A 4.5-year-old boy presented to our hospital with complaint of recurrent abscess on the right hip since he was 7 months old. He had been diagnosed as having gluteal abscess accompanied with penile abscess previously on seven separate occasions and incision and drainage were performed. He was operated on for hypospadias by using Snodgrass technique at two years old. A month later, recurrent abscesses in the gluteal region had been excised; pathology reported chronic inflammation and congestion in fibroadipose tissue. During our hospital admission, abscesses on penile and gluteal sides were detected at the same time. Physical examination revealed discharging sinus surrounded with 2 × 2 cm induration on the right gluteus and discharging sinus on the penoscrotal junction. Abscess tract was palpated through to perineal region. Anorectum was normal.
Laboratory findings of the patient were as follows: white cell count was 11.9 × 103/μL (normal range, 5.1–15.5 × 103/μL), hemoglobin 9.5 g/dL, platelet count 460 × 103/μL, and C-reactive protein 32 mg/L (normal range, 0–8 mg/L). He was hospitalized and ceftriaxone was commenced after pus culture was obtained from both sites. Ultrasound examination revealed 31 × 22 mm lobulated contoured abscess forming dense content with the acoustic empowerment in the right gluteal region which reached to intergluteal region. Penoscrotal USG revealed 5 × 4 mm sized dense content abscess within the corpus cavernosum in the proximal part of the ventral penile adjacent to the left lateral side of the urethra. Enterococcus spp. had grown on his both pus cultures. Antibiotic treatment was switched to teicoplanin. The swellings in the gluteus and penoscrotal junction were gradually decreased in size with antibiotic treatment. A fistulography was performed and showed a long sinus tract extending from the region of the penoscrotal junction to the right gluteal region (). There was no connection with the urinary and gastrointestinal tract.
Surgical treatment was required to be an extensive procedure with great risk of developing intraoperative damage to vital organs and nerves. Instead, sclerotherapy was administered to induce healing of the lesion. Penoscrotal sinus was catheterized and diluted bleomycin at a dose of 0.25 mg/kg was administered under general anesthesia. Postoperative recovery was uneventful, and the patient was discharged after 3 days. Six months later, the skin healed completely. The patient has been followed for one and half years and abscess was not repeated until now.


A 63-year-old Japanese man presented with speech difficulty, standing instability, drinking difficulty, and slow movement at first. At 12 months after his initial presentation, his neurological examination revealed cognitive decline, masked face, vertical oculomotor disturbance, dysarthria, bradykinesia, trunk-dominant muscular rigidity, and a tendency to fall. Magnetic resonance imaging of his head showed mild atrophy of the midbrain tegmentum. Probable PSP was diagnosed according to the National Institute of Neurological Disorders and Stroke and the Society for PSP (NINDS-SPSP) diagnostic criteria []. At 10 months after the diagnosis, he was confined to a wheelchair, and aspiration pneumonia occurred three times at monthly intervals. Although a percutaneous endoscopic gastrostomy (PEG) was performed immediately after his last pneumonia, pneumonia reoccurred twice at 18 and 20 months after his PEG regardless of treatment with clarithromycin and amantadine (Figure ). A daily dose of 9g of qing fei tang (Tsumura & Co., Tokyo, Japan) was started, and aspiration pneumonia reoccurred only once, at 5.5 months after the start of treatment (Figure ). The bacteria in his sputum were the same as before starting qing fei tang (Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA)), except for Streptococcus agalactiae.


A 74-year-old Japanese man presented to us with a three-year history of difficulty in moving his upper limbs, a tendency to fall, and slow movements. His neurological examination revealed supranuclear vertical gaze palsy, dysarthria, bradykinesia, muscular rigidity, and loss of postural reflex. Magnetic resonance imaging of his head demonstrated severe atrophy of his midbrain tegmentum. These clinical manifestations led to a diagnosis of probable PSP according to NINDS-SPSP criteria []. A PEG was performed in a bedridden condition because of progressive dysphagia 23 months after the diagnosis, but then aspiration pneumonia and bronchopneumonia developed nine times during 10 months, at intervals of about one month, with medication including ambroxol, L-carbocysteine, clarithromycin, bromhexine, and amantadine (Figure ). Qing fei tang was given daily at a dose of 9g, and then aspiration pneumonia occurred only once, six months after starting the treatment (Figure ). The types of bacteria in his sputum did not change compared with before starting qing fei tang (P. aeruginosa, MRSA and Klebsiella pneumoniae).


On July 26, 2012, a 78-year-old African American woman was referred to our pharmacotherapy consult service with a diagnosis of refractory postherpeticneuralgia (PHN) of the head and neck. This was a recurrent episode of PHN following an original diagnosis in 2010. Pain was noted along the right sternocleidomastoid and masseter muscles per the referring physician. Insomnia and difficulty in speech secondary to pain were also noted. Other relevant medical conditions were rheumatoid arthritis and bilateral osteoarthritis of the knees. Past surgical history included bilateral knee replacements.
Medication history included previous treatment with oral amitriptyline and topical capsaicin 0.025%, neither of which was tolerated by the patient and had been consequently discontinued. Oral amitriptyline was discontinued due to cognitive dysfunction and fatigue. Topical capsaicin was not tolerated due to local pain and discomfort on application of the cream. Her current medication regimen consisted of oxycodone, 20 mg by mouth twice daily, gabapentin, 300 mg by mouth three times daily, oxcarbazepine, 150 mg by mouth three times daily, and tocilizumab administered intravenously using weight-based dosing once monthly. Further increases in titration to the oral gabapentin and oxcarbazepine were not possible due to patient-reported adverse effects.
When the patient presented to our pharmacotherapy consult service, she reported intermittent neuropathic pain that “comes and goes” over the past 2-3 years. According to the patient, this most recent exacerbation had been the worst in her memory. The patient described the pain as “electric,” “tingling,” and occurring with “bursts of lightning,” which originated and were concentrated at the base of the jaw and which subsequently radiated up the lateral and posterior right sides of the cranium. She complained of skin and oral mucosal sensitivity, which was painful to the touch, on the inside and outside of her right cheek. The patient further complained of pain on swallowing, which had lead to the inability to eat full meals. She also complained of insomnia due to persistent baseline pain throughout the night. Severe pain symptoms were described as intermittent, lasting from minutes to hours, with several reported episodes of intense pain surrounding baseline pain. Despite the patient's own description of two separate types of pain—a baseline pain and an intermittent severe pain—on a VAS, she reported both types of pain as “10” on a 10-point visual analog scale (VAS). Due to the acutely severe and intense pain and the patient's severe decline in quality of life, it was decided that the addition of a lidocaine 5% patch alone would likely be insufficient for pain relief, although in most situations a trial of topical lidocaine 5% would have been the recommended next step in treatment. The treating team decided to continue her baseline oral medications and also to initiate immediate treatment with a compounded combination topical analgesic cream composed of gabapentin 6%, ketoprofen 10%, amitriptyline 2%, and lidocaine 5%. The team's anecdotal successful experiences with this combination on other neuropathic pain syndromes led to this initial step. Patient directions were to apply sparingly to the face and neck at the site of pain no more than four times daily, avoiding the area around the eyes. Follow-up was to be conducted by the pharmacy team three days following the initiation of treatment and conveyed to the prescribing physician. Due to the time needed to compound the topical cream, the patient did not begin treatment until the 27th of July.
At the first patient follow-up on the 30th of July, the patient reported a decrease in baseline pain to 7/10 on a VAS; however, peak pain remained constant at 10/10. The patient described her baseline pain as “quieted down” on cream but complained that pain “flare-ups” still remained a problem. At this point, the referring physician and consulting pharmacist made a change to a new topical analgesic cream formulation of gabapentin 6%, ketoprofen 10%, lidocaine 5%, and ketamine 10%. Topical ketamine replaced the amitriptyline due to the patient's concern of side effects based on her previous experience with the amitriptyline oral preparation. An oral mucosal topical analgesic gel was added as well. The antineuropathic agent used was again gabapentin in 10% concentration compounded with commercially available Orabase (a gel with benzocaine 20%). Follow-up with the consulting pharmacist was scheduled for one week after the initiation of the new treatment.
At the next follow-up, the patient reported further decreases to the overall pain. The patient described pain as being at a tolerable level, which allowed her to sleep through the night and 5/10 on a VAS. However, breakthrough pain was still reported to be 8/10. The previous topical regimens were continued, and the addition of a ketamine 100 mg/mL (10%) metered-dose intranasal spray delivering 0.1 mL/spray was initiated. Patient directions were to inhale 1 spray (0.1 mL), alternating nostrils 90 seconds apart, up to three times daily (with a maximum of 5 sprays per dose) for breakthrough pain. The patient was asked to lie in a supine position with her neck extended at a 45-degree angle and to maintain this position for 30 seconds after administration. This dosing recommendation was based on previously successful intranasal ketamine therapy already reported in the literature [].
Two weeks later, the patient reported further reduction in pain both at rest and when speaking, eating, and drinking. Breakthrough pain was managed on the intranasal ketamine regimen, and an overall reduction in baseline pain to 4/10 was experienced with combination, multimodal pain treatment. The patient reported breakthrough pain relief on intranasal ketamine within 2–5 minutes after administration, on average 2–4 sprays (0.2–0.4 mLs) of the solution. Throughout the duration of therapy, no adverse effects were reported for either the nasal or topical therapies. Therapy was continued for the next several months until full, spontaneous remission of pain.
On November 7, 2013, the patient requested a refill of all medications secondary to a “flare-up.” Due to the patient's age and concomitant immunosuppressive therapy with tocilizumab, recurrent PHN was confirmed on examination. This was the patient's third reported recurrence of PHN. The patient's previous three-prescription regimen was ordered. Again the patient reported a response to treatment, reporting pain score reduction on the VAS from 10/10 to 5/10.


