A 65-year-old man presented to our emergency department with clinical dehydration and disturbance of consciousness. Systemic computed tomography showed obstructive ileus secondary to an ascending colon tumor, and he was diagnosed with ascending colon cancer with multiple liver metastases (Fig. ). Insertion of an ileus tube and administration of intravenous therapy improved his hydration and level of consciousness. After the patient’s condition improved, we performed a right hemicolectomy. The postoperative pathological examination revealed penetration of cancer cells into the subserosa, subserosal vessels, and subserosal lymphatic ducts. Histological examination revealed well-differentiated tubular adenocarcinoma. Metastasis was detected only in the paracolic lymph nodes. After primary tumor resection, he received systemic chemotherapy comprising oral fluoropyrimidine (S-1), oxaliplatin, and cetuximab in a clinical trial setting. However, his disease became progressive within 3 months; therefore, we planned to perform second-line chemotherapy (irinotecan + S-1). Before he started the second-line chemotherapy, he was diagnosed with a silent brain infarction based on brain magnetic resonance imaging (MRI) findings following the clinical trial criteria. Although he exhibited no associated symptoms, brain MRI showed multiple bilateral small cerebral infarcts and essentially normal MR angiography (Fig. ). He was carefully examined for evidence of cardioembolic stroke or carotid atherosclerosis. However, Holter electrocardiography, echocardiography, and carotid ultrasonography revealed no abnormal results. Therefore, the infarction was considered to be most likely caused by its relationship to cancer (Trousseau syndrome). Because of the risk of hemorrhage and lack of symptoms, the infarction was not treated with anticoagulant drugs first. Although the patient’s progress had been stable, paralysis of the right upper limb occurred 1 week later. MRI showed that the area of the infarction in the left cerebral hemisphere had spread (Fig. ). Both the fibrin degradation product and D-dimer levels continued to increase, and treatment with edaravone and aspirin was begun. Although the anticoagulant therapy was continued to prevent recurrence, the patient experienced repeated recurrences of the infarction with limb paralysis during the second-line chemotherapy. MRI showed that the infarction area in the cerebral hemisphere had spread with the progression of liver metastases (Fig. ). In addition, both the serum fibrin degradation product and D-dimer levels had continuously increased along with an increasing serum carcinoembryonic antigen level (Fig. ). Despite the possibility of thrombosis, we carefully administered regorafenib as third-line chemotherapy because of its anticancer effect. However, there was no response to the regorafenib. The patient therefore received best supportive treatment and died 1 month later.
We have presented a case involving a patient with Trousseau syndrome during systemic chemotherapy for metastatic colon cancer. The patient developed repeated recurrences of the infarction with the progression of liver metastases.
Trousseau syndrome is defined as unexplained thrombotic events that precede the diagnosis of an occult visceral malignancy or appear concomitantly with the tumor []. However, the term Trousseau syndrome is often applied to patients with malignancy who develop some form of thrombosis because of a thrombotic tendency such as immobility, dehydration, mechanical compression of veins, an infectious processes, or chemotherapy.
Although the molecular mechanism of Trousseau syndrome is not completely understood, it involves the interplay of multiple variables. Early reports suggest that tumors associated with thrombotic complications were mucin-secreting adenocarcinomas of the gastrointestinal tract []. However, not all cases of Trousseau syndrome are associated with mucin-producing carcinomas. A number of substances may contribute to the thrombotic tendency in patients with cancer. The main contributors that have been isolated from human tumors with procoagulant activity are classified into two major categories: tissue factor (also called thromboplastin) and cancer procoagulant [, ]. Tissue factor forms a complex with factor VIIa to activate factors IX and X, thereby initiating the coagulation protease cascades. Tissue factor is a cell surface receptor for factor VII and is found more frequently in epithelial malignant tumors; pancreatic tumors tend to secrete particularly high levels of tissue factor.
In one study of the infarct pattern in patients with cancer who developed stroke, diffusion-weighted imaging patterns of multiple lesions involving multiple arterial territories were more frequently observed in patients with cancer, whereas single/multiple lesions involving one arterial territory were observed more frequently in patients with conventional stroke mechanisms such as atherosclerosis, cardioembolism, or lacunar stroke [].
In the present case, both first- and second-line chemotherapy were ineffective; even with third-line chemotherapy, the patient’s overall survival was only 11 months, which is shorter than the current median survival in patients with metastatic colorectal cancer. The association between coagulation abnormalities and a poor prognosis of colorectal cancer has been reported []. Once brain infarction has occurred in a patient with cancer, the overall prognosis is poor. The median survival is only 4.5 months, and survival is strongly correlated with initial neurologic disability, similar to the general population with stroke. Furthermore, several reports have evaluated the efficacy of chemotherapy or radiotherapy and the presence of pretreatment coagulation abnormalities in cancer therapy. Such evidence would help oncologists and their patients to make treatment decisions.
The standard approach to Trousseau syndrome is early initiation of an anticoagulant such as a heparin-containing product. The decision to anticoagulate a patient with a limited life expectancy can be difficult because of the need for close laboratory monitoring and the risk of bleeding. The most common therapy for patients with brain infarction is prevention of dehydration and administration of anticoagulation therapy by warfarin in the acute phase and warfarin in the chronic phase. However, some oral fluoropyrimidines, which are key anticancer drugs for treatment of colorectal cancer, potentiate the effect of coumarin derivatives, inducing hemorrhagic adverse events. In several reports, low-molecular-weight heparin was successfully substituted for unfractionated heparin in the management of Trousseau syndrome, in part because of its improved pharmacokinetics, the ability to give single daily doses, and the reduced incidence of heparin-induced thrombocytopenia [, ]. In addition, it should be remembered that anticancer therapy for the causative tumor, if able to be performed, is equally important. We also used antiplatelet agents, aspirin, or clopidogrel. Antiplatelet therapy is used for both the management of acute ischemic stroke and for the prevention of stroke []; however, the effect of antiplatelet therapy for Trousseau syndrome is unknown. Some oral factor Xa inhibitors have recently become widely used in the clinical setting. The combination of anticancer therapy and oral Xa inhibitors or antiplatelet therapy is recommended for treatment of patients with Trousseau syndrome.


A 29-year-old Hispanic male presented with a week of blurriness in his left eye that progressed to complete vision loss. He was HIV positive for 6 years with a latest CD4 count of 100 and a viral load of 617 copies/mL on HAART therapy. He noted fevers and chills, but no other symptoms. On examination, the left pupil was fixed with no response to light. A reverse relative afferent pupillary defect was present in the right eye. The left optic nerve was edematous with blurring of margins. A CT scan showed enhancement of the retrobulbar optic nerve of the left eye with an adjacent, discrete soft tissue enhancement bordering the posterior globe (Figure 1 ). Two weeks later, an MRI showed diffuse thickening and contrast enhancement involving the retrobulbar portion of the left optic nerve associated with a surrounding soft tissue lesion within the intraconal orbital fat, and the lesion seemed to be extending more posteriorly than the previous CT image (Figure 2 ). The mass abutted the posterior aspect of the sclera. The lesion demonstrated low T1 and intermediate T2 signal intensities and heterogeneous contrast enhancement. There was also nodular contrast enhancement of the left optic nerve disc. The size of the lesion measured 17.4 mm x 15 mm x 10.6 mm. Cerebrospinal fluid studies were unremarkable. An anterior orbitotomy with exploration and biopsy of the left orbital mass was performed.
Histology of the mass showed tissue diffusely infiltrated with large, dysplastic lymphocytes with vesicular nuclei (Figure 3A ). Immunohistochemical stains showed that the lymphoid cells were positive for CD10 and CD20 (Figure 3B and 3C ) and were negative for CD3 and keratin AE1/AE3. Ki-67 demonstrated proliferative activity in greater than 90% of tumor cells (Figure 3D ). Additional immunohistochemical stains showed that the tumor was positive for BCL-2 and BCL-6. The patient was diagnosed with DLBCL (germinal center type) and was referred to oncology. He underwent staging and there was no other evidence of the disease in any other system in the body. He was started on R-CHOP chemotherapy. He was given one round of R-CHOP before he was unfortunately lost to follow-up; one round of R-CHOP administration did not improve his visual acuity.


A 51-year-old gentleman was referred with a six-month history of blurred vision in the right eye and a suspicious right optic disc. He did not complain of any other ocular symptoms and did not have any other past medical history.
On examination he was found to have a Snellen's visual acuity of 6/18 in the right improving with pinhole to 6/12 and 6/5 in the left. Anterior segment examination was unremarkable. Intraocular pressure was 15 mmHg in the right and 16 mmHg in the left. Dilated fundoscopy revealed a double optic disc pit in the right eye (). Retina and macula were flat; there was no fluid or detachment. The left optic disc was normal.
OCT of the macula and disc was otherwise unremarkable. Humphrey's visual field test revealed a paracentral scotoma in the right () and a normal left field. As he did not have any pit related maculopathy, he was able to be discharged with advice regarding signs of maculopathy. He will continue to attend his opticians every 2 years.


A 30-year-old man suffered a mangling injury of his right hand after it was caught in a meat grinder. All fingers were severely crushed with the exception of the little finger, which was intact distal to the proximal interphalangeal joint (a). The hand was also crushed and ablated. We planned an ectopic implantation of the little finger to provide enough time to fully debride and optimize the hand in preparation for reimplantation of the little finger. The superficial circumflex iliac artery perforator (SCIP) and subdermal vein were first identified near the anterior superior iliac spine (b). The diameter of the SCIP and the little finger digital artery were 0.4 mm and 0.6 mm, respectively. The digital artery of the little finger was anastomosed to the SCIP by using IVaS method.
Three months after ectopic implantation of the little finger, the little finger was elevated with an SCIP flap (12 × 3 cm), containing the lateral femoral cutaneous nerve (4 cm), a superficial circumflex iliac artery and vein (SCIA and SCIV), and superficial inferior epigastric artery (SIEA) (c and d). Because the litter finger is shorter than a normal size finger, the right second metacarpal bone with a dorsal metacarpal artery was harvested and placed distally on the 5th metacarpal bone (a and b). The SCIA and SIEA originate from a common trunk, which was anastomosed to the base of the 5th common digital artery. The dorsal metacarpal artery of the second metacarpal bone was anastomosed to the distal end of the SIEA (d). The SCIV and subdermal vein of SCIP flap were anastomosed to the dorsal veins of the hand. The vascularized lateral femoral cutaneous nerve was anastomosed to both ends of the 5th digital nerve. Sensation in the little finger recovered, with a Semmes-Weinstein test result of 4.08 and moving 2 PD of 8 mm at 10 months, and SCIP flap also had sensation with a Semmes-Weinstein test of 4.31.
Four months after transplantation of the little finger, toe to thumb transplantation was performed. (a-c). The maximum distance between the thumb and the little finger is 10 cm.


