axillary sentinel lymph node (SLN) biopsy was also performed. The SLN was found to contain isolated tumor cells (), and according to the NCCN Clinical Practice Guidelines in Oncology of Breast Cancer (), cases of no metastases can be considered as SLN. Therefore, the patient could avoid complete axillary dissection.
Since the mass was close to the breast areola and the patient was younger than 35 years old, the patient seemed better to receive a radical mastectomy. However, the patient wished to undergo a partial resection for the tumor, rather than the radical mastectomy. The breast magnetic resonance imaging revealed no multiple lesions and the patient subsequently underwent a left breast conservative surgery. The histopathology of operative specimens revealed no evidence of residual neoplasia within the breast. After multidisciplinary consultation (including with a pediatric oncologist), adjuvant chemotherapy was administered to the patient. This comprised doxorubicin (60 mg/m2, IV) and cyclophosphamide (600 mg/m2, IV) on day one, cycled every 21 days for four cycles, followed by docetaxel (100 mg/m2, IV) on day one, cycled every 21 days for four cycles. No radiotherapy treatment was performed.
Periodic follow-up examinations after completion of the surgical and chemotherapeutic treatment have shown no evidence of either local regression or distant metastases to date and, one year later, the patient remains free of disease.


A twenty-three-year-old African-American female with sickle cell trait presented to the emergency room with periumbilical and right-sided back pain associated with poor appetite and ten-pound weight loss over 4 months. She denied gross hematuria, dysuria, or additional urinary symptoms. She was a previously healthy nonsmoker with paternal family history of sickle cell trait. Physical examination was pertinent for fullness in the right flank and left supraclavicular lymphadenopathy. Laboratory findings revealed hemoglobin of 11.3 g/dL, platelet count of 269,000 per mm3, and normal LDH of 147 IU/L. Computed tomography (CT) scan of the neck, chest, abdomen, and pelvis demonstrated a 12 cm heterogeneous right renal mass () with retrocaval, aortocaval, and paraaortic lymphadenopathy. In addition, there were bilateral pulmonary nodules (largest in right upper lobe measuring 1.8 × 1.4 cm), left pleural-based nodules (largest at the level of diaphragmatic pleura measuring 2.6 × 1.9 cm), and right hilar (2.5 × 2.2 cm), left supraclavicular, and bilateral cervical lymphadenopathy. MRI of the brain showed no evidence for intracranial metastasis.
Biopsy of left supraclavicular lymph node revealed high-grade renal medullary carcinoma with prominent lymphovascular tumor emboli. The tumor cells were eosinophilic, containing large nuclei and focally prominent nucleoli with brisk mitotic activity. The neoplastic cells stained positive for AE1/AE3, cytokeratin CAM 5.2, epithelial membrane antigen (EMA), E-cadherin, cytokeratin 7, and cytokeratin 19 on immunohistochemical analyses (). The cells stained weakly positive for c-Kit and negative for cytokeratin 20, S100 protein, carbonic anhydrase IX, mucicarmine, and CD10. Cytogenetic studies performed on the lymph node isolated a clone of cells with duplication of the long arm of chromosome 1 (resulting in partial trisomy 1q) and a derivative chromosome 22 with chromatin material of unknown origin attached to the long arm (resulting in partial monosomy 22q). Fluorescence in situ hybridization (FISH) for transcription factor E3 (TFE) gene translocation was negative.
Treatment was initiated with dose-dense (dd) MVAC consisting of methotrexate 30 mg/m2 on day 1 followed by vinblastine 3 mg/m2, doxorubicin 30 mg/m2, and cisplatin 70 mg/m2 on day 2 of a 14-day cycle as described for metastatic urothelial carcinomas []. She received growth factor support with pegfilgastrim on day 3 to reduce the risk of neutropenic fevers. Treatment with four cycles of dd-MVAC was associated with a significant reduction in size of renal mass from 9.3 cm to 5.9 cm with areas of necrosis on a CT scan of chest, abdomen, and pelvis (). There was near-complete resolution of right upper lobe and left lower lobe parenchymal lung nodules and retroperitoneal lymphadenopathy. Multiple pleural-based nodules in the left hemithorax and right hilar lymph node decreased. Two additional cycles of dd-MVAC were administered and a follow-up CT scan showed continued improvement in size of renal mass to 4.4 cm, improvement in retroperitoneal, hilar lymphadenopathy, and parenchymal lung lesions. The subject developed grade I renal insufficiency and grade II chemotherapy-induced nausea and vomiting (CINV) for which the cisplatin dose was reduced by 25% after the initial two cycles. Overall, she tolerated six cycles of dd-MVAC extremely well, with no hospitalizations.
