The patient presented herein, is a 29-year-old man with history of unilateral alkaline chemical injury 14 years ago. Upon referral, visual acuity was 20/20 and the examination was unremarkable in the right eye. Vision was hand motions (HM) in his left eye and a small angle exotropia (10–15 Prism Diopters) was evident. Slitlamp examination revealed severe corneal opacification and vascularization (). Intraocular pressure (IOP) was 13 and 10 mmHg in the right and left eyes, respectively. B-scan ultrasonography ruled out gross posterior segment pathologies and impression cytology revealed total limbal stem cell deficiency (LSCD) in the left eye.
The injured eye underwent cultivated autologous stem cell transplantation on amniotic membrane (AM) after punctal cauterization. The patient received a topical steroid (betamethasone 0.1%, Sina-Daru, Tehran, Iran), and an antibiotic (chloramphenicol 0.5%, Sina-Daru, Tehran, Iran). Antibiotic drops were continued for 1 to 2 weeks until complete epithelialization. Steroid drops were tapered off according to the level of ocular inflammation over 6–8 weeks. A preservative-free artificial tear (Artelac, Bausch and Lomb, USA) was used for lubrication as needed. The patient received systemic prednisolone 1 mg/kg (Sina-Daru, Tehran, Iran) for 3 to 4 weeks. Visual acuity in the left eye improved to counting fingers at 75 cm along with modest decrease in corneal vascularization and opacity 3 months after the procedure ().
Due to deep corneal stromal opacification, penetrating keratoplasty (PKP) was performed 6 months later. One month after PKP, visual acuity improved to 20/120. The patient complained of diplopia which was due to improvement in vision and the small angle exotropia. Six weeks later, IOP increased to 32 mmHg which was controlled by topical timolol 0.5% (Sina-Daru, Tehran, Iran) two times per day and systemic acetazolamide 250mg, three times per day. Cup-disc ratio was 0.3. Systemic acetazolamide was discontinued due to elevated liver enzymes and replaced by topical dorzolamide 2% (Sina-Daru, Tehran, Iran) two times per day.
Eight weeks after corneal transplantation, the patient developed epithelial rejection, which was treated with topical steroids. Four months after surgery, IOP rose to 30 mmHg and brimonidine 0.2% (Alphagan, Allergan Inc., Irvine, USA) and latanoprost 0.005% (Xalatan, Pfizer Inc., New York, USA) were added to the regimen. Five months after PKP, visual acuity improved to 20/80 but IOP was poorly controlled (). The patient underwent Ahmed Glaucoma Valve (AGV) surgery. Two months later, a mild posterior subcapsular cataract was observed. Five month after AGV, corneal endothelial and subepithelial rejection were observed which was aggressively treated with systemic prednisolone and topical betamethasone. Overall, the patient experienced three attacks of corneal endothelial rejection 5, 9 and 16 months after AGV. There was a slightly progressive vascularization in the graft periphery 8 months after PKP.
Considering multiple episodes of corneal endothelial rejection and progressive corneal conjunctivalization in an eye with defective ocular surface, systemic cyclosporine (Sandimmune®, Novartis Pharma Stein AG, Stein, Switzerland) 300 mg per day was started. One month later, it was replaced by mycophenolate mofetil (Cellcept®, Hoffmann-La Roche Inc., Nutley, USA) 2 grams per day due to elevated liver enzymes. Two weeks later liver enzymes levels improved but 2 months thereafter, rose critically again and mycophenolate was also discontinued. After that, the patient was put on fluorometholone 0.25% eye drops once daily together with topical cyclosporine 2%.
One year after PKP, impression cytology confirmed corneal conjunctivalization in the superior and inferior temporal quadrants by the presence of goblet cells on the corneal side of the specimens. About 20 months after PKP, vascularization and conjunctivalization was continuing but did not reach the central 5 mm zone of the cornea (). At final visit, visual acuity was maintained at 20/80 and IOP was 16 mmHg without any glaucoma medications.
Herein we present the views of two anterior segment specialists on the management of LSCD in this patient.
To maximize the outcomes of transplantation of ex vivo cultured limbal epithelial cells (LECs), several issues need to be considered. First of all, the ocular surface should be optimized before performing any kind of limbal stem cell transplantation. Although both puncti of the recipient eye were cauterized prior to transplantation, it is unclear whether the ocular surface was actually ready for surgery. For example, it has not been mentioned whether the recipient eye had any other factor which may interfere with ocular surface health, such as surface inflammation, symblepharon, closure and blinking problems, or lid margin abnormalities.
After any form of ex vivo culture of LECs and before transplantation of the product to the ocular surface, it is necessary to demonstrate that the product really contains viable stem cells. A number of methods have been employed for this purpose such as functional assay of colony forming ability of transplanted cells, immunohistological assays, evidence of donor cell survival, and confocal scanning. In this case report, the evaluation method for the product has not been stated. Transplantation of a product with inadequate viable stem cells can result in long-term failure, which finally developed in this patient.
Although the surgical technique for transplantation of ex vivo cultured LECs is fairly similar in different studies, postoperative medical regimens may differ among them. The basic principles of this regimen include immediate control of inflammation, prophylaxis against infection, and mechanical protection of the graft. Application of autologous serum eye drops may further optimize the environment for stem cell survival. The early postoperative course of the patient has not been mentioned which may be a clue to final graft survival.
The patient in this report showed improvement in visual acuity with moderate decrease in corneal vascularization and opacification 3 months after surgery (). However, these could not be considered to be absolute measures of success. There were still many areas of corneal vascularization with a clinical appearance of residual conjunctivalization (). There is no data on fluorescein staining patterns or the results of impression cytology at this postoperative time point. Due to lack of these data, there is a possibility that the patient was still suffering from residual LSCD at that time. It should be mentioned that in addition to clinical findings, a more definitive way to evaluate the success of surgery is to perform impression cytology on the corneal surface postoperatively. This test, which was not performed in the case report, is necessary before proceeding with corneal transplantation. This may explain why the patient finally developed partial LSCD.
Performing an eccentric full-thickness graft in a vascularized cornea () should be considered as a high risk corneal graft. This is why the patient developed multiple episodes of graft rejection. In these cases, if there is no full-thickness corneal involvement, it is always preferable to perform lamellar rather than full-thickness corneal transplantation.
The postoperative management of this immunologically high risk graft is vital in determining the outcome. The main measure to be used for prevention of rejection in high risk grafts is immunosuppression. Although corticosteroids have traditionally been used for this purpose, new agents have been available in the past years. In high risk patients, topical steroids are used frequently in the postoperative period, followed by their long-term use if there is no contraindication. Sometimes, low dose steroids need to be used indefinitely after surgery. Therefore, potential complications of steroids, such as cataracts, glaucoma, delayed wound healing, and infectious keratitis should seriously be considered. Systemic steroids can also be used as an adjunct to topical therapy, particularly in high risk cases with concomitant systemic inflammatory diseases. Recently, steroids with lower rates of complications have been introduced; examples include loteprednol etabonate and fluorometholone which can be used for keratoplasty patients who require long-term maintenance therapy.
In addition to corticosteroids, cyclosporine A (CsA), a calcineurin inhibitor, has been used extensively in organ transplantations including high risk corneal allografts. Many studies have demonstrated the effectiveness of CsA, either topically or systemically, to reduce rejection rates in high risk keratoplasty patients. Although 0.05% CsA is commercially available, a 2% concentration has been shown to be effective for this purpose. Oral CsA may be used in very high-risk cases when topical medications may not be sufficient to prevent corneal graft rejection. However, oral CsA is associated with a number of dose-related side effects, most commonly nephrotoxicity, hypertension, and hepatotoxicity, which developed in this case. Various other systemic immunosuppressive agents have been used in patients with high risk corneal grafts such as tacrolimus, azathioprine, mycophenolate mofetil, and rapamycin, sometimes in combination. However, all of these agents may be associated with adverse effects, which developed in this case after using mycophenolate. In my personal experience, the preferable initial immunosuppressive medication is topical 2% CsA which may be used alone or in combination with topical steroids. This may be why the patient did not develop any episode of graft rejection while on topical CsA.
This case report shows how difficult it may be to manage patients with significant ocular surface disease. A comprehensive multidisciplinary approach is necessary to deal with these grave eye conditions.
This 29-year-old man with severe vascularization, conjunctivalization and diffuse haziness of the cornea has unilateral total LSCD. He had history of chemical injury 14 years before presentation. At this stage, any type of corneal transplantation (penetrating or lamellar) would have a short survival and may fail rapidly. Because the right eye is normal in appearance and has no history of exposure to chemical agents, limbal stem cells could be harvested for ex vivo expansion. This technique which has become available in some centers in recent years, enables patients to make benefit of their own stem cells. This technique brings hope for traditionally poor chance cases with LSCD. At this stage it is very important to optimize the status of the fornices. Severe symblepharon and foreshortening of the fornices prevents adequate tear film lubrication and lid function. Therefore, reconstruction of the fornices and release of symblepharon using amniotic membrane can be helpful.
After limbal stem cell transplantation, it would be better to use preservative-free medications. The medications used in this case are not preservative-free and can be toxic to the transplanted tissue.
After PKP in cases who are considered to be high risk due to previous limbal stem cell (LSC) transplantation, immunosuppressive treatment must be used. Steroids alone are not enough and can be used in the immediate post-PKP period, but systemic or topical immunosuppression with medications such as cyclosporine A (Sandimmune®) or mycophenolate mofetil (Cellcept®) are important preventive measures against rejection of corneal transplants. It would be better to start these medications earlier and prior to immune system activation.
IOP rise with coticosteroids can be due to steroid responsiveness. This risk is higher with topical betamethasone than other steroids. If the use of these types of medications is mandatory, alternative medications, e.g. fluorometholone or loteprednol can be considered.
In summary, the management of LSCD has remarkably changed over the recent years. Cultivation of LSC and application of immunosuppressive medications will help clinicians improve the final outcomes. Glaucoma is a sight-threatening complication in these cases. Manipulation of cicatrized and scarified conjunctiva, extensive use of steroids, and multiple operations are important factors predisposing to glaucoma.
Surgical management of LSCD depends on the laterality and severity of corneal involvement. Partial LSCD can be managed using amniotic membrane transplantation (AMT) or sequential epitheliectomy. In partial or total unilateral cases, conjunctival-limbal autograft (CLAU) is a good choice. Recently, transplantation of limbal epithelial stem cells cultivated on carriers such as AM or transplantation of ex vivo cultured autologous oral mucosal epithelial cells has been considered as alternative procedures for unilateral or bilateral LSCD.
The main objective of any kind of stem cell transplantation is to supply new corneal epithelium for a prolonged, if not indefinite, period of time so that patients can be relieved from annoying photophobia and regain useful vision. Cultivation of a small part of the limbus may provide epithelial progenitor cells, which might survive for a while on the ocular surface. In eyes with superficial corneal vascularization and pannus, a single procedure is frequently enough. However, if there is concomitant deep corneal stromal scarring, penetrating or lamellar keratoplasty is needed to restore vision. Drawback to CLAU and conjunctival-limbal allograft (CLAL) is that due to removal of fairly large segments of limbal tissue, the donor eye is at risk of surgically induced LSCD. The use of autologous cultivated limbal stem cell transplantation has been suggested to overcome this limitation. Cultivating a small amount of limbal tissue provides adequate limbal stem cells for treatment of total LSCD.
Use of AM as a carrier medium for cultivated limbal stem cells entails the following advantages. Its stromal matrix is similar to conjunctival basement membrane and is a suitable medium for growth of limbal stem cells, it is antigen-free and resorbed gradually. AM facilitates ocular surface epithelialization, it down-regulates inflammatory cytokines, facilitates epithelial cell differentiation and may be used for ocular surface reconstruction.
The use of ex vivo cultured limbal epithelial stem cells for treatment of corneal LSCD in humans was first described by Pellegrini et al in 1997. Since then several additional reports on the use of this technology to treat patients have been published. In addition, other studies have reported the transplantation of ex vivo cultured autologous oral mucosal epithelial cells to treat LSCD. Numerous reviews have dealt with the scientific theory and evidence behind this treatment. In almost all studies, the authors conclude that this method is a successful procedure to treat unilateral corneal stem cell deficiency. Some key questions still need to be answered. The exact proportion of stem cells present in ex vivo cultured limbal epithelial cell sheets is unclear and needs to be determined. The behavior of limbal epithelial stem cells post-transplantation also needs to be elucidated. It has been proposed that the success of this treatment relies on the re-integration of exogenous cultured limbal stem cells into the ocular surface, and that these cells function to continuously replenish the corneal epithelium. It is interesting that despite the different methodologies employed, the success rate and outcomes are remarkably similar.
The surgeon subsequently performed optical PKP in this case. He selected fresh donor cornea with a very good coverage of epithelial cells; therefore some transient amplifying cells (TACs), which support corneal clarity have been theoretically transferred by the corneal graft. It is not possible to judge whether the cause of corneal clarity is related to TACs transferred by the corneal graft or due to transplanted epithelial progenitor cells cultivated on the AM. However, it seems that the period of corneal clarity was relatively longer than usual corneal grafts without stem cell transplantation.
In summary, cultivated stem cell transplantation on AM might be an effective way to improve the health of the injured ocular surface. Despite uncertainties, published clinical evidence supports the continued advancement of this procedure for treatment of corneal epithelial stem cell deficiency. To date, this procedure has been regarded as experimental, but in the light of the clinical outcomes, it seems that it has the potential to become a viable option for treatment of many patients with severe limbal stem cell deficiency.


Case 1 is a 63 years old male patient, under follow up in our hospital, with a grade IV glioblastoma (determined by histopathology) in the right temporal lobe. As it can be observed in , at the time of diagnosis the tumor is located very close to the cortex. This corresponds with a higher probability of seizures, symptom that led this patient to a first medical consultation. Patient-specific analysis of this glioma determined that it was characterized by a net proliferation rate of 0.107 cells/day and a net diffusion (migration) rate of 0.255 in white matter. Corresponding tumor mass velocity and invisibility index were 120.8 mm/year and 2.38 , respectively. Considering the range of values reported for high grade gliomas (velocities of 10 to 200 mm/year and invisibility index of 2 to 20
), those values meant that this tumor had a relatively intermediate growth velocity and low invisibility index. These parameters describe a relatively ‘benign’ tumor in relation with the glioblastoma spectrum. In correspondence with (but independently from) this prediction, this was a relatively rare case that was left without surgical intervention up to five months from diagnosis.
Simulation of case 1 in a ‘virtual patient’ began with the localization of an initial unique tumor cell in the white matter of the superior temporal gyrus. Malignization of the tumor was predicted around 152 days (five months) after its onset and diagnosis after 267 days (nine months). The whole simulation of this case can be observed in the File Case S1 video submitted as a supporting information file. shows the real and simulated tumor at the diagnosis time for different tumor views. In simulated images ( and 1(e)), the central white area represents the concentrated tumor mass while the black surrounding area indicates tumor infiltration, with low concentration of tumor cells invading normal brain tissue.
A good correlation between real and simulated radios of the tumor mass can be observed (8.9 vs. 9.7 mm, respectively). When the simulated image is generated with the same detection level as the MRI technique (around 400 cells/
), there is also a fairly good correlation between real and simulated infiltrative areas (compare with 1(d), axial view). Simulated infiltrative areas detected at 1 cell/, nevertheless, indicate that they would be underestimated by current diagnostic imaging. This is something also reported by others and it is related to one of the main potential clinical utilities of this type of models.
presents the tumor mass and infiltration 20 days after diagnosis time. At this time, real and simulated tumor mass radios are 12.1 and 12.2 , respectively. Simulated infiltrative areas also correlate well with those derived from real images when generated at the same detection level (see , axial view), but a higher level of detection indicates again that this area may be larger than that evidenced by real MRI images. These two moments (diagnosis time and 20 days after) were used to estimate the main parameters of the model (net proliferation and diffusion rates) in a patient-specific way. Tumor evolution to the next time stage (40 days after diagnosis) was then predicted by the model.
shows the predicted tumor-mass and infiltrative areas 40 days after diagnosis, over different slices from the axial plane, given a better overview of the 3D tumor evolution. A good correspondence can be observed between real and simulated images generated at a detection level of 400 cells/mm
2 (compare first with second row of images). Here, tumor mass radii are 14.8 and 15.8 mm, respectively. Again, a higher detection level of 1 cell/ indicates larger invasion than that observed by MRI real images (third row). These results indicate a fairly good prediction accomplished by the numerical model.
superimposes the predicted tumor mass at different times upon the Talairach atlas, indicating the main brain structures that are being affected by tumor evolution. At diagnosis time (270 days from tumor onset, ), tumor mass affects 8.2% of the Brodmann area 41 and 12.6% of the Brodmann area 42 (references 2 and 3, respectively). These areas belong to the primary auditory cortex (Heschl’s gyrus). Related main functions are basic processing of auditory stimuli (speech and non-speech) , and processing of sound intensity , .
50 days after diagnosis (320 days from tumor onset, ), the tumor mass invades great part of transverse and superior gyrus of the temporal lobe (references 1 and 6, respectively) and 10.9% of the Brodmann area 22 (reference 4). If the dominant cerebral hemisphere were the right one, this area would be part of the Wernicke’s area, fully related to auditory comprehension of language . If it was not, as in the majority of cases, this area would have also roles related with receptive language but in a subordinated way, leading to a bilateral dissociation design . This seems to be the case with functions related to lexical ambiguity resolution, where left and right Wernicke’s areas function as processors of dominant and subordinated meanings of ambiguous words, respectively.
100 days after diagnosis (370 days from tumor onset, ), the tumor has expanded to the pre-central gyrus of the frontal lobe (10) and up to the right lateral ventricle (7). It also affected 21.4% of the Brodmann area 43 (9), 10.7% of the Brodmann area 13 (8) and 3.3% of the Brodmann area 39 (5). Brodmann area 43 is associated with some motor responses to vibrotactile digit stimulation and to spoken language . Brodmann area 13 belongs to the insular cortex, that is reported to participate in somatosensory , olfaction and taste , and verbal memory functions , among others. Finally, Brodmann area 39 is also part of the Wernicke’s area or its contralateral homologous. In the right hemisphere, it is generally associated to visuospatial processing and music reading . predicts that, at the time of death (survival time of 140 days after diagnosis or 410 days from tumor onset), the tumor mass has extended through the insula (11), lentiform nucleus (12) and thalamus (13).
presents tumor status at the predicted time of death. The estimated tumor mass diameter (assuming an spherical shape) at this moment is 62.9 mm, a value slightly smaller than the lethal size parameter used (70 mm, see ). This might be attributed to the corrections added to the model in relation with tumor location. Indeed, at this time the tumor mass edge reaches the ‘foramen magnum’, as is evidenced by the Talairach atlas in . This means that herniation, and consequently death, could be imminent.


Case 2 is a 32 years old male with a histopathology of anaplastic oligodendroglioma (grade III) reported in previous literature . The whole simulation of this case can be observed in the File Case S2 video submitted as a supporting information file. compares simulations of this case at different times made with two distinct mathematical models: left column corresponds to simulations obtained with the present model, right column corresponds to simulations derived from our implementation of a model previously described in the literature (this model does not include differential migration based on topological brain structures). This figure should be compared with from that shows the real MRI images from this patient. Real tumor dimensions correspond well with those predicted by the present model. At diagnosis, real and simulated tumor mass radii are 8.9 and 8.7 mm; while tumor infiltration radii are 28.4 and 28.9 mm, respectively (compare from with axial view from ). Eighteen days after diagnosis, real and simulated tumor mass radii are 11.4 and 10.6 mm; and tumor infiltration radii are 33.1 and 31.2 mm, respectively (compare from with axial view from ). Simulations made with a previous model ( and 6(d)) also reach tumor dimensions similar to real ones.
However, if we analyze tumor spreading the situation is different. Our model seems to be more accurate regarding tumor spreading than previous ones and these differences between models become significant 18 days after diagnosis. Real images show that tumor invasion through the corpus callosum is significantly augmented at that time ( from ). They also evidence a mass-effect that compresses the lateral ventricles. Although this kind of mathematical models do not include the mass-effect, this type of spreading through the corpus callosum can be observed in simulations made with our model (see axial view form ) but not in those derived from previous ones (axial view from ).
This consideration is extremely important, as its consequences worsen with time: differences between both models become more evident 100 days after diagnosis, as it can be evidenced in and 6(f). At this time point, simulations made with the present model predicts a larger spreading of the tumor through the corpus callosum with tumor cells reaching the contralateral hemisphere and anterior zones of the brain. Simulations with previous models, on the contrary, do not evidence this type of spreading. Though this time stage does not have real images to correlate with, it evidences the natural evolution of the previous tumor status.