A 29-year-old man suffered an injury to his right hand after it was caught in a printing machine. The index finger was amputated at the distal interphalangeal (DIP) joint, and the skin was avulsed distal to the MP junction. The subdermal tissue of the amputated index finger was severely damaged. As immediate replantation seemed too hazardous, we opted for temporary ectopic implantation of the amputated part. The digital artery (diameter: 0.6 mm) was directly anastomosed to the right deep inferior epigastric artery perforator (DIEP/diameter: 0.8 mm) at the level of the DIP joint (a and b). The digital nerve was marked with 6-0 nylon. The avulsed skin of the index finger was grafted onto the abdominal fat layer like a skin graft. The exposed bone and tendon of the proximal part of the index finger were covered with a pedicled DIEP flap. A month later, the chimeric DIEP flap with the index finger was harvested from the abdominal wall. The deep inferior epigastric artery and vein were anastomosed to the radial artery and the subdermal vein located in the snuff box.
Two days after this operation, the tip of the index finger became pale and partially necrotized. Index fingertip pulp was debrided and subsequently reconstructed with hemipulp transplantation from the great toe. The active postoperative motion was 0° of extension and 90° of flexion on the metacarpophalangeal joint of the injured index finger (c and d). The proximal interphalangeal joint and DIP joint on the index finger were fixed. The uninjured fingers maintained their full range of motion.
The fingertip recovered good sensation. Semmes-Weinstein test was 2.83 and moving 2 PD was 8 mm after 2 years.


A Caucasian, 27-year-old female was being followed up during her second pregnancy. Her past medical and obstetric history was unremarkable. This was her second pregnancy; her older child from the first pregnancy was well. There was no family history of renal diseases or congenital abnormalities. She was not on treatment with any medications. A dating ultrasound scan was performed at 15 weeks of gestation showing a single live foetus.
The pregnancy advanced uneventfully. The anomaly ultrasound scan at 20+2 weeks of gestation showed evidence of duplex right kidney with dilatation of the upper moiety. The ultrasound scan was repeated at 23+6 weeks of gestation with the same findings. The dilatation of the upper moiety was measured at 10.8 mm. The right kidney was in normal position and there was satisfactory parenchymal differentiation. The left kidney, the ureters, and the bladder appeared normal. The amniotic fluid index was normal throughout the pregnancy. A follow-up scan at 32+1 weeks of gestation showed the right duplex kidney with resolution of the dilatation previously seen. The foetal growth was optimal. No other abnormalities were detected in the antenatal scans.
She delivered a male infant via normal vaginal delivery at 39+2 weeks of gestation. The infant was born in good condition without any perinatal complications. An ultrasound scan () was performed at 12 days of age. This scan showed features consistent with an uncomplicated right duplex kidney measuring 6.1 cm. The left kidney had a single collecting system and was measuring 5.2 cm. Both kidneys were visualised within the renal fossae and had normal parenchymal differentiation. There was no pelvic dilatation and the ureters were not visible in either of the kidneys. The bladder looked normal. Clinically, the infant was asymptomatic with normal blood pressure and renal function. There were no other evident congenital abnormalities.
The infant had a follow-up ultrasound scan at 3.5 months of age. During that scan, it was difficult to visualise the right kidney which was not within the renal fossa but in a higher position behind the liver. MRI () was performed at 4.5 months of age to determine the locus of the right kidney and possible associated abnormalities. It became evident that the right kidney was lying posteriorly and superiorly to the liver, below the diaphragm. There was no suggestion of duplex system and no features consistent with herniation were demonstrated. The size and the differentiation of both kidneys were normal. The diaphragm was intact and apart from the movement of the right kidney, there were no other abnormalities seen. There was no history of trauma.
A DMSA scan () was performed at 6.5 months of age which showed normal differential renal function; 52% on the right kidney and 48% on the left kidney were without any evidence of scarring. There was equal function in the upper and the lower poles of both kidneys with no evidence of duplex system. The infant had normal renal function and blood pressure and grew along his centile lines.


Patient 1 was a 26-year-old female without underlying diseases. She developed fever and cough on 24 December 2015 and deteriorated with a high fever (40.2 °C) on 26 December. The patient was hospitalized on 27 December and treated with mechanical ventilation. Tamiflu was immediately administered to the patient. The patient eventually died from severe pneumonia, respiratory failure and septic shock on the 30 December 2015. Respiratory samples were collected on 28 December and found to be HPAI H5N6-positive.


Patient 2 was a 25-year-old healthy man who runs a small restaurant in Shenzhen. On 1 January 2016, the patient developed a high fever (39.5 °C), cough and dyspnea. On 6 January, the patient was hospitalized and diagnosed with severe pneumonia, Type 1 respiratory failure, acute respiratory distress syndrome, left pleural effusion and an electrolyte disorder. He was immediately administered antiviral treatment with Tamiflu (150 mg bid). Respiratory samples were collected on the 6th of January and found to be HPAI H5N6-positive. Combined antiviral therapy with Tamiflu (150 mg bid), zanamivir (10 mg each time, bid) and peramivir (300 mg qd) was then administered on 7 January. The patient eventually recovered from his severe condition.
Epidemiological investigations of the infection sources of both human H5N6 infections were conducted when the patients were confirmed as H5N6-positive. Patient 1 bought a duck from a neighboring LPM approximately four days prior to the onset of her illness. Patient 2 reported a history of visiting an LPM prior to the onset of his illness. Environmental samples and swabs of poultry feathers collected from the epidemiologically identified LPMs tested positive for the H5N6 virus (). This result indicated that the LPMs were the potential sources of the human infections.


The patient is a 67-year-old gentleman who presented to the oncology clinic in September of 2015 with a non-tender, left neck swelling. The patient had lost approximately 8 kgs over the previous six months. He denied any history of fever, chills, dysphagia, recent dental procedure, or trauma to the area. A CT scan of the neck showed a heterogeneous mixed cystic solid mass 3.2 x 4.5 x 4.0 cm adjacent to the left internal jugular lymph nodes. A fine needle aspiration and core biopsy of the mass showed a monomorphic population of large lymphoid cells. Biopsy and flow cytometry findings were consistent with diffuse, large B-cell lymphoma. Post-procedure, the patient developed a worsening of the neck swelling. Investigation with a CT scan of the cervical region showed interval development of a soft tissue hematoma with no evidence of active bleeding. The patient agreed to participate and was explained the nature and objectives of this study, and informed consent was formally obtained. No reference to the patient's identity was made at any stage during data analysis or in the report.
The patient was started on chemotherapy with dose-adjusted R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, adriamycin). He was treated for three cycles without any adverse events. Nevertheless, he continued to have low-grade fever and no significant decrease in the size of the neck mass. Four months after the initial diagnosis, a repeat CT of the neck was done that showed persistence of the neck hematoma, now 5.8 cm in greatest dimension (previously 7.6 cm), with a new peripheral rim enhancement suspicious for an infectious process. The fluid portion of the mixed mass was therefore aspirated under ultrasound guidance, and the patient was started on empirical antibiotic therapy with Clindamycin and Ampicillin/Sulbactam. The cultures of the aspirated fluids, including aerobic, anaerobic, mycobacterial, and fungal-specific media, were all negative for growth. The patient continued to spike a fever despite broad-spectrum empiric therapy. This prompted an otolaryngology evaluation for excision of the mass. The patient underwent a modified radical neck dissection with sparing of the internal jugular vein, sternocleidomastoid muscle, and spinal accessory nerve. The histopathology was consistent with extensive necrosis containing Actinomyces clones with adjacent suppurative granuloma (Figures -).
Of note, Gram, Ziehl–Neelsen, Grocott's methenamine silver, and Periodic acid–Schiff stains of the fluid taken from the surgical procedure were all negative. The patient was treated with ampicillin-sulbactam 3 mg intravenously every six hours for a total of eight weeks. The abscess cleared after completion of antibiotic therapy. He completed his fourth cycle of chemotherapy and remains in remission to date.


A 58-year-old woman (smoker, 30 packs/year) with no past medical history was admitted to the outpatient Pulmonary Department of the Athens Medical Center for the evaluation of fever and dyspnea 4 days before admission. Two days before, the patient received empirical treatment with orally administered moxifloxacin (400 mg/day) and oseltamivir (75 mg/12 h) for community acquired pneumonia (CAP). Upon admission, clinical and laboratory testing as well as echocardiogram, chest X-ray (CXR), and chest computerized tomography (CCT) with intravenous contrast material were performed.
On examination upon first admission, the patient appeared with normal appetite and no apparent weight loss. She was febrile (38.5°C) without chills and hypoxic with oxygen saturation (SO2) of 94% on room air. On auscultation, dullness and decreased breath sounds were noted over the left lower chest. The echocardiogram was normal. Her blood tests demonstrated elevated white blood cells (WBC) count (10,760 cells/μL, neutrophils 81%), erythrocyte sedimentation rate (ESR) (102 mm/h, control < 30 mm/h), and C-reactive protein (CRP) (36.1 mg/dL, control < 0.5 mg/dL). Repeated blood cultures and urinary antigen tests for Pneumococcus and Legionella were negative. CXR (Figure A) and CCT (Figure B) on the admission day showed left-sided pleural effusion with consolidation and atelectasis of the left lower lung field.
The patient continued the treatment for CAP complicated by pleural effusion, with intravenous moxifloxacin (400 mg/day) and supplemental oxygen therapy. However, on the third day of hospitalization, her clinical condition dramatically deteriorated with severe dyspnea, without orthopnea (respiratory rate 30 breaths/min), hypoxemia (SO2 of 92% on a FiO2 100%), and fever (38.9°C). The new CXR (Figure C) and CCT (Figure D) revealed a significant increase of the left-sided pleural effusion with compressive atelectasis of the left lung and development of extensive consolidations in the right lung, especially in the upper lung fields. Moxifloxacin was discontinued and followed by the administration of intravenous meropenem (1 g/8 h), amikacin (500 mg/12 h), and linezolid (500 mg/12 h).
Chest drainage was performed and pleural fluid analysis exhibited elevated WBC count (14,850 cells/μL, neutrophils 95%) and lactate dehydrogenase (LDH) levels (1257 U/L), decreased levels of glucose (2 mg%), and pH 7.0. Pleural fluid Gram-stain showed the presence of Gram-positive bacilli and was both aerobically and anaerobically cultured. After 48 h incubation, two morphologically distinct types of Gram-positive rods colonies appeared. The bacterial isolates were oxidase-negative, catalase-negative, and non-motile. Both isolates were preliminary identified as Lactobacillus spp.
Species identification was performed using a previously described 16S polymerase chain reaction (PCR) and sequencing protocol (, ). Total DNA was extracted from bacterial colonies harvested from the agar plates using the commercially available QIAamp DNA Mini Kit (Qiagen, Hilden, Germany) and the tissue protocol, according to the manufacturer’s instructions. PCR was performed using the GoTaq Hot Start Colorless Master Mix (Promega Corp., Madison, WI, USA) and a MyCycler Thermal Cycler (Bio-Rad Laboratories MEPE, Athens, Greece) in 50 μL final reaction volumes. PCR products were visualized under UV illumination and purified using the NucleoSpin Gel and PCR Clean-up kit (Macherey Nagel GmbH, Düren, Germany). Sanger sequencing was performed in a 3130 Genetic Analyzer (Applied Biosystems Life Technologies Ltd., Paisley, UK). Sequencing results were aligned and edited using the Data Analysis in Molecular Biology and Evolution (DAMBE) software ver. 5.1.5 (University of Ottawa, Ottawa, ON, Canada). The consensus sequence results that were obtained were compared with those submitted to the GenBank using the BLAST algorithm. The isolates were identified as L. delbrueckii (16S accession number KU207148) and L. gasseri (16S accession number KU207149). The pure isolation of the L. delbrueckii and L. gasseri strains in the culture of pleural fluid and their further molecular identification were suggestive of extraintestinal colonization and infection by these two species. It was suspected that the two lactobacilli strains were involved in the clinical manifestations of pneumonia and empyema.
Susceptibility testing was performed according to the guidelines of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for Gram-positive anaerobes using the E-test diffusion method, on Mueller–Hinton agar supplemented with 5% mechanically defibrinated horse blood and 20 mg/L β-Nicotinamide adenine dinucleotide (β-NAD) (MH-F) for 48 h at 37°C in anaerobic conditions. Antibiotics with available breakpoints were tested [minimum inhibitory concentration (MIC) values in milligrams per Liter; S = susceptible, R = resistant]: ampicillin (0.5; S), amoxicillin–clavulanic acid (0.25; S), ampicillin–sulbactam (0.5; S), ticarcillin–clavulanic acid (0.25; S), piperacillin–tazobactam (0.25; S), imipenem (0.25; S), meropenem (0.25; S), clindamycin (0.25; S), and vancomycin (>32; R). Fluoroquinolones were not included as lactobacilli bear intrinsic resistance to this antimicrobial class and respective breakpoints are not available.
Following identification of Lactobacillus species and susceptibility testing, intravenous clindamycin (600 mg/6 h) was added to the antibiotic regimen. The patient presented steady improvement with complete symptom resolution and clearance of the abnormal findings in the CCTs (Figures E,F).
During a 5-month follow-up, referring to the preceding respiratory tract infection, the patient exhibited no clinical signs and symptoms, as ascertained by standard clinical examination and routine laboratory tests with normal values (blood cell count, ESR and CRP, blood glucose, creatinine, and enzymes). However, on the fifth month after hospital discharge, she developed signs of dysphagia. Subsequent gastroscopy and biopsy revealed an inoperable esophageal carcinoma (invasive squamous cell carcinoma–SCC) localized in the lower thoracic esophagus proximal to the gastroesophageal junction. Thorough retrospective reconsideration of the imaging examinations (CXR, CCT, and CT of the upper and lower abdomen) performed on admission and during hospitalization did not reveal any signs of prior esophageal malignant process. The patient succumbed to the cancer 11 months later.


A 68-year-old African American woman with well controlled type II diabetes mellitus, hypertension, and hyperlipidemia was diagnosed with CLL (Rai stage III with negative CD38 and ZAP-70) in September 2012 when she presented with night sweats and 4.5 kg weight loss over the preceding eight months. She received six cycles of chlorambucil and prednisone over the following two years with partial response in her white blood cell count (WBC). Polymorphonuclear cells (PMN) and lymphocytes ranged from 1.1 to 4.7 × 103/μL and 32 to 125 × 103/μL, respectively. In October 2014, she was started on ibrutinib 420 mg daily. In late November 2014, she was admitted for fever of 39.6°C and sore throat. After admission, she developed septic shock which was thought to be due to hospital acquired pneumonia and presumed Clostridium difficile colitis. Endotracheal culture grew Klebsiella pneumoniae, methicillin susceptible Staphylococcus aureus, and Candida krusei. She required mechanical ventilation, hemodynamic support with norepinephrine and vasopressin, chest tube placement, and broad spectrum antibiotics (vancomycin and piperacillin/tazobactam). She recovered slowly and was discharged to a nursing home after two weeks of hospitalization. Ibrutinib was held during this hospitalization while PMN and lymphocytes ranged from 2.2 to 4.7 × 103/μL and 9.6 to 24.1 × 103/μL. One week after discharge, in December 2014, WBC increased to 67 × 103/μL; hence, ibrutinib was restarted. In January 2015, she presented with dry cough for one month and lower lip numbness for one hour. In the emergency department, she had no focal neurological deficit and CT brain without contrast showed no acute intracranial pathology; however, she had fever of 39.1°C, tachycardia, and tachypnea and was admitted. Blood pressure and oxygen saturation on ambient air were normal. Physical examination revealed expiratory wheezing in the right lower lung field; WBC on admission was 20.4 × 103/μL with 24% of neutrophil and 65% of lymphocyte. CT chest without contrast showed consolidation within the superior segment of the left lower lobe suggestive of pneumonia. She was started on empiric vancomycin and piperacillin/tazobactam and later transitioned to ceftazidime for presumed healthcare associated pneumonia, with gradual improvement of fever. Given patient's clinical response to empiric antibiotics, no further diagnostic testing for pneumonia was performed. However after five days, one set of admission blood cultures grew yeast and oral fluconazole (800 mg load and then 400 mg daily) was initiated on the same day. She was later discharged to a nursing home on oral levofloxacin, clindamycin, and fluconazole pending identification of the yeast. Subsequently, the yeast blood isolate was identified as Cryptococcus neoformans. She was readmitted and underwent lumbar puncture after 8 days of fluconazole. Cerebral spinal fluid (CSF) analysis was unremarkable with WBC of 1/μL, opening pressure was normal, and CSF and serum cryptococcal antigen were negative. Repeat blood cultures and CSF fungal culture were negative. Immunoglobulin G and M levels were low (immunoglobulin G level 558 mg/dL, reference range 594–1,618 mg/dL; immunoglobulin M level 47 mg/dL, reference range 77–220 mg/dL) but immunoglobulin A level was within normal range (333 mg/dL, reference range 68–378 mg/dL). CD4 lymphocyte count was not obtained. She received a 2-week course of induction therapy with liposomal amphotericin (3 mg/kg/day) and flucytosine for disseminated cryptococcal disease and was discharged on oral fluconazole 400 mg daily. Ibrutinib was restarted at lower dose given potential hepatic cytochrome P450 interaction with fluconazole. She remained clinically stable at one-year follow-up visit.


A 17-year-old man with NF-1 was referred for evaluation of painless reduction of visual acuity in both eyes since several weeks before. The patient had diffuse cutaneous café-au-lait spots on his abdomen and back. In ocular examination, best corrected visual acuity (BCVA) was 1/10 in the right eye and 1.5 meters counting finger in the left eye, evaluated with standard E-chart at 20 feet distance. Intraocular pressure was 15 mm Hg in both eyes (evaluated with goldman tonometer). Anterior segment examination showed numerous Lisch nodules.
Dilated posterior segment examination of the right eye showed 1+ to 2+ cells in the anterior vitreous and subretinal exudation which involved macula and premacular membrane (Figure 1 ). Moreover, in the periphery, an elevated pink vascular mass with areas of surrounding subretinal fluid and lipid accumulation was seen. Dilated tortuous feeder vessels, as seen with retinal capillary hemangioma, were not observed. Fluorescein angiogram showed diffuse telangiectatic vessels with leakage (Figure 2 ). Fundus examination in the left eye showed subretinal old refractile exudations in the periphery and macula as well as premacular and optic disc fibrous proliferation with macular dragging. Fluorescein angiography revealed optic disc leakage and diffuse perivascular leakage (Figure 3 and Figure 4 ). In macular optical coherence tomography (OCT), in the right eye severe macular thickening with central thickness of 764 µm and subretinal fluid were seen, and in the left eye macular atrophy and intra- and subretinal hyper-reflective material were observed (Figure 5 and Figure 6 ). The findings were consistent with vasoproliferative tumor associated with macular edema and retinal exudation. Various therapeutic methods were discussed, and the patient was treated with three monthly injections of bevacizumab (1.25 mg in 0.05mL) in the right eye. After 3 months, macular thickening and subretinal exudation were significantly decreased, retinal detachment overlying the vasoproliferative tumor had resolved, and the tumor appeared less vascularized with fibrotic changes. Macular thickness decreased to 354 µm and vision improved to 3/10 (Figure 7 ). After 6 months, the condition was stable and the follow-up interval was decided to be 3 months.


A 75-year-old, right-handed Caucasian man with a history of embolic stroke and atrial fibrillation was admitted on 30 January 2016 to the stroke unit of our primary care hospital for severe aphasia and right-sided hemiparesis with sudden onset of symptoms about 1 h before presentation. He was receiving NOAC therapy with dabigatran 110 mg twice daily. His CHA2DS2-VASc score was 6 points (on scale representing congestive heart failure [or left ventricular systolic dysfunction] 1 point, hypertension [blood pressure consistently above 140/90 mmHg or treated hypertension on medication] 1 point, age ≥75 years 2 points, diabetes mellitus 1 point, prior stroke or transient ischemic attack or thromboembolism 2 points, vascular disease [e.g., peripheral artery disease, myocardial infarction, aortic plaque] 1 point, age 65–74 years 1 point, sex category [female sex] 1 point), and his HAS-BLED score was 3 points (with scale representing hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol). Correct dabigatran therapy of 110 mg twice daily could be verified by the accompanying spouse with last intake on the same morning approximately 9.5 h before. Besides cardioembolic stroke, the patient’s medical history consisted of structural epilepsy based on middle cerebral artery ischemia in March 2015 treated with levetiracetam 500 mg twice daily and arterial hypertension treated with amlodipine, metoprolol, and torasemide.
The patient’s impairment of production and comprehension of speech was severe. It was possible for him to communicate, but only to a very limited extent. His hemiparesis was rather mild. His initial National Institutes of Health Stroke Scale (NIHSS) score was 5. No convulsions or lack of consciousness was reported or noticed. According to the patient’s spouse, his symptoms were not comparable to prior seizure symptomatology displayed by sudden loss of consciousness and generalized tonic-clonic convulsions. As a residual of his prior stroke, the patient had a slight outer rotation of his right foot without gait impairment.
Laboratory examinations done upon admission revealed a slight coagulation disorder (international normalized ratio 1.01, activated partial thromboplastin time [aPTT] 39.0 seconds [upper limit of normal 42 seconds], thrombin time 66.8 seconds [upper limit of normal 22 seconds]). Besides a defect zone arising from ischemic stroke in May 2015, computed tomographic (CT) scans (Fig. ) displayed no early signs of acute stroke. Taking into account the patient’s NIHSS score of 5, no CT angiography or perfusion protocol was performed, in accordance with effective stroke guidelines. Except for the existing oral dabigatran anticoagulation therapy, the patient’s history did not reveal any contraindications against systemic thrombolytic therapy. After the patient provided written consent, we applied two doses of 2.5 g idarucizumab according to the current product characteristics and prescribing information within 20 minutes to antagonize dabigatran. Another blood sample showing normalized coagulation parameters preceded immediate weight-adapted intravenous rt-PA therapy. Within 1 h, all symptoms resolved to baseline levels.
A clinical examination done the next day revealed fluent speech with hardly noticeable word-finding difficulties in an aphasia assessment. Detailed conversation was possible again, and the patient reported subjective well-being. Because the patient’s symptoms resolved within 1 h and because of the lack of therapeutic consequences, we abstained from follow-up magnetic resonance imaging scans as part of the stroke workup. The patient’s electroencephalogram was free of any epileptic discharges. Echocardiography revealed no evidence of intracardial thrombotic material, and an ultrasound of the brain-supplying arteries did not reveal relevant stenoses. With the patient’s low-density lipoprotein cholesterol values being elevated (160 mg/dl), we initiated therapy with simvastatin 20 mg. Dabigatran therapy was reestablished after 24 h. However, on the basis of the patient’s age and normal renal function, we chose an increased dose of 150 mg twice daily according to the effective prescribing information. During idarucizumab application and throughout the entire hospital stay, no thrombotic or bleeding complications occurred. The patient’s laboratory examination results remained normal, and he was released to home in good health.


A 42-year-old female with hypertension (HTN), ESRD, secondary to IgA nephropathy and a history of deceased donor renal transplant, presented with acute kidney injury (AKI). Her AKI was presumed to be prerenal due to ongoing gastroenteritis. Her S Cr was elevated to 3.3 mg/dL (from baseline of 2–2.2 mg/dL) and admission blood pressure (BP) ranged with 190/100–210/110 mmHg. She was on mycophenolic acid 360 mg QID, sirolimus 1 mg daily, prednisone 5 mg daily, and carvedilol 50 mg BID. Her renal transplant ultrasonography (USG) showed normal resistive indices (RI) with no hydronephrosis. An allograft biopsy was performed to rule out transplant rejection, as her S Cr continued to be elevated at 3.3 mg/dL even after 72 hours of hydration and negative GI workup. Her antihypertensive regime was adjusted with the addition of nifedipine, clonidine, and minoxidil and her blood pressure ranged within 140–160/80–95 during 48 hours prior to procedure. On postprocedure day 1, her blood pressure was again elevated (170–210/90–110 mmHg) and she had a noticeable drop in her hemoglobin (Hgb) from 10 g/dL to 8.5 g/dL. Her CT scans showed large subcapsular hematoma. Renal allograft angiography failed to show any active bleeding, an AV fistula, or any pseudoaneurysm formation. On postbiopsy day 2, her BP remained high and the S Cr peaked at 4.2 mg/dL prompting the drainage of subcapsular hematoma and a Jackson-Pratt (J/P) drain placement for continuous drainage. This resulted in significant improvement in blood pressure () and her IV antihypertensives were tapered off within 24 hours of drainage. Her S Cr improved to 3.1 mg/dL and her J/P drain was removed on day 5. She was soon discharged on PO antihypertensive regime. Her allograft biopsy showed moderate fibrosis with no evidence of antibody or cell mediated rejection or any other acute process.
Unfortunately, six weeks later she was readmitted with severe anemia (Hgb 6.4 g/dL), AKI (S Cr of 8.3 mg/dL), and hypertensive emergency (BP range of 190/90–210/110 mmHg). Her CT scans confirmed recurrence of the subcapsular hematoma. Again, renal allograft angiography failed to show any active bleeding or any AV malformations. This time, the hematoma was surgically drained to ensure the bleeding stopped after drainage. A J/P drain was again placed which was removed after 2 weeks. She required four sessions of hemodialysis treatments for this episode of AKI but her renal function stabilized at discharge with S Cr of 3.1 mg/dL and improved BP control (). A repeat USG at discharge showed complete resolution of hematoma. An overt cause for recurrence of hematoma was not elucidated by angiography. She was not on any anticoagulation and her coagulation profile was normal.
She was admitted again seven weeks later, for a large perinephric seroma with uncontrolled HTN (190/90–200/110 mmHg). The collection was drained emergently with an immediate and significant improvement in her BP (range 110–130/60–70) (). Her renal function remained at baseline and she had no acute kidney injury. She had no more recurrence of Page Kidney phenomenon and her antihypertensive regime is managed successfully as an outpatient.


A 65-year-old male presented with an episode of hematemesis and intermittent melena for one week. He reported some stomach upset with decreased appetite, dizziness, and exertional shortness of breath lately. As per his wife, pt also had an episode of syncope, the day before admission. He was diagnosed with diverticulitis a week before, when he presented with fevers, chills, left lower abdominal pain, and was started on oral cephalexin and metronidazole, which he was on day 6 of the antibiotics at the time of presentation. He reported increased use of ibuprofen since he had the diverticulitis, using up to four tablets of 200 mg daily. He denied having any fevers, chills, weight loss or other sites of bleeding. His past medical history included hypertension, hyperlipidemia, cholelithiasis and Abdominal Aortic Aneurysm (AAA). Past surgical history included bilateral visceral hernia repair and vasectomy. There was no history of heart burn or reflux disease. He was a previous smoker with fifty plus pack year smoking history and quit smoking 10yrs ago, consumed alcohol socially. He denied recreational drug use. Family history included coronary artery disease on both sides of the family. He was only on simvastatin at home and did not have allergies to any medications.
In the emergency room, he was hemodynamically stable. Nasogastric lavage showed some coffee ground emesis. On physical exam, he was well oriented, chest and heart examination was normal. Abdominal examination showed mildly hyperactive bowel sounds, otherwise normal. No organomegaly was noted. Heme occult was positive. Admission lab work showed hemoglobin of 12.4 mg/dL with hematocrit of 38. Complete metabolic panel was normal. Patient was given nothing by mouth, started on intravenous fluids and protein pump inhibitor (PPI) drip. It was thought to be non-steroidal anti-inflammatory drug (NSAID) related gastropathy or peptic ulcer related bleeding and ibuprofen was stopped. Overnight, he had couple of episodes of melena resulting in hemoglobin drop and needing blood transfusion. Computerized tomography (CT) scan of abdomen/pelvis with contrast that was taken at other hospital for diverticulitis incidentally showed a gastric mass, gall stones, stable AAA (). No other masses were noted in the abdomen or pelvis. Esophagogastroduodenoscopy (EGD) showed a partially obstructing, polypoid mass with central ulceration arising from gastric body which might be the cause of bleeding (). Mild antral gastritis with no active bleeding was noted. Biopsies were taken. The differential diagnosis at that time was lipoma, gastric carcinoma versus gastrointestinal stromal tumor (GIST). Pantoprazole drip was stopped and changed to oral Pantoprazole twice daily.
Surgical team was consulted and resection of gastric mass was planned. On laparoscopy, a mass was seen in the distal stomach which appeared to be intraluminal only. Through a small upper abdominal incision, anterior gastrostomy was done and the mass was delivered through the opening. Mass was entirely within the wall of stomach with overlying ulcer. A submucosal resection of the mass was done and sent for frozen section analysis. Intra operatively, it was consistent with intramural lipoma. Gross evaluation of the specimen revealed a homogeneous yellow-tan colored submucosal fatty mass measuring 6 × 3 × 3cm. There were no areas of hemorrhage or necrosis. Microscopic examination showed a circumscribed nodule composed primarily of mature adipose tissue with prominent vascularity (). There were scattered foci of smooth muscle proliferation which were desmin () and smooth muscle actin positive (). CD 117, human melanoma black (HMB)-45 were negative. CD34 highlighted the prominent vascularity (). No cytologic atypia, appreciable mitotic activity or necrosis was noted. The final pathological diagnosis was a benign gastric angiomyolipoma.


A 19-year-old boy was referred to our hospital because of abdominal dullness and night sweats of 15 days duration. His medical history was normal. Physical examination on admission identified grade III (tense) ascites. In ascites; alpha-fetoprotein (AFP) and CA 125 were determined: AFP was 1200 IU/mL (upper reference value, < 5.5 IU/mL), CA 125 was 500 u/mL (upper reference value, < 16 U/mL) whereas other tumor markers were within the normal range. The serum-to-ascites albumin gradient (SAAG) was calculated as 0.6 g/dL and ascidic adenozine deaminase level was reported as 40 U/L (upper reference value, < 16 U/L).
Ultrasonography and CT scan of the abdomen revealed large ascites and omental cake (, ). Additional studies (chest radiograph, colonoscopy and upper gastrointstinal tract endoscopy) were negative for additional masses. There was no evidence of an extraabdominal primary source. A left sided minimal epididymo-orchitis was detected on urinary ultrasonography. The patient underwent laparotomy, which revealed massive peritoneal carcinomatosis and a large amount of ascites. Pathological examination of the peritoneal specimen confirmed the presence of EST and stained for alpha fetoprotein and cytokeratin (, ).
Post-laparotomy, the patient received combination chemotherapy consisting of cisplatin, etoposide and bleomycin every 3 weeks for a total of 4 cycles. At the end of the treatment his clinical status worsened and the patient refused to take any further treatment including radiotherapy and the patient decided to go to home, 15 days later, he reportedly died due to cardiac arrest.


A 61-year-old man was admitted with a 1-week history of melena. He had undergone an operation of valve replacement and coronary artery bypass grafting for aortic valve stenosis and angina at the age of 59 years, and had been taking warfarin and low dose aspirin (LDA) after surgery.
Physical examination showed tachycardia and anemia. Blood tests revealed a low hemoglobin level of 7.4 g/dL and prolonged PT-INR of 1.84 (because of warfarin therapy).
Upper gastrointestinal endoscopy showed a large, pedunculated polyp (3.5 cm in length), the base of which was located in the anterior wall of the duodenal bulb. Extensive erosions were seen on the top of the polyp, and the pedicle of the polyp had become twisted on its axis (). Oozing hemorrhage from the area of the top in contact with the surrounding structures was found (). The polyp except in the areas of erosion was covered with normal mucosa, and was considered to be non-epithelial. Grossly, polyps related to Brunner’s glands, GIST, and inflammatory fibroid polyp were suspected.
The patient was fasted, and placed on PPI therapy. Warfarin and LDA were discontinued, and heparin was administered. After improvement of the anemia and normalization of the PT-INR, heparin was withheld temporarily, and endoscopic polypectomy was performed.
Upper gastrointestinal endoscopic examination showed that the bleeding from the erosions on the top of the polyp had stopped (), and the twisting of the polyp pedicle had been reduced (). Since the pedicle was relatively thin, hemostatic clips were placed around its base, and snare polypectomy was performed.
Although gross examination of the resected specimen revealed a thick blood vessel in the pedicle (), no bleeding occurred during polypectomy. Histopathological examination showed that the surface of the polyp was covered with an eroded duodenal epithelium, and hyperplastic Brunner’s glands were densely packed mainly in the submucosal layer (). Atypia was not found in the hyperplasia (). These findings led to a diagnosis of Brunner’s gland hyperplasia.
No bleeding occurred after polypectomy, treatment with warfarin and LDA was resumed, and the patient was discharged.


A 58 years old male with a background of hypertension presented to the emergency department with 3 days history of worsening low back and left flank pain. It came on suddenly and was sharp stabbing, non-radiating, non-migratory pain associated with nausea and decreased appetite. He had no urinary symptoms and no change in bowel habits. On physical examination he was overweight with central obesity (BMI of 26) and appeared uncomfortable and grimacing in pain. He was afebrile and haemodynamically stable. His abdomen showed signs of localised peritonism in the left iliac fossa with voluntary guarding and percussion tenderness. He complained of dull ache around the left lower lumbar area over the erector spinae, but no muscle or bony tenderness. He was neurologically intact.
Blood tests showed mildly elevated neutrophil of 8 x 109/L and raised inflammatory markers with a C-reactive protein (CRP) of 54 mg/L. Liver and renal function tests were within normal limits. Chest and abdominal radiograph were performed, which did not show any evidence of infection, pneumoperitoneum, or bowel obstruction.
He was initially diagnosed with acute diverticulitis in the emergency department and treated with intravenous antibiotics. Further radiological investigation was performed with a computed tomography (CT) scan of the abdomen and pelvis with and without contrast showed inflammatory changes in the left iliac fossa anteriorly with mesenteric stranding surrounding an area of fat density. These changes were anterior to the distal descending colon. There was no bowel wall thickening or features of obstruction. No significant diverticulosis was demonstrated. These changes in the left iliac fossa were consistent with epiploic appendagitis. He was admitted for overnight observation and treated non-operatively with analgesia, intravenous fluids and bowel rest. He was discharged home with an oral analgesia and anti-inflammatory agent.


A 43 year old male presented to the emergency department with sudden onset of severe left groin pain, which was not associated with fever, nausea, vomiting, or diarrhoea. His past medical history include depression and being treated with Escitalopram. He had no bladder or bowel symptoms. On physical examination, the patient was noted to be in distress, diaphoretic, supporting his abdomen with a pillow. Haemodynamically he was in sinus tachycardia with a pulse rate of 112 beats per minute, but not febrile. The abdomen was tender in the left lower quadrant, particularly over the inguinal ligament area, with voluntary guarding but no rebound or percussion tenderness. No inguinal hernia was found.
Blood test showed elevated CRP of 88 mg/L. Full blood count and liver function tests were within normal limits. Abdominal radiograph was reported normal. He was initially diagnosed with acute diverticulitis in emergency department and treated with intravenous antibiotics. Further imaging with a computer tomography (CT) scan of abdomen and pelvis showed ill-defined mesenteric fat stranding of the mesenteric fat adjacent to the descending and sigmoid colon surrounding an area of fat density, findings consistent with epiploic appendagitis. Antibiotics were stopped and he was treated non-operatively with analgesia, non-steroidal anti-inflammatory and intravenous fluids. He was admitted and observed overnight with good improvement and discharged the following morning on oral analgesia.


A 65-year-old man presented with a 2-month history of dysphagia. Endoscopy showed a neoplastic lesion at the esophageal inlet. Pathological examination with biopsy revealed moderately differentiated squamous cell carcinoma. Computed tomography (CT) showed esophageal wall thickening and superior mediastinal lymph node enlargement. CT also showed that the tumor was in close proximity to the thoracic vertebrae, but there was no evidence of invasion on magnetic resonance imaging. Positron emission CT showed no distant metastasis. The preoperative diagnosis was clinical T3N2M0 stage III cervical esophageal cancer according to the tumor, node, and metastasis classification []. The patient underwent preoperative chemotherapy (5-fluorouracil and cisplatin) and radiation therapy (41.4 Gy). Two months later, endoscopic examination showed that the neoplastic lesion had changed to scar tissue. CT showed a reduction in the esophageal wall thickness and size of the lymph nodes. The patient underwent subtotal esophagectomy, gastric tube reconstruction, and three-field lymph node dissection. The following lymph nodes in the neck and upper and middle mediastinum were dissected: the cervical paraesophageal (#101), supraclavicular (#104), upper thoracic paraesophageal (#105), recurrent nerve (#106recL and #106recR), tracheobronchial (#106tbL), subcarinal (#107), middle thoracic paraesophageal (#108), and main bronchus (#109 L and #109R) lymph nodes []. The right bronchial artery was ligated and cut in our usual manner. Severe fibrous change secondary to the neoadjuvant chemoradiotherapy was observed in the upper mediastinum. The gastric tube was pulled up to the neck incision through the retrosternal route. An anastomosis between the esophagus and gastric tube was created with a 21-mm-diameter circular stapler in an end-to-side fashion. The anastomotic position was located adjacent to the left side of the trachea. The intubation, anesthetic course, and surgical procedure were uneventful. Pathological examination of a resected specimen of the esophageal wall showed mild chronic inflammation, accompanied by dense transmural fibrosis and no carcinoma cells. All 71 lymph nodes were free of carcinoma cells. Curative resection (R0) was achieved.
On postoperative day (POD) 5, purulent discharge was observed in the drainage tube inserted near the anastomotic site. CT revealed free gas adjacent to the left side of the cervical anastomotic site. Anastomotic leakage was suspected, and the patient was managed conservatively with antibiotics and, enteral nutrition via a jejunostomy. In spite of conservative therapy, the patient’s fever was prolonged and his respiratory condition gradually worsened. Bronchoscopy on POD 44 revealed that the staples originating from the circular stapler used for the anastomotic site or the linear stapler used for the lesser curvature were exposed at the cartilage portion of the trachea about 5 cm peripheral to the vocal cords (Fig. ). CT showed a fistula at the left-side cartilage portion of the trachea (Fig. ). The patient was treated under medical respiratory management and sent to the intensive care unit. Surgical division of the fistula without combined resection of the cartilage, direct suturing of the anastomotic leakage site, left pectoralis major muscle flap placement, and tracheotomy was performed on POD 48 (Fig. a). Surgical repair of the cartilage site was performed with whole layer interrupted 4-0 synthetic absorbent monofilament sutures crossing over two adjacent cartilages. The pectoralis major muscle flap was mobilized to the cervical site. The muscle flap covered the repair portion and was fixed to the surrounding tissue using 4-0 synthetic absorbent monofilament sutures. After surgical repair, blood tests showed improvement in the signs of inflammation, and the patient’s respiratory condition clinically improved. He was withdrawn from the respirator and returned to the general ward on POD 55. A gastrografin swallow study performed on POD 75 revealed no signs of anastomotic leakage or stenosis. He was introduced to an oral diet on POD 81. The patient was discharged home on POD 120 on an oral diet.


A 61-year-old French Canadian female presented to hospital with a two-week history of obstructive jaundice, pruritus, tea-coloured urine, acholic stools, fatigue, anorexia, and unintentional weight loss. Her history also included vague abdominal pain that had been ongoing for years prior to her visit, although the pattern of pain did not change with the onset of jaundice. Her past medical history included type 2 diabetes mellitus and hypertension. She did not have a personal history of cancer, but her family history included two aunts who had pancreatic cancer in their sixth decades of life. She denied any tobacco, alcohol, or recreational drug use.
Abdominal ultrasound revealed a lesion in the uncinate process of the pancreas. A subsequent CT scan of the abdomen confirmed a fairly well circumscribed hypovascular mass in the head and uncinate process of the pancreas, radiographically consistent with pancreatic adenocarcinoma (Fig. ). The mass encircled the first jejunal branch of the superior mesenteric artery by approximately 180°. Endoscopic retrograde cholangiopancreatography (ERCP) was ultimately unsuccessful due to inability to cannulate the common bile duct. The pancreatic duct was patent and could be cannulated but seemed to end abruptly.
The patient underwent an endoscopic ultrasound, which revealed a 4.8 × 3.5 cm hypoechoic mass in the pancreatic head/uncinate process along with numerous cystic changes in the body, tail, and distal tail of the pancreas, measuring 2.4 mm, 3.9 mm, and 4.3 mm, respectively. Fine-needle aspiration (FNA) biopsy at the time of endoscopic ultrasound demonstrated cytology consistent with adenocarcinoma (Fig. ).
At the time of diagnosis, the patient’s functionality was consistent with Eastern Cooperative Oncology Group (ECOG) grade 1: restricted in physically strenuous activity, but ambulatory and able to carry out light work. The CA19-9 levels were ordered but deferred by the patient. Her total bilirubin at the time of diagnosis was 160 μmol/L. The patient underwent placement of a percutaneous transhepatic biliary drainage catheter, with resolution of her jaundice. The patient was reviewed at a weekly hepatobiliary and pancreatic cancer multidisciplinary conference. Consensus was that her tumor was borderline resectable on the basis of partial encasement of the superior mesenteric artery. Although there was encasement of the first jejunal branch, the tumor was staged based on abutment of less than ≤ 180° of the SMA. Radiologically, the patient was staged as T3 N0 M0. It was recommended that the patient begin systemic chemotherapy with four cycles of FOLFIRINOX (Irinotecan 180 mg/m2; Oxaliplatin 85 mg/m2; 5-Fluorouracil 400 mg/m2; Folinic acid 400 mg/m2), after which she would be re-imaged for assessment of treatment efficacy.
The patient tolerated the four cycles without undue toxicity, after which she underwent re-staging with CT scans of the chest, abdomen, and pelvis. This revealed multiple non-calcified small pulmonary nodules detected bilaterally in the lower lobes, the largest of which measured 4 mm. These nodules were previously not present and were thus considered suspicious for metastatic disease. As a result of the equivocal pulmonary nodules, resection was not indicated and the decision was made to continue FOLFIRINOX to further assess both local response, and the response of the potential metastatic nodules.
The patient received a further nine cycles of FOLFIRINOX. Follow up MRI revealed that the pancreatic lesion had impressively decreased in size from 3.9 × 3.2 cm to 2.7 × 2.3 cm compared to the previous CT (Fig. ). Furthermore, the lung lesions had remained stable since the last CT scan, raising the possibility that they were not metastatic. Given these results, and after discussion at multidisciplinary cancer conference, a resection was offered to the patient as a potentially curative treatment. She continued two more cycles of therapy before undergoing a pancreaticoduodenectomy, six weeks following discontinuation of FOLFIRINOX and 33 weeks from the date of diagnosis. No major technical difficulties were encountered in the procedure, although there was considerable tissue edema as expected from the chemotherapy. No vascular resection or reconstruction was required. Her postoperative course was complicated by pneumonia. She was discharged home on day 11. She was readmitted 9 days later with acute kidney injury, secondary to vomiting, poor intake and diarrhea, requiring one round of hemodialysis (peak creatinine 847 μmol/L or 9.58 mg/dL, Dindo-Clavien grade 4a).
Histological examination of the surgical specimen revealed no evidence of residual adenocarcinoma (Fig. ), consistent with a complete response to treatment (College of American Pathologists grade 0) []. As is required in this situation, the entire specimen was submitted for histological assessment, confirming the complete pathological response (ypT0). Severe acute and chronic pancreatitis and areas of fibrosis were noted, together with scattered foci of grade 1 pancreatic intraepithelial neoplasia. All 23 resected lymph nodes were negative for malignancy (ypN0).
Following surgery, adjuvant therapy was not given. Her CT scans at 3 and 6 months postoperatively show no evidence of recurrence, with no appreciable change in her previously noted lung nodules. Her CA 19–9 is normal at 20 kU/L. She remains disease-free 15 months after surgery, and 24 months after diagnosis. Given her strong family history of pancreatic cancer, she was referred for genetic testing. She was found to be a carrier of a BRCA2 mutation that is not uncommon among French Canadians (BRCA2: E3002K).