After achieving an excellent partial response to neoadjuvant chemotherapy, the patient underwent right radical nephrectomy with complete, bilateral retroperitoneal lymph node dissection without complications. Pathology revealed a gross tumor resection size of 6.2 cm. Viable carcinoma comprised approximately 2–4% of the tumor volume showing neoplastic cells with rhabdoid features in a background of extensive fibrosis and chronic interstitial inflammation. All surgical margins were negative for tumor. Two of 11 lymph nodes (one paracaval and one preaortic from the level of the aortic bifurcation) were involved with carcinoma (0.7 cm in greatest dimension) with no extracapsular extension. Pathologic TNM stage was assessed as pT1b N1 M1. Immunohistochemistry revealed a complete loss of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) expression. Subsequently, she underwent video assisted thoracoscopy and wedge resection of right lower lung lobe. Pathology showed inflammatory changes with no evidence of residual malignancy.
Follow-up imaging in the form of CT chest, abdomen, and pelvis was obtained every four months and at one year from diagnosis she showed no recurrence of disease. At 16 months from initial diagnosis, she developed shortness of breath and restaging scans showed disease recurrence with hepatic, pulmonary lesions and bilateral pleural effusions. She had a rapidly progressive decline after relapse and died without receiving any further therapy.


A 15-month-old male, with a past medical history significant for microcornea, was admitted to our hospital with progressive peripheral edema for two weeks. Parents reported 4-5 explosive diarrheal bowel movements per day for approximately 4 weeks prior to presentation. The bowel movements were described as yellow-green in color, with associated “little globules,” liquid to pasty in consistency without blood or mucus. Shortly before admission, he began vomiting after almost every meal. On physical exam he was ill-appearing, afebrile, with significant facial and upper and lower limb edema. Laboratory investigations revealed the following: white blood cells, 14.5/mm3; C-reactive protein, <0.03 mg/dL; total protein, 3.6 g/dL; plasma albumin, 2.4 mg/dL; no abnormalities in liver, renal, and thyroid function tests; normal results of urinalysis and no proteinuria. Immunoglobulin A tissue transglutaminase, Epstein-Barr virus profile, and Cytomegalovirus profile were all negative. Stool for bacterial and viral cultures, Giardia antigen, white cells, and blood occult were also negative. Stool for alpha-1 antitrypsin was elevated at >1.33 mg/g (normal <0.62 mg/g), consistent with protein losing enteropathy. Upper endoscopy showed edematous antral and duodenal mucosa. The rectal and sigmoid mucosa appeared normal on flexible sigmoidoscopy. Biopsies from the colon and rectal mucosa showed patchy increased subepithelial bands of collagen of variable thicknesses consistent with collagenous colitis. The collagen deposition was highlighted with Masson trichrome staining (). The gastric biopsy contained chronic gastritis with increased fibrosis and collagen deposition but no clear subepithelial collagen band (). The duodenal biopsy showed foci of possible increased collagen in the mucosa, but not enough to be diagnostic for duodenal involvement of collagenous mucosal inflammatory disease (). Budesonide was then initiated at 3 mg per day for 5 days but he continued with diarrhea and protein loss requiring parenteral nutrition replacement. Intravenous methylprednisolone was then added at 2 mg/kg/day and a marked improvement in his symptoms was noticed. He gradually tolerated oral intake and was weaned off total parenteral nutrition over a one-week period. He was discharged home on prednisolone 1 mg/kg/dose in addition to 3 mg per day of budesonide. He continued to do well after weaning off prednisone over two months. An attempt to discontinue budesonide led to worsening diarrhea and a requirement for reinduction for remission with oral steroid along with budesonide. He was then maintained on 3 mg of budesonide per day and continued to do well clinically. Upper endoscopy and colonoscopy were repeated 5 months later and showed persistent collagenous colitis without gastric or duodenal involvement. Biopsies at endoscopy and colonoscopy one year after presentation were normal on maintenance budesonide. He continued to do clinically well thereafter with no GI symptoms.


A 50-year-old woman from Montenegro presented to our institution with shortness of breath that was associated with pleuritic chest pain. Her symptoms began during a long overseas flight and progressively worsened after disembarking the plane.
She also complained of left leg pain and swelling. The patient's past medical history was significant for hypertension and diabetes mellitus. She never smoked and was not on any hormonal treatments. On physical exam, heart rate was 115, respiratory rate was 32, and she appeared to be in mild distress. Bilateral breath sounds were clear to auscultation. Of note, the patient had swelling of the left lower extremity and foot with some dark discoloration, absence of distal pulses, and impaired sensation. Initial laboratory tests revealed respiratory alkalosis (pH 7.45, pCO2 28, paO2 111, and HCO3 22.5), a normal coagulation profile, and a D-dimer of 1300 ug/L. Cardiac enzymes were within normal limits. EKG showed sinus tachycardia. A CT scan of the chest revealed bilateral pulmonary embolisms (). Arterial and venous Doppler imaging of both lower extremities showed an occlusive left popliteal vein thrombus and an occlusive left common femoral artery thrombosis.
A heparin drip was initiated immediately and the patient was admitted to the intensive care unit with a low threshold to proceed to the operating room for either thrombectomy or catheter-based thrombolysis. Fortunately, few hours following the initiation of treatment a significant improvement was noticed in the patient's shortness of breath and chest pain. Additionally, her left leg swelling and skin discoloration were markedly improved as well; however, she continued to have a dull aching pain in her left foot with weak, monophasic, dopplerable distal pulses. The patient underwent a CTA of her left lower extremity with distal runoff, which demonstrated a subocclusive filling defect extending from the origin of the left common femoral artery to the distal superficial femoral artery, with normal popliteal and three-vessel runoff to the ankle (). With an unclear source of this arterial thrombosis, an echocardiogram was obtained to rule out a cardiac source of an acute embolus, as well as a paradoxical systemic arterial embolism through a patent foramen ovale (PFO). The transthoracic echocardiogram was normal with no evidence of an intracardiac shunt, right heart strain, or mural thrombus. Given the acute nature of the patient's condition and her only partial response to nonoperative management, the patient was taken to the operating room. An open mechanical left iliofemoral arterial thrombectomy was performed using a Fogarty catheter. A large clot was retrieved from both the superficial femoral and external iliac arteries (). Postoperatively the patient's symptoms dramatically improved and her physical exam revealed palpable distal pulses in her left foot with mild reperfusion symptoms.
Although the initial results for hypercoagulation workup such as protein C, protein S factor II assay, and ANA screen were all within normal limits, these results are difficult to interpret in the setting of acute thrombosis and anticoagulant medication therapy. She was discharged on Warfarin with a plan for full hypercoagulation workup after discontinuing the Warfarin in 6 months with a potential need for long life anticoagulation pending the workup. After discharge, the patient traveled back to her homeland and was unfortunately lost for followup.


A 76-year-old man of Caucasian ethnicity was hospitalized for syncope 2 years before index hospitalization. Comorbidities included liver cirrhosis (Child-Pugh A) due to non-alcoholic fatty liver disease, type-2 diabetes, hypertension, and suspected Alzheimer-type dementia. Etiologically unclear transitory ischemic attacks had been diagnosed before. Holter electrocardiogram (ECG) showed a first-degree atrioventricular block and three episodes of bradycardia with minimal cardiac frequencies of 37bpm that were deemed unlikely as a cause for syncope. Schellong test revealed a hypodynamic cardiac response, that is, his heart rate stayed at 50bpm after change from supine to upright position. Hypoglycemia (under insulin therapy) was not detected prior, during or after hospitalization. A concomitant AKI (AKIN 2, maximum creatinine: 297μmol/L) was regarded as pre-renal, and syncope was attributed to arterial hypotension and hypovolemia. Following intravenous rehydration, he was discharged with spironolactone 150mg/day and propranolol 100mg/day for liver cirrhosis, donepezil 10mg/day for suspected dementia, amlodipine 10mg/day, and insulin subcutaneous injection (average: 50IU/day).
At index hospitalization, he (body mass index: 35.2) was admitted with nausea and vomiting for 3 days, as well as dizziness due to a presumed hepatic encephalopathy. On admission, vital parameters including blood pressure (150/80mmHg), heart rate (62bpm), and temperature and physical examination including cardiopulmonary state were unrevealing. Specifically, ascites and peripheral edema were absent. He was oriented to person, place, and time. Physical reactions were slowed though. Compared to baseline values prior to hospitalization (serum creatinine: 139μmol/L, estimated glomerular filtration rate
[]: 43.2μmol/L/1.73m2), serum creatinine was elevated on admission (Table
). Glutamate-oxaloacetate transaminase (0.64), gamma-glutamyltransferase (2.46), and international normalized ratio (1.13) were slightly elevated; serum albumin (31g/L) was decreased. Other laboratory values including inflammation parameters (leukocyte count, C-reactive protein), total serum protein, bilirubin, glutamate-pyruvate transaminase, and alkaline phosphatase were within normal range. Partial respiratory insufficiency and metabolic acidosis (pH: 7.326, oxygen partial pressure: 55.8mmHg, carbon dioxide partial pressure: 29.0mmHg, bicarbonate: 14.7mmol/L, base excess: -9.7) were found on admission. His urine test showed microalbuminuria (<300mg/day), microscopic hematuria, and leukocyturia consistent with urinary tract infection. Concomitant medication largely remained unchanged since discharge 2 years ago. ECG showing sinus rhythm and the known first-degree atrioventricular block was without change since the last ambulatory cardiology check 1 year before. During hospitalization, he was bed-bound. Gastroscopy proved helicobacter-negative gastritis. An intravenous fluid challenge using sterile saline was performed for suspected, however clinically inapparent, hypovolemia. Despite fluid challenge, oliguria suddenly developed shortly after admission, serum creatinine remained high (Table
). A pre- and post-renal cause of AKI was excluded. Myocardial infarction as a possible cause of hemodynamic instability was ruled out in repeat laboratory and ECG examinations. Echocardiography showed a normal systolic left-ventricular function, yet left-ventricular hypertrophy and diastolic dysfunction accompanied by a mild mitral regurgitation and an enlarged left atrium. Nephrotoxins and/or nephrotoxic medications were not applied. Euglycemia was verified during the whole index hospitalization. Kidney sonography revealed normal-sized kidneys with a centralized arterial perfusion (Figure
), and an increased renal resistive index (1.0 on both sides) reflecting a diastolic no-flow condition. Of importance, a bradycardia (less than 50bpm) was present during ultrasound. Propranolol was discontinued at once, thereafter urine output improved (Table
). In a Holter ECG 3 days following propranolol cessation, an intermittent third-degree atrioventricular block with pauses for less than 3 seconds was found (Figure
). He was subjected to pacemaker insertion on day 11 after admission. Thereafter, renal function in terms of urine output and serum creatinine remained stable. Beta-blocker therapy was reinstituted. By discharge to a rehabilitation facility 14 days after pacemaker insertion, renal function in terms of serum creatinine further improved (Table
), body weight remained constant in comparison to admission, and peripheral edema was absent.