A quadriplegic edentulous 30-year-old male with a history of head trauma caused by a car accident 3 years ago was referred for replacement of missing teeth. He had extracted all his teeth because of severe caries due to a 10-month coma and the jaw ankylosis resulting from the trauma. His chief complaint was inability of chewing, and mouth opening range was normal. After meticulous diagnostic survey, maxillary and mandibular overdentures were selected as the treatment plan. He had type 3, divisions A, D, C in different part of maxillary arch and type 1 division A in mandibular arch [].
Eight implants (4.1 × 12 mm; ITI Dental Implant System, Straumann AG, Basel, Switzerland) were inserted in the maxilla and mandible according to surgical stents (). A bar- (ITI Dental Implant System) retained maxillary overdenture and ball- (Rhein 83, Bologna, Italy) retained mandibular overdenture were processed using conventional procedures [].
The patient's general condition improved after a year, and his speech therapist requested palatal lift prosthesis to correct the patient's hypernasal speech and also emphasized that his soft palate muscle activities may be corrected after a period of using palatal lift prosthesis.
To construct a new maxillary prosthesis with palatal lift, preliminary impression was made with irreversible hydrocolloid (Jeltrate, Alginate, Fast set, Dentsply Philadelphia, PA, USA) and a custom tray was fabricated with light cured resin (Triad VLC, Dentsply). Border molding in vestibules was performed by impression compound (Kerr, Orange, NJ, USA) and completed with the Iso Functional compound (GC Dental Corp., Tokyo, Japan) in the soft palate site. Final impression was made by polyether material, (Impergum F, 3M ESPE, St. Paul, MN, USA, ). An overimpression of the placed mandibular overdenture with irreversible hydrocolloid was also obtained. The impressions were poured with type III stone (Fujirock, GC Dental). After obtaining the maxillomandibular records with a record base and occlusion rim, the casts were transferred to a semiadjustable articulator (ARH type, Dentatus AB, Stockholm, Sweden) using a face-bow transfer (AEB face-bow, Dentatus AB). A protrusive record was made to set the articulator's condylar elements, and a lingualized occlusal schema was achieved. Denture teeth were arranged on the record base with an index to duplicate the same position of the first overdenture teeth. The trial arrangement was evaluated intraorally, for esthetics, occlusal vertical dimension, and centric relation. The 1 mm thickness vacuum heat-pressed polyethylene was adapted around the bar portion of maxillary cast as a spacer, and the prosthesis was processed using heat cure acrylic resin material (Triplex hot, Ivoclar Vivadent, Schaan, Liechtenstein). The 1 mm thick spacer was removed from the intaglio surface of the denture, and this area was lined with autopolymerizing resilient material (Mollosil, Detax, GmbH, Ettlingen, Germany). The denture was placed on the cast until the resilient material setting was completed (). After delivery, denture care instructions were given to the patient. Patient was told to clean the tissue surface using soft cloth. Recall appointments were scheduled at 1 day, 1 week, 1 month, and every 6 months. The soft liner replacement was scheduled every 6 months, but the soft liner maintained its resiliency after a year, so it was replaced only once in 2 years. In this period the dentures were well maintained, and the patient was comfortable using them (). His hypernasal speech was improved, and the patient returned to use his old denture.


A 48 years-old white man was followed for a 20-years history of severe chronic plaque psoriasis. In 1990 HCV infection was demonstrated with raised liver enzymes and ongoing viral replication. The patient presented to us with persistently elevated aminotransferase levels (ALT; three times normal), HCV infection with genotype 2a-2c (Simmonds Classification) and HCV-RNA titer (measured by the quantitative-chain-reaction assay, detection limit, 50 IU/mL) of 2,050,000 IU/mL []. A liver biopsy showed moderate to severe fibrosis with moderate to severe portal, per-portal and globular mononuclear infiltrate (metavir A3, F3) []. The patient denied his consensus for interferon IFN-α/ribavirin therapy because of the possible worsening of psoriasis during IFN therapy. In the past, the patient received numerous topical courses of corticosteroids, vitamin D derivates, tar derivates and salicylic acid with partial improvement. Ultraviolet B phototherapy was introduced for 4 months with only slight response. At baseline, the patient presented with a Psoriasis Area and Severity Index (PASI) of 19. 8 (), a Body Surface Area of 19, with a severe palmo-plantar involvement that impaired his quality of life (QOL), measured by the Dermatology Life Quality Index (DLQI) questionnaire, with a score of 19 (range 0 to 30, being 30 the worse QOL). Because of the severity, extension and QOL impairment, systemic therapy was essential and cyclosporine was chosen in the HCV setting, considering the contraindication for methotrexate and the scarce response after two months of acitretin. Cyclosporine was introduced at 5 mg/kg/day with progressive tapering of the dose by 50 mg/weekly after PASI-90 achievement (90 % of PASI improvement; ). During cyclosporine therapy, liver function tests (transaminases and gamma glutamil transferase) were measured every and HCV viral load was measured every six months using the same quantitative polymerase-chain reaction assay (detection limit, 50 IU/mL). A total of five courses (duration range: three - six months) of cyclosporine (5 mg/kg/day) were followed by the patient during a 38-month period. The viral load diminished during the 38 months of intermittent cyclosporine therapy to the lowest level measured at month-36 (6.5 x 105 IU/mL). The transaminases levels diminished during the whole therapy, with a 42 % of improvement from baseline to 38th month (). Blood pressure, triglycerides, total or LDL-cholesterol levels and renal function remained on the normal range during the whole cyclosporine intake period.


The patient is a 55-year-old female with known stage III b serous ovarian cancer. She had undergone an abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy, followed by 6 cycles of carbo/taxol chemotherapy with complete clinical response. She was free of disease for 2 years until her disease recurred and was treated with Carboplatin and Taxol. The carboplatin was eventually switched to Doxil. However, the repeat positron emission tomography (PET) scan at that time showed progression of her disease. Thus she underwent exploratory laparotomy with removal of a splenic mass. She was noted to have peritoneal carcinomatosis at that time and was then treated with Gemzar. The patient had stable disease after this treatment. Five years after the initial diagnosis, the patient was admitted to the hospital with anemia, hemoglobin of 7.0 gm/dl, fatigue, and melena. Computerized Tomography (CT) of the abdomen without IV contrast was obtained on admission, which revealed calcified, heterogeneous, mixed intermediate and high-density deposits worrisome for peritoneal carcinomatosis (, arrows). No IV contrast was administered due to her poor kidney function. She was referred for an EGD, which showed a 7 mm erythematous lesion at the gastroesophageal junction and a 1.5 to 2 cm subepithelial mass () with a superficial overlying erosion in the antrum, but no obvious source for any active bleeding. Initial endoscopic biopsies of the gastroesophageal junction lesion showed granulation tissue polyp with foveolar hyperplasia, and the antral biopsies were normal. Due to the presence of a subepithelial lesion in the antrum, the patient was referred for EUS. Two subepithelial lesions were discovered by EUS, one in the antrum measuring 3.4 × 3.7 cm () and one in the body of the stomach 1.2 × 0.8 cm (). The lesion in the body of the stomach was not appreciated during the EGD. The lesions were hypoechoic masses emanating from the muscularis propria and had the typical appearance of gastrointestinal stromal tumors. FNA was performed of both masses. Both sites revealed papillary adenocarcinoma from an ovarian papillary serous adenocarcinoma primary (). Immunostains for progesterone receptor, estrogen receptor and p 53 were focally positive and confirmatory. The patient was treated with Taxol and is undergoing surveillance imaging.


A 58-year-old Malay woman had ulcerative colitis that was diagnosed 21 years ago when she presented with recurrent diarrhea. Five years ago, she started to develop peripheral polyarthritis. There were no other extra-articular manifestations such as uveitis or pyoderma gangrenosum. She had multiple relapses of colitis with polyarthritis and therefore had received multiple courses of tapering-dose oral prednisolone with maintenance of 1 g of mesalazine three times a day and subsequently 100 mg of azathioprine once daily. Finally, two years later, with the above treatment, the primary disease managed to be brought to remission.
In spite of the clinical and histological remission of the IBD, the left knee arthritis seems to be persistent, but other peripheral joints mentioned above were in remission without any permanent deformity. A clinical assessment revealed that the left knee was swollen, warm, and tender. The inflammatory marker C-reactive protein was increased to 1.14 mg/dL (normal is less than 0.5 mg/dL). A knee aspirate revealed clear synovial fluid and did not yield any growth. She received two courses of 500 mg of intravenous methylprednisolone daily for three days followed by a tapering dose of oral prednisolone for one year for active and persistent left knee arthritis, but the effects were temporary. Mesalazine was changed to 1 g of sulfasalazine twice a day, and the azathioprine dose was subsequently increased to 150 mg once daily. Unfortunately, she developed leukopenia; therefore, the azathioprine dose had to be reduced back to 100 mg daily. Despite aggressive treatment with multiple courses of high-dose systemic and local steroid with the maximum tolerated doses of sulfasalazine and azathioprine, she still had recurrent left knee effusion and synovitis. Indeed, the disease had caused significant pain and restriction of mobility. Also, after almost two years of corticosteroid therapy, our patient has endured significant iatrogenic morbidity, including Cushingoid habitus, impaired fasting glucose, hypertension, and bilateral cataract with increased intraocular pressure.
In view of persistent unbearable pain and swelling of the left knee with severe secondary osteoarthritis, a total left knee replacement was done in the same year. During the operation, there was active synovitis of the left knee, and a histopathological examination of the synovial tissue revealed 'rice bodies', which are fibrocollagenous connective tissue stroma admixed with fibrinous exudates and abundant foci of vascular proliferation, suggestive of inflammatory arthritis (Figure ). One month after the operation, the left knee effusion recurred and there was persistent elevation of the inflammatory markers. Subsequently, a left knee arthroscopic debridement and near-total synovectomy were performed five years ago. Ten milligrams of oral methotrexate weekly was added one month after the operation, on top of 1 g of sulfasalazine twice a day, 10 mg of prednisolone once daily, and 100 mg of azathioprine once daily. Unfortunately, despite the above treatment for four months, our patient continued to show poor response and persistent recurrence of knee effusion. Subsequently, 25 mg of subcutaneous etanercept twice weekly, together with the other DMARDs and azathioprine, was initiated after three months.
Eventually, the joint showed resolution of knee joint swelling and synovitis at the fifth week of treatment, visual analogue scale score improved from 70 to 20 mm, and the C-reactive protein level decreased to 0.8 mg/dL. After six months of treatment with etanercept, azathioprine was stopped and sulfasalazine was changed to 1 g of mesalazine three times a day as our patient had a mild flare of ulcerative colitis with community-acquired pneumonia. The steroid was also tapered off after six months of treatment.
Twenty-five milligrams of subcutaneous etanercept biweekly and 10 mg of methotrexate weekly were continued, and after 12 months of follow-up, the colitis or arthritis was in remission and no serious side effects were noted.