An 81-year-old Caucasian woman with a medical history of hypertension and cholecystectomy for perforated acute cholecystitis was admitted to a community medical ward. At the time, she presented with asthenia, weight loss, occasional vomiting, abdominal pain and anemia. At clinical examination a parietal swelling was observed and at surgical consultation an incisional hernia through the previous cholecystectomy incision was suspected. A gastroscopy revealed the presence of a neoplasm shrinking the gastric antrum. In the following days a small cutaneous ulcer above the parietal swelling was observed followed by the appearance of a fistula a few days later. After surgical consultation she was moved to our university surgical ward.Our laboratory tests revealed hypoproteinemia (4.6g/dL), hypoalbuminemia (2g/dL) and anemia (8.3g/dL) which required transfusion of three blood units. A computed tomography (CT) scan (Figure ) showed a huge mass (10×14×15cm) arising from her gastric antrum, without a clear cleavage from the left lobe of her liver with internal necrosis and hemorrhage. The mass appeared to infiltrate her transverse mesocolon and her rectus abdominis muscles bilaterally, and to overrun them anteriorly causing a large parietal deficit and a complete external fistula. Furthermore the CT scan did not show large vessel infiltration or distant metastases.At surgery, laparotomy was performed using a skin elliptical incision centered from the neoplastic lesion surrounded by 2cm of healthy perilesional skin tissue (Figure ). Lateral margins of elliptical incision were enlarged with two other linear incisions.
An en bloc resection of stomach, colon and abdominal wall was performed (Figure ) along with systematic lymph node dissection, followed by mechanic gastrojejunostomy and hand-sewn ileocolic anastomosis. Two intra-abdominal drains were positioned and the parietal defect (Figure ) was reconstructed by positioning a biological prosthesis. The skin defect was closed with reverse abdominoplasty flap [] (Figure ). The intra-abdominal pressure (IAP) through intravesical measurement was lower than 10mmHg during the operation and during the postoperative course.
Histology reported a poorly differentiated adenocarcinoma with growth pattern and differentiation phenotype of neuroendocrine type. At microscopy, extension had reached the transverse colon mucosa and the extraserosal tissues up to the skin. (Figure a-c). The immunohistochemistry was positive for pan-cytokeratin chromogranin and CD56, (Figure 6d) while negative for vimentin, synaptophysin and S-100.
The immediate postoperative course was satisfactory. The patient did not present relevant laboratory abnormalities except for a mild anemia which was treated with hemotransfusions on the first three postoperative days. On day 3 her bowel movements began. On day 6, after an oral X-ray contrast examination, she started drinking and eating.
Unfortunately, on day 10 she experienced severe respiratory distress that resulted in pneumonia. Despite antibiotic therapy and her transfer to the intensive care unit, she died 20 days after surgery (Additional file ).


The patient is a 13-month-old girl born at 36 weeks of gestation to non-consanguineous and healthy Caucasian parents aged 27 years (mother) and 33 years (father). In utero, intra-uterine growth retardation with meconium staining in the amniotic fluid was observed. She was delivered by elective caesarean section. At birth her weight was 1,600 g (−2.5 SD), her length was 40 cm (-2.5 SD), and the head circumference was 30 cm (−1 SD). Apgar scores were 4–8. Severe congenital pes equinovarus was detected from birth. She was also noted to have hypotonia. Shortly after birth, treatment with the Ponseti method was started with surgical correction of the Achilles tendon at 3 months of age. Neurosonoscopy revealed mild widening of the ventricles, but re-evaluation after 1 month was normal. She was found to have normal hearing acuity after birth. A cardiac ultrasound examination showed a large patent ductus arteriosus. She had no feeding difficulties. Abdominal organs were without structural abnormalities. At the age of 4 months, bronchial asthma was diagnosed and she has been receiving medical treatment ever since. Examination at the age of 7 months revealed delayed speech and gross motor skills. Her height, weight, and head circumference were significantly less than the 3rd percentile. Furthermore, the patient had dysmorphic features consisting of microcephaly, slight metopic ridge, low-set ears, downslanting and narrowing of palpebral fissures, broad nasal bridge, stubby nose, smooth philtrum with thin upper lip and everted lower lip, microstomia, narrow palate, short neck, inverted and widely-spaced nipples, broad hands, tapering fingers, single palmar crease on the left palm, and broad feet with short toes and small nails (Figure ). Mild divergent strabismus was documented at that time. Otolaryngological evaluations revealed a deviated septum. Skull roentgenograms revealed no synostosis.
On the last examination at 13 months of age, her development milestones were found to be delayed. She could not sit unsupported and her head control was insufficient. She showed good visual fixation. There was no speech development. Muscle tone was decreased and deep tendon reflexes were normal. She displayed unusual repetitive hand movements, continuously pressing her palms together in the midline and repetitively stroking her thumbs. A brain MRI was declined by her parents. At the age of 7 months, the proband was referred to a clinical geneticist.
Cultures of the patient’s peripheral blood were established and harvested according to standard laboratory protocols. Chromosome preparations were treated with trypsin and stained with Giemsa. A total of 30 metaphase cells were analysed at the 550-band resolution level. The karyotypes were described according to the guidelines of the International System for Human Cytogenetic Nomenclature [46,XX,r(10)(p15.1q26.1)]. Additionally, 370 cells were counted to verify ring instability. The parents declined to undergo chromosomal analysis.
DNA was extracted from the patient’s peripheral white blood cells using the phenol-chloroform extraction method. A subsequent array-comparative genomic hybridisation (array-CGH) test was performed to determine the chromosomal breakpoints of the ring, as well as other possible chromosomal abnormalities that may have been missed by routine G-banded chromosomal analysis. Agilent Human ISCA CGH 180 K microarrays with an average spatial resolution of 25 kb were used in the study (Agilent Technologies, Santa Clara, CA). Genomic DNA from the proband and pooled normal male reference DNA (Agilent Technologies) were digested with Covaris S220 (Life Technologies, Grand Island, NY) and labelled with an Agilent Genomic DNA labelling kit according to the manufacturer’s recommendations. Patient and reference DNA were labelled with Cy5 and Cy3 respectively and were co-hybridised to arrays for 24 h at 67°C in a rotating oven (Agilent technologies) at 20 rpm. The arrays were then washed and scanned with an Agilent Microarray Scanner. Data were extracted using Feature Extraction 10.7.1 software (Agilent Technologies) and analysed using Cytogenomics 2.9.2.4 software (Agilent Technologies). Genomic copy number changes were identified with the assistance of the Aberration Detection Method 2 algorithm with the sensitivity threshold set at 6.0. Copy number changes identified in the samples were evaluated by using the UCSC Genome Browser website () and the Database of Genomic Variants (). The array data was analysed using annotation GRCh37/hg19. The DECIPHER () database was used to support genotype-phenotype correlation.
Cytogenetic analysis revealed an apparently stable non-mosaic ring chromosome 10 [46,XX,r(10) (p15.1q26.1)]. Secondary aberrations (two separate rings and interlocked rings) were found in less than 5% of the mitoses counted, 1.7% and 0.5% respectively. High-resolution breakpoint mapping with a Human ISCA CGH 180 K microarray re-defined the karyotype as 46,XX,r(10)(p15.2q26.3).arr[hg19]10p15.3p15.2(1–3,678,763)×1,10 q26.3(131,276,836–135,534,747)×1, indicating an approximately 3.68 Mb deletion in 10p and a 4.26 Mb deletion in 10q (Figure ). No other relevant genomic imbalance was found.
Ring chromosome 10 is a rare disorder. Only seventeen cases of ring chromosome 10 have been reported in literature and mostly defined by G banding [-] and only four cases with molecular cytogenetic definition [,,]. This is the fifth case with precisely defined r(10) helping to better establish a karyotype-phenotype correlation.
We compared the phenotype and genotype of our patient with previously published patients having precisely defined breakpoints [,,]. The patient we present has the largest ring chromosome 10 reported to date. In all previously reported patients with ring chromosome 10, the breakpoints in 10q are variable but more proximal to the centromere (Figure ).
Common clinical features in patients with ring chromosome 10 include prenatal and postnatal growth retardation, varying degrees of intellectual disability, microcephaly, and dysmorphic features (broad nasal bridge, strabismus, hypertelorism, low-set malformed ears) [,] that are non-specific to distal 10q deletion and are common to many chromosome anomalies. It is unlikely that 3.68 Mb terminal 10p15.2 deletion in the present ring chromosome or smaller deletion in case of ring chromosome reported by Gunnarson et al. would make a significant contribution to the phenotype. However the patient with a larger deletion of chromosome 10 short arm has additional clinical features such as talipes equinovarus, hepatomegaly, splenomegaly that cause severe phenotype [].
We also compared the clinical features of our patient with patients from DECIPHER (Table ). Cases with complex chromosomal rearrangements or with larger deletions than those identified in our patient and cases without a detailed clinical description were excluded from the comparison. Based on comparison of the clinical features of our patient with the clinical features of the patients with ring chromosome and the clinical features of patients with pure terminal deletions of 10p and 10q, the contribution of the terminal deletion 10q to the clinical phenotype of our patient is the most significant.
The study of patients with a distal pure 10q deletion has revealed the existence of a minimal critical region (MCR), which was recently assigned by Yatsenko et al. [] to an approximately 600 kb segment in the distal part of chromosome 10, which encompasses two annotated genes, C10ORF90 (chromosome 10 open reading frame 90) and DOCK1 (dedicator of cytokinesis 1). We predict that the overlapping phenotype of pure 10q deletions at 10q26.2 region could be caused by haploinsufficiency of one or more genes or position effect, since 10q26.3 deletion detected in our patient does not involve these genes.
The deleted region 10q26.3, 4.26 Mb in size, contains 31 protein coding genes of which PPP2R2D (protein phosphatase 2, regulatory subunit B, delta), JAKMIP3(Janus kinase and microtubule interacting protein 3), DPYSL4 (dihydropyrimidinase-like 4), INPP5A (inositol polyphosphate-5-phosphatase), GPR123 (G protein-coupled receptor 123), GLRX3 (glutaredoxin 3) and ADAM8 (ADAM metallopeptidase domain 8) could be considered important contributors to the clinical phenotype. Based upon function and high expression in the brain [], we suggest that the haploinsuffiency of PPP2R2D, JAKMIP3, DPYSL4, and GPR123 could play significant roles in neurodevelopmental delay. PPP2R2D is essential for many signal transduction pathways []. JAKMIP3 is associated with caveolin-1, which recruits synaptic components and regulates the signal transduction of a variety of neurotransmitter and neurotrophic receptors in the central nervous system (CNS) []. The collapsin response mediator protein encoded by DPYSL4 is thought to be involved in semathorin-induced growth cone collapse during neural development. Down-regulation of DPYSL4 expression using siRNA shows an early increase in neurite outgrowth, further supporting the idea that DPYSL4 inhibits microtubule polymerisation and neurite outgrowth []. The CNS-specific expression of GPR123, together with the high sequence conservation between the vertebrate sequences investigated, indicate that GPR123 may have an important role in the regulation of neuronal signal transduction [].
Craniofacial dysmorphisms, foot abnormalities, and short stature could be attributed to the loss of the GLRX3 gene. Although growth delay is usually associated with the ring chromosome of any autosome, possibly due to ring instability [], stature might also correlate with the haploinsuffiency of genes that encode protein and play a role in cell growth. The ubiquitous expression of Glrx3 in mouse embryos and tissues indicates that Glrx3 is required for cell growth, organ development, and normal metabolism during growth and development []. Thus, deletion of GLRX3 might influence the severity of growth delay. The patent ductus arteriosus could be associated with the haploinsuffiency of DPYSL4, PPP2R2D, and INPP5A, the expression of which is predominant in the heart [].
The second deleted region, 10p15.2-pter, could also contribute to the observed phenotype. The 10p15.3p15.2 deleted region contains 11 protein-coding genes (TUBB8 (tubulin, beta 8 class VIII), ZMYND11 (zinc finger, MYND-type containing 11), DIP2C (DIP2 disco-interacting protein 2 homolog C), PRR26 (proline rich 26), LARP4B (La ribonucleoprotein domain family, member 4B), GTPBP4 (GTP binding protein 4), IDI2 (isopentenyl-diphosphate delta isomerase 2), WDR37 (WD repeat domain 37), ADARB2-AS1 (ADARB2 antisense RNA 1), PFKP (phosphofructokinase, platelet), PITRM1 (pitrilysin metallopeptidase 1), from which DIP2C and ZMYND11 could be considered important contributors to growth delay, since they were most commonly deleted in DECIPHER patients with common clinical features, short stature and microcephaly (Table ). ZMYND11 [] and DIP2C [] are expressed in various tissues, including the brain, but little is known about their function. Gunnarson et al. stated that loss of 10p15.3 region including ZMYND11 would contribute little to the clinical phenotype because of significant larger terminal deletion at 10q []. However ZMYND11 was suggested by DeScipio et al. as a main contributor to the clinical features associated with 10p15 deletions based on genotype-phenotype of the cases with isolated 10p deletions [].
In addition to the clinical features commonly found in patients with ring chromosome, bronchial asthma was present in our patient. This clinical feature had not previously been reported in patients with ring chromosome 10. The ADAM8 mapped at 10q26 could be involved in asthma pathogenesis. In humans, ADAM8 is expressed by most leukocytes [,], lung epithelial cells [], and osteoclasts []. More recently, ADAM8 has been strongly associated with allergic airway inflammation (AAI) in humans and mice, and additional studies of ADAM8 are beginning to shed light on its roles in asthma pathogenesis [].


A 21-year-old man presented with chronic right testicular pain which appeared between 1 and 2 years before he consulted. He had a medical history of Crohn’s disease of the small bowel, successfully treated by monoclonal antibody infliximab (5 mg/kg every 9 weeks). No extra-intestinal manifestation, before or after the therapy, had been noticed prior to this genital pain. Clinically, the testicles were of normal volume and consistency. Examination by palpation was painless and did not retrieve any nodule. Ultrasound examination revealed a heterogeneous and hypoechoic lesion measuring 2 cm in length and 0.7 cm in width at the upper portion of the right testicle. Doppler examination showed that the lesion was hypervascularized. An injected scan of the chest, abdomen and pelvis revealed several lymph nodes in the mediastinum less than 1 cm in size, accompanied by centimetric mesenteric lymph nodes. Given the suspicion of malignancy, right orchiectomy was decided. Pre-operative blood tests were strictly normal, such as alpha-fetoprotein (142 IU/L), lactate dehydrogenase (142 IU/L) or human chorionic gonadotrophin (<1 IU/L).
After formalin fixation, the specimen consisted of a 6-cm long testicle, weighing 53 grams. The spermatic cord was 7 cm long. The cut surface showed a peripheral cuneiform lesion measuring 15 mm long, darker in color than the rest of the testis. The whole lesion was submitted for histological examination. Histological samples of macroscopically normal testicle were also performed.
Histologically, Hematoxylin, Eosin and Safran staining revealed a chronic inflammatory infiltrate consisting predominantly of small lymphocytes accompanied by few plasma cells. These inflammatory cells were mainly located around the seminiferous tubules and some of these elements in exocytosis were observed in the tubules (Figures and ). There were very few histiocytes within the tubules. In some territories, the lamina propria was predominantly edematous, without inflammatory cells. Neither giant cells nor granulomas were present. No vascular lesion was observed. Inflammation was strictly absent in the rest of the testicular tissue. Importantly, intratubular germ cell neoplasia, atrophy or lithiasis were not observed. Periodic Acid-Schiff (PAS) staining did not reveal any microbiological agent but highlighted the fact that the basal membrane of the seminiferous tubules was sometimes breached by the inflammatory infiltrate. Immunohistochemistry was performed and demonstrated that the inflammatory cells were composed of a majority of T cells (CD3 +, Figure upper picture) mixed with some B cells (CD20 +, Figure lower picture), few plasma cells (CD138 +) and very few histiocytes (CD68 +). Immunoreaction with the antibody anti-treponema was negative.


A 76-year-old male Caucasian patient with a previous history of repeated episodes of acute alcoholic hepatitis was referred to our Liver Unit in June, 2007, because of the incidental finding on CT scan of a tumoral mass in segment IV of the liver. He was also known with arterial hypertension and with recurrent stomach ulcers for which he was treated since many years with perindopril and with omeprazole, respectively. On admission, the clinical examination was normal except for palmar erythema. Laboratory evaluation showed an alpha-foetoprotein (AFP) concentration of 525 μg/L (nl < 14); haemoglobin was 14,7 g/dL, alkaline phosphatase 110 U/l (nl < 270), AST 46 U/l (nl < 38), ALT 39 U/l (nl < 41), and gamma-GT 54 U/l (nl < 53). Oesophageal varices were excluded, and a tumorectomy was performed. The resection specimen showed an undifferentiated hepatocellular carcinoma with vascular invasion; the nontumoral liver parenchyma was characterized by the presence of Mallory bodies and a septal stage of fibrosis. In October, 2008, and in February, 2009, radiofrequency ablation (RFA) was performed for recurrent HCC in segment IV. In February, 2009, previous to the second ablation therapy, AFP was 14 μg/l, alkaline phosphatase 147 U/l, AST 63 U/l, ALT 45 U/l, and gamma-GT 104 U/l. There was no further use of alcohol since the diagnosis of cirrhosis, and HCC had been made.
In November, 2009, a repeated CT scan of thorax and liver was performed because of a rise in AFP up to 75 μg/l; several small lung metastases were observed. In March, 2010, AFP had risen up to 743 μg/l, and an increase in size of the lung metastases as well as a single, 17 mm large HCC-nodule in segment VII of the liver were visualized. At that time, alkaline phosphatase was 154 U/l, AST 125 U/l, ALT 60 U/l, and gamma-GT 304 U/l. Serum albumin was 46,9 g/dL, and the prothrombin time was 1,1 INR, indicative of a well-preserved liver function. The Child-Pugh status was A5. Sorafenib was started the first week of May, 2010, at a dosage of 400 mg per day during the first week and with an increase up to 800 mg daily from the second week of treatment onward. One week after the start of the 800 mg regime, the patient developed a flu-like syndrome with high spiking fever up to 40°C, tinnitus, nausea and severe vomiting, severe muscle cramps, anorexia, and watery diarrhea with a frequency of more than 10 stools per day. He was seen as an outpatient the first week of June, 2010. Clinical examination at that time revealed the presence of scleral jaundice and of a marked hepatomegaly, findings that had never been observed during previous examinations. Total bilirubin was 3,6 mg/dL with a direct fraction of 2 mg/dL; alkaline phosphatase was 135 U/l, AST 525 U/l, ALT 343 U/l, gamma-GT 215 U/l, ferritin 2099 μg/l, albumin 3,2 g/l, and the prothrombin time was now 1,5 INR. The total white blood cell count was 7.4 × 109/l with a neutrophil count of 5.7 × 109/l; blood eosinophils were normal. Serology for hepatitis A, B, and C, as well as antinuclear antibodies were negative. Sonography showed a large liver without focal liver lesions or dilated bile ducts and with only a minimal amount of ascites so that a diagnostic paracentesis was not considered to be useful. As the diarrhea had already improved at the time of the consultation, stool cultures have not been performed. Sorafenib was stopped but the patient went rapidly into a severe jaundice and a deep liver coma and died on June 16, 2010. As his family refused any further hospitalisation, we were not able to perform a liver biopsy.


A 76-year-old woman with a six-month history of recurrent, nocturnal, right epigastric pain radiating to the right shoulder and to the back presented to her general practitioner with an acute exacerbation of abdominal pain. An outpatient blood analysis revealed elevated liver transaminases suspicious of an acute hepatitis; thus the patient was referred to our department. On admission the patient had a C-reactive protein of 4 mg/L (normal <5 mg/L), total bilirubin 39 μmol/L (<17 μmol/L), aspartate aminotransferase (AST) 1886 IU/L (<35 IU/L), alanine aminotransferase (ALT) 1462 IU/L (<35 IU/L), γ-glutamyltransferase (γ-GT) 468 IU/L (5–36 IU/L), alkaline phosphatase (ALP) 174 IU/L (35–105 IU/L), and lipase 38 IU/L (13–60 IU/L). Physical examination did not reveal any abnormalities except for a slight right abdominal tenderness on palpation and bilateral Heberden nodes. Ultrasonography showed several concrements of the gall bladder, with a maximum diameter of 1.4 cm. An abdominal computerized tomography (CT) scan showed neither intra- or extrahepatic cholestasis nor any other pathologies of the abdomen including the liver. Hepatitis serology was significant for anti-hepatitis A virus IgG positivity, indicative of a status after hepatitis A infection, whereas hepatitis B and C infections could be ruled out.
There was no evidence for an autoimmune hepatitis. The patient was on pantoprazole 20 mg/d, vitamin D3 100 μg/d, and rose-hip powder long time before complaints and admission. Additionally, she started taking the lipid extract of the green-lipped mussel (Lyprinol) 2 months prior to admission as a complementary treatment of polyarthrosis, raising the suspicion of a drug-induced acute hepatitis. Strikingly, liver biopsy () was compatible with a drug-induced hepatitis. Indeed, after withdrawal of Lyprinol transaminases significantly decreased by a factor of 3–9, and the patient could be discharged after few days. At an outpatient control six weeks after hospitalisation, the patient had no complaints and blood values were completely normalized.


A 40-year-old woman, previously healthy, Colombian, was admitted to the Department of Rheumatology at Hospital Militar Central, with a fever of 39 C, generalised arthralgia involving the elbows, wrists, proximal and distal interphalangeal joints, metacarpophalangeal and metatarsophalangeal joints, knees and ankles, and fatigue. She had been in her usual state of good health until 2 weeks before admission and these symptoms starting shortly after the patient had a sore throat for 7 days.
Examination revealed angioneurotic edema detected on soles, palms and tongue (Figure a) and widespread red, urticated plaques in a symmetrical distribution affecting the arms, dorsal hands, upper and lower chest and back (Figure b). The rest of the examination was unremarkable. These lesions were present for less than 10 h per day and were not more pronounced at night with no associated bruising. She was diagnosed as having infection-associated-urticaria in a peripheral hospital and was treated with antibiotics (ciprofloxacin) and antihistamines (loratadine) without diminishment of her symptoms. Followed 5 days later by fever, the patient presented dyspnea, cough and hypoxemia. A chest x-ray film showed a patchy right lower lobe infiltrate (Figure a) and computed tomography showed unilateral consolidation and pleural effusion (Figure b).
An early bronchoscopy with bronchoalveolar lavage was indicated revealing hemorrhagic lavage and pathological examination showed hemosiderin-containing macrophages in 80%. Bronchoalveolar lavage specimen was sent for routine bacterial cultures, fungal, viral and Pneumocystis carinii; all of the results were negative. A skin biopsy demonstrated dermal oedema, and a marked perivascular and neutrophilic infiltrate with no evidence of structural vasculitis. These features were consistent with neutrophilic urticaria (Figure ). Other investigations revealed a normocytic anaemia Hb 11.5 g/dL erythrocyte mean corpuscolar volume 86 fl platelet count 408.000/mm3, a marked white blood cell count (WBC) 67.200 mm3 with 91% neutrophils, 5% lymphocytes, 1% eosinophils, 3% monocytes and markedly elevated acute phase reactants: erythrocyte sedimentation rate 49 mm in the first hour, C-reactive protein 11,43 mg/dl and ferritin 1650 μg/L, alanine aminotransferase was mildly elevated at 74 IU/L, lactate dehydrogenase 1200 IU/L and serum albumin reduced at 3,4 g/L. Antinuclear antibodies (immunofluorescence-Hep-2 cells), rheumatoid factor (nephelometry), antistreptolysin O, cold agglutinins, cryoglobulins and serum electrophoresis were unremarkable. There was no serological evidence for active or recent infection with the following organisms: Toxoplasma gondii, group B streptococci, hepatitis A, B or C, HIV, cytomegalovirus, tuberculosis and syphilis. Blood cultures were negative. Ultrasound investigation of the liver and biliary tract was normal. In the bone marrow aspiration, we found remarkable hyperplasia and granulocytes of each mature state, without an increase of myeloblasts, the neutrophil alkaline phosphatase score was high, Ph chromose was negative. Immunophenotyping showed mature neutrophils expressing surface antigens CD13 and CD15 at a level higher than 95% and negative for CD34 and HLA-DR.
She was diagnosed with AOSD and methylprednisolone (mini-boluses of 125 mg/ day per 3 days) was initiated as prednisone sparing therapy. The patient’s pulmonary symptoms improved with the doses of pulsed corticosteroids. After 3 days of pulsed methylprednisolone, therapy was maintained with 0.5 mg/kg of prednisone orally. Treatment with NSAIDs and prednisone controlled the rash, fever, arthritis, angioedema and significantly reduced the serum ferritin levels and all markers of activity disease. Two weeks after the pulse treatment, the chest radiography became normal. Methotrexate was prescribed for long term control of the disease at a dose of 7,5 mg/week. One month later prednisone was slowly decreased to 12,5 mg/day and withdrawn over three months. No activation period was observed during the one-year follow-up period.


An 81-year-old Caucasian woman with a history of anticoagulated atrial fibrillation (AF), had a sudden cardiac arrest during a hospital visit, requiring 10 minutes of cardiopulmonary resuscitation (CPR) performed immediately after the arrest, allowing the restoration of atrial fibrillation rhythm. She remained intubated for three days. A coronary angiogram showed no significant coronary disease, with a left ventricular ejection fraction of 35%. Pulmonary embolism was ruled out by a computed tomography (CT) scan on day 3, which showed no other anomalies. There was neither electrolyte disturbance nor drugs that could favor such an event. Coronary spasm or idiopathic ventricular fibrillation was finally retained as the cause for her cardiac arrest and an internal defibrillator was implanted. Due to her past AF history (CHADS score = 3), our patient received intravenous anticoagulation with unfractionated heparin (UFH) upon arrival at the intensive care unit (ICU).
On day 8, she presented with fever, hypotension and tachycardia. Broad-spectrum antibiotics and inotropic support with dobutamine and noradrenaline were started.Her platelet count dropped from 656 G/L on admission (our patient was known for an essential thrombocytosis Jak-2 positive status) to 131G/L on day 10 and 129G/L on day 11 (Figure ). Her 4T’s score was 8 and positive anti-PF4-heparin antibodies were confirmed by enzyme-linked immunosorbent assay (ELISA) (day 12). UFH was stopped and therapeutic doses of fondaparinux were immediately started. A thoraco-abdominal CT- scan performed on day 14 showed multiple pulmonary embolisms, splenic infarction and bilateral adrenal ischemia with subsequent hemorrhagic transformation on a CT scan done later on day 21 for non-specific abdominal pain (Figure ). Diagnosis of HIT with thrombotic complication was retained (HITT) and fondaparinux was switched to lepirudin, at the same time her platelet count was increasing (Figure ). A Doppler ultrasound (US) scan showed a distal deep venous thrombosis (DVT) of the left peroneal vein (day 17). Her procalcitonin level was lower than 0.5μg/L from day 7 to day 15, with high fibrinogen, which reasonably excluded the diagnosis of sepsis with disseminated intravascular coagulation (DIC). Antiphospholipid syndrome was investigated; anticardiolipin immunoglobulin G (IgG) was slightly positive in this elderly patient, whereas anticardiolipin IgM, anti beta2-glycoprotein antibody IgM and IgG were all negative. Since the thrombotic events happened during heparin therapy and the platelet count increased after heparin cessation, the diagnosis of HITT was maintained.
Basal cortisol on day 15 was 63nmol/L (normal value greater than 500nmol/L) and increased to 136nmol/L 60 minutes after injection of 250μg ACTH (considered normal if the cortisol value exceeds 500nmol/L). The diagnosis of adrenal insufficiency due to bilateral adrenal damage in the context of HITT was made and our patient was given intravenous hydrocortisone 50mg three times a day for five days and then received a maintenance oral dose of 20mg in the morning and 10mg in the afternoon, allowing for a quick hemodynamic improvement. Inotropes and antibiotics were therefore stopped.Following ICU discharge, she was weaned off hydrocortisone progressively over the following weeks (Figure ), with close blood pressure surveillance, along with plasmatic assessment of potassium and sodium levels twice weekly. After one month of hospitalization, our patient was discharged on 10mg hydrocortisone once daily after a normal ACTH stimulation test. Substitution was tapered further until a complete stop on day 45. Fifteen days after cessation of hydrocortisone (day 60, Figure ), another ACTH stimulation test without oral substitution showed complete normalization. (Basal cortisol was 224nmol/L and increased to 568nmol/L one hour post-injection of 250μg of tetracosactide.) Two years later, the ACTH test remained normal and showed a basal cortisol at 138nmol/L that increased to 1540nmol/L one hour post-injection of 250μg of tetracosatide (day 600, Figure ). The patient died of another cause three years after the essential event.


A 77-year-old Caucasian man consulted his general practitioner concerning a two-week history of worsening weakness and was referred to our emergency department upon detection of an abdominal bruit. At arrival, the patient was pale and diaphoretic; he was apyretic, eupneic, conscious and oriented (blood pressure 110/75; heart rate 85; respiratory rate 12; O2sat 98%). Physical examination confirmed a faint mesogastric bruit associated with an abdominal pulsatile mass. Melenic stool was found in the rectal vault on rectal examination. The patient had a medical history of myocardial infarction, hypertension and previous cigarette smoking, with no history of surgery. His treatment was acetylsalicylic acid and angiotensin-converting enzyme (ACE) inhibitor (enalapril). Blood tests showed leukocytosis (white blood cell 15 × 103/uL), mild anaemia (haemoglobin 10.1 g/dL; hematocrit 32.2%) and alteration of the renal function (urea 93 mg/dL; creatinine 1.54 mg/dL). An electrocardiogram (ECG) confirmed previous anterior necrosis. An urgent esophago-gastroduodenoscopy (EGD) was arranged, but after a sudden drop in the patient’s blood pressure (60/45; heart rate 100), an enhanced abdominal CT was obtained first. The examination revealed a large (63 × 55 mm) thick-walled infrarenal aortic aneurysm, associated with distension of the small bowel loops by fluid content ().
The patient was immediately transferred to the operating theatre and a significant amount of fresh blood (400 mL) was aspirated through the nasogastric tube during anaesthetic preparation. The laparotomy disclosed a ruptured aneurysm of inflammatory appearance, tenaciously adherent to the fourth portion of the duodenum and surrounded by a small retroperitoneal haematoma, mainly confined to the paraduodenal area. Following aortic and iliac cross-clamping, dissection of the aneurysmatic aortic wall from the duodenum was performed and a 1 cm aorto-duodenal fistula was found upon removal of a fresh clot (a and -b). The peritoneal cavity was irrigated with rifampicin, the duodenal wall was sutured with Vycril® (Ethicon, New Jersey) (c) and the aorta was repaired by prosthetic interposition (bifurcated Intergard® silver knitted 16 × 8 mm), sutured with Prolene® 2-0. The aneurysmatic wall was closed above the prosthesis after collection of samples and a pedicle of omentum was interposed between the aortic wall and the duodenum.
On post-operative day (POD) one, the patient was re-operated for persistent anaemia and abundant blood loss into the abdominal drainage. Diffuse haemostasis was performed on the retroperitoneal para-aortic tissues with cauterization and sealants, in the absence of a relevant active haemorrhagic finding. The remaining post-operative course was uneventful. Histology of aortic wall samples confirmed an aspecific, chronic inflammatory pattern. Blood cultures were negative for bacterial or fungal infection; therefore a wide-spectrum antibiotic therapy with imipenem was administered for 30 days. On POD 15, the patient was transferred to a rehabilitation centre and discharged two weeks later. At 18 months' follow-up, the patient is fine and no evidence of infection was detected on imaging and laboratory tests.


A 66-year-old man with unremarkable past medical history presented with dull abdominal pain lasting 5 days. He complained of nausea and vomiting without changes in bowel habit. Physical examination revealed diffuse tenderness and abdominal distention in the presence of shifting dullness. There was slight guarding of the abdominal wall without rebound tenderness. Laboratory data were within normal limits. Computed tomographic (CT) scan showed dilation of small bowel loops, large amount of ascites, and peritoneal thickening with coarse calcifications (). A jelly-like mucinous material was obtained on ultrasonography-guided abdominal paracentesis. The cytological examination was positive for malignant cells. Exploratory laparotomy revealed a ruptured mucinous lesion of the appendix with gelatinous pseudomyxoma peritonei. The patient underwent appendectomy and aggressive cytoreductive surgery with no residual macroscopic tumor (R1 cytoreduction). Pathological examination confirmed the diagnosis of low-grade appendiceal mucinous neoplasm (). His postoperative recovery was uneventful. The patient declined further adjuvant chemotherapy.
One and a half years later, the patient manifested a firm, non-tender abdominal wall mass. The abdominal CT scan revealed several rim-enhanced lesions with calcification over peritoneum, rectus abdominis muscle and mesentery (). Intraperitoneal fluid was not seen. A relaprotomy with debulking intent was performed. At exploration, carcinomatosis with a dominant tumor, measuring 8.6 × 6.7 × 2.5 cm, at the left upper quadrant of the abdomen was noted. Biopsy from the peritoneal cavity, mesenteric soft tissue, and part of the tumor-encased intestinal wall showed sarcomatoid carcinoma (). The patient died of disease 1 month after the second operation. No autopsy was performed.


We present the case of a fifty-seven-year-old male who required an orthotopic liver transplant in 2010 due to a trifocal hepatocarcinoma (Stage A4 of the BCLC, inside Milan criteria) with an alcoholic cirrhosis and hepatitis B (Child's class B (9 points) and a Model for End-Stage Liver Disease score of 18).
Posteriorly he developed a stenosis of the biliary anastomosis that required hepaticojejunostomy in 2011, leading to a small leak which did not require reintervention. Two years later in 2013 he required quirurgic drainage of an abdominal collection. In postoperatory follow-up the patient showed alimentary regurgitation, vomiting, and dyspepsia. The diagnosis was made by an oesophagogastroduodenal transit with barium () and an abdominal CT scan () that showed a left diaphragmatic herniation with the gastric fundus into the thorax.
With these findings we decided to perform a programmed surgery. After takedown of adhesions and replacement of the stomach into the upper abdomen, the palm-sized diaphragmatic opening () was closed with a synthetic material (). The patient's condition remained stable throughout the entire operation. The postoperative course was uneventful and he was discharged at the fifth day after surgery with a normal digestive intake. In a 12-month follow-up the patient shows no symptoms.


A 50-year-old lady presented to our hospital with a 4-month history of progressive dysphagia. Her symptoms worsened progressively resulting in total dysphagia, pain mainly in the epigastric and lower chest area radiating to her back, and one recent episode of haematemesis. At presentation, she was unable to swallow even her saliva. She had no associated medical comorbidities, except for being an ex-smoker and having a BMI of 41. The physical examination was unremarkable. Standard laboratory test results were within normal range, with haemoglobin of 11 mg/dL. An oesophagogastroscopy revealed a large submucosal obstructing oesophageal mass, partially ulcerated, situated 42 mm above diaphragmatic hiatus, and extending over a distance of at least 10 cm. Biopsy revealed a GIST with diffuse positivity for CD117 and CD34 and a mitotic index of 3/22 hpf (insufficient material to count mitoses/50 fields). Gene analysis with direct sequencing revealed a 6 bp deletion in exon 11 of the KIT gene [mutation details: c.1670_1675del p.Trp557_Val559delinsPhe (reference cDNA sequence: NM_000222.2)].
A computed tomography (CT) scan of chest and abdomen revealed an annular polypoidal mass, 99 mm × 50 mm × 104 mm in diameter in the mid oesophagus, arising 42 mm above the diaphragmatic hiatus and extending cranially over a distance of 10 cm to the subcarinal level (). There was evidence of extension through the oesophageal wall over a distance of at least 10 mm but without lymphadenopathy or metastatic disease. The tumour was classified as high risk according to Fletcher's classification [].
The patient was admitted to our hospital for pain and symptoms of total dysphagia and an 8F nasogastric tube was inserted endoscopically.
Her case was further discussed in the sarcoma Multidisciplinary Team (MDT) meeting. Despite the tumour being resectable at presentation, its size and location rendered it to an increased risk of intraoperative rupture. Furthermore, GIST with mutations in exon 11 of KIT is generally associated with sensitivity to imatinib. Therefore, the MDT decided on preoperative administration of imatinib 400 mg daily.
She had an excellent clinical response with dysphagia gradually improving, and 12 days later, she was able to tolerate solid food once again.
The first follow-up CT scan two months after initiating treatment showed an excellent partial response, with the mass measuring 65 mm × 42 mm × 51 mm and reduction of tumour mass to 27% of the initial volume. New CT three months after showed further response, with mass reduction to 53 mm × 33 mm × 42 mm (Figures and ). During this period, she had been tolerating treatment very well, apart from Grade 1 fatigue.
After ten months of treatment, the tumour had been stabilized at 54 mm × 33 mm × 42 mm, suggesting plateau response. According to our policy, this would be the correct timing for surgery. However, because the patient was considered high risk for operation, as indicated by her cardiopulmonary exercise testing (CPX) revealing an anaerobic threshold of 9.3, the MDT decided the patient should continue treatment with imatinib and further take up an exercise program in an attempt to reduce her risks of perioperative complications.
Unfortunately, the next CT scan after 13 months of treatment demonstrated localized but progressive disease (90 mm × 42 mm × 60 mm) (Figures and ). Although disease progression under treatment with imatinib is a well described phenomenon, the previous excellent response in combination with the very fast disease progression raised the question of drug compliance []. On further questioning, the patient admitted not being compliant with drug therapy because of side effects of dry skin and periorbital oedema.
Further management of this patient was challenging. On one hand, we were not keen to lose the surgical window of opportunity for a bulky but localised tumour of the oesophagus, but on the other hand, the risk of intraoperative tumour rupture was similar to that prior to treatment.
After extensive discussion with the patient regarding the advantages and disadvantages of continuing imatinib therapy, the patient agreed to restart treatment.
She received her treatment regularly, and the follow-up CTs during the next year showed progressive reduction of the tumour size (Figures and ). 26 months after diagnosis, and with the latest CT demonstrating the oesophageal tumour measuring 44 mm × 36 mm × 35 mm, equal to 13.84% of the volume at diagnosis, the patient underwent an uncomplicated and without tumour rupture laparoscopic-assisted Ivor-Lewis oesophagectomy and was discharged 12 days after surgery.
Histopathology revealed a GIST with extensive areas of hypocellularity with hyalinised stroma and haemosiderin deposition, consistent with therapy effect, and viable tumour was estimated at approximately 30–50%. There was mucosal ulceration and the lesion extended from the mucosa to the adventitia. The tumour margins measured 10 mm from the oesophageal resection margin, >30 mm from gastric resection margin, and <1 mm from the serosal surface. Nine lymph nodes were identified, with no evidence of metastatic tumour. The mitotic index was 14/50 hpf.
Both the original size of the tumour and the mitotic index (14/50 hpf) classified the tumour as “high risk” and the decision was taken for further adjuvant imatinib, according to the Scandinavian Sarcoma Group Trial [].
At the last follow-up, 1 year after operation and 38 months from the diagnosis, the patient remained disease free.


The patient, a 22-year-old man, experienced a back throw during a game of judo, when his left foot caught on the tatami mat. He sustained a left knee injury resulting from varus and hyperextension force of the knee. He was unable to walk at the scene. Upon presentation to the emergency department, the left knee had large effusions and noticeable tenderness on the posterolateral knee joint. Passive range of motion (ROM) of the injured knee was 115° of flexion, with an extension deficit of 10° (0°–10°–115°). The ROM of the uninjured knee was 5° of hyperextension and 145° of flexion (5°–0°–145°). The patient exhibited a positive Lachman test with a soft endpoint. There was significant laxity (3+) evident during varus stress testing of the left knee at both 0° and 30° of knee flexion, and dial testing was positive at 30° but negative at 90°, when compared to the contralateral side.
The patient could not dorsiflex his left ankle and hallux, and the manual muscle test (MMT) grade of the tibial anterior muscle (TA) and extensor hallucis longus muscle (EHL) was 0, indicating a drop foot, and the sensory function of the CPN area had disappeared. The nerve conduction velocity could not be derived 5 days after injury ().
Radiography showed no fracture in the injured knee. Magnetic resonance imaging showed evidence of a complete anterior cruciate ligament (ACL) rupture, PLC injury that included injury to the popliteus and LCL, and distal rupture of the biceps femoris (Figures –).
A two-staged operation was performed to prevent the loss of ROM owing to arthrofibrosis and the fact that the patient did not require early ACL reconstruction because of the effect of the CPN palsy on activities of daily living (ADL).
Following informed consent, the patient underwent surgery 7 days after injury. Examination under general anesthesia revealed a positive Lachman test, positive external recurvatum test, stable posterior drawer test, 3+ laxity with varus stress at both 0° and 30° of knee flexion, and good stability with valgus stress testing. We commenced open repair of the PLC and biceps femoris. A curved incision was made laterally between the femoral condyle and the fibula. Upon splitting the skin and subcutaneous tissue, complete avulsion of the posterolateral structures from both the tibia and fibula became apparent, with complete avulsion of the LCL, PFL, and biceps femoris from the fibula head. Avulsion of the popliteus muscle tendon from the femoral condyle had also occurred. The peroneal nerve was located and inspected. There was evidence of contusion, and the patient underwent neurolysis (Figures and ). Suture anchors were inserted at the attachment of the LCL, PFL, and biceps femoris to the fibular head, and the LCL, PFL, and biceps femoris were sutured.
For the first 3 postoperative weeks, the knee was immobilized with a cast at 30° flexion, and the patient did not bear weight on his surgical leg, to protect the PLC repair from undo forces. After the 3-week cast, the patient advanced to weight bearing, as tolerated, and walking with a soft knee brace and orthosis for the drop foot. The soft knee brace does not immobilize the knee but supports the knee. Adequate quadriceps control for ambulation was achieved at 10 weeks postoperatively, at which time the soft knee brace was taken off for general activity, and the patient's weight-bearing status was progressed to full, unassisted walking. The CPN area gradually recovered after 3 months, and the MMT of the TA and EHL gradually improved 8 months after the first operation.
Nineteen months after the first operation, the MMT of the TA and EHL improved to grades 4 and 1, respectively. There was excellent knee ROM (5°–0°–140°) and good stability with valgus and varus. Because of improved ADL, an anatomical single bundle ACL reconstruction was performed ().
Following the ACL reconstruction, the injured knee was progressing favorably. There was excellent knee ROM (5°–0°–145°) and muscle strength, and he returned to competition 27 months after the injury (). At the final follow-up, 31 months after the injury, the MMT of the TA and EHL improved to grades 5 and 4, respectively, and sensation in the CPN area had almost completely recovered (Video 1 in Supplementary Material available online at ). There was good stability with valgus and varus, and the Lachman, pivot shift, and dial tests were negative. At the final follow-up, the subjective International Knee Documentation Committee (IKDC) score was 92.0.


A 34-year-old, multiparous woman had been admitted to a rural clinic with the complaint of postcoital bleeding. Due to the detection of a cervical mass, she has been referred to our hospital. We saw a minimally ulcerated mass lesion 3 cm in diameter at the upper ectocervix. On the basis of these clinical findings we performed a colposcopy directed biopsy which resulted as a malignant epithelial tumor. The tumor was staged as 1B1 according to International Federation of Gynecologists and Obstetricians staging system. We performed radical hysterectomy, pelvic-para-aortic lymphadenectomy, bilateral salpingectomy, and ovarian transposition ( shows the pathology specimen). The final pathology result revealed mucoepidermoid carcinoma of uterine cervix, grade 2, with intact vaginal surgical border and parametria (Figures and show histopathologic images with haematoxylin and eosin staining and periodic acid-Schiff staining). There was no lymphovascular space invasion and no metastasis to dissected 43 lymph nodes. On the follow-up we decided chemoradiation therapy on basis of the poor differantiated nature of tumor at our gynecological oncology council. The patient achieved her chemoradiation therapy successfully. After the radiation therapy she had radiation cystitis; she was treated for that and now 12 months after the surgery she is alive with no complaints and no recurrent disease.