At discharge, spironolactone 50mg daily, propranolol 25mg thrice daily, amlodipine (5mg daily), donezepil (10mg daily), and antidiabetic medication including sitagliptin and insulin were maintained. Ramipril (5mg daily), torasemide (20mg daily), acetylsalicylic acid (100mg daily), simvastatin (20mg daily), and pantoprazole (20mg daily) were prescribed.
Renal recovery continued after discharge, the prehospitalization level of creatinine was reached within 1 month following discharge.During the 4 months following discharge, amlodipine and ramipril were discontinued. Otherwise, medication has not changed. Syncope has not occurred again. His overall condition improved considerably. He was not bed-bound; he was alert and he could walk short distances with walking aid. Symptoms consistent with hepatic encephalopathy or progressive dementia were not present. Four weeks after discharge, his mini-mental state examination yielded 22 (out of 30) points. A neurologic reassessment was recommended regarding the ongoing donepezil treatment. At 4-months follow-up, sonography of his kidneys showed persistent renal resistive index of 1.0 on both sides (Figure
).


An 20-year-old male presented to the hospital with chief complaints of fever, chills, and shortness of breath. The chest radiograph at admission showed right middle lobe pneumonia with heavy growth of Streptococcus pneumoniae from his sputum without any bacteremia in his blood. On further evaluation, CT scan of the chest revealed right middle lobe and lingular infiltrate with evidence of central bronchiectasis () and CT scan of the sinuses showed severe congestion and inflammation of the frontal, maxillary, and ethmoid sinuses. The pulmonary function test showed predominantly obstruction of the small airways with no improvement after albuterol administration. A marked decrease in the diffusion capacity of the lung with a restrictive pattern was also noted. Further tests were ordered to explore the possibility of a multisystem disease and semen analysis showed a marked absence in motility of the sperm, thereby explaining PCD to be the probable cause of all his symptoms.
Biopsy of the nasal mucosa was obtained to prove the preliminary diagnosis and to obtain tissue for genetic testing. On electron microscopy of the biopsy specimen most of the cilia present in the epithelial cells of the ciliated epithelium lacked the inner dynein arms and some cilia lacked both dynein arms, thereby confirming the diagnosis of PCD.
During the subsequent visit for followup, the patient complained of worsening of his shortness of breath without any response to medical and respiratory therapy. At this time the patient was also found to have pancytopenia with platelet count of 57,000 cells/cu·mm, WBC count of 4,700 cells/cu·mm, and hemoglobin was 7.2 g/dL. Vitamin B12 and folate levels were normal and no source of infection could be identified after repeated tests and serial scans. Serology for Epstein-Barr virus, HHV1, HHV2, and mumps was negative. The workup for anemia only revealed a low reticulocyte count indicating bone marrow failure being the probable cause of pancytopenia. The patient underwent a bone marrow biopsy to identify the cause of marrow failure in the absence of any infection which revealed high-grade dysplasia and atypical localization of immature precursor cells in the bone marrow clinching the diagnosis of myelodysplastic syndrome (MDS). The bone marrow aspirate was sent for flow cytometry analysis and the results showed deletion of the D7S522 region in the long arm of chromosome 7 (also deletion of D20S108 of chromosome 20 at q12) characteristic of myelodysplastic syndrome or an evolving acute myeloid leukemia. Also observed in flow cytometry was a deletion in the short arm of chromosome 7 at sites 7p14-21, responsible for protein DNAH11, one of the proteins involved in the assembly of the dynein arm. FISH analysis was also done on this patient and was observed to be in concordance with flow cytometry results. Further cytogenetic testing did not reveal the presence of any further mutations. This concurrent presence of two deletions in the same chromosome helped to understand the probable etiology in development of these two distinct rare conditions simultaneously and their presentation in such a short rapid time interval. IPSS-R score was 4, classified as intermediate with a median survival time of 3 years and time for 25% of patients to progress to AML: 3.2. The severity of the disease processes warranted referral to a bone marrow transplant center where he was promptly pretreated with Fludarabine and Busulfan and underwent homologous stem cell transplant from his HLA compatible brother.
Regular followup at the tertiary care center showed good response of the transplanted bone marrow without any evidence of graft versus host disease (GVHD). He is also regularly followed up by a pulmonologist for management of his PCD.


A 50-year-old patient Caucasian female is an outpatient of the Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Brazil. She has declared to be neither tabagist nor elitist. The clinical examinations (involving physical and laboratory determination) have suggested the diagnosis of metabolic syndrome (MS). This diagnosis of the patient was established for a clinical physician of this multiprofessional team involved in the project who has followed, as inclusion criteria for metabolic syndrome, the guidelines described by the International Diabetes Federation []. The patient was not doing another modality of exercise; she was under medication and has followed the recommendations of this clinical physician. As some authors [, ] have suggested that the WBV exercises might interfere in some clinical conditions of the patient with MS, participating in an investigation involving the effect of vibrations generated in an oscillating platform was suggested to her.
This investigation was approved by Ethic Committed under the reference CEP/HUPE 2874/2011, CAAE 0025.0.228.000-11, and the authors have followed the concepts of the Declaration of Helsinki and this research has protected the life, health, privacy, and dignity of the human. All the patients, as well as this patient of this work, read and signed a written informed consent.
The oscillating platform (Novaplate fitness evolution, DAF Produtos Hospitalares Ltda, São Paulo) used in the study is based in a reciprocating vertical displacements system. It is a side-alternating vibration device working as a teeterboard (28 cm × 58 cm) with amplitude of 0 (zero) in the center of the platform up to the maximum (7.07 mm) in the edge. The displacements are on the left and right side of a fulcrum; while one is up, the other side is down and vice versa. The position of the feet of the subject on the platform will define the amplitude that is used in the exercise and it is controlled during the exercise.
Sessions of the whole body vibration protocol: in the first session, to aid in the proprioception, the subject was sat in a chair [] with the feet under the teeterboard of the platform. The frequency used was 5 Hz during 1 min and both feet were in position with amplitude of 2.07 mm in both sides of the teeterboard with a rest of 1 min. This procedure was repeated once again. Then, the patient changed her feet to the amplitude of 4.04 mm in both sides of the teeterboard. The frequency used was the same during 1 min with a rest of 1 min. This procedure was repeated once again. Then, the patient changed her feet to amplitude of 7.07 mm in both sides of the teeterboard, using the 5 Hz of frequency during 1 min, with a rest of 1 min. This procedure was repeated once again.
In the second session, the subject was stood up with both feet under the platform in the amplitude of 2.07 mm of the teeterboard and the frequency used was 5 Hz during 1 min. In this step the man was instructed to be in a comfortable squat position for 1 min of rest. It was repeated once again with a rest of 1 min. Then, the patient still stood up and changing her feet to the amplitude of 4.04 mm sustained the squat comfortable position for 1 min rest. The procedure was repeated once again at the same frequency and amplitude with 1 min of rest. Finally, the patient stood up and changing her feet to the amplitude of 7.07 sustained the squat comfortable position with 1 min of rest. The procedure was repeated once again at the same frequency and amplitude with 1 min of rest.
In the next sessions, the procedures of the second session were repeated in the same conditions in the next sessions; however, in each session, the frequency used was increased in one Hz up to 14 Hz.
In the several steps of the protocol, a physiotherapist was close to the subject.
Anterior trunk flexion [] was assessed with the subject in orthostatic position with the knees passively extended followed by carefully of an anterior flexion of the trunk. The distance between the third finger of the hand to the floor (DBTFF) was determined, in each session, just before starting the session and just after the end of each session, as described in the protocol reported in the .
The biggest DBTFF was found just before the first session and was considered 100%. The percentages to the other measurements in the different session were determined related to the 100% of the first session.
An automated device (OMRON, model HEM-7113, China) was used to verify the systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHg) and the heart rate (HR) (beats per min-bpm), which were measured on the right arm of seated subjects after a 10-minute rest. These determinations were done just before the first session and just after the last session. Means of three readings of SBP, DBP, and HR were used in the analyses.
Statistical analysis was performed to compare the change in anterior trunk flexibility, SBP and DBP and HR before the first and after the last session of WBV exercise. The level of significance was set at P < 0.05.