A 5-year-old castrated male Labrador Retriever was presented to a referring veterinarian for a swelling in the neck region. On physical examination a hard, painless, not retractable spherical mass, the size of a golf ball (+/ 55cm), was palpated just caudally of the left mandibula, in the region of the mandibular lymph node. A fine needle aspiration was performed and the dog was placed on antibiotics pending the outcome. As cytology results were inconclusive, mainly consisting of necrotic cell debris, antibiotic therapy was stopped and it was decided to remove the mass for histopathological examination. During surgical exploration a second, more oval, 154cm mass, located caudally from the first one, was noticed. This caudal mass was left in place and no biopsy samples were taken from it.
On histopathological examination, the first cranial spherical mass noticed, turned out to consist of a reactive lymph node with metastasis of an anaplastic carcinoma. The metastatis consisted of small nests composed of large pleiomorphic polygonal or oval cells with a large round nucleus with coarse chromatin and inconspicuous nucleoli, and a variable amount of granular, slightly basophilic cytoplasm. Anisocytosis, anisokaryosis and karyomegaly was prominent (Figure ). Mitotic figures were numerous, ranging from 58 mitotic figures/high power field (HPF). The neoplastic nests were surrounded by a fine fibrovascular stroma. Randomly distributed, there were small foci with necrosis. Immunohistochemical evaluation with a panel of commercially available mouse and rabbit anti-human primary monoclonal antibodies (DAKO Corp.; Heverlee, Belgium) remained negative for pan cytokeratin (clone AE1/AE3), Melan A (clone A103), CD20 (polyclonal), CD3 (polyclonal) and a mouse monoclonal anti canine CD18 (clone CA16.3C10; P. Moore; University of California, Davis, USA) antibody remained negative. Positive immunohistochemical staining was detected with human mouse monoclonal anti-vimentin (V9) and Chromogranin A (polyclonal) antibodies (Figure ). Based on morphology of the tumor and immunoreactivity the diagnosis of neuroendocrine tumor, more specific paraganglioma was made. Because of the anatomical location, a paraganglioma of the carotid body was suspected.


A two-day-old term baby girl of Arab origin was the first child for young non-consanguineous parents. The pregnancy was uneventful without any history of maternal illness, fever or rash. The baby was delivered by normal spontaneous vaginal delivery outside our hospital. The family pedigree is negative for congenital malformation.
The baby was referred to the neonatal intensive care unit of the Suez Canal University Hospital, Egypt, when she was two days old due to malformed upper extremities, multiple purpuric eruptions and bilateral corneal opacities (Figures A, B).
Physical examination at presentation revealed a baby with stable vital signs who was alert, pink and active, with a length of 49 cm, a weight of 2,800 g, and a head circumference of 34 cm (all on the 50th percentile), bilateral corneal opacities without any facial dysmorphic features, multiple purpuric eruptions mostly on the anterior aspect of the lower limbs and abdomen. She had bilaterally absent radii and radial deviation of both upper limbs with no thumb deformity. There were no deformities in the lower limbs. Abdominal examination revealed no organomegaly, there was no clinical evidence of congenital heart disease and the other systems were normal.
Initial laboratory investigations gave the following results: complete blood count: hemoglobin, 10 g/dL; mean corpuscular volume, 105 fl; mean corpuscular hemoglobin, 34 pg; reticulocytic count, 6%; TLC: 49,000/uL, 60% s. neutrophils, 5% myelocytes, 5% metamyelocyte, 10% normoblasts; platelet count, 20,000/uL; prothrombin time, 12.8 seconds (cont 12); partial thromboplastin time, 28.0 seconds (cont 28). Liver function tests had the following results: bilirubin (total), 6.14 mg/dL; (direct), 0.24 mg/dL; glutamic pyruvic transaminase, 28 U/L; and glutamic oxaloacetic transaminase, 34 U/L. Electrolytes and kidney function were: Na, 136 mmol/L; K, 4.8 mmol/L; serum creatinine, 0.9 mg/dL. TORCH screens were normal with rubella IgG antibodies, 12 Eu (0–20) and Rubella IgM antibodies, 0.20 Eu (0–40). Radiography of the forearm showed bilateral absence of radii (Figure C). Her abdominal and cranial ultrasonography were normal. Based on these physical findings, thrombocytopenia, and X-ray results, the diagnosis of TAR syndrome was made. At this time she received two platelet transfusions and had a post transfusion platelet count of 55,000/uL. Bone marrow aspiration performed when she was seven days old revealed previously undetected megakaryocytes in the examined smears. It also showed that the myeloid cell line was mildly hyperactive with preservation of normal sequential maturation, the myeloid/erythroid ratio was slightly decreased, the erythroid cell line had mild hyperplasia with dysplastic changes and an increase in the early stages. Ophthalmology consultation revealed irregular red reflex with bilateral nuclear congenital cataract, both eyes were equal and normal in size.
She is now on prophylactic platelet transfusion twice weekly and is scheduled for cataract surgery by the age of six weeks to prevent irreversible amblyopia and sensory nystagmus, starting with the right eye as it is denser. The parents refused to do genetic studies for their baby.


A 72-year-old woman presented with a 1 year history of progressive rigidity, bradykinesia and ideomotor limb apraxia (IMA) of her right arm at the time of initial volumetric MRI. Neuropsychological evaluation and diagnostic MRI scans were normal. During the 26-months follow-up period (examinations after 16, 20, 23, 26 months) the hypokinetic-rigid syndrome (UPDRS-III 18 → 33), and ideomotor apraxia worsened significantly and additionally affected the left upper extremity. Furthermore, a right-sided cortical sensory loss in terms of a tactile agnosia, speech apraxia, Babinski sign and alien limb syndrome appeared. There were no clinical features of clonus or muscle atrophy. After 26 months of follow-up, she revealed no cognitive impairments besides mild visuoconstruction and attention deficits (MDRS 133/144).


A 69-year-old man complained that over the last 2 years his left upper extremity became clumsy and useless. At initial follow-up examination he revealed a moderate left-dominant hypokinetic-rigid syndrome (UPDRS-III 21) as well as myoclonus and ideomotor apraxia of the left hand. Diagnostic brain MRI scans were normal. Neuropsychological testing detected mild deficits in the subitems attention, initiation-perseveration as well as construction of the MDRS (total score 126/144); memory subscales were normal. During the 25-months follow-up period (examinations after 3, 6, 10, 13, 18, 22, 26 months) the hypokinetic-rigid syndrome dramatically worsened (UPDRS-III 21 → 46) and a left upper alien limb syndrome appeared. Furthermore, ideomotor apraxia became bilateral and a speech apraxia was evident. He developed a vertical supranuclear palsy and postural instability. His abilities on formal psychometric testing deteriorated and MDRS declined to 96, showing worsening of attention, initiation-perseveration and construction as well as onset of memory deficits.


A 76-year-old man progressively developed a stiffness and uselessness of his left arm and leg over the course of 2 two years. At initial examination he presented with a left-dominant moderate hypokinetic-rigid syndrome (UPDRS-III 33). Furthermore, he was affected by a solely left-sided ideomotor apraxia and dystonia. Diagnostic MRI scans demonstrated cortical atrophy pronounced in fronto-parietal regions accompanied by a ventricular widening. The neuropsychological examination was limited since the patient was nearly blind due to a senile macular degeneration. Therefore, only verbal testing was possible and MDRS was reduced to a maximum of 103 and MMSE to a maximum of 25 points. He initially revealed minimal deficits in the domains initiation-perseveration and attention. Memory functions, orientation and conceptualization were normal. During the 24-months follow-up (examinations after 11, 14, 20, 24 months), he developed a severe bilateral but left-dominant akinetic-rigid syndrome (UPDRS-III up to 58) and ideomotor apraxia of all limbs. He became chairbound due to the apractic gait dysfunction. Furthermore, he developed an alien limb syndrome and astereognosia of the left arm as well as a supranuclear palsy. Psychometry revealed worsening of initiation-perseveration and onset of mild memory deficits.


A 68-year-old woman developed a severe akinetic-rigid syndrome (UPDRS-III 44) with dystonic and painful contraction of the left upper and lower extremity over the last 2 years. The left leg became apractic with consecutive gait difficulties. Babinski sign was positive, but there were no clinical findings of weakness, hyperreflexia or fasciculations. Diagnostic MRI scans showed mild to moderate cortical atrophy but detailed neuropsychological testing was normal. After a 14-months follow-up period (examinations after 7, 14 months) she was chairbound due to a gait apraxia. The hypokinetic-rigid syndrome worsened and manifested bilaterally (UPDRS-III 44 → 64). Furthermore, a painful left-dominant dystonia affected all limbs, wherefore initiation of botulinum toxin injection was necessary. Moreover, a speech apraxia and astereognosia developed. She still performed normal on psychometric testing. Two months after the last follow-up examination the patient died of a subacute ileus.


A 62-year-old woman presented with a progressive stiffness, slowness and difficulty using the right arm. At initial examination, she had moderate hypokinetic-rigid syndrome (UPDRS-III 20), ideomotor apraxia, alien limb phenomenon and myoclonus of the right upper limb. Diagnostic MRI scans and detailed neuropsychological testing were normal. During a 16-months follow-up period (examinations after 4, 7, 10, 12, 16 months) the hypokinetic-rigid syndrome rapidly worsened and became bilateral (UPDRS-III up to 45). The ideomotor apraxia as well as the alien limb syndrome further increased and she developed a painful dystonia of the right hand. At final visit, formal psychometry revealed severe constructional apraxia as well as slight initiation-perseveration impairment; memory functions were normal.


A 65-year-old man suffered of a 4 year history of progressive right-dominant upper ideomotor apraxia, dystonia, bradykinesia and rigidity as well as right-sided alien limb syndrome. At the time of first scanning neuropsychological examination revealed reduced verbal fluency due to dysphasia, a moderate dyscalculia and slight deficits of additional cognitive functions. Diagnostic brain MRI demonstrated mild left-sided parietal-frontal atrophy. During the 19-months follow-up significant worsening of right-dominant ideomotor apraxia and hypokinetic-rigid syndrome (UPDRS-III 25 → 32) was evident and a right-sided stereoagnosia developed. Furthermore, pronounced memory impairment and onset of visuoconstructive and attention deficits were obvious.


A radiographic examination of the left wrist was performed in a 17-year-old Colombian man as a result of a direct incidental trauma. No fracture was seen, but an osteolytic area was found in the ulnar meta-epiphysis. The initial diagnosis was ‘juvenile bone cyst’. The patient presented with a painful swelling at the wrist dorsal ulnar side, about 2.5 cm, in the absence of any epidermal dyschromias. The skin was elastic and smooth. Wrist examination showed a range of motion (ROM) of 45 ° of extension, 70 ° of flexion, 15 ° of radial deviation and 10 ° of ulnar deviation; pronation, supination and circumduction were painful. Contralateral wrist ROM was normal. The diagnosis of ‘juvenile bone cyst’ did not seem right and a second radiographic examination was performed. At this time, a multilocular osteolytic area inducing an expansion of the distal ulna was seen. A cortical bone interruption was also visible. Although the patient had been the victim of a trauma, this was a poor prognostic sign. Therefore an Magnetic resonance imaging examination was performed. It showed a hypointense signal in the T1 sequences and a hyperintense signal in the short TI inversion recovery (STIR) sequences, characterized by enhancement after contrast administration, due to the presence of newly formed tissue (Figure ).
After an incisional biopsy, the diagnosis of GCT was finally made, although it was in an atypical site.
The lesion was classified as a grade II with fracture (Figure ), according to the Campanacci Classification and as a stage II according to the Enneking Classification for benign bone tumors (Figure ).
Subsequently, the patient was surgically treated with intralesional curettage, adjuvant therapy with 5% phenol and a synthetic bone graft reconstruction.
A cortical bone rawplug was removed through a skin incision at the dorsomedial side of the deformity. Accessing the cystic cavity revealed a gelatinous ‘chocolate brown’ material, with many areas of darker color.
The cavity was carefully emptied and curetted (Figure ), and then 5% phenol was applied in three cycles (Figure ), with subsequent neutralization by hydrogen peroxide.
Then, using synthetic cancellous bone substitutes, a bone defect fill was performed (Figure ) and the bone rawplug was synthesized using a cannulated screw (Figure , Figure ).
A clinical and radiographic follow-up was performed one, three, six, 12, 24 and 48 months post-operatively to evaluate the bone consolidation. Chest radiographs were performed every six months. Within the first post-operative month, the patient completely recovered the wrist ROM. After 3 years, there have been no signs of recurrence.


A 23-year-old woman was admitted to our hospital due to the development of a non-healing postoperative wound for approximately 4 months. In January 2011, she found a slightly painful subcutaneous mass that measured 1 × 1.5 cm in the left buttock and underwent local excision at a local hospital. On postoperative day 2, she developed bleeding from the wound and received hemostatic interventions. However, the wound remained unhealed and continued to produce purulent exudates, with no obvious improvement after repeated dressing changes. On March 26th, 2011, the patient was referred to another hospital, where she underwent surgical debridement. Postoperatively, the wound deteriorated rapidly and developed a cauliflower-like growth. Meanwhile, she developed pitting edema of the lower extremities. Her general condition worsened.
On April 21st, 2011, she was referred to our hospital. At the time of presentation, her general condition was poor and she had severe pallor. Her body posture was constrained and she could only sleep on the right side. There was obvious pitting edema of the bilateral lower extremities (especially the left side) and the lower abdomen. A T-shaped incision was noted on her left buttock. The cauliflower-like lesion measured 15 × 20 cm and was sufficiently deep to reach the ischial tuberosity, with a large amount of purulent discharge (Figure ). Multiple inguinal lymph nodes were enlarged, hard, painful palpable, and fused together. Laboratory investigations revealed a red blood cell count of 1.39 × 1012/L, hemoglobin was 31 g/L, white blood cell count was 16.54 × 109/L, neutrophil percentage was 83.6%, platelet count was 322 × 109/L, and the albumin level was 14.3 g/L.
A magnetic resonance imaging (MRI) scan was performed, which revealed a large heterogeneous, irregular mass in the buttocks, buttock ulceration, and multiple enlarged pelvic and inguinal lymph nodes that were fused together (Figure ). An initial diagnosis of soft tissue sarcoma with lymph node metastasis was made. Small biopsy specimens were then taken and subjected to pathological examination, which revealed focal necrosis and tumor components. Numerous small round cells, with mostly oval nuclei and scarce cytoplasm, were seen (Figure ). Immunohistochemically, the tumor cells were strongly positive for vimentin and calretinin (Figure A,B), moderately positive for CD99 and epithelial membrane antigen (EMA) (Figure C,D), partially positive for cytokeratin and Ki67 (Figure E,F), but negative for actin, S-100, desmin, and HMB45. Based on these results, a poorly differentiated synovial sarcoma was diagnosed.
As the patient developed severe anemia, hypoproteinemia and severe edema, she was treated with a blood transfusion, fluid infusion, supplementation with albumin and plasma, and regular dressing changes to maintain stable vital signs. However, her condition deteriorated dramatically and she rapidly developed systemic edema. As a result, she developed dyspnea, anorexia and anuria (<100 mL/d). The patient died of respiratory failure within a week after admission.


A 15-year-old Caucasian girl with Crohn’s disease, who was on immunosuppressive therapy with oral 6-mercaptopurine, presented with fevers and sore throat, six months after her diagnosis of inflammatory bowel disease. On examination, she had bilateral tonsillar hypertrophy with basilar exudate. Epstein-Barr virus (EBV) serologies showed the presence of viral capsid antigen immunoglobulin M, immunoglobulin G and positivity for EBV nuclear antigen suggesting reactivation of the infection (Table ). She went on to develop significant jaundice and liver function tests revealed elevated transaminases and direct hyperbilirubinemia (Table ). An ultrasound of her liver did not show any obstructive pathology. The patient was hospitalized because of her persistent fevers along with jaundice, with the admitting diagnosis of EBV-induced cholestatic hepatitis. Serologies for hepatitis A, B and C, cytomegalovirus and human immunodeficiency virus (HIV) were negative. EBV copies continued to rise throughout the course of her illness, from 1,500 to 20,000 copies/mL. She continued to be febrile and developed severe respiratory distress and hypoxemia, requiring transfer to the pediatric Intensive Care Unit.
A bone marrow biopsy and a diagnostic lumbar puncture were performed. Her cerebrospinal fluid showed evidence of pleocytosis. The bone marrow biopsy showed pancytopenia and increased lymphohistiocytic infiltrates with prominent hemophagocytosis (Figure ). The significant inflammatory response with high fevers and pancytopenia was attributed to her being infected with EBV. A decision was made to administer one dose of rituximab and high dose immunoglobulins to control the exaggerated immune response.
There was laboratory evidence of cytopenia, with results notable for falling neutrophil count, severe anemia and thrombocytopenia (Table ). There was moderate elevation of ferritin and triglycerides. Her soluble CD25 (soluble interleukin-2 receptor) level was elevated at 39,322U/mL. (this information was not available at initial presentation). There was complete absence of CD16 and CD56 positive NK cells. NK cytotoxicity, porphyrin and granzyme testing could not be done with the initial presentation due to the absence of NK cells. Fibrinogen and coagulation studies remained within normal limits. Our patient was diagnosed with EBV-driven HLH as she fulfilled five of the eight required criteria for diagnosis, and she was started on chemotherapy with etoposide, dexamethasone and ciclosporin based on HLH 2004 protocol.
Testing was also done to rule out HIV and other immune deficiencies. Genetic testing was carried out to rule out PRF 1, UNC13D, STX11 and STXBP2 mutations as well as signaling lymphocytic activation molecule-associated protein expression (SLAM) on cytotoxic lymphocytes.
Our patient had moderate cervical lymphadenopathy (2cm), which was attributed to her EBV viremia at the time of diagnosis of HLH. There was moderate splenomegaly on a computed tomography scan of her abdomen but no other significant lymphadenopathy was noted, hence the diagnosis of lymphoma was not strongly considered. No further doses of rituximab were administered once HLH therapy was started. Her chemotherapeutic regimen included dexamethasone, etoposide and ciclosporin. Our patient received eight weeks of therapy on this protocol. She responded to therapy and improved clinically.
Due to progressive enlargement of the lymph nodes in her cervical region two months after the initiation of therapy, an excisional biopsy of the cervical mass was performed (Figure ). Pathology results were consistent with EBV-positive diffuse large B-cell lymphoma. EBV viremia at the time of diagnosis of lymphoma was reported at 1,500 copies in the blood (Table ). Immunohistochemistry results were positive for CD20, CD19 and CD79a. A positron emission tomography scan showed extensive involvement of her supraclavicular and cervical lymph nodes as well as some involvement of her liver (Figure ). A bone marrow biopsy showed no evidence of involvement of lymphoma or hemophagocytosis. Treatment for lymphoma was given with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) based on our institutional standard of care for patients sixteen years of age and older. Treatment related complications included prolonged fever and neutropenia. Restaging with positron emission tomography at the end of her R-CHOP therapy showed complete resolution. Our patient is now disease-free after completion of therapy. She has been off immunosuppressives for her Crohn’s disease since her recovery from lymphoma, and has also been in remission for over 24 months now.


A 23-year-old lady presented to our hospital complaining of dysphagia for more than one year. Radiographic and manometric evidence supported the diagnosis of achalasia. After obtaining the institutional review board approval and informed consent, peroral endoscopic myotomy (POEM) was performed by an experienced endoscopist (Dr. Zhou, P.H.) with HybridKnife (T-type, ERBE, Germany).
The patient was under general anaesthesia with intubation. The equipment and settings were presented in detail in supplementary data in supplementary material available online at doi:10.1155/2012/325479. The POEM procedure was carried out as previously described []. Briefly, it consisted of four steps: mucosal incision, submucosal tunnelling, myotomy, and mucosal closure (, Videos 1–4). The main difference between Hybrid POEM and standard POEM was the use of the water-jet system. The water-jet allows for the rapid submucosal infusion of saline solution while tunnelling avoiding repeated changes of equipment. The tip of the knife was used to catch circular muscle bundles first and then to lift them up towards the tunnel for cutting. The length of myotomy was 13 cm (10 cm above the gastroesophageal junction (GEJ) to 3 cm below the GEJ). After careful hemostasis, metallic clips were applied to close the mucosal incision site. The whole procedure took 39 minutes.
The patient was on proton pump inhibitor for the prevention of reflux symptom. She was given full liquid diet on postoperative day 1. Discharged on postoperative day 2, the patient expressed an experience of “a great relief” in sternum area. During follow-up time, there was improvement in dysphagia symptom score and manometric findings ().