A 53-year-old female was referred to our hospital due to a round opacity in the right upper lung field on a radiograph. She denied any symptoms or a history of smoking. Family history was negative for relevant diseases. A hemogram was normal, and there were no increases in the concentrations of tumor markers.
A chest radiograph demonstrated a mass in the right pulmonary hilar region (). Chest computed tomography (CT) scanning revealed a 3.1 cm mass in the right pulmonary hilum, between the right upper lobe and the right intermediate bronchus (). The mass was well circumscribed, with several scattered calcifications (). After intravenous iodinated contrast media injection, the mass showed heterogeneous enhancement (). There was no associated mediastinal lymph node enlargement. Bronchoscopy showed no endobronchial invasion. The patient underwent a CT-guided biopsy to investigate the mass, and pathologic examination revealed sclerosing hemangioma. The patient then underwent another chest CT scan six months later, which showed no significant change of the mass. Thoracoscopic tumor excision was subsequently performed, and the tumor appeared grossly brownish and firm (). On pathohistologic study, the tumor was well defined and composed of round stromal cells and surface cells arranged in a papillary, sclerotic, solid and hemorrhagic pattern. Cuboidal surface cells morphologically resembled type II pneumocytes (Figures and ). Lymphoplasmacytic infiltrates, xanthoma cells, hemosiderin, and calcification were observed. In immunochemical study, the round cells were positive for thyroid transcription factor-1 (TTF-1) and epithelial membrane antigen (EMA) and negative for cytokeratin (Figures , , and ). The surface cells were positive for TTF-1, EMA, and cytokeratin. Therefore, a final diagnosis of sclerosing hemangioma was confirmed. The patient recovered well after the operation, and a follow-up chest CT scan showed no recurrence of the tumor.


A 27-year-old female presented to the Gout Clinic of Peking Union Medical College Hospital with recurrent arthritis and infertility. Fourteen years before presentation, she noticed protrusion of her right ankle but did not undergo evaluation at a hospital. Eight years before presentation, at age 19, she experienced acute pain and swelling of her right ankle. The pain resolved spontaneously but recurred 6 to 7 times/year, involving the bilateral metatarsophalangeal (MTP) joints, bilateral ankles, and right knee. Her serum urate level (SUA) was elevated to 789 μmol/L. A diagnosis of gout was made, and she was prescribed NSAIDs for pain relief and allopurinol and benzbromarone to lower her urate level. However, she discontinued allopurinol and benzbromarone on her own as these medications triggered acute flares. Five years before presentation, she noticed multiple nodules in her MTP joints, ankles, and fingers. The nodules on her feet interfered with normal walking. She also complained of the inability to conceive after 3 years of attempts. Her age at menarche was 14 years, and her cycles were irregular. She was reported to prefer snacks and fatty food during her childhood. Her father had hypertension. Her grandfather had an SUA level greater than 400 μmol/L but without gout. On physical examination, the patient was generally healthy, with a height of 168 cm and a weight of 55 kg. Her blood pressure was 120/80 mmHg. Cardiac and pulmonary examinations were normal. On abdominal palpation, the liver was enlarged with a normal soft texture. A joint examination revealed multiple nodules on the bilateral MTP1 joints, ankles, and fingers.
A serological examination after overnight fasting revealed a SUA level of 548 μmol/L, serum creatinine (Cr) level of 49 μmol/L, fasting glucose level of 3.6 mmol/L, total triglyceride level of 6.22 mmol/L, and total cholesterol level of 6.60 mmol/L. Her resting lactate level was 7.4 mmol/L. Her 24-h urine urate level was 2.262 mmol/24 h, and her fractional excretion of uric acid (FE-UA) was 2.48 %. Her liver enzymes were normal. The estrogen level and basal body temperature curve were normal for her age and menstrual status. Renal ultrasonography revealed normal kidney size with possible calcium deposits in the bilateral renal medulla. Computed tomography (CT) imaging of her abdomen showed hepatomegaly without nodules. The pelvic ultrasonography and salpingography findings were normal. Serum examinations of her parents and her husband were normal.
Whole blood DNA was extracted from all four family members (the patient, both parents, and her husband) after signing an informed consent form. A genetic study was first conducted with a target gene sequencing approach. A search of the OMIM, NIH, and PubMed databases using the key words “FEMALE,” “GOUT,” and “HYPERLACTACIDEMIA” indicated familial juvenile hyperuricaemic nephropathy, glycogen storage disease type I, and glycogen storage disease type II. Next-generation sequencing was used to sequence each of the exons of the UMOD, RENIN, G6PC, SLC37A4, and GAA genes, as well as two SNP loci (rs2231142 and rs72552713) of ABCG2 found in our previous report of a family including a female with gout.
The genetic sequencing results showed that UMOD, RENIN, SLC37A4, GAA and rs72552713 of ABCG2 were all normal in the patient and her family. Sequencing of the G6PC gene revealed composite heterozygous c.190G>T/c.508C>T mutations in the patient, a heterozygous c.190G>T mutation in her father, and a heterozygous c.508C>T mutation in her mother. The genetic analysis of her husband was normal. The c.190G>T mutation was located on exon 1 and encoded a missense mutation of p.V64L, whereas the c.508C>T mutation was located on exon 4 and encoded a nonsense mutation of p.R170X (Fig. ). Sequencing of 50 healthy females and 100 healthy males at the two loci produced normal results. To our knowledge, the c.190G>T mutation has not been reported in previous literature.


A 19-year-old morbidly obese Caucasian woman was given preoperative esophagogastroduodenoscopy before bariatric surgery. During endoscopy, she was found to have a one centimeter subepithelial, white nodular lesion in the distal part of the esophagus, 30 cm from the oral cavity, which was further evaluated by endoscopic ultrasound (EUS; see Figure ).
Further evaluation using EUS confirmed the presence of a 10.3 x 6 mm well-demarcated hypoechoic lesion confined to the submucosa without invasion into the muscularis propria (Figure ).
The lesion was successfully resected en bloc by a cap-assisted EMR technique (Figure ).
The mucosal defect was subsequently closed with three endoclips. Careful observation of the excised specimen confirmed the complete removal of the lesion. The cross-section was composed of pink polypoid tissue measuring 0.9 × 0.8 × 0.5 cm in volume. A microscopic analysis revealed large polygonal cells with abundant granular cytoplasm. Cytoplasm, as well as the cell nuclei, showed diffuse Periodic Acid Schiff (PAS) positivity. The immunohistochemical (IHC) analysis exhibited strong reactivity for S-100 protein, thus confirming the GCT diagnosis (Figure ).
Informed consent has been obtained from the patient. No patient-identifying information is disclosed in this paper.


On May 2013, a 27-year-old female was referred to an Oral Medicine Department in Tehran, Iran, with the chief complaint of a mass in her palate (Figures and ). Initially, she complained about the lesion a week prior to the referral. The patient's medical history revealed that she had End Stage Renal Disease (ESRD) and received hemodialysis treatment three times a week for the past 11 years; she also had hypertension. A parathyroid scan revealed parathyroid adenoma in the lower portion of the left thyroid lobe.
Intraoral examination showed an exophytic dome-shaped lesion with smooth surface in the midportion of the hard palate with an approximate size of 40 × 50 mm. The color of the lesion was pink to purple with firm-to-hard consistency and nontenderness in palpation ().
In panoramic view, bony rarefaction was evidenced in the right quadrant of maxilla, in the region of canine and premolars. Also accidentally in panoramic and periapical radiography, a well-defined unilocular radiolucent lesion with scalloped border on the right quadrant of mandible from the central incisor to second premolar was observed (Figures and ). shows the results of laboratory tests.
According to patient's medical history, she was referred to her physician about controlling of hyperparathyroidism. Parathyroidectomy was done on August 2013. A whole body bone scan showed multiple foci of increased radiotracer uptake in the nasofacial bones, spine, lower third of the right humerus, bilateral ribs, pelvic bones, and both tibiae. Regarding patient history, the scan pattern favored metabolic bone disease (hyperparathyroidism and renal osteodystrophy) ().
Six months after, the patient was referred to our clinic with swelling of her right maxilla with progressive growth and pain.
Extraoral findings showed a large mass with bony hard consistency on the right maxilla, causing nasal deformity with nasal obstruction and a nodular firm mass with purple color in the infraorbital region. Also, superior displacement of the right glob was seen (Figures and ).
In addition to hard palate lesion intraoral findings shown, a firm mass of the right buccal sulcus and displacement and loosening of the right upper teeth were seen ().
Panoramic radiograph revealed large radiolucent lesion involving the right maxilla, and the maxillary sinus had no obvious margins. Teeth displacement was seen in the right maxilla (). Contrast enhanced CT scan of the coronal axis showed a heterogeneous mass in the right maxilla; the lesion crossed midline and invaded to medial wall of the left maxillary sinus. Also, in the buccal side, the alveolar process was destructed and a soft tissue mass was formed ().
In CT there was an osteolytic lesion in the right side of the mandibular body with extension from the midline to premolar area. Expansion and thinning of the buccal cortex, thinning of the lingual cortex, and buccal movement of teeth were seen ().
According to medical history of this case and clinical and radiological findings Brown tumor and central giant cell granuloma were suspected.
Patient informed consent was obtained. Excisional biopsy by hemimaxillectomy under general anesthesia and Weber-Ferguson approach was done, also in the mandible, incisional biopsy with extraction of right lower canine was done (). The excised specimen was sent for microscopic examination. A blood-filled space with varying size without endothelial lining, surrounded by fibroblastic connective tissue, was seen. Chronic inflammatory cell infiltration and multinucleated giant cells with hemorrhage and hemosiderin pigmentation were seen. Fragments of new bone formation and osteoid were seen. The features were consistent with an ABC ().
The patient's postoperative course was uneventful. There was no recurrence after 18 months of follow-up. She visited with the aim of reconstructing the maxilla, after 18-month recall ().
Spiral CT of the coronal axis showed a large defect of the right maxillary alveolar process. Areas of the right maxillary antrum, lower portion of the nasal cavity, and floor of the orbit were replaced with soft tissue and the glob structure was normal (). In radiographic evaluation of the mandibular region, the lesion area was healed and bone scar was seen (Figures and ).
In the time of follow-up, the patient was not reconstructed and unfortunately after 2.5 years, she had not survived due to cardiac ischemic attack.


A 34-year-old woman noticed a swelling in her right mastoid process approximately seven years before her first medical consultation regarding the condition. The lesion gradually enlarged and a facial spasm appeared on the right side of her face. She visited a city hospital and was diagnosed with a facial schwannoma via a brain and neck magnetic resonance imaging (MRI) scan (Figure ).
She consulted multiple head-and-neck surgeons, and all of them told her to wait until the facial nerve palsy subsides. This is because surgical tumor resection inevitably causes facial nerve palsy and requires a scheduled neuroanastomosis. Two months later, she was referred to our hospital for radiation therapy. She had a facial spasm that was triggered by grimacing. She also exhibited reproducible right facial nerve palsy (House-Brackmann Grade I) induced by the compression of the mass in the right parotid. We planned a fractionated CyberKnife radiosurgery for three consecutive days aiming for good tumor control as well as preservation of the neural function.
We planned the procedure based on computed tomography (CT) imaging and referenced an MRI as needed (Figure ). The initial tumor volume was 9.1 mL. We prescribed 20.11 Gy of the marginal dose, which was divided into three equal doses of 6.7 Gy 82.4%D95 delivered in three consecutive stages at a 24-hour interval.
After CyberKnife radiosurgery, the mass in the right parotid gradually decreased in size from 9.1 mL to 2.1 mL over 15 months. The volume reduced to 23% of the original mass (Figure ). The facial nerve palsy disappeared and was not induced by compression of the mass.
At her eight-month follow-up, her facial spasm had completely disappeared. There was no recurrence and the facial nerve function has been normal. The treatment did not require hospital admission.


A 54-year-old woman presented with loss of touch, temperature, position, and vibration sense and taste disorder, and she was insensitive to pain at the body surface since infancy. She also suffered from an autonomic disorder, with symptoms, such as orthostatic hypotension, fluctuation in body temperature, and lack of urge to defecate.
She had normal mental growth and development, although she did not walk until 18 months of age. Her family history was unremarkable; she had a healthy younger sister and her parents were not related (Fig. ). She had repeated injuries during childhood because of insensitivity to pain, and she was diagnosed with Freiberg disease at 6 years. She experienced frequent fainting episodes and was diagnosed with an autonomic nervous system imbalance at 21 years. Even in cold temperatures, she perspired on her back and reported not needing a snowsuit. She did not have high blood pressure.
After repeated jumping from a squatting position in gym class at 14 years, the sole of her left foot developed severe blisters, and the wounds transitioned into metatarsal osteomyelitis after a few weeks. As a result of the refractory osteomyelitis, a left metatarsal was replaced by an autogenous bone graft when she was 18 years. It took approximately 10 years to recover fully from the wounds.
She had migraine since childhood until she was 20 years and took a painkiller (an antipyrine medication) daily during that time. Although she could feel a toothache/headache, she lacked sensation on the surface of her face, except around the jaw. She showed a “stocking and glove distribution”, and the detection range of sensation varied along a gradient from the periphery to center. She could perceive visceral pain, such as menstrual or gastroenteritis pain, which she controlled with an antipyrine medication. Since 42 years of age, she started using a cane for walking outside.
Although she had known that she was different from others concerning pain perception since childhood, she and her parents had never consulted a doctor regarding the impaired pain sensation until 48 years of age.
At 48 years of age, the patient developed sudden severe pain and swelling in her right joint, and her previous physician diagnosed Charcot arthropathy (X-ray photograms are shown in Fig. ). At 50 years of age, she was confined to a wheelchair to avoid putting weight on her joints. The pain gradually affected multiple joints over subsequent years. Non-steroidal anti-inflammatory drugs (NSAIDs) improved her joint pain to a limited degree. At 54 years of age, her joint pain became intolerable. NSAIDs were not effective enough for her to resume activities of daily living. Mexiletine hydrochloride treatment was not effective. She experienced side effects of pregabalin and duloxetine. Subsequently, her physician referred her to our multidisciplinary center for pain management. She was diagnosed with HSAN type II using molecular genetic analysis and was prescribed acetaminophen (2400 mg/day), which controlled her pain very well and improved her quality of life.
During our follow-up, she reported: “one day severe ‘electric-shock-like or piercing pain’ occurred, and which made me suffer few times per hour and keeping for months after this episode, and which was naturally decreased.”
Brief Pain Inventory (BPI), including numerical rating scale (NRS) [, ], was used to assess pain intensity and interference. Pain-related psychosocial factors were quantitated using the Hospital Anxiety and Depression scale (HADS) [] and Pain Catastrophizing Scale (PCS) []. NRS and pain interference scale of BPI decreased from 6/10 to 3/10 and from 52/70 to 20/70 points, respectively, over 3 months. PCS scores also decreased from 22/52 to 3/52 points. At baseline, HADS indicated normal mental state; both the anxiety and depressive scales of HADS were relatively low (both 5/21 points) despite severe pain. After 3 months, the anxiety and depressive scales of HADS decreased from 5/21 to 3/21 points and from 5/21 to 4/21 points, respectively.
A neurological examination revealed normal mental status, speech, and comprehension and intact cranial nerve-innervated muscles. Manual muscle testing revealed moderate weakness in the distal parts of the extremities and mild weakness in the proximal parts. Grip strength was significantly reduced (right, 4.0 kg; left, 6.0 kg). Deep tendon reflexes were absent. Plantar responses were flexor on both sides. The sensory examination revealed that the tactile and pinprick sensations were moderately decreased in the face and trunk and severely diminished in the upper and lower distal extremities. Sensations were diminished in a stocking and glove pattern. The vibration sense was reduced till the knees and absent in the ankles. The joint position sense was absent at the hallux. There was no apparent laterality of the sensory disturbance. Pseudoathetosis was observed in the upper limbs, and Romberg’s test was not positive in the seated position. With the exception of abnormal sweating, thermoregulatory failure, and lack of urge to defecate, there were no signs of autonomic dysfunction, such as pupillary responses, dry eyes, or dry mouth. Her blood pressure was 138/85 bpm in the supine position and 126/72 bpm while standing. The head-up tilt test did not reveal any orthostatic intolerance. On electrocardiogram, the coefficient of variation of the R-R intervals (CVR-R) measured at rest was normal. The early and delayed heart-to-mediastinum (H/M) ratio was not decreased on 123I-MIBG myocardial scintigraphy (early: 3.14, delay: 2.97).
The nerve conduction study revealed normal compound muscle action potentials (CMAPs) values, except for a slightly reduced motor nerve conduction velocity of 50.0 m/s, 41.0 m/s, and 39.0 m/s in the median, peroneal, and tibial nerves, respectively. The velocity was in the normal range in the ulnar nerve (>50.5 m/s) and in the tibial and peroneal nerves (>48.0 m/s). The sensory nerve action potentials of the median, ulnar, and sural nerves were not evoked. The electromyography revealed a reduction in recruitment in the distal muscles of the upper and lower limbs. The patient was diagnosed with pure sensory neuropathy.
Sural nerve biopsy revealed a severe loss of myelinated and unmyelinated nerve which were observed by light microscopy of the epon section with toluidine blue staining (Fig. ) and electron microscopy (Fig. ). Collagen pockets, which were indicative of unmyelinated nerve loss, were observed by electron microscopy (indicated by the arrows in Fig. ). Myelinated nerve tissue was completely lost. The density of unmyelinated nerve tissue (7620 per mm2), calculated by electron microscopy, was significantly decreased. Skin biopsy was not performed.
Mutation screening was conducted as previously described []. Target sequencing with 16 HSAN disease-related genes were conducted using Illumina MiSeq (Illumina Inc., San Diego, CA, USA). The WNK1 mutation observed in this patient was validated by Sanger sequencing. A homozygous frame shift mutation was identified in the WNK1/HSN2 gene c.3237_3238insT (p.Asp1080fsX1; ENST00000537687), which was previously reported as c.1134_1135insT (p.Asp379fsX1; ENST00000574564) [, ]. This mutation is absent in 1000 Genomes, ExAC, or HGVD, which comprises exome sequencing of 1208 Japanese individuals ().


A 4-year-old boy was diagnosed with common ALL and started treatment according to ALL IC-BFM 2009. Patient was stratified into high risk group, but there was remission achieved on time (day +33). Since the beginning of chemotherapy, routine antifungal prophylaxis of fluconazole was used. On day +35 of remission induction chemotherapy, he developed severe lower gastrointestinal tract (GI) hemorrhage, necessitating transfer to the intensive care unit. He received red blood cells, platelet, and plasma transfusions along with inotropic support and empirical antibiotics. Abdominal ultrasonography (US) and computed tomography (CT) scan were unremarkable. After initial stabilization, an urgent endoscopy revealed extensive mucosal ulceration involving the entire colon. Biopsy was not performed due to the risk of perforation. Complete blood count and coagulation profile were within normal ranges. Over next 24 hours, the hemorrhage was successfully stopped and the clinical status of patient became stable. However, 2 weeks later the patient developed febrile neutropenia refractory to empiric broad-spectrum antibiotic treatment (meropenem, metronidazole, and teicoplanin). Blood cultures, pharynx, and stool swabs were negative. Voriconazole (8 mg/kg twice a day) and then Amphotericin B (up to 5 mg/kg) were empirically added to antimicrobial treatment, but fever persisted. Based on abdominal magnetic resonance imaging (MRI) hepatic microabscesses () were diagnosed. They were also found in hepatic ultrasonography (). A biopsy of these lesions under US was performed. The culture was negative and histopathological examination revealed only lymphocytes and neutrophils lesions, but no fungus. As mannan antigen was positive, according to European Organization for Research and Treatment of Cancer Mycosis Study Group, “probable” invasive fungal infection (IFI), that is, hepatic candidiasis, was diagnosed and we switched the treatment to caspofungin (50 mg/m2). The persistent fever and elevated inflammatory markers (C-reactive protein, CRP 10,34 mg/dL) despite good clinical condition, appropriate antifungal treatment, still negative blood cultures, and neutrophil recovery raised a suspicion of candidiasis-related IRIS and corticosteroids (dexamethasone 0,5 mg/kg) were added to caspofungin therapy. Fever disappeared after 3 days, CRP level was normalized within 10 days, and significant decrease in size and number of liver microabscesses after 2 weeks was achieved (). Corticosteroid treatment was tapered in 7 days and then stopped. Caspofungin treatment was continued for 3 months together with continuation of chemotherapy. After significant regression of liver microabscesses we tried to switch into itraconazole, but radiological progression in US occurred. Finally, patient was treated for 6 months with caspofungin and, after the antifungal therapy completed, the MRI returned to normal with no pathological lesions in the liver. The patient is already in ALL remission for 25 months.