A female infant of Hispanic descent was born large for gestational age (LGA) at 4.61 kg at 37 weeks gestation to a 31-year-old mother. Pregnancy was uncomplicated except for fetal macrosomia. At birth she had clinical features consistent with BWS that included macroglossia, hemihypertrophy, small omphalocele and high α-fetoprotein (36300 ng/ml). Genetic testing showed L1T1 (KCNQ1OT1) hypomethylation and H19 hypermethylation. On day of life (DOL) 1 she developed severe hypoglycemia, requiring continuous glucose infusion. While she was on frequent feeds she had severe hypoglycemia with relative hyperinsulinism: nadir glucose 10 mg/dl, insulin 2 uIU/mL, β-hydroxybutarate 1.2 mg/dl, and noncontributory cortisol and growth hormone levels. Her brisk glucose rise in response to glucagon was supportive of hyperinsulinism as well. She was started on diazoxide for persistent hypoglycemia on DOL10 and despite very high doses, up to 22 mg/kg/day she remained hypoglycemic, and developed pulmonary congestion. She was then switched to sc octreotide every 8 hours, starting at 15 mcg/kg/day and was titrated up to 40 mcg/kg/day. She was converted a week later to LAR starting at 6 mg monthly, which was 30 times her daily dose that kept her glucose steady. However, she was not fully controlled with her hypoglycemia on that initial LAR dose, and she received an extra dose of 3 mg LAR a few days later. Following that she received 9 mg every month and remained euglycemic past the age of 2 years old, when we felt we can lower her dose of LAR gradually. She is currently 3 years old and maintains euglycemia on a monthly dose of 7 mg of LAR and tolerates 8 hours or longer of overnight fast.
Her high α-fetoprotein trended down over 12 months (36300 to 20 ng/ml). Having being monitored with frequent ultrasounds, she was diagnosed with Wilms tumor stage I favorable histology at age 2 and underwent a right lower partial nephrectomy and had received chemotherapy without any complications.
Patient didn’t develop any side effects from the LAR and maintained normal linear growth and weight; IGF-1 was normal prior to treatment and she continued to grow well with her height at the 75th percentile at the beginning of treatment and she remained at that percentile and above, therefore IGF1 level was not repeated. She had no gallstones or sludge.


A female infant of Hispanic descent was born LGA at 1.46 Kg at 26-4/7 weeks to a 32-year-old mother. Neonatal course complicated by tracheostomy secondary to macroglossia, hemodynamic instability and hypotension requiring daily hydrocortisone replacement at 15 mg/m2/day, transient primary hypothyroidism with TSH over 300 uIU/mL likely due to iodine exposure during NICU stay when she underwent PDA closure, and elevated α-fetoprotein. Genetic testing showed variant BWS due to unbalanced translocation with partial trisomy 11P and partial monsomy of chromosome 8. The daily hydrocortisone (HC) together with continuous nasogastric feeding, prevented her from becoming hypoglycemic initially but once she was transitioned, at age 11 weeks of life, off of continuous nasogastric feedings, she developed severe hypoglycemia right away, and to address this, initially her HC dose was increased to 20 mg/m2/day. She had relative hyperinsulinemia: glucose 10 mg/dl, insulin level 1uIU/ml, β-hydroxybutyrate 0.6 mg/dl and cortisol 2.3 mcg/dl. The cortisol levels were drawn as part of the critical sample for hypoglycemia evaluation and the patient was already receiving HC. The low level represents adrenal insufficiency secondary to suppressed ACTH-adrenal axis due to high dose hydrocortisone treatment. The HC was tapered gradually and was discontinued at age 11 months. She didn’t exhibit any clinical signs of adrenal insufficiency since then. She remained hypoglycemic on a relatively high dose of hydrocortisone of up to 20 mg/m2/day. She was only partially responsive to diazoxide, so she was switched to sc octreotide, and was kept euglycemic (blood glucose values over 70 mg/dl) on 19 mcg/kg/day given in 4 daily doses. She continued to receive Octreotide and low dose levothyroxine of 25 mcg/day, till she was 18 months of age, when she was tried off both. She remained euglycemic on frequent feeds given every 2 hours during the day and overnight feeds running at 50 ml/hr for 10 hours with 8 tablespoons of cornstarch. She remained euthyroid, but she had developed excessive weight gain on this feeding regimen and an attempt to decrease her frequency of feeds and weaning cornstarch resulted in episodes of hypoglycemia with blood glucoses range 50–60 mg/dl. Therefore, Diazoxide was started as the first line of therapy at age 4. Due to extensive hypertrichosis due to diazoxide she was switched to LAR octreotide three months later, initially at 10 mg monthly based on prior experience of her attending physician with other cases of hyperinsulinism of infancy. Dose raised to 10 mg every 21 days as she was having hypoglycemia with weaning feeds overnight on the monthly dose. Patient was then weaned off overnight feeds, was able to maintain blood glucose values > 70 mg/dl in the range of 80–90 mg/dl and an 8 hour or longer overnight fast. No tumors to date. At age 6 years and 7 months old she was weaned off the Octreotide and she remains euglycemic with blood glucose values > 70 mg/dl, up to 6 months later.