A six-year-old female presented for definitive procedure of persistent cloaca (Fig. ). She had colostomy on 5th day of life. Ultrasound of abdomen was reported as normal. Distal colostogram showed high recto-cloacal fistula (Fig. ). Endoscopic evaluation revealed an opening at bladder neck. At operation anal sphincter was identified by nerve stimulation and dissection started by making anterior sagittal incision. The sites for the future vagina and ano-rectum were made. Abdomen was then opened by mobilizing the stoma. Urinary bladder was opened and ureteric catheterization done to avoid their damage during surgery. The anomaly was identified as high confluence of rectum and vagina opening into the cloaca at the level of bladder neck (Fig. ). The opening of vagina was very minute that could not be identified on endoscopy as well as at operation. Distal loop of the colon was mobilized and detached from common cloaca. It was tailored distally, to be used as vaginal substitute and pulled down at the perineum, while its proximal end anastomosed with lower end of the vagina that was about 1/3rd in length. Similarly proximal loop of colon mobilized to bring it down as ano-rectum, through the already identified site for anus. Feminizing clitoroplasty was added. The common channel was left as urethra. Finally perineal body was constructed (Fig. ). Patient had uneventful recovery.
Examination done after 02 weeks of surgery showed healed patent vaginal and anal passages. On 10th week post operative visit, the mother was satisfied the urinary continence. She observed occasional soiling (Kelly’s continence score 3). She was on follow up and on vaginal dilatation program.


A 4-month-old male baby presented to our hospital with the complaint of palpable mass in the right hemi-abdomen noted by the parents one day back. The patient was born at full term with uneventful birth history. The baby achieved milestones normally. Abdominal examination revealed a non-tender mass with vague margins in the right hemi-abdomen. Laboratory investigations including alpha-fetoprotein were within normal limits. X-ray abdomen showed mass impression pushing the gut shadows to one side. Bones and calcifications were also evident in the right hemi-abdomen. Ultrasound of the abdomen revealed a heterogeneous mass with calcifications suggestive of teratoma. Abdominal CT scan showed a 9.2cm × 10.0cm heterogeneous mass containing fat, bones and soft tissues. The various bones were vertebrae, long bones like femur, tibia and fibula, and bones of hand/feet (Fig.1). Provisional diagnosis of FIF was made.
At operation, a mass covered in whitish-gray membrane, pushing the gut loops to the opposite side in the upper retroperitoneum, was found (Fig.2). The membrane was incised to find a fetiform mass floating in clear fluid having a few well differentiated and other rudimentary organs. The fetiform mass was suspended in the amnion like cavity with an umbilical cord like stalk (Fig.3). The mass with sac was mobilized and excised completely.
Post operative recovery was uneventful. Patient was allowed orally on 3rd and discharged on 7th post operative day. The patient is currently being followed with alpha-fetoprotein and ultrasound abdomen. At six months follow up patient is doing well.
The FIF was of 13.75cm×12.5cm×6.25cm size with a weight of 500 grams. It was anencephalic having otic and nasal placodes and optic vesicles. The left upper limb was meromelic; lower limbs were sirenomelic. The umbilical cord had two vessels in it. The FIF had a scrotum like skin at the site of genitalia that lacked gonad in it. The FIF also lacked anus and genitalia (Fig.4). Plain radiography of the specimen revealed axial skeleton in the form of vertebrae, along with ribs, long bones of upper and lower limbs, and facial bones (Fig.5).


A 50-year-old female presented to the ER of an inner city teaching hospital after experiencing a generalized seizure episode. She had a medical history significant for immune thrombocytopenia for 30 years and seizure disorder since experiencing a right occipitoparietal stroke at the age of 47 years, for which she took lacosamide and aspirin. She reported being allergic to sulpha drugs. She had smoked 1/2 packs per day for 30 years but quit 3 years before. She reported feeling out of breath after walking less than a block and a persistent cough without much expectoration for the past 8 to 10 months. Upon hospitalization, she received supplemental oxygen in addition to her home medications. A chest radiogram done on admission () showed bilateral patchy infiltrates; pulse oximetry done the day after showed oxygen saturation of around 94% on room air dropping to 90% after a 6-minute walk. A repeat chest radiogram done on the third hospital day () revealed significant clearance of the infiltrates with much improvement in her oxygen saturation values both at rest and with ambulation. Cardiac markers and 2D echocardiogram were normal. The patient did not experience any more seizures during hospitalization and was discharged on the fourth day to be followed up in the office. The diagnosis of NPE was made based on rapid resolution of the symptoms.


A 75-year-old gentleman of Indian origin presented to a regional Ear, Nose, and Throat Department as a tertiary referral. The history of a painful lump over the left side of his upper neck was for approximately one year. The patient reported that the lump fluctuated in size and was initially painful but this improved with time. The accuracy of history was limited by the fact that the gentleman had a thick beard and may not have noticed the enlargement during shaving or from the external appearance. The pain was intermittent but worse after talking for long periods. He did not have any difficulty eating, shortness of breath, or alteration of hearing. There was no history of preceding trauma. Otherwise the patient was in good health, with no significant comorbidities.
On examination the lump was located in the level 2 area of the neck extending into the preauricular area. The mass was firm and pulsatile. There was no facial nerve weakness or paralysis.
All routine blood investigations, which included full blood count, renal function, clotting, C-reactive protein, liver function, fasting glucose, and lipids, were within normal limits. An ultrasound scan (US) of his left parotid region demonstrated a large aneurysm measuring 45 mm in maximum diameter, closely related to the left parotid gland. A subsequent computed tomographic (CT) angiogram was performed (Figure ()). This showed a thick walled aneurysm superficial to the mandible arising from the maxillary branch of the external carotid artery (Figure ()). Doppler US of his aorta and popliteal vessels excluded any further concurrent aneurysms.
After discussions in the vascular surgical multidisciplinary meeting and with the patient it was decided to attempt endovascular embolisation.
The external carotid artery was selectively catheterised with a 5 French vertebral catheter. Angiography during the procedure showed a very tortuous maxillary artery and the giant aneurysm arising from its midportion. The outflow branches appear to be arising from the sac itself and therefore we concluded that this was a true aneurysm. A microcatheter (Progreat-Terumo, Japan) was used to superselectively embolise the outflow vessel and the aneurysm inflow with (Vortex Coils-Cook Inc, USA) coils (Figure ()). Immediate angiography showed a successful procedure with no demonstrable flow in the aneurysm (Figure ()). Subsequently Doppler US of the aneurysm was performed which confirmed that there was thrombus and no flow in the aneurysm sac. There were no postprocedure complications and the patient was safely discharged home the following morning. At 6-month follow-up the mass has disappeared on clinical examination. Doppler ultrasound shows a tiny (<5 mm) area of residual flow at the aneurysm neck. No further treatment is planned.


The patient, a 43-year-old nulliparous premenopausal Greek woman, presented to the Department of Obstetrics and Gynecology of the University of Patras Medical School with a complaint of abdominal pain and abnormal uterine bleeding. Her surgical history was unremarkable. She was suffering from SSc the last 21 years. She received methotrexate, D-penicillamine, and corticosteroids after initial diagnosis of SSc. Her family history revealed no evidence of cancer among the first-degree relatives.
On gynecologic examination, there was a palpable pelvic mass. There were no palpable inguinal lymph nodes, and the rest of pelvic examination was normal.
Preoperative computer tomography (CT) of the abdomen and pelvis and abdominal ultrasound (U/S) revealed an intra-abdominal mass 15 × 15 × 12 cm. Preoperative computer tomography (CT) of the chest, chest X-ray, intravenous pyelography (IVP), colonoscopy, and urethrocystoscopy were normal. Preoperative CA-125 was elevated as 426 U/mL.
On exploratory laparotomy, the left ovary was markedly distended, measuring 20 × 15 × 10 cm. Frozen section showed malignancy, and the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, total omentectomy, appendectomy, and pelvic lymph node dissection.
The histopathology revealed synchronous primary cancers of the endometrium and left ovary. The endometrial tumor invades less than one half of myometrium (). The ovarian tumor invades and ruptures the capsule of the left ovary, invades left fallopian tube, and extents to the omentum (). The right ovary was normal. The peritoneal washing smear was negative for malignant cells. Tumor cells in both primary cancers were positive for vimentin, cytokeratin, epithelial membrane antigen, estrogen receptor, progesterone receptor, CA-125, CA19-9, and B72.3 and negative for CEA.
The final diagnosis was stage Ib endometrial cancer endometrioid type and stage IIIc ovarian cancer endometrioid type.
The patient underwent postoperative adjuvant chemotherapy. She received six courses of carboplatinum (AUC 5) and paclitaxel (175 mg/m²).
Follow up 89 months after initial surgery, with CT of the chest, abdomen, and pelvis, abdominal U/S, chest X-ray, IVP, colonoscopy, and urethrocystoscopy, revealed no evidence of recurrence.


A 31-years-old male patient was referred to the Chest Medicine Department with a history of dysphonia and dyspnea. Laryngeal subglottic mass was detected with bronchoscopic evaluation. The patient was consulted to the Department of Otolaryngology. 2 cm sized, ill-defined, porous, and hard mass on posterior surface of cricoid cartilage in subglottic area was detected in microlaryngoscopic evaluation. This mass was covered by regular mucosa. This lesion was scraped from posterior wall of cricoid cartilage with sickle scalpel. Mitomycine was applied to the lesion locally to prevent the development of postoperative scar. Clinically tracheostomy was not required and no complication was seen. He was discharged next day.
Macroscopically total volume of 2 cc, 0.2–0.5 cm sized, fragmented, gray-pink colored, medium-hardness, homogenous materials were seen. Microscopically well-defined, lobulated-contoured mass was seen near of the focally calcified cartilaginous tissue (). The tumor was very hypocellular and homogenous. Tumor cells were monotone and had small oval-round nuclei. Mostly 20 nuclei were counted in one HPF. Mitosis, necrosis, hemorrhage, and binucleation were not detected (). The patient was diagnosed as “Laryngeal chondroma” with these morphologic findings.
This patient was referred to the Department of Otolaryngology with stuck feeling in the throat after 2 years from first operation. 1 × 0.8 cm sized, hard, gray-coloured mass, which is covered by regular mucosa, was detected in same localization (right subglottic area). Second microlaryngoscopy was applied and the lesion was excised in november 2007. This lesion was diagnosed as “laryngeal chondroma” too. In routine follows-up no complaints and lesion were detected (42 months).


In September 2008, a 68-year-old man visited his local doctor with the chief complaint of left-sided chest pain. Hematology tests examination showed a white blood cell (WBC) count of 133.1 × 109/L with 85.5% blasts. The patient was referred to our hospital for further examination and treatment. Laboratory studies revealed a WBC count of 146.5 × 109/L with 70.0% of blasts, hemoglobin of 12.4 g/dL, and platelet count of 50 × 109/L. The serum lysozyme level was elevated. Bone marrow examination revealed 68.0% of blasts, which were positive for myeloperoxidase (MPO) and negative for esterase staining. Surface antigen analysis by flow cytometry (FCM) indicated that 82.5, 66.8, 23.4, 43.7, 85.9, and 90.7% of the blasts were positive for CD19, CD79a, CD13, CD33, CD34, and HLA-DR, respectively, while the blasts were negative for CD2, CD3, CD5, CD7, CD8, CD10, CD20, and MPO (using a cutoff of 20%). Monocytic markers such as CD11c, CD14, CD36, and CD64 were not tested by FCM. Screening for leukemia-associated fusion genes resulted in identification of the MLL-AF4 fusion gene. Cytogenetic analysis of bone marrow cells using the G-banding technique demonstrated 47, XY, +X, t(4;11;7)(q21;q23;q22) in five of the 20 analyzed cells (), and spectral karyotyping confirmed this alteration (). The karyotype of the other 13 analyzed cells was 48, sl, +6 and 2 analyzed cells was 46, XY. Application of the European Group for Immunologic Classification of Leukemia (EGIL) criteria produced a diagnosis of biphenotypic acute leukemia, because the score for both B-lymphoid (CD19 and CD79a) and myeloid lineages (CD13 and CD33) was higher than two points. He received induction chemotherapy (daunomycin 40 mg/m2 on days 1–5 and cytarabine 80 mg/m2 on days 1–7) but failed to achieve remission. Subsequently, the patient was treated with other chemotherapy regimens, including high-dose cytarabine and combination chemotherapy for acute lymphocytic leukemia (ALL). However, complete remission was not achieved, and he died of cerebral infarction in June 2009.


The patient is a 47-year-old right-handed Caucasian woman with a history of left frontal meningioma and intractable headaches for more than 15 years. The headaches are described as dull holocephalic headaches with no light or sound sensitivity. Treatment of the left frontal meningioma by surgical resection and gamma-knife radiation for recurrence did not provide sustained relief of the patient's headache. Likewise, treatment for possible hydrocephalus with placement of ventriculoperitoneal shunt with multiple revisions did not provide any relief, and the shunt was removed by age 42. Since the age of 46, the patient was reported to have progressive cognitive decline and frequent falls. She was admitted to a local hospital and diagnosed with myasthenia gravis (MG). She was started on pyridostigmine, and after a brief rehabilitation, she was discharged home. On followup with a neurologist, the diagnosis of MG was challenged and excluded based on the clinical picture, serological testing (negative antiacetyl choline receptor antibody), and neurophysiological testing (negative repetitive nerve stimulation). Hence, pyridostigmine was discontinued, and the patient was started on valproic acid for headache control. Three months prior to admission to our tertiary center, the patient continued to experience a rapidly progressive cognitive decline. By the time the patient presented to our institution, she was bedridden and almost nonverbal.
On admission, the patient was noted to be tachycardic but afebrile. She was awake but unable to answer questions or follow any commands. Her spontaneous speech consisted only of repeated short phrases. She was noted to move her left side spontaneously but not the right side. Plantar reflexes were flexor on the left and extensor on the right (Babinski sign on the right). Laboratory investigations were remarkable for positive antiribonuclear protein (RNP) antibody at high titer in the serum and high protein levels (378 mg/dL) with normal cell count in the cerebrospinal fluid (CSF). Extensive infectious disease workup including viral, bacterial, and fungal studies were reproducibly negative. Magnetic resonance (MRI) of the brain, arteriography (MRA), and venography (MRV) were performed. The most striking finding was “beading appearance” of small- and medium-sized intracranial vessels bilaterally with multiple regions of white matter hyperintensities (Figures and ).
The patient was started on a course of high dose intravenous methylprednisolone (IVMP) (1 gram IV daily for 5 days). Her neurologic status showed modest improvement. She was able to follow one-step commands and respond to direct questions with simple sentences though her spontaneous speech continued to consist only of repeated phrases and moaning. Repeated MRA showed progression of the disease with severe attenuation of intracranial blood vessels. Repeated lumbar puncture showed an opening pressure of 13 cm H2O with high protein (103 mg/dL) with normal glucose and cell count.
A leptomeningeal biopsy was done and showed mild chronic perivascular inflammation and fibrosis with reactive astrocytosis. The anti-RNP antibody test was repeated and showed persistently high titers. The patient's husband declined to more aggressive immunosuppression like cyclophosphamide. The patient was discharged to a nursing home and died within six months of discharge.


An 18-month-old boy was admitted for evaluation of resistant rickets. The boy had been treated in a local hospital with 2 mega doses of vitamin D without any clinical or radiological improvement. Detailed history taking revealed that he had failure to thrive, abdominal distension, and motor developmental delay. The baby was the first issue of nonconsanguineous Hindu parents and had been born through normal vaginal delivery at term (37 weeks) with birth weight of 2.5 kg; without any significant antenatal and postnatal history. According to the parents, exclusively breastfeeding was continued for only 2 months followed by top feeding. Family diet was started from 12 months of age. Social smile had developed at 3 months, head holding at 6 months, and sitting with support at 11 months. He could not sit without support till the age of 18 months.
Clinical examination detected; weight 8 kg, head circumference 42 cm, and length 72 cm (all were below and 3rd percentile). Anterior fontanel was wide open, widening of wrist and ankle joints with genu valgum was noticed. Abdominal examination detected hepatomegaly (10 cm) which was firm, smooth, and nontender; without any other organomegaly or ascites (). Nervous system examination showed generalized hypotonia. The developmental age of the child was approximately seven months. Other systems revealed no abnormality.
Investigations revealed normal serum calcium (9.4 mg/dL), phosphorus was reduced to 2 mg/dL (normal 2.7–4.5 mg/dL), and markedly elevated serum alkaline phosphatase 1184 IU/L (normal 145–420 U/L) and normal potassium (4.1 meq/L). Fasting blood sugar was 80 mg/dl and two hours after eating, blood sugar was 96 mg/dL (normal 60–100). Thyroid profile was within normal limits. 25(OH) D level was 42 nmol/L (25–120 NMol/L) and 1, 25(OH)2D was within normal limit, it was 67 pmol/L (48–144 pmol/L). Parathormone level was mildly elevated; it was 6.2 pmol/L (normal 1.1–5.5 pmol/L). Fasting insulin level was 15 mcU/mL (normal values are 5–20 mcU/mL). Liver function tests were within normal limits. Serum cholesterol was 217 mg/dL (normal 45–182 mg/dL) and triglycerides were 268 mg/dL (normal 32–99 mg/dL) with normal serum HDL cholesterol and LDL cholesterol levels. Blood urea and serum creatinine, uric acid and lactate levels were within normal limits. Urine biochemistry showed pH of 6.2 (normal 4.5–8), specific gravity 1.026, glucosuria 2+, albumin 2+. Arterial blood gas detected; pH 7.22, HCO3- 15, BE −6.7. Wrist X-ray showed features of active rickets (). Ultrasonography of abdomen revealed hepatomegaly with normal echotexture; other organs were within normal limits. Liver biopsy was done which detected large pale staining hepatocytes with centrally placed nuclei giving appearance of plant cells and mosaic pattern with fibrous septa extending from portal tracts which not pathognomonic but suggestive of GSD ().
FBS was diagnosed and treatment started with supplementation of oral vitamin D2 (2000 IU/kg/24 hours as a single daily dose) and phosphate (0.6 g/24 hr) as Joulie's solution (4 mL given every 4 hourly, 5 times daily) for the hypophosphatemic rickets. Oral bicarbonate supplementation was also given as sodamint tablets (3 tablets three times a day) to correct the metabolic acidosis [, ]. Regarding diet, he was put on frequent and small meals with adequate caloric intake [, ].
Follow-up visit on 4 months; detected significant weight (3 kg) and gain in length (4 cm). Now he can stand with support. Repeated X-ray wrist showed significant recovery from rickets (). However, it was not possible to assess histopathological improvement because parents did not give consent for repeat biopsy. Liver size did not change much on followup.


A 50-year-old black woman was admitted to the hospital with dyspnea and left hemibody swelling (breast, thorax and upper and lower limbs). These symptoms had started eight days before the admission and had gradually become more severe.
The patient had a severe form of a rare, heterogeneous, congenital cyanotic heart disease with pulmonary artery atresia, ventricular septal defect, and multifocal circulation with multiple aortopulmonary collaterals (type C) [] with resulting heart failure (NYHA class III) and chronic respiratory failure with oxygen home therapy (3 L/min).
Recent transthoracic echocardiogram revealed large ventricular septal defect, ascendant aortic aneurismatic dilatation, biventricular hypertrophy, pericardial effusion, and pulmonary atresia, with left ventricular ejection fraction of 32%.
Furthermore, she was HIV-positive and had been on highly active antiretroviral therapy (HAART) for 5 years; recent examinations showed undetectable HIV viral load (HIV-VL) and CD4 cells count of 169 for cubic millimeter of blood.
There was no history of drug allergies, nor of previous central venous cannulation.
Daily medications included furosemide 40 mg, digoxin 125 mcg, acetylsalicylic acid 100 mg, lorazepam 1 mg, HAART (tenofovir 245 mg, emtricitabine 200 mg, nevirapine 200 mg).
On physical examination the patient showed central cyanosis, jugular venous distention at 45 degrees, superficial venous circulation on the anterior chest wall, left hemibody swelling (particularly of the upper limb), and digital clubbing (Figures and ).
Her body temperature was 37°C, pulse rate was 92 bpm, respiratory rate was 24/min, and blood pressure was 118/56 mmHg.
There was no superficial lymphadenopathy. Lung examination showed decreased breath sounds over the left posterior lower chest and bibasilar rales. There was a grade III/IV loud systolic murmur heard all over the precordium and moderate hepatomegaly on abdominal examination. Blood examination showed leukocyte count 6800 × 103/mcL [4500–11000], hemoglobin 13.7 g/dL [11.5–15.5], platelet count 241 × 103/mcL [150–450], urea 44 mg/dL [17–43], creatinine 0.62 mg/dL [0.51–0.95], aspartate aminotransferase 28 U/L [<35], alanine aminotransferase 19 U/L [<35], gamma-glutamyltransferase 104 U/L [<38], alkaline phosphatase 116 U/L [30–120], lactate dehydrogenase 466 U/L [<247], BNP 1278 pg/mL [<100]. The hypercoagulability study was negative for deficiencies including protein S, protein C, and antithrombin III. Serum homocysteine was normal. Neither factor V Leiden mutation nor prothrombin gene mutation was detected. Anticardiolipin antibodies and lupus anticoagulant were negative too.
The electrocardiogram showed normal sinus rhythm with right bundle branch block.
The chest radiograph showed marked cardiomegaly and aortic aneurismatic dilatation ().
High-resolution computer tomography (CT) of the chest showed global cardiomegaly with pericardial effusion, thrombosis of the left axillary, subclavian and brachiocephalic veins, left chest and left upper limb edema, ascendant aortic aneurismatic dilatation (4.8 cm), descendant aortic ectasia, pulmonary atresia, small caliber of the right pulmonary artery and mural thrombosis of the left lower aortopulmonary collateral.
Color Doppler Ultrasonography highlighted no compression and no variability in flow velocity of left axillary-subclavian veins and normal morphology and compressibility of lower limbs circulation.
CT of the abdomen and pelvis confirmed hepatomegaly and detected normal permeability of the caval and iliac-femoral venous sector.
The diagnosis was left axillary, subclavian and brachiocephalic veins thrombosis, left lower aortopulmonary collateral arterial thrombosis and left lower limb lymphedema.
Due to patient comorbidities and thrombosis extension, we decided not to carry out thrombolysis, angioplasty or stent placement. A treatment with low molecular weight heparin (LMWH) in full dose was started, followed by warfarin, in order to maintain INR between 2.0 and 3.0. The patient also underwent lymphatic drainage with resolution of the edema of the left hemibody after 8 weeks of treatment.