A 70-year-old African-American male with a history of hypertension, COPD, cryptogenic cerebrovascular accident, and paroxysmal atrial fibrillation presented after he was hit by a van whilst crossing a road. On admission, his physical exam was remarkable for mild abdominal distention and an externally rotated left lower extremity. He was diagnosed with a nondisplaced fracture of the left femoral neck, for which he underwent a total hip arthroplasty. Following the arthroplasty, his hospital course was complicated by a pulmonary embolus, which was treated with low molecular weight heparin and warfarin. Later on, during his hospital stay, he developed watery diarrhea and marked abdominal distension with hypoactive bowel sounds. He did not have any nausea, vomiting, or abdominal pain. Clostridium difficile colitis was ruled out by a PCR based assay. Abdominal X-ray and CT abdomen showed marked gaseous distension of large bowel (Figures and ). At this point, he was diagnosed with Ogilvie's syndrome. He subsequently underwent 2 successive decompressive sigmoidoscopies, which resulted in minimal improvement of his abdominal distention. His colon enlarged to a maximum diameter of 12 cm. Lab results were remarkable for hypokalemia to 2.8 mEq/L. Despite aggressive repletion with over 160 mEqs of potassium a day his serum potassium remained at <3 mEq/L after 4 days. Due to this persistent hypokalemia urine and stool electrolyte studies were obtained. His urinary potassium was <10 mEq/L, stool sodium was <15 mEq/L, and stool potassium was elevated to >140 mEq/L. This pattern was consistent with Ogilvie's syndrome. At this point, besides continued potassium repletion and ambulation as tolerated with the help of the physical therapist, he was also started on spironolactone 50 mg twice a day to help decrease stool losses. After starting spironolactone his potassium levels improved and his stool output decreased gradually over the next 3-4 days. His potassium remained stable and he was discharged to a skilled nursing facility for further physical therapy. On follow-up, 20 days after discharge his potassium was found to be stable at 5.1 and his colonic distention had improved.


Case 1: An 89-year-old man presented to us in 2013 with a 10-year history of a mass originating from the right parotid and involving the neck. The mass grew rapidly for 3 months before the patient was examined. At presentation, the diameter of this rubbery hard mass was approximately 8 cm. There was no facial paralysis. Computed tomography (CT) showed an irregular mass of the right parotid gland with partially defined margins and no lymph node metastases (Fig. ). Magnetic resonance imaging (MRI) was not performed because of presence of metal implants for a left leg fracture. Fine-needle aspiration cytology (FNAC) of the parotid mass indicated PA. We suspected that the mass was a malignant tumor, particularly a carcinoma ex PA. Therefore, superficial parotid gland resection was performed in March 2013. Intraoperatively, the facial nerve was found attached to the tumor, although the tumor was resected without sacrificing the facial nerve. Pathological analysis of the tumor revealed MEC ex PA (pT3N0M0), MEC component was clear cell type, and the resection margin was free of carcinoma. The histological grade was low according to the grading system of Savera []. (Fig. , Fig. ). PA was completely surrounded by carcinoma that indicated pathological invasiveness []. Immunohistochemical (IHC) analysis was positive for S-100 protein, pan-cytokeratin (AE1/AE3), smooth muscle actin, p63, and p53 (Fig. ). Moreover, the nucleus was moderately positive for mindbomb E3 ubiquitin protein ligase 1 (MIB-1) (active area, 20 %) (Fig. ). The patient was considered as high risk because of the findings of invasive MEC ex PA and mutant p53 protein positivity; thus, radiotherapy for the locoregional area was recommended. However, the patient refused adjuvant therapy because of his age. At the 36-month postoperative follow-up, he was still without recurrence.


Case 2: A 54-year-old woman presented to us in 2013 with a >10-year history of right submandibular lesion. The growth of the mass was slightly faster 1 year before presentation. At presentation, the elastic hard mass was approximately 6 cm in diameter, and there was no facial paralysis. MRI showed an irregular mass in the right submandibular gland with partially defined margins (Fig. ). There was no indication of lymph node metastases on ultrasonography and MRI. Both dynamic MRI and FNAC from the submandibular mass indicated PA. However, we also suspected carcinoma ex PA because of the rapid growth of the tumor. Submandibular gland resection was performed in July 2013. During resection, part of the platysma muscle with suspected adhesion was removed, and the mass was excised along the capsule. The marginal mandibular branch of the facial nerve was preserved because it was not adhered to the tumor. Pathological analysis of the tumor revealed invasive MEC ex PA, pT3N0M0, whereas the carcinoma portion had an extracapsular spread into and invaded the platysma muscle. The excision stump was close to the carcinoma portion (Fig. , Fig. ). The MEC component comprised clear cell type. The histological grade was high []. IHC analysis was positive for S-100 protein, AE1/AE3, and p53 (Fig. ). Moreover, the nucleus was strongly positive for MIB1 (active area, 40 %) (Fig. ), whereas IHC analysis was negative for p63. Because of the close margin, right neck dissection (levels I–III) and additional resection of the submandibular tissue, including the platysma muscle around the tumor, was performed in August 2013. Pathological analysis revealed no regional metastases or residual carcinoma in the additional resected tissue. Because of several positive risk factors (invasive MEC ex PA, high MIB1 index, and mutant p53 protein positivity), radiotherapy and chemotherapy were recommended as adjuvant therapy. At that time, she refused additional therapy and was followed as an outpatient. One year after surgery, distant metastasis to the right pulmonary hilar node and lungs was revealed by follow-up CT and 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography integrated with CT. There were typical multiple metastases to both lungs, with a maximum tumor diameter of 3 cm. We diagnosed the lesions on observation of distant metastases from the known salivary gland malignancy according to the typical CT imaging and the clinical course of the enlarging multiple nodules at the peripheral lung field and right hilar node. Eight cycles of chemotherapy with cyclophosphamide 500 mg/m2, cisplatin 50 mg/m2, and adriamycin 50 mg/m2 were intermittently initiated []. No serious adverse events were observed during chemotherapy. The lung metastases were controlled; therefore, at the follow-up 30 months after the first surgery, she was still alive with cancer.


A 54-year old male self-presented to the emergency department with a 4-day history of awareness of irregularities of his heart rhythm. This was not accompanied by any chest pain but he revealed a one-month history of shortness of breath, tiredness, and leg swelling. He also reported general malaise and decreased libido. He had recently stopped smoking when the symptoms first started and used to smoke 15 cigarettes a day prior to that for 25 years. He had no prior medical or surgical history other than mild asthma for which he had not been hospitalized previously.
On admission, he was found to have a narrow complex tachycardia, which reverted to normal sinus rhythm with intravenous verapamil. Initial investigations showed Troponin I of 0.22 (normal < 0.04), a BNP of 899 (normal < 100), and raised D-dimers of 664. A CT pulmonary angiogram excluded a pulmonary embolus. A transthoracic echocardiogram showed mildly dilated left and right ventricles with global hypokinesia and severe biventricular systolic dysfunction. The left ventricular ejection fraction (LVEF) was calculated, by Simpson's method, to be 15% (normal > 55%). The echocardiogram also showed there was no left ventricular hypertrophy or valve disease of any significance. A full cardiomyopathy biomarker screen was negative for any secondary causes. Coronary angiography revealed only mild atheroma in the proximal left anterior descending and mid-right coronary arteries. The patient had no further rhythm disturbances on CCU and lost 6.2 kg in weight during his 5-day stay as an inpatient.


Case 1. Ten years before, a 67-year-old man was diagnosed with PMF. Although he had been treated with hydroxyurea, his spleen had progressively enlarged and extended to his pelvis (). He exhibited fatigue, abdominal pain, and transfusion-dependent anemia. Laboratory blood tests showed bicytopenia (WBC, 6.6 × 103/L; Hb, 7.6 g/dL; platelets, 7.4 × 1010/L) and leukoerythroblastosis. A bone marrow biopsy showed hypocellular marrow with severe fibrosis and changes in megakaryocyte morphology (). We detected the JAK2 V617F mutation in the peripheral blood using allele-specific PCR. The disease was classified as “intermediate-2 risk,” according to the prognostic classification of the DIPSS, and the patient was evaluated as a candidate for HCT. After written informed consent was obtained, he was treated with 4 Gy splenic irradiation on day −7 to day −6 prior to HCT. With splenic irradiation, there was a rapid reduction in splenomegaly, and the spleen shrank to 10 cm below the left costal margin. Furthermore, the MF-related abdominal pain was alleviated. The conditioning regimen consisted of fludarabine (Flu) 30 mg/m2 × 5 (day −6 to day −2), intravenous busulfan (Bu) 3.2 mg/m2 × 2 (day −3 to day −2), and 4 Gy of total body irradiation (TBI) on day −5 to day −4. The patient underwent HCT from a human leukocyte antigen- (HLA-) mismatched unrelated donor (mismatch in HLA-DRB1). The infused bone marrow contained 3.7 × 108/kg nucleated cells. Graft-versus-host disease (GVHD) prophylaxis consisted of continuous infusion of tacrolimus and short-term methotrexate. Neutrophil engraftment occurred on day 21. The chimerisms in the bone marrow and peripheral blood were 100% donor. A bone marrow aspiration and biopsy showed complete remission. A skin biopsy assessment showed that Grade I acute GVHD of the skin occurred on day 34. There was no GI toxicity as a result of the splenic irradiation. Furthermore, the JAK2 V617F mutation was not detected after the neutrophil engraftment. A bone marrow biopsy specimen showed that the fibrosis regressed on day 377 (). Although chronic GVHD of the liver and mouth occurred 20 months after transplantation, the symptoms disappeared following the administration of corticosteroid. The patient's spleen gradually decreased in size until it was not palpable, and computed tomography showed that the massive splenomegaly was reduced (Figures , , and ). The patient is still alive without relapse for 52 months after HCT.