A 63-year-old, multiparous woman was admitted to our outpatient clinic with the complaint of vaginal bleeding. During the pelvic examination we detected a cervical mass 3.5 cm in diameter and took a biopsy from the lesion. Biopsy result was malignant epithelial tumor. She was staged as 1B1 cervical carcinoma. We performed radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic-para-aortic lymphadenectomy. Pathology result defined mucoepidermoid carcinoma of uterine cervix ( shows the histopathologic evaluation). Parametria and vaginal border was tumor-free; nevertheless, a lymphatic metastasis was detected at one obturator lymph node out of total of 34 lymph nodes. We detected mucin stained areas during the histopathologic evaluation of metastatic lymph node (). Postoperatively she received chemoradiation therapy successfully and now 6 months after the surgery she is without any recurrent disease.


A 23-year-old man presented with left leg pain. Radiographs revealed an aggressive lesion of the distal tibia (Fig. ). Biopsy (Fig. ) and appropriate staging studies confirmed stage IIB chondrosarcoma []. He was treated with wide en bloc resection, including the distal third of the tibia and the cartilage of the talus in the tibiotalar joint. He then underwent a distal tibia lengthening with a unilateral external fixator (Fig. ). Gradual distraction started 5–7 days after surgery and was applied at a rate of 1 mm per 36 hours, and 8 cm of length was gained and corticalized over a 6-month period. Fusion of the tibiotalar joint was then allowed to proceed for 3 months before removal of external fixation (Fig. ). The current limb-length discrepancy is minimal (Fig. ). He has remained disease free for 3 years since the initial surgery and can maintain normal limb athletic function.
The external fixation index calculated by dividing the entire duration of external fixation by the length of bone regeneration was 36 days/cm; the distraction index calculated by dividing the duration of distraction by the length of bone regeneration was 11.08 days/cm, and the maturation index calculated by dividing the duration of external fixation by the length of bone regeneration was 25.8 days/cm, as measured from the completion of distraction to the removal of external fixation. The patient was evaluated via physical examinations and radiographs throughout the follow-up period. The function of the affected limb was assessed according to the revised 30-point functional classification system established by the International Society of Limb Salvage and the Musculoskeletal Tumor Society (MSTS) []. The MSTS score was 94 at the final follow-up, and the Foot and Ankle Disability Index (FADI) for patients with a tumor around the ankle joint was 90.


A six month old male entire BMD presented to the Wroclaw University of Environmental and Life Sciences at the Department of Internal Medicine with a Clinic of Horses, Dogs and Cats, with a history of knuckling and tremors in the hind limbs. The symptoms slowly progressed over a period of 2 months to problems with balance, incoordination, generalized ataxia, drifting to the left, head tilt to the left, knuckling on all four limbs, an aversion to touch, a reluctance to move and excessive fear. At the time of presentation, the general examination revealed an increased body temperature (40.5°C) and reddened mucous membranes. The neurological examination revealed a lateral recumbency, general stiffness, normal mentation, decreased proprioceptive positioning on all four limbs, a reduced menace response, decreased physiological nystagmus, myotonic spasms, and increased spinal reflexes. A diffuse central nervous system (CNS) lesion was suspected. There were three differential diagnoses reached: metabolic or degenerative encephalomyelopathy and an infectious disease. A complete morphological and biochemical blood examination revealed no changes.
Electrophysiological assessment was carried out under general anesthesia at an ambient temperature of 22°C with the use of the Nicolet Viasys Healthcare portable electrodiagnostic equipment, with 11.0 version of Viking Quest software. The body temperature dropped to 38.0 after the administration of premedication and maintained at that level during anesthesia. Electromyography (EMG) was performed by intramuscular insertions of the standard electromyographic concentric needle electrode and a subdermal monopolar ground electrode. EMG revealed normal insertional activity and normal resting activity in the tested muscles. The motor nerve conduction velocity (MNCV) and F-wave assessment were obtained from the left sciatic and tibial nerves, with the use of stimulating needle electrodes, a recording concentric needle electrode and a ground electrode, which was placed between the stimulating and recording electrodes. The MNCV was measured at three points: proximal (A1) - caudal to the greater trochanter of the femur, middle; (A2) - at the level of the stifle, caudal to distal end of the femur; (A3) distal - above the hock, lateral to the insertion of the gastrocnemius tendon of the tuber calcanei. The recording electrode was placed in the plantar interosseus muscle of the left foot. The results were compared with those of 6 month old healthy dogs [,] and showed a decreased conduction velocity (12–38 m/s compared with 53 ± 2.8 m/s in normal dog). The proximal latency of the compound muscle action potential (CMAP) in the BMD was 15,4 ms in comparison to 8,4 ± 0,4 ms in the normal dog []. The middle latency was 11,5 ms vs 6,2 ± 0,3 ms and the distal latency was 7,3 ms vs 3,4 ± 0,1 ms []. The duration of CMAP was also prolonged as follows: proximal latency 7 ms (reference 4,9 ± 0,4 ms), middle latency 6,7 ms (ref. 4,6 ± 0,4 ms) and distal latency 5,4 ms (ref. 4,4 ± 0,3 ms) []. This which is indicative of temporal dispersion (Figure ). Sensory nerve conduction was not performed. The F-wave evaluation was based on the measurement of the minimal latency of the recorded F-waves in comparison to the expected minimum F-wave latency calculated according to the following formula: 3.45 + 0.33 × limb length [cm] for the sciatic/tibial nerve []. The limb length (56 cm) was measured as a distance between the greater trochanter of the femur and the distal tip of the 3rd digit. The measured minimum F-wave latency was prolonged (30.5 ms) when compared to the expected minimum F-wave latency (21,93 ms) (Figure ). The F ratio of the sciatic/tibial nerve was calculated according to the formula: (LatF–LatM-1)/2LatM [] and compared to the 0.883 ± 0.052 reference value at the stifle. The F ratio was 0.446, which is below the reference range described above.
Prior to the brainstem auditory evoked response (BAER) evaluation, an otoscopic examination was carried out in the dog to exclude any ear canal obstructions. The dog’s BAER was recorded (Figure ) with the reference electrodes placed at the mastoid processes of both ears. The control group was retrospectively formed BAER recordings of our facility, from 20 healthy dogs of various breeds (8 females, 12 males), with a mean weight of 32 kg and a mean age of 6 months, using the same recording protocol as the BMD. The mean amplitude and latency of each wave was calculated and the results were compared with those obtained from the BMD. Wave latency differences between the dog and the control group were greater than 0.5 ms (shorter wave latencies in the studied dog) at 90 dB for wave III and V as well as at 105 dB for wave V in the left ear. Wave amplitudes in the BMD were generally smaller than in the control group. Wave II amplitude differences greater than 1 μV were present in both ears at all three sound intensities in the subject.
Magnetic resonance imaging (MRI) was performed using a low-field scanner (0,2 T system, Esaote Vet MR, Genova, Italy). Imaging parameters, sequences, and planes were tailored according to the patient size. Sequences included sagittal, transverse plane T1- and T2-weighted (T1W, T2W) images, dorsal plane T2W and transverse plane contrast enhanced T1W images (following an injection of 0,1 mmol/kg of gadobenate dimeglumine a). The MRI changes included mild generalized symmetric distension of the cerebral ventricular system (ventriculomegaly) (Figure ), and asymmetric distension of the recessus rostralis (left > right) (Figure ). No features of increased intracranial pressure, indicative of compensatory hydrocephalus due to neuronal tissue loss (ex vacuo), were found. Linear, symmetrical, bilateral T2W hyperintense signal was observed on the border between the white and gray matter in the cerebral cortex of the frontal, temporal and occipital lobes (Figures and ). No pathological contrast enhancement was found. Three differential diagnoses were reached: leucodystrophy, other degenerative encephalopathies or metabolic disease. Cisternal cerebro-spinal fluid (CSF) analysis showed an elevated total protein concentration of 35 mg/dl (reference range <25 mg/dl) with no pleocytosis. Due to a bad prognosis, the owners decided to euthanize the dog.
Gross pathological examination of the cerebrum and spinal cord was unremarkable. Sections (5 μm) were stained with haematoxylin and eosin (HE), Luxor fast blue (LFB) and toluidine blue, using the periodic acid-Schiff (PAS) and Bielschowsky silver impregnation methods. The histopathological examination of the brain and spinal cord revealed diffuse degenerative changes of the white matter throughout the neuraxis, with a varying degree of severity (Figure ). A proliferation of astrocytes with an open faced nucleus and large glassy eosinophilic to pale cytoplasm was observed in the affected areas (Figure ). In the forebrain, the proliferation of the abnormal astrocytes tended to be more intense at the border between the white matter and the cortex. A massive accumulation of eosinophilic RF was noted presumably in the astrocytic endfeet especially around blood vessels, (Figure ). These fibrous accumulations often contained intensely stained eosinophilic droplets reminiscent of fibrinoid material (Figure ). Involvement of brainstem and spinal cord gray matter was also noted with marked diffuse accumulation of RF and diffuse proliferation of abnormally large astrocytes, unaffecting neurons (Figure ). The Rosenthal fibers often extended along the ventral horn axons traversing the spinal cord white matter (Figure ). The fibers were also found in subpial and some subventricular locations.


A 41-year-old female presented with malaise, severe fatigue, nausea, and vaginal bleeding in April 2011. In her past history she was healthy, except that she reported taking terbinafine pills for 8 weeks for the treatment of longstanding recurrent toenail onychomycosis. She did not report any immune reactions or allergies to any drugs or substances. Her previous gynecological examination was normal, with a normal β-human chorionic gonadotropin level. Her complete blood count (CBC) revealed pancytopenia with white blood cell count of 3.2x109/L, absolute neutrophil count of 0.8x109/L, hemoglobin of 7.4 g/dL, and platelet count of 34x109/L. Her physical examination was unremarkable with no evidence of lymphadenopathy or organomegaly, except for a few petechiae and ecchymoses on bilateral legs. Peripheral blood smear was consistent with pancytopenia. Reticulocyte count was 0.7. Liver enzymes were elevated [AST: 61 U/L (N: 10-37 U/L), ALT: 117 U/L (N: 10-40 U/L), ALP: 434 U/L (N: 0-270 U/L), GGT: 471 U/L (N: 7-49 U/L)]. Renal function tests and lactate dehydrogenase were normal. Bone marrow aspiration and biopsy revealed severe reduction of all cell lineages without evidence of neoplastic infiltration, dysplasia, or fibrosis. The counted cellularity was 5% in bone marrow. Bone marrow karyotype analysis was normal. A gastroenterology consultation performed for the liver enzyme abnormalities did not provide an etiologic factor, pointing toward drug-induced hepatitis. Further work-ups, including levels of vitamin B12 and folate; neck, chest, and abdominopelvic computerized tomography; serology and polymerase chain reaction (PCR) tests for viral hepatitis, human immunodeficiency, Epstein-Barr virus, parvovirus B19, and cytomegalovirus; FLAER test for paroxysmal nocturnal hemoglobinuria; antinuclear antibody test; HLA-DRB1*15; and quantiferon test for tuberculosis, were all negative. The patient was diagnosed with AA, which was not severe at that time. Terbinafine treatment was stopped. Due to the use of a drug with probable hematologic toxicity, follow-up with supportive care was planned for the patient. During 3-4 weeks of follow-up time, blood values worsened with the need for erythrocyte and thrombocyte transfusions, in accordance with very severe AA (SAA). She did not have a matched related donor for transplantation. After confirming the diagnosis with a second bone marrow biopsy, she received rabbit antithymocyte globulin (ATG) plus cyclosporine-A (CYC). The clinical outcome after ATG + CYC was poor due to transient worsening of hematopoiesis and infectious complications. She spent 3 months in the hospital with perianal abscess, invasive aspergillosis, zoster virus reactivation, and several catheter infections. She required physical and psychological rehabilitation. Fortunately, the blood values began to recover at the end of the fourth month and full hematologic recovery was achieved at the end of the sixth month. The patient is still in complete remission after 18 months of ATG + CYC treatment ( and ).


A 57-year-old Korean man with no underlying disease visited our hospital emergency department for progressive dyspnea over the course of several days. The initial history revealed he was conscious, alert, and oriented. Vital signs showed that the patient was tachypneic (39/min), tachycardic (115/min) and normotensive (130/90 mm Hg). However, he was not hypoxic (O2 saturation 98 % on room air). Laboratory findings were non- specific. Initial chest x-ray and CT showed massive pleural effusion in the right hemithorax, diffuse pleural thickening, and several small nodules in the left lung, suggesting malignant pleural effusion (Fig. ). At first, an 8.3- French pig tail catheter drainage for the pleural effusion was performed. The pleural effusion study showed sanguineous and lympho-dominant exudate. Carcinoembryonic antigen level was 367.6 μg/L and adenosine deaminase was measured at 41 IU/L. However, the cytology findings of the effusion were negative for malignancy. Because the pleural effusion was not effectively drained, a 24-French tube thoracostomy without any negative pressure suction was performed in the right pleural cavity. The initial amount of drainage was 1500 ml. The patient tolerated the procedure well and his symptoms improved. However, the patient’s dyspnea worsened, and his oxygen saturation dropped to 66 % on room air the next morning. The patient required a 100 % FiO2 via mask with a reservoir bag to maintain and stabilize his oxygen saturation. A chest radiograph and chest CT taken at that time showed a right half- collapsed lung, and diffuse and severe infiltrative patterns, suggesting reexpansion pulmonary edema in the left whole lung field (Fig. ).
After conservative treatment with oxygen therapy, steroid administration, and negative suction application (-20 cm H2O) in the right pleural cavity for five days, the right lung could be fully expanded without the development of ipsilateral reexpansion pulmonary edema and the reexpansion pulmonary edema in the left lung resolved. Fortunately, the negative suction application (-20 cm H2O) in the right pleural cavity did not lead to development of reexpansion pulmonary edema or exacerbate the clinical course. The patient was weaned from oxygen supplementation.
For accurate diagnosis to determine proper management, we performed a VATS biopsy of the right pleura on the 10th hospital day. The operative findings showed diffuse emphysematous lung, diffuse pleural nodularity, and sanguineous pleural effusion. The final pathology revealed a primary adenocarcinoma lung cancer with pleural metastasis. The patient’s postoperative course was uneventful. He is now undergoing palliative chemotherapy.


A 25-year-old male came with complaints of pain in both groins for 1 month. Pain was more in the left groin compared to the right side. He is mason by occupation and his work involves lifting heavy objects such as stones but does not involve walking long distances. The weight of the stone was 10–15 kg and he had to lift the stones at least 3 to 4 hours a day amounting to a total of 100 to 150 stones. The pain was dull aching in nature, continuous, and nonradiating. Pain was aggravated on standing and walking. Patient was able to do all his routine activities but with pain. He was able to squat, sit, and walk. There was no history of any other comorbidities and past history and social history were not significant.
On clinical examination patient had an antalgic gait and there was no limb length discrepancy. There was tenderness present over the anterior joint line of both hip joints bilaterally. Extremes of rotation were painful with internal rotation being more severe. Power in both lower limbs was normal and neurovascular examination was normal.
The patient was evaluated by X-ray of both hip joints which showed a possible fracture line in the femoral neck on the left and no abnormality on the right (). On further investigation with MRI scan, a complete fracture line in the femur neck on the left side and an incomplete fracture line on the right side were seen (Figures , , and ). Patient was admitted, immobilised, and evaluated for the stress fracture with blood tests and DEXA scan. The tests revealed a normal blood picture and no abnormality was seen on tests done to rule out metabolic disorders. DEXA scan of lumbar spine also showed a normal T score.
The patient underwent surgery with internal fixation done using a 3 holed dynamic hip screw bilaterally on two sittings 2 days apart (). Weight bearing was initiated one and half months following the surgery with the aid of a walker. At 6 months and one year postoperatively patient was doing all his activities of daily living. On radiographic examination at 6 months and one year the X-ray did not show any evidence of avascular necrosis of the femur head ().


A three-month-old female Rottweiler puppy, weighing 11.6 kg, was referred to the cardiology service of the Veterinary Teaching Hospital of Perugia University, Italy for further assessment and treatment of CTD. When presented to the referring veterinarian, the dog had a history of gradual abdominal enlargement over the previous weeks. CDT was diagnosed by transthoracic echocardiography and medical treatment included furosemide(2 mg/kg orally twice daily), spironolactone (2 mg/kg orally once daily), and ramipril (0.25 mg/kg orally once daily). On clinical examination, the dog was bright and alert with a heart rate (HR, beats/min) of 136 and a respiratory rate (RR, breaths/min) of 36, but showed poor body condition (body condition score 3/9) and a markedly enlarged abdomen with a fluid wave. Abdominal ultrasound revealed severe ascites associated with evident hepatomegaly and hepatic venous congestion. Abdominocentesis revealed modified transudate ascitic fluid (specific gravity 1020, total protein 2.2 g/dL, poor cellularity). Cardiac auscultation revealed no heart murmur or arrhythmia.
Transthoracic echocardiography5 showed a thin, hyperechoic membrane that divided the right atrium into a cranial and caudal chamber. The tricuspid valve, cranial vena cava inlet, and right auricle were included in the cranial chamber, whereas the caudal chamber included the caudal vena cava inlet and the coronary sinus. A 4.5 mm opening allowed the blood to flow from the caudal to the cranial chamber. A colour Doppler5 examination showed turbulent flow from the caudal to the cranial chamber of the right atrium across the anomalous membrane, with a peak velocity of approximately 2.2 m/sec.
From these findings, CTD was confirmed and correction of the anomalous membrane by a balloon dilation technique was scheduled for the following day. Hematologic parameters had revealed alterations in both blood count and in biochemical analysis (Table ).
Prior to the anaesthetic procedure, the two cephalic veins were aseptically catheterized with a 20 gauge cannula. Patient preoxygenation (flow-by: 5 L/min of pure oxygen) was allowed before and after premedication. Pre-anaesthesia included consecutive intravenous (IV) administration of 0.5 μg/kg sufentanil and 0.2 mg/kg midazolam. Five minutes after premedication, general anaesthesia was induced with 2 mg/kg propofol, administered as a single, progressive IV bolus. The dog’s trachea was intubated with a 6.5 mm cuffed tube, which was connected to a non-rebreathing system (Bain-type). General anaesthesia was maintained with isoflurane diluted in oxygen (fresh gas flow: 3 L/min); concurrently, a constant rate infusion (CRI) of 0.5 μg/kg/h sufentanil9 and 5 mL/kg/h of lactated Ringer’s solution were administered IV by infusion pumps.
When an adequate depth of anaesthesia was achieved, the dog was positioned in right lateral recumbency for the cardiovascular corrective procedure. The patient was allowed to spontaneously breathe during the entire anaesthetic procedure and did not required artificial ventilation support.
A 24 gauge cannula was aseptically inserted into the metacarpal artery to measure direct blood pressure. HR, RR, electrocardiogram (ECG), invasive arterial blood pressure (systolic arterial pressure, diastolic arterial pressure, mean arterial pressure (MAP); mmHg), haemoglobin oxygen saturation (SpO2, %), end-tidal carbon dioxide partial pressure (EtCO2, mmHg), end-tidal isoflurane concentration (EtIso, %), and rectal temperature (T,°C) were continuously monitored and recorded every 5 min. During inflation and deflation of the balloon catheter (BC), the same parameters were recorded every 2 min. The transducer was zeroed at the level of the manubrium of the sternum.
The interventional procedure included percutaneous access from the right femoral vein by the Seldinger technique [] and the subsequent positioning of two balloon valvuloplasty catheters20 (first 12 mm and then 22 mm) across the intra-atrial membrane, under transthoracic echocardiography guidance5. Ten consecutive hand inflations with a 12 mm BC20 were performed. The dilation procedure was then repeated by using a 22 mm BC20.
The HR from the beginning to the end of the anaesthesia ranged from 126 to 163 and the MAP from 62 to 82 (Fig. ). Table shows the values of RR, SpO2, EtCO2, EtIso, and T. During the interventional procedure, several arrhythmias were noted and recorded (ventricular and supraventricular tachyarrhythmias). Transient supraventricular extrasystoles were observed during the placement of the guide wire and BC20, but spontaneously resolved following the withdrawal of the dilation instrumentations from the atrial wall. During balloon inflations (22 mm BC20), ventricular and junctional beats (Fig. ) and non-sustained supraventricular tachycardia (Fig. ) occurred, with spontaneous conversion to sinus rhythm after the end of the dilation procedure. These arrhythmias did not show any haemodynamic impact on the arterial pressure.
Table provides the total anaesthesia and cardiovascular procedure time, the total inflation-deflation time of the BC20, the number of BC20 inflations, and the total dose and CRI time of sufentanil9.
The dog was extubated 9 min after the end of the anaesthesia and was able to stand after 14 min. The recovery was uneventful and the patient was hospitalized post-operatively for two days.


A 54-year-old man noticed enlargement of the proximal aspect of the right clavicle. He made an appointment to undergo positron-emission tomography (PET)-based cancer screening 1 month later, which revealed a lesion with abnormal accumulation in the right clavicle. He was referred to our department for further examination. Plain X-ray revealed lytic change and ballooning of the proximal end of the right clavicle (Fig. a). Computed tomography (CT) showed an expanded medullary cavity and thinning of the cortex without periosteal reaction (Fig. b). No lung metastasis was demonstrated by thin-slice chest CT. The tumor was isointense on T1-weighted magnetic resonance images and showed a mixture of low- and high-intensity areas on T2-weighted images. However, the tumor did not extend to the surrounding soft tissues (Fig. c–e). Bone scintigraphy showed uptake of 99mTc-methylene diphosphonate in the proximal clavicle (Fig. a), and thallium-201 scintigraphy showed strong accumulation (normal/tumor ratio, 2.31), suggesting an abundant blood supply to the tumor (Fig. b). PET revealed strong accumulation of fluorine-18-2-fluoro-2-deoxy-d-glucose (SUVmax, 6.0) in the proximal part of the right clavicle, but no other primary cancer or metastases were demonstrated in other sites of the body (Fig. c). All hematological tumor markers (CA19-9, CEA, AFP, NSE, IL-2R, urinary Bence-Jones protein, and serum M-protein) were negative.
Based on the characteristic roentgenographic and CT imaging findings with ballooning of the affected bone, the primary differential diagnosis was a GCT. However, we could not completely exclude malignancy because of the affected site, patient age, and degree of accumulation on PET. We thus performed an open biopsy of the tumor. Preoperative angiography was performed to prevent dissemination due to massive perioperative bleeding; however, large nutrient vessels requiring embolization were not demonstrated. Fragile, yellowish-brown tumor tissue was obtained by the biopsy (Fig. a). Pathologically, the tumor comprised mononuclear stromal cells and multinuclear giant cells (Fig. b). The stromal cells showed oval nuclei with fine, uniform chromatin, and nucleoli were frequently found (Fig. c). Many multinucleated giant cells resembling osteoclasts were surrounded by mononuclear cells (Fig. c). The case was pathologically diagnosed as a GCT of bone, and surgical treatment was planned.
Because this was determined to be a grade II tumor (cortical erosion, deformity, and expansion of bone) according to the Campanacci classification [], curettage was considered initially. However, we chose resection to minimize the chance of recurrence because adhesion between the clavicle and major vessels was anticipated, which would make reoperation very difficult. Additionally, the clavicle does not necessarily require reconstruction after resection, and this patient was not engaged in physical work. An osteotomy was performed 8 cm from the proximal edge of the clavicle (Fig. b), and the sternoclavicular joint was then disarticulated (Fig. c). The tumor was resected en-bloc with half of the clavicle. It contained a thin, fragile cortex, but extension to the surrounding soft tissue was absent (Fig. d). The residual clavicular length was 7.5 cm on postoperative roentgenography (Fig. e), and no displacement of the resection edge of the clavicle was observed (Fig. f).
No shoulder disproportion was observed postoperatively (Fig. a). The range of motion of the right shoulder was normal (Fig. b), and the Japanese Orthopaedic Association shoulder score (JOA score) [] was 99 points. The patient was satisfied with the surgical outcome, and the Musculoskeletal Tumor Society score [] was 96 %. He returned to his original job as a land and house investigator without any signs of recurrence for 1 year after surgery.


A 2-year-old female child presented with pain in abdomen with abdominal distention and fever since 8 days, as per the history narrated by her mother. She also had history of nausea, vomiting (nonbilious), and constipation since 2 days. As per abdominal examination, there was a generalized distention of abdomen and a mass was palpable which was arising out of pelvis more on the right side. The mass was extending from the right iliac region up to just below umbilicus and crossing the midline towards the left side in the suprapubic region (). Mass on palpation was of mixed consistency, tender with no localized increase in temperature, and a size of 10 cm × 12 cm approximately. There were no signs of peritonitis on palpation.
The ultrasonography (USG) abdomen and pelvis revealed a thick-walled mass measuring 9.2 cm × 6.0 cm × 7.6 cm in the pelvis. The right ovary was not seen separately from the mass and it showed irregular solid areas with large cystic changes and thin strands inside. The uterus and left ovary were normal. There was no free fluid in abdomen. Computed tomography (CT) scan showed a large heterogeneous mass arising from of right ovary. X-ray erect abdomen showed air fluid levels ().
Hematological investigation showed a hemoglobin of 6.0 gm%, total leucocyte count of 12,000/mm3 with polymorphs 80%, lymphocytes of 20% and platelet count of 2 lakhs/mm3, and ESR 26 mm/hr, serum creatinine was 0.7 mg%, liver function test, urine routine, and microscopy were within normal limits, and urine culture showed no organism. Alpha-fetoprotein value was 11.45 ng/mL (normal value: 0–15 ng/mL). Other tumor markers like CA 125 and CEA were also within normal limits. On exploratory laparotomy, we found a right tuboovarian mass of size approximately 10 cm × 6 cm × 5 cm with distended small bowel loops and no ascites or pus in the abdominal cavity (). We did right salpingooophorectomy of the patient and specimen was sent for histopathology reporting ().
On histopathology report, the specimen of the mass was yellowish in color grossly, had smooth outer surface, and measured 9 cm × 6 cm × 5 cm and the fallopian tube of the right side measured 2 cm in diameter and 4 cm in length with exudates on its surface and serous fluid in its lumen. The cut section showed multiple solid and cystic areas with small patchy areas of necrosis too. There was diffuse and dense infiltration of ovarian tissue by sheets of foamy histiocytes, lymphocytes, plasma cells, and polymorphs on microscopic examination. Microscopic examination also showed multiple microabscesses with extensive areas of hemorrhagic and infarctoid necrosis, with areas of marked fibrosis (). The specimen tissue was subjected to special stains like Acid fast stain, PAS, and GMNS stain and was negative for microorganisms. Based on these unique and characteristic histopathology features, the diagnosis of xanthogranulomatous salpingooophoritis was confirmed. Postoperatively, patient was given intravenous antibiotics (3rd generation Cephalosporins) for 5 days. Patient made good and uneventful recovery postoperatively and was discharged on the 7th postoperative day.


A 60-year-old woman with oroantral communication presented for treatment at the Specialization Course in Implant Dentistry of the University Center of the Barretos Educational Foundation (UNIFEB).
The main complaint was foul smelling, purulent discharge and intense facial pain, for which she continued to take analgesic ketorolac trometamol (10 mg). The patient reported to be in good general health, not having undergone radiation therapy, or consumed drugs, alcohol, or tobacco. On clinical examination, total edentulism was observed.
The patient had undergone maxillary sinus lift surgery, and six months later, 6 implants were implanted in the maxilla. Less than a month later, the patient realized that both the implant and prosthetic component installed in the region of tooth 16 had dislocated and was housed within the maxillary sinus. Oroantral communication was the result. A surgical procedure was performed by an otorhinolaryngologist, which only resulted in the removal of the implanted body. Some days later, the patient reported that the prosthetic component was expelled through the nose. However, the communication and local infection persisted, and four months later, the patient sought treatment.
On initial inspection (), the presence of a 5 mm diameter communication was confirmed, with mild mucosal inflammation of the surrounding region. Tomographic examination was requested along with prototyping of the jaw, and a 5 mm bone gap was detected. The treatment plan involved the remission of infection, followed by surgical closure of the injury. The patient was instructed to wash with saline and 0.12% chlorhexidine in a ratio of 1 : 1 using a hypodermic needle attached to a sterile rubber hose without cutting the tip. Furthermore, amoxicillin-clavulanic acid (875 mg) and metronidazole (200 mg) were prescribed for 14 days. After this period, there was no pain, and the local secretion became transparent. However, local palpation revealed that the suspected bone defect was greater than that shown on prototyping.
On the day of surgery, the patient underwent extrabuccal antisepsis with povidone iodine solution and intrabuccal antisepsis with chlorhexidine 0.12%. The patient underwent infiltration anesthesia around the communication and palate using 4% articaine chloride and epinephrine 1 : 100,000. An incision was made around the communication in order to remove the epithelialized soft tissue collar (). At this time, the actual size of the bone lesion was measured at 12 mm at its largest diameter (mesiodistal), which was not consistent with the prototype examination.
A mucosal pedicled flap was elevated () and slid sideways from the palate to cover the communication (). Subsequently, local compression was performed for 2 min, followed by suturing with nylon 5.0 simple sutures (). The residual denuded area was covered with surgical cement.
After surgery, the patient received instructions on postoperative care; she was instructed not to brush the operated area. The following procedures were prescribed: intrabuccal mouthwash without rinsing with 0.12% chlorhexidine digluconate solution for two weeks, amoxicillin and clavulanic acid 875 mg given orally every 8 h for 7 days, nimesulide 100 mg 12 in 12 h for 3 days, paracetamol 750 mg 6 in 6 h for 3 days, and nasal decongestant oxymetazoline hydrochloride 0.05% every 12 h for 3 days.
There were no intercurrences in the postoperative period, and a week later the sutures were removed. After 4 months of observation (), the communication remained closed, no pain, foul smelling, or purulent discharge was observed, and the patient was satisfied with the treatment outcome.


A 6-year-old boy was referred with double stream urination. Physical examination revealed the presence of the double glans accompanied by second urethral meatus positioned dorsally (). Further evaluation by voiding cystourethrogram (VCUG) showed duplex bladders in the coronal plane (). The accessory bladder lies anterior to the main bladder with no evidence of vesicoureteral reflux. Dimercaptosuccinic acid (DMSA) scan showed horseshoe kidney with acceptable cortical function in the right kidney (60%) and diffuse decrease in the cortical function of the left kidney (40%). Cystoscopy was performed and the cystoscope easily passed through the ventral meatus unlike the dorsal orifice due to severe stenosis. The right ureteral orifice drained at the entrance of the accessory bladder to the main bladder while the left orifice entered the main bladder at its normal position. However, both urethral orifices originated from the main bladder. Further study by spinal magnetic resonance imaging revealed butterfly vertebrae in L1, L2, and L3 (). Overall, the patient had bladder duplication in the coronal plane with two distinct urethras, both originating from the main bladder, accompanied by glans diphallia with dorsal stenotic urethra (). The patient was taken to surgery and the bladder was exposed through a lower midline incision. The main and accessory bladders were separated by adjacent fascia. After opening the main bladder, the septum between the two bladders was resected and the two lumens were anastomosed (). Due to the patent ventral urethra and stenotic dorsal urethra, the closure of dorsal urethra was planned. A catheter was placed in the stenotic dorsal urethra to demonstrate the orifice, and the orifice was subsequently ligated and cauterized. The biopsy of the intravesical septum revealed a muscular tissue lined by a transitional epithelium with congestion and hemorrhage. Postoperatively, the patient had good caliber urination at ventral orifice with no stream at dorsal orifice and he was discharged with good condition. The patient has no complication after 1 year follow-up.