A 17-week pregnant 42-year-old woman, with a history of Hashimoto's thyroiditis, treated with levothyroxine 150 μg/day, and homozygous mutation of methylenetetrahydrofolate reductase (MTHFR), treated with Aspirin 50 mg twice a day, folic acid, and vitamins, was referred to our hospital because of onset of severe early-onset preeclampsia, characterized by high blood pressure (180/108 mmHg), proteinuria, and headache. Nifedipine 1 g three times a day was started.
Her past obstetric history was characterized by vaginal delivery of a healthy baby and three miscarriages before the 12th week of gestational age (GA).
Due to the presence of high TSH (14.9 mU/L) and low levels of free triiodothyronine and thyroxine (resp., 1.6 pg/mL and 0.65 ng/dL), levothyroxine intake was increased from 150 μg to 175 μg per day. The ultrasound examination revealed high uterine arteries' Doppler waveforms resistance (average RI: 0.70).
A 24-hour urine collection revealed a protein amount of 1.575 g which increased to 6.8 g within a week. Renal and adrenal ultrasonography resulted negative. Screening tests for glomerular-based diseases were all negative. Complete screening for other autoimmune diseases resulted negative. Due to the persistent high blood pressure, alpha-metildopa was added to therapy.
TSH and proteinuria reached, respectively, 34.5 mU/L and 9.8 g/24 h, and the levels of free triiodothyronine and free thyroxine continued to decrease (1.4 pg/mL and 0.50 ng/dL). Atenolol 0.5 g/day was added to therapy. An ultrasound Doppler examination performed at 19 + 3 weeks of GA showed increased resistance in the uterine arteries (average RI: 0.77) and bilateral notches; the umbilical artery Doppler waveform presented absent diastolic flow.
Abdominal ascites and pleural bilateral effusion appeared at 20 + 4 weeks of GA, so albumin and diuretics were administered.
Persistent high blood pressure required the introduction of labetalol 25 mg three times per day; high TSH values lead to an increase in levothyroxine administration (275 μg/day) and proteinuria reached a peak of 13.11 g/24 h. To reduce the fast-growing TSH levels, liothyronine sodium was added to therapy (20 μg twice a day). Furthermore, the woman started to manifest oliguria, treated with fluid infusion and plasma transfusion. Nitrates were added to therapy. In the following days, proteinuria started to decrease, reaching lower levels (3.1 g/24 h).
At 23 + 6 weeks of GA, the ultrasound evaluation showed rapid deterioration of the fetal condition, compatible with fetal acidosis, which resulted in death of the fetus few hours later. Immediately after miscarriage, hydralazine (8 and 6 mL) and magnesium sulphate IV were administered. In the evening, hydralazine administration was suspended and hypertension was controlled with nifedipine (1 g twice a day).
After 3 days, therapy was adjusted with 300 μg/day levothyroxine and labetalol, liothyronine was stopped. Finally, hypertension and hypothyroidism seemed to be well controlled, and the patient was discharged nine days after miscarriage.


A 25-year-old Caucasian woman presented to our emergency department with a three-day history of abdominal pain, distension and absolute constipation with vomiting. There was no significant medical or surgical history. She took no regular medications, and was a non-smoker and non-drinker. Bedside observations were normal. A physical examination revealed a distended tympanic abdomen with tenderness across the lower abdomen but no signs of peritonism. A urine dipstick test was unremarkable and blood tests showed a raised white blood cell count (14.4 ×109 cells/L) and C-reactive protein (35mg/L). Urea and electrolytes, hemoglobin and liver function tests were all normal.
Radiographs of the abdomen (Figure ) and chest (Figure ) showed gross dilatation of the right side of the colon with Chilaiditi’s sign. A computed tomography (CT) scan of the abdomen showed massive dilatation of the caecum, which measured greater than 14 cm in diameter (Figures , , and ). The distal colon was collapsed with a transition point in the mid abdomen suggestive of a volvulus or band.
A nasogastric tube was inserted, intravenous fluid resuscitation commenced and our patient underwent an emergency exploratory laparotomy. Intra-operatively, the bowel was found to be significantly dilated from the caecum to the distal transverse colon and the distal small bowel was mildly dilated, giving the impression of decompression through an incompetent ileocaecal valve. There was a volvulus of the transverse colon in the right upper quadrant. The transverse mesocolon appeared to take origin from the right upper quadrant as opposed to the usual location as an extension of the peritoneum from the posterior abdominal wall centrally. There was no evidence of colonic ischemia or serosal injury.
The large bowel was decompressed with a 14 gauge needle allowing the tightly held bowel to be manipulated more easily. The large bowel was fully unraveled and the volvulus corrected then decompressed distally into the descending colon. The greater omentum on the transverse colon was then fixed at both the hepatic and splenic flexures by creating pouches in the lateral anterior abdominal walls, and fixing the omentum within this with polydioxanone sutures (PDS). The central portion of the omentum was purposefully caught in the mass closure of the wound to ensure additional central fixation.
Post-operatively our patient made a good recovery. By day five she was tolerating a full diet and was discharged six days post-operatively. Despite a superficial wound infection at two weeks, she made a full recovery with no complications noted at her three month and six month follow-up.


A 58-year-old female patient presented to the surgical oncology department with a 6-month history of abdominal discomfort, constipation and pain in her back irradiating to the right femoral and inguinal area. An increased frequency of micturition initiated at the same time period, was also reported. The laboratory examinations were within normal limits indicating only a minor sideropenic anaemia and hyperlipidemia. The physical examination of the abdomen was negative but the digital vaginal examination showed the presence of a palpable mass in the right pelvic wall. A subsequent US examination, performed elsewhere (not available), verified the presence of the lesion and characterized it as highly suspicious for malignancy.
A following multidetector computed tomography (MDCT) examination demonstrated that the lesion was located in the right ischiorectal fossa, invaded the obturator muscles and the right ischiopubic ramus and extended in the femoral anatomical compartment displacing anteriorly the right pectineus muscle (). The tumour was isodense to skeletal muscles in the non contrast series and showed intense enhancement in the arterial and delayed phase.
The patient was referred for additional MR imaging evaluation. MR imaging showed the tumour to exhibit low signal intensity on T1-w and high but heterogeneous signal intensity on T2-w images (). Intense and heterogenous enhancement was shown following the gadolinium injection (). The application of DWI showed areas of increased signal intensity that were indicative of a high cellular tumour ().
The patient underwent a CT-guided biopsy targeted in the intratumoural areas that corresponded to areas of the maximum diffusion restriction and the diagnosis of hemangiopericytoma was established (). Findings, consistent with malignant biological behaviour, such as necrosis, cellular atypia and high mitosis count, were absent. MDCT examinations of the chest and abdomen were negative for metastatic disease.
Due to the local extent and infiltration the tumour was considered unresectable. The radical excision of the tumour should have led to hemipelvectomy, which was not justified in absence of apparent malignant features. In a multi-disciplinary meeting the initial treatment with radiotherapy was suggested. Radiotherapy consisted of 50.4 Gy (28 × 1.8 Gy, 3 fields) external beam radiation with weekly intravenous administration of 20 mg Caeylix and 20 mg Cisplatin as radiation sensitizers. Unfortunately, radiotherapy was applied as a palliative radiation and not as the primary treatment, because the patient did not give her full consent in fear of the possible radiation injuries and complications. Four weeks after finishing radiotherapy the patient revisited the surgical department, with new imaging studies. The MDCT examination of the chest and abdomen was again negative for metastatic disease, while the MR imaging showed a small reduction in tumour size. Gradually, there was a complete relief of symptoms. The radiotherapist considered that there was no indication to persuade the patient to complete radiotherapy to the full therapeutic dose especially after such a long period without the treatment and preferred the remaining dose to be administered in case of the tumour growth.
Six months following treatment the patient was scheduled for a follow-up MR imaging, which verified a decrease in the lesion’s enhancement characteristics post gadolinium. Intratumoural areas that did not enhance were considered to be a positive response to therapy (). Furthermore, DWI showed a slight increase in the intralesional signal intensity of the femoral component of the mass with a concomitant signal increase in the apparent diffusion coefficient (ADC) map. This finding was considered an indication of the reduction in the restriction of water molecules and correlated with the nonenhancing areas (). In other words, the mass seemed to begin to become less cellular and liquefied as a result of the radiation therapy.
The effectiveness of the therapy was further assessed and established on a follow-up MR imaging study twelve months post radiotherapy. Despite no change in the outer shape and contour of the tumour, more than 60% of its volume showed no evidence of the enhancement and at the same time DWI showed further indications of the unimpaired diffusion as a result of possible tumour necrosis and liquefaction (). One year after radiotherapy the MDCT examination of chest and abdomen remained also negative for eventual metastatic disease and the patient was free of symptoms.