Patient didn’t develop any side effects while receiving the LAR; no gallstones or sludge and she maintained normal linear growth and weight. IGF-1 level was not measured since her linear growth remained appropriate with height range 50-60th percentile.


A 20-year-old Caucasian woman presented with lateral neck nodes, sweating, and pruritus and was diagnosed with stage IIB nodular sclerosis HL. Relevant background factors included a jaw abscess and an allergy to vancomycin. Serology revealed only positive EBV. From the first episode until her death eight years later, several treatments were applied. Firstly, chemotherapy adriamycin-bleomycin-vinblastine-dacarbazine (ABVD) for six cycles during the first seven months with complete radiological response lasting four months. Subsequent treatment involved chemotherapy gemcitabine-dexamethasone-cisplatin (GDP) for three cycles and ifosfamide-etoposide for two cycles, followed by a hematopoietic progenitor cell transplant, which achieved a complete response during the second year. Treatment continued with gemcitabine-vinorelbine for eight cycles from March to September of the third year, with a partial response, and everolimus (off-label) 5mg/day for the following 12 months, which stabilized the illness and eliminated the B "weight loss, drenching night sweats, and fever" symptoms. The following treatment was cyclophosphamide-vincristine-prednisone (CVP) for two cycles until the beginning of the fifth year of therapy, with progression. GDP for two cycles was then re-administered, followed by a cycle of bendamustine 90mg/m2, with progression in both cases. Treatment continued with gemcitabine-vinorelbine-liposomal doxorubicin (GVD, off-label) for eight cycles in the middle of the same year with a partial response and, during the sixth year, metronomic therapy with cyclophosphamide, vinblastine, and celecoxib, which stabilized the illness. She was then included in the clinical trial RV-HL-GOTEL-440 (EUDRACT: 2009-016588-12) which consists of lenalidomide and metronomic doses of cyclophophamide for refractory HL patients, but again there was disease progression, and so treatment was switched to high-dose dexamethasone (40mg/day, four days a week) in the first months of the seventh year, which obtained a partial response lasting two months. SNG-35 (brentuximab vedotin) which formed part of the laboratory’s extended-use program, was requested and five doses were administered, finishing five months later in the same year due to progression of the disease. Treatment began with oral etoposide, followed by chemotherapy with carboplatin and gemcitabine. At the beginning of the eighth year, she was admitted for palliative symptomatic treatment, beginning with thalidomide and dexamethasone, but died at the third month due to respiratory failure caused by compression of the airway by lymphoma.
Throughout this period the pruritus was ever-present. Improvement was achieved with some of the chemotherapy treatments, but the symptom returned when the drugs were withdrawn due to disease progression or poor tolerance. During the GVD treatment, the pruritus remained unchanged and during the R-HL-GOTEL-440 trial, she suffered a subjective increase in the itching sensation, which prevented sleep and caused the appearance of papulopustular lesions. Treatment with high-dose dexamethasone produced an improvement but when it was gradually withdrawn, the pruritus began to reappear.
In the middle of the seventh year, she was admitted with pancytopenia and deep vein thrombosis of the left leg, together with uncontrolled pruritus that resulted in severe lesions due to scratching. In response, aprepitant (off-label) at 80mg/day was added to the chemotherapic treatment of the pruritus, after studying the various treatment options and the scientific research available. She reported a score of 9 on a visual analogue scale (VAS) for the pruritus, and a score of 3 on the Eastern Cooperative Oncology Group (ECOG) performance status scale of performance status. After two weeks of treatment with aprepitant, she reported a score of 5 for pruritus on the VAS, and this improved to a score of 4 in a month, which allowed her to lead a better quality of life, with an ECOG level between 1 and 2. The pruritus remained controlled until she had to be readmitted, when it returned to VAS 9. Throughout this period, the lymphoma therapy remained unchanged.
Within the severe context of lymphomas, HL is generally considered to have a favorable prognosis, with 75% of patients achieving a cure if appropriate chemotherapy is received
[]. However, some cases are refractory, such as the one presented here, in which her age and quality of life led the healthcare team to consider many types of therapeutic alternatives. Thus, in this case our patient received more than 10 different treatment approaches.
Severe paraneoplastic pruritus is a symptom associated with HL for which there is no specific, effective cure, and treatment is currently based on antihistamines and corticosteroids. In the case presented, the severity of the pruritus seriously affected her quality of life and after exhausting the standard treatment alternatives, the off-label use of aprepitant was proposed in a clinical session.
Several cases and case series have been reported on the use of aprepitant for paraneoplastic pruritus, but none have referred to its use for HL. A prospective study was carried out to evaluate the efficacy of this drug in refractory pruritus secondary to Sezary syndrome, a type of non-Hodgkin’s lymphoma that primarily affects the skin and is usually secondary to mycosis fungoides. In the latter study, 80mg/day aprepitant was administered for 10 days and then on alternate days. The patients’ improvement was assessed on the Dermatology Life Quality Index (DLQI) and on a VAS. By the end of the study, a statistically significant reduction in the pruritus was reflected in both indices (P <0.005) and no adverse effects were detected
[]. Stander et al. also studied the effect of a daily dose of aprepitant 80mg/day for 3 to 13 days to treat refractory pruritus in 20 patients with various underlying pathologies. Their results also showed a significant decrease in the VAS (P <0.001), with a response being achieved in 80% of the patients
[].
Other authors have studied the effectiveness of aprepitant against pruritus, secondary to biological therapy with erlotinib, conducting a pilot study and administering three doses of aprepitant in a week (125mg on the first day and 80mg for the next two days). This study reported a significant decrease in the pruritus at one week after starting treatment
[]. Another paper described a case series of five patients with cutaneous T-cell lymphoma, for whom the same treatment schedule was prescribed. A response was achieved in 80% of these patients, with reductions in both the DLQI and VAS scores. Although these differences were not statistically significant, in view of the small number of patients, they were quantifiable
[].
In our case report, treatment was started with daily doses of aprepitant 80mg. This produced a marked improvement in her quality of life and in the control of the pruritus, as evidenced by the reduced score on the VAS scale, from 9 to 5 after two weeks and down to 4 after one month. This outcome improved her ECOG result, as a pruritus score of 9 on the VAS significantly affected her quality of life and forced her to remain in bed for long periods. This improvement appears to be attributable exclusively to the administration of aprepitant, as during this period the other aspects of the treatment remained unchanged.
Our patient did not present any unexpected side effects that could be related to this drug. In none of the studies reviewed was any evidence found of adverse reactions that might have resulted from the continued use of aprepitant
[-].


A 36-year-old woman was admitted to our hospital with a complaint of vaginal bleeding and infertility. Her medical history revealed she had regular menstrual cycles with no history of endocrine abnormalities. She had undergone four pregnancy terminations: one at 12 weeks’ gestation 12 years ago, one at 20 weeks’ gestation 9 years ago, one at 12 weeks’ gestation 6 years ago and one at 6 weeks’ gestation 2 years ago. The abortions were all electively terminated by dilatation and curettage. A pelvic examination revealed a normal size and normal adnexa. The results of laboratory investigations, which included a blood count, urine analysis, serum calcium, phosphorus, endocrine hormone levels and her partner’s spermiogram, were within normal limits.
During the tests, the transvaginal ultrasonography displayed two strong echogenic stripes with attenuation in the uterine submucosa and mesosalpinx (Figure
). Two separate bony nodules were seen on three-dimensional multislice computed tomography (MSCT-3D) (Figure
). Diagnostic hysteroscopic and laparoscope examinations performed in the operating room also revealed two separate bony nodules in the submucosa and mesosalpinx (Figure
). A biopsy was obtained and the histology established the diagnosis of osseous metaplasia of the submucosa and mesosalpinx (Figure
).
At 2 weeks postoperatively, the patient underwent a transvaginal ultrasound examination; the abnormal ultrasound appearance had resolved.


A 45-year-old woman had presented with recurrent pain in her left hip for 2 years and that had become severe in intensity for 6 months. The dull pain was located around the groin area, not radiating to the lower back or the lower extremities. There was no previous trauma noted. In recent months, discomfort was induced by climbing a few stairs or walking for a long distance. The pain had not become sharp until 2 months before admission and conservative treatment with analgesics brought no relief.
Physical examination showed complete normal passive range of motion (ROM), which was substantially pain-free except in maximum flexion-internal rotation, negative impingement signs and Trendelenburg test, and no tenderness points around the bony landmarks. The Patrick’s (Fabere) test and resisted flexion-internal rotation of the hip were painful. Laboratory test results were normal.
Anteroposterior- and lateral-projection radiographs of the left hip revealed a triangular homogeneous radio-opacity with well-formed borders just adjacent to the superior lip of the acetabulum (Figure A,B). This area corresponded to the tendinous origin of the rectus femoris. Subsequent CT scans confirmed the presence of calcification (Figure C).
The preoperative diagnosis was calcific tendinitis of the origin of the rectus femoris tendon. Because the conservative treatment was unsuccessful in alleviating symptoms, arthroscopic debridement was considered.
The surgical procedure started with an intra-articular diagnostic arthroscopy. With the aid of a sparing resection of the superficial capsule fibrous tissue, arthroscopy showed degeneration and calcific deposits at the origin of the reflected head of the rectus femoris tendon. With a longitudinal opening in line with the degenerated tendon course, white, soft, toothpaste-like material spurted out, which was then completely removed with blunt instruments (Figure D-F). During the procedure, a shaver was not systematically used so as to minimize the damage to the reflected head integrity and the possibility of tendon rupture. Intra-articular debridement was also performed. The specimen was submitted for pathologic examination, which confirmed the presence of hydroxyapatite crystals and chronic inflammatory infiltration.