We present a 30-year-old male diagnosed with both tuberous sclerosis (TE) and autosomal dominant polycystic kidney disease. Clinical manifestations began a few months after his birth. He was also suffering from mental retardation, cardiac rhabdomyoma, and various other tumours (angiomyolipomas, hamartoma, cysts, and angiofibroma) including the liver, spleen, and kidneys (). He had ungual and cutaneous fibromas and was further afflicted by complex partial seizures controlled with phenobarbital and carbamazepine.
He suffered from end-stage renal disease, and this had been treated with peritoneal dialysis from the age of 24. Two years later he received a renal cadaveric graft from a donor of the same age with two common HLA identities and reached a serum creatinine of 132.6 μmol/L.
Immunosuppression was initiated with baxilisimab, steroids, tacrolimus, and mycophenolate mofetil (this last drug was withdrawn 7 days after treatment began due to persistent diarrhoea). After one month he suffered from an acute graft rejection grade IIa. After being treated with 6-metilprednisolona (6 bolus of 250 mg each), serum creatinine remained around 265.2 μmol/L. Increments of anticalcineurinic drugs, up to 22 mg per day (plasma levels between 6 and 8 ng/mL), were necessary, presumably due to enzymatic induction caused by antiepileptic drugs. Nephrotoxicity, secondary to high doses of anticalcineurinic drugs, was suspected as the cause of renal failure. A switch from anticalcineurinics to rapamycin was made 70 days after the kidney transplantation, starting with 3 mg per day. This was gradually increased and maintained at a level of 6 mg per day (plasma levels 4 to 6 ng/mL). Serum creatinine levels rapidly decreased to the present levels of 114,92 μmol/L. The patient currently remains with a proteinuria of 0.6 g per day and a slight dyslipidaemia.
Since the change to rapamycin, the signs of TE in our patient have diminished remarkably, including a significant reduction in both cutaneous lesions and seizures. This allowed for a gradual reduction of antiepileptic drugs until their complete withdrawal. Furthermore, it also led to the disappearance of cardiac rhabdomyoma and other tumours ().


A 59-year-old male presented to a tertiary care center in Edmonton, AB, Canada, with monocular left-sided vision loss and left retrobulbar pain. An hour and a half prior, he had been struck by a piece of heavy equipment at work resulting in a blunt traumatic injury to his left eye. No other symptoms suggestive of head injury were described. Orbital examination revealed left proptosis and swelling. The left pupil was fixed and dilated, measuring 5 mm in diameter. The patient was unable to visualize light with the affected eye, which was also nonreactive. Normal bilateral extraocular muscle movements were maintained.
Unenhanced CT orbits revealed moderate edema and fat stranding surrounding the left optic nerve complex. The distal optic nerve adjacent to the globe measured 7 mm and demonstrated an irregular contour. Additionally, a small preseptal hematoma tracked along the lateral aspect of the globe measuring 4 mm in thickness and extending approximately 1 cm posteriorly along the lateral orbital wall. The left globe was intact. The right optic nerve was normal in caliber, measuring 4 mm in diameter. No other injuries were seen ().
Within the clinical context, partial transections of the optic nerve complex or a nerve sheath hematoma were the likely diagnoses. Given the possible diagnosis of a nerve sheath hematoma, the patient was emergently taken to the operating room for nerve sheath fenestration in order to relieve the pressure on the optic nerve. The surgery began approximately 2 hours following presentation to the emergency department and confirmed the presence of a nerve sheath hematoma, which was successfully evacuated.


A 17-year-old girl of Mongoloid ethnicity presented to our hospital with a history of diarrhea and edema in her eyelids and lower limbs for three weeks, which were secondary to a transient fever lasting one week. About one month prior to this admission, the patient complained of a fever (the highest temperature being 39°C) accompanied by sore throat, cough, and runny nose, but no fear of cold or shivering. These symptoms lasted for about one week and disappeared. Then the diarrhea and edema in her eyelids and lower limbs began. The frequency of stools was about two to three times a day. The stools were like yellow water with a little foam, and contained undigested foods. The patient also complained of poor appetite, occasional abdominal distention and abdominal pain. Her food intake was reduced to between one-third and half of her usual amount. She usually had gruel and did not like meat. She lost two kg in this one month. She denied hair loss, rash, skin erythema, oral ulcers, photosensitivity, joints pain, foamy urine, palpitations, night sweats, headache, chest pain, paroxysmal nocturnal dyspnea, insomnia, irritability, and tremor. There was nothing of significance in her medical history or drug therapy.
Her physical examination demonstrated malnutrition and edema in her eyelids and lower limbs. A few lymph nodes of 0.5×0.5cm in size were found in her submandibular area, in her axillas and inguina on both sides, with clear borders and no tenderness. Her body mass index was 15kg/m2. Her heart rate was 120 beats per minute and other systematic examinations revealed no positive signs.
She was admitted to the Rheumatology department of our hospital at first. Investigations showed decreased white blood cells (2.71×109/L; neutrophils 1.64×109/L, lymphocytes 0.34×109/L), anemia (hemoglobin 100g/L), hypoalbuminemia (serum albumin 20.5g/L), hypoimmunoglobulinemia (globulin 12g/L), hypolipoproteinemia (cholesterol 2.8mmol/L; triglyceride 0.28mmol/L), and hypocalcemia (1.52mmol/L). During her hospital stay, the patient had numbness and convulsions in both hands several times and these symptoms were relieved by calcium and vitamin D therapy. The results of a Coombs’ test and anticardiolipin antibodies were both negative. Results of tests related to Sjögren’s syndrome, systemic lupus erythematosus, rheumatoid arthritis, and vasculitis were almost normal. The results of the investigation indicated that rheumatologic disease could be ruled out.
Further investigations showed mildly increased free triiodothyronine, anti-thyroid-stimulating hormone receptor antibody, parathyroid hormone, phosphorus, and decreased thyroid-stimulating hormone in serum. Emission computed tomography showed a diffuse goiter, and an increased thyroid technetium uptake function. Ultrasound showed ascites of 32.6mm in depth. The patient was transferred to the Department of endocrinology.
The patient had paroxysmal paralysis in her palms many times. The attacks were always accompanied by the hyperextension of her fingers. Each attack lasted a few minutes. The symptoms could be relieved by the intravenous injection of calcium gluconate. The serium calcium levels fluctuated in the range of 1.33 to 1.52mmol/L. After the patient was given calcium and vitamin D supplementation, the symptoms stopped. Her 24-hour urinary protein excretion and lymphangiography were both normal. The Epstein–Barr virus and hepatitis virus were not detected in her serum. An electronic gastroscope revealed superficial antral gastritis. Capsule endoscopy showed that villi edema were present in the small intestinal (descending part of the duodenum and upper jejunum part of duodenum) mucosa. So at last she was transferred to the Department of gastroenterology.
A double-balloon enteroscopy revealed lymphangiectasia-like changes in the small intestinal mucosa (descending part of the duodenum and upper jejunum part of duodenum; Figure A, B). The pathologic analysis of small intestinal tissue showed chronic inflammation, edema in the submucosa, and lymphangiectasia (Figure C).
Based on these findings, a therapy composed of albumin and calcium supplementation and parenteral nutrition support was given to the patient. The patient undertook recipes that strictly conformed to the low-fat and MCT diet. The daily intake of cooking oil on MCTs was 25 g and the total fat intake must not exceed 40g/day.
After 10 weeks of dietary treatment, the patient’s clinical manifestations and nutritional status were improved. The patient no longer felt any discomfort in her daily life and work. Results of the laboratory examination conducted after the 10-week diet therapy are shown in Table . A repeat double-balloon enteroscopy showed that the lymphangiectasia-like change in the small intestines had vanished. The double-balloon enteroscopy results are shown in Figure D and E, and the pathology is shown in Figure F.


We report on an obese 21 years old male with a Body Mass Index (BMI) of 38,2, who presented to our department with Calciphylaxis after phenprocoumon intake in consequence of pulmonary embolism. The target partial thrombin time (pTT) was between 50-60s. In addition the patient lost overtime 100 kg body mass after getting a gastric banding in 2007. Comorbidities were a dilative cardiomyopathy, insulin dependant diabetes, obesity, allergic asthma, hypothyreoidism and lack of anithrombine factor III (AT3).
Calciphylaxis was already diagnosed histologically in the former hospital, where he was treated with Natriumthiosulphate intravenously for about 9 weeks. Initial symptoms were tender and painful lesions with defined edges in the upper and lower thighs and the abdomen, where some showed signs of necrosis. Further histological examinations showed typical signs of microthrombosis and calcification of the arterioles subcutaneously and substantiated the diagnosis of calciphylaxis.
The patient needed high doses of opiates over the whole duration of inpatient treatment. Unfortunately the initial calcifications became necrotic and possible surgical options were evaluated.
A combination of Natriumthiosulphate was administered intravenously, which is a common therapy for calciphylaxis and a specific surgical approach to this complex disease was initiated when the patient arrived at our department. The patient had necrosis on the abdomen and both thighs as well as partially superinfected wounds with oxacillin resistant staphylococcus aureus (Figure
). A bone scintigraphy revealed no increased activity of calcium carbonate in thighs or the abdominal area.
After the patient consented to a surgical treatment we started our surgical approach with extensive debridement of the affected areas on the abdominal wall and both thighs (Figure
). A consecutive VAC therapy for the lesions on the thighs was mandatory to establish a clean environment. At this level, attempt to close the wounds on the abdomen via advancement flaps were unsuccessful.
A main problem to deal with was not only a permanent level of extensive pain which was encountered through our pain specialists in concordance with the WHO – pain schedule with opiates but also the recurrent wound infections with complicated germs, which were treated with different antibiotic patterns. Over time the Calciphylaxis therapy was adjusted and complemented with Pamidronat, a biphosphonate agent to reduce decomposition of osseous structures and Renagel (Sevelamer), a phosphate binder.
Initial skin grafts did not show satisfactory results in the beginning of the surgical treatment; hence another attempt with skin grafts in buried chips technique was preceded 6 months after admission.
From the plastic surgical point of view, the complexity of the wounds demanded a combination of consecutive debridements, jet lavages, repetitive VAC therapies and Buried chip skin grafting (both thighs and abdomen). In addition dressings were changed with an ointment pad and silver coating dressing (Atrauman Ag, Paul Hartmann Ges.m.b.H, Wiener Neudorf – Austria) as well as antiseptic solution (Polyhexanid, Lohmann & Rauscher GmbH & Co. KG, Neuwied – Germany) on a daily basis. The patient could be sufficiently mobilized and had no further signs of infection. Daily sea salt baths and physiotherapy sessions improved the patient’s status until he was able to walk alone on the ward.
Finally, pain medication could be reduced drastically and sedoanalgesia was not further necessary for dressing changes. The laboratory on discharge showed a single slight elevated phosphate of 1.88 (0.84-1.48 mmol/l). Calcium was in normal range (2.10-2.60 mmol/l). Creatinine was 1.5 (0.7-1.2). We could successfully discharge the patient into rehabilitation, where his status was further improved by mobilization, physiotherapy and lymphatic drainage massages.


A 38 years-old moderate hemophiliac A male patient was diagnosed to be co-infected with HIV (Subtype B, CCR5+) and HCV (Subtype 4), both transmitted by a blood transfusion received in 1982 during hip surgery for a fracture. Diagnoses of these infections were respectively ascertained in 1988 and 1998.
Since 1989, he received different lines of anti-retroviral treatment (ART) then HAART (Highly Active Anti-Retroviral Therapy) with poor compliance, voluntary interruption until 2008, and correct compliance since then. A 215S mutation of the HIV virus reverse transcriptase, which induces resistance to the anti-retroviral drug azidothymidine was consequently identified. His HCV infection (Metavir score A0A1-F1F2 determined by biopsy and checked regularly by noninvasive markers of hepatitis inflammation/fibrosis) was never treated. Moreover his hepatic assessment, as observed with L-aspartate aminotransferase (ASAT), L-alanine aminotransferase (ALAT) and γGT gamma-glutamyltransferase markers is not so much disrupted (Figure A).
The patient received prosthesis of the left eye in 1996 after a paintball accident and a hip replacement in 2011 for osteo-necrosis known since 1982. None of these surgeries were accompanied by infectious side effects. Indeed, over these 30 years and despite an extremely low number of T lymphocytes, the patient displayed neither opportunistic infections, nor HIV-related cancer, nor HCV-hepatitis damages. In 1989 his initial CD4+ T-cells count was 196/mm3 and since 1995 remains between 5 and 59/mm3 (Figure B). HIV viral loads have been mostly undetectable (below 40 copies/mL) or very low (matching deliberate HAART interruptions) since 2008 (Figure B).
Over the past two years, the immunophenotypic and functional status [] of his CD3-CD56+ NK-cells were explored by multi-parameter flow cytometry (reagents from Becton Dickinson, MountainView, CA, Figures A-D). Surprisingly, an abnormally high percentage of NK-cells has been steadily observed, representing approximatively 40% of peripheral lymphocytes and characterized by an expansion of the CD56bright subset (~30 to 50% of NK-cells) (Figures A and B). The percentage of CD56bright cells seems to increase when the number of CD4 decreases moreover HIV viral load is below 40 copies/ml when % of CD56bright cells is the more important (Figure B). These cells display high levels of natural cytotoxicity receptors NCR1 (NKp46), NCR3 (NKp30) and NKG2D compared to CD56dim cells, and have a low expression of NCR2 (NKp44) and CD69, with no labeling for CD57 nor CD25 (data not shown). The inhibitory CD94/NKG2A receptor is expressed by all CD56bright cells and a majority of CD56dim NK-cells while there is a low expression of CD158b on CD56dim and CD56bright NK-cells and a faint labeling with CD158a (Figure C).
Surprisingly, the NK degranulation potential (% of CD107a) that correlates with target cytolysis [,], usually exerted by the CD56dim NK subset [], is here mainly performed by CD56bright NK-cells. Strikingly, these cells did not produce IFN-γ following NK activation by K562 (Figure D).
In addition, no Th1/Th2 cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-5, IL-10) have been detected in the patient’s serum (data not shown).


A 58-year-old black woman sought the Stomatology Outpatient Clinic of the São José dos Campos Dental School in March 2008 because of a “blood stain on the roof of her mouth” (sic). The patient used a removable upper denture and had noted the presence of black-brownish spots on the hard palate 3 months ago. The spots had increased in size during this period and presented discrete itching when touched by the tongue.
Clinically, the lesions appeared as spots with imprecise borders, had a brown to dark brown color, and presented a tendency towards nodule formation (Figure ). Radiography was non-contributory. Based on the differential diagnosis of melanoma, a punch biopsy (4 mm in diameter) was performed. The material was fixed in 10% formalin, embedded in paraffin, and stained with hematoxylin-eosin or submitted to immunohistochemical analysis [,]. Histopathological analysis revealed a mucosal fragment lined with hyperorthokeratinized stratified pavement epithelium. The epithelium exhibited mild acanthosis and melanin pigmentation in the basal layer. Several dendritic melanocytes were observed in the spinous layer and melanin pigment was present in the cytoplasmic processes interposed with keratinocytes. In the lamina propria consisting of fibrous connective tissue, melanophages were present in the juxtaepithelial region and a scarce and diffuse mononuclear inflammatory infiltrate was noted. In view of the histopathological findings, a diagnosis of MA was made (Figure ).
Immunohistochemistry using antibodies against protein S-100, melan-A, HMB-45, MCM-2, MCM-5, Ki-67 and geminin was performed for a better understanding of oral MA. Reactivity for protein S-100 was observed in Langerhans cells, melanocytes and some cells of the underlying submucosa. Immunostaining of HMB-45 and melan-A was only detected in melanocytes, with the observation of a larger number of HMB-45-positive cells. Anti-Ki-67, anti-MCM-2 and anti-geminin antibodies only reacted with cells of the basal and suprabasal layers of the epithelium, whereas MCM-5 staining was negative (Figures and ).
The biopsy region healed normally and no new intervention was necessary. The patient has been followed up for 30 months and shows no clinical alterations.
Many terms have been proposed for MA, including melanocytic reactive hyperplasia and mucosal melanotic macule, reactive type [-]. In a literature review, Fornatora et al. (2003) [] analyzed 28 cases of MA and observed a mean patient age of 27.9 years (range: 9 to 54 years). Twenty-five (89.3%) of the 28 patients were black and there was a female preference (female:male ratio of 2.1:1). Although the cheek mucosa was the site most commonly affected (18 of 28 cases), MA occurred at other sites such as lip mucosa, lower lip, palate, gingiva, alveolar mucosa, and oropharynx. The size of the lesions, if reported, ranged from 0.3 to 5 cm in maximum diameter. MA presented as a smooth or slightly raised, hyperpigmented (brown to black) lesion that rapidly reached various centimeters. Traditionally, MA is asymptomatic but pain, a burning sensation and itching have been reported [-]. The present patient reported discrete itching upon touch.
MA is believed to be a reactive lesion that typically affects mucosal surfaces susceptible to trauma and rapidly develops after an episode of acute trauma or at a site of chronic mucosal irritation [-]. The rapid growth, resolution after incomplete removal, and the presence of an inflammatory infiltrate in the underlying connective tissue support the reactive nature of MA. This fact explains the higher incidence of MA in mobile mucosa vulnerable to trauma (e.g., cheek mucosa, lip mucosa, and palate). In the present case, the patient used a removable mucosa-supported upper denture. The diagnostic hypothesis was melanoma considering the clinical characteristics of the case, including rapid progression of the lesion, color, irregular contours, and tendency towards nodule formation. Although Kaposi's Sarcoma is common in hard palate it was not considered in our diagnostic hypothesis. The algorithm proposed by Kauzman et al. (2004) [] to guide the assessment of pigmented lesions of the oral cavity on the basis of history, clinical examination and laboratory investigations includes Kaposi's Sarcoma in the group of diffuse and bilateral pigmentation with predominantly adult onset. Early lesions of Kaposi's Sarcoma appear as flat or slightly elevated brown to purple lesions and the advanced ones may appear as dark red to purple plaques or nodules that may exhibit ulceration, bleeding and necrosis [].
Histologically, MA is characterized by the proliferation of melanocytes in the basal layer and by the presence of strongly pigmented dendritic melanocytes throughout the acanthotic epithelium. The presence of large dendritic melanocytes in the superficial portions of the epithelium is the cause of the histological resemblance with melanoma, particularly acral lentiginous melanoma. In the latter case, atypical pigmented dendritic melanocytes are irregularly distributed in the acanthotic epithelium and atypical non-dendritic melanocytes may proliferate along the basal layer (lentiginous proliferation). This type of melanoma can also exhibit a dense subepithelial lymphocytic infiltrate [,-].
According to Goode et al. (1983) [], the inflammatory infiltrate in MA exhibits eosinophilia associated with increased vascularization and mild chronic inflammation. Cases of MA usually present a slight increase of vascularization and a chronic heterogeneous inflammatory infiltrate in connective tissue. In MA, melanin is generally restricted to melanocytes, whereas adjacent keratinocytes contain no pigment. In the case of other hyperpigmented lesions such as oral melanotic macule and physiological pigmentation, melanin is transferred from dendritic epidermal melanocytes to epidermal keratinocytes that form the epidermal melanin. Once the histological diagnosis of MA is established, no further investigation is required since there are no reports of malignant transformation of MA [].
The present histopathological findings showing no sign of malignancy agree with reports in the literature. Although some investigators emphasize the frequent occurrence of a heterogeneous inflammatory infiltrate in cases of MA [], the present patient presented a scarce and diffuse mononuclear inflammatory infiltrate.
Immunohistochemical analysis was performed in order to better understand the etiology and behavior of MA. For this purpose, specific markers of cellular elements that might be compromised during the genesis of the disease and cell proliferation markers were used. Epithelial cells stained positive for protein S-100, demonstrating the involvement of cells of neuroectoderm origin in the etiology of MA []. Protein S-100 shows a sensitivity of 97 to 100% for the detection of melanoma. However, the specificity of this protein for melanocytic lesions is limited, with this marker also being expressed on neural cells, myoepithelial cells, adipocytes, chondrocytes, Langerhans cells, and in tumors arising from these cells []. Melan-A, a marker that recognizes normal melanocytes as well as antigens present on melanomas, was detected in the present study in some epithelial cells. Likewise, HMB-45, a melanoma marker, also stained epithelial cells but to a lesser extent than melan-A. Staining for Ki-67, MCM-2 and geminin was only detected in cells of the basal and suprabasal layers of the epithelium. Since these proteins are markers of cell proliferation, they might be responsible for the acanthotic phenomenon seen in the epithelium of MA []. In contrast, immunostaining for MCM-5, a marker that seems to exert a function similar to that of MCM-2, was negative.
No neoplastic progression of melanocytic lesions has been observed in the cases reported in the literature. Regression of the lesions within a period of 2 to 6 months after diagnosis has been reported after removal of the local irritating agent or after excisional and/or incisional biopsy []. In contrast, in the present case the lesion had not regressed and continued to be stable after 20 months of follow-up. Spontaneous resolution after elimination of the source of trauma has been reported in the literature. Therefore, investigation of local mechanical sources of irritation and their consequent elimination are recommended as the first-line treatment after diagnosis [].
According to Carlos-Bregni et al. (2007) [], since MA grows rapidly a biopsy is indicated to rule out the hypothesis of melanoma, among others. A biopsy is necessary for the diagnosis of any recent pigmented lesion in the oral mucosa.


A 65-year-old male patient presented to our institution with lower urinary tract symptoms and elevated serum urea and creatinine levels. He was under followup for type II diabetes mellitus for the last 6 years and prostate cancer for the last 3 years. Maximal androgen deprivation therapy (GnRh analogue and nonsteroidal antiandrogen) was initiated 3 years ago, but the patient did not receive the treatment in a regular way. He had had 2 sessions of hemodialysis previously in emergency settings in another center. Blood tests at the time of first inspection were serum urea: 135 mg/dL, creatinine: 6.2 mg/dL, and prostate specific antigen: >153 ng/dL. Evaluation of the urinary tract revealed a maximal urinary flow rate of 6 mL/s, an international prostate symptom score (IPSS) of 29, and grade III dilation of bilateral kidneys and ureters on the sonogram. Invasion of the trigone and left ureteral orifice was observed, and right unit was double-j stented during cystoscopy. Diversion of the left unit with a percutanous nephrostomy was recommended, but was refused by the patient. Transurethral resection of the prostate (TUR-P) was performed after serum creatinine was stabilized at a level of approximately 3 mg/dL 1 month after stenting of the right collecting system. Patient was discharged with a serum creatinine level of 2.9 mg/dL and with conservative recommendations like increased oral hydration and low-protein diet. The patient was meticulously followed after the TUR-P with monthly routine blood biochemistry and PSA measurements and urinary ultrasound. Four months later, the patient applied with a sudden onset tachycardia. Laboratory analysis revealed serum hemoglobin, total calcium, ionized calcium, urea, creatinine, potassium, and glucose levels of 8.7 g/dL, 8.2 mg/dL, 4.7 mg/dL, 87 mg/dL, 3.61 mg/dL, 7.2 mmol/L, and 190 mg/dL, respectively. Coagulation panel and urine analysis were normal. There were wide QT interval and upright T waves in the Electocardiogram (ECG). Nephrologist suggested infusion of Ca and initiation of hemodialysis by these findings. The baseline and predialysis blood pressures of the patients were 147/85 mmHg and 150/90 mmHg, respectively.
A dialysis duration of 2.5 hours was scheduled in order to achieve the target uro-reduction rate of 30%. 1.2 m2 synthetic biocompatible membrane (Fresenius F6 polisulfone low flux fully synthetic biocompatible membrane) was employed. Dialysate bicarbonate value was set to 30 mEq/L. Heparin was not used as this was the first hemodialysis of the patient.
During dialysis, acute bilateral loss of vision developed in the patient and therefore the intervention was terminated. The highest and lowest systolic/diastolic blood pressures recorded during hemodialysis were 90/60 and 80/50 mmHg, respectively.
Ophthalmological inspection revealed that patient's vision was at the hand-motion level, the light reflexes were normal, there was no afferent pupillar defect, bilateral posterior segments, and bilateral intraocular pressures were normal. Findings suggested a central pathology, and the CT scan performed afterwards revealed large hypodense infarct areas in the bilateral occipital and parasagittal posterior region of right parietal lobes (Figures and ). Bilateral carotid artery doppler and echocardiography for differential diagnosis of thromboembolism were normal.
Patient was conscious, cooperating, and well oriented, and all deep tendon reflexes were found to be hyperactive in the neurological evaluation. Also a few days later right hemiparesis appeared in the patient. Therefore patient was accepted in the intensive care unit of the neurology department and received two times of 0,6 cc clexane and three times 10 mg dexametasone a day. Thus our purpose was to protect the ischemic penumbra with anticoagulant and anti-inflammatory effect.
Despite the recovery of hemiparesis, loss of vision continued during followup of the patient. Patient's loss of vision continued and did not recover throughout the followup.


A 45-year-old woman came to endodontic department of Mashhad Dental School complaining of sever toothache especially during mastication. The patient medical history was negative. Clinical examination revealed extended mesial decay on the left maxillary second molar, tenderness to percussion and palpation of peri-radicular zone. Vitality tests were negative. Radiographic image (periapical) revealed radiolucency around palatal apex; moreover, there was the opacity in the furcation area which was detected as the enamel pearl ().
The tooth was diagnosed with symptomatic apical periodontitis with necrotic pulp. After 2% Lidocaine with epinephrine 1:100.000 (Persocaine, DarouPakhsh, Tehran, Iran) was administered the tooth was isolated with rubber dam. As usual, in the initial access cavity, three orifices were found, but the palatal one was mesially deviated. So the access cavity was further prepared into a square shape (). Second palatal canal was found after meticulous exploration of the pulp chamber floor with a fine precurved hand K-file. Palatal canals were hardly negotiated with #10K-file (Dentsply, Maillefer, Ballaigues, Switzerland) and RC-Prep (Meta Biomed Co., Seoul, Korea) due to canal calcification. Working length was determined with apex locators ROOT ZX (Morita, Kyoto, Japan) and confirmed radiographically ().
All canals were instrumented with stainless-steel hand k-files accompanied by Flex Master Introfile (VDW, Munich, Germany) rotary instrument using crown-down technique. Root canals were irrigated by sodium hypochlorite 5.25% and dried completely. Calcium hydroxide-distilled water paste was placed as an intra-canal dressing then access cavity was sealed temporarily with Cavit (Ariadent, Tehran, Iran).
After a week, patient was completely asymptomatic. Before root canal obturation, the working length was radiographically confirmed with gutta-percha (). Root canals were obturated with gutta-percha (Meta Biomed Co. Ltd, Cheongju city, Chungbuk, Korea) and AH26 (Dentsply, DeTrey, Konstanz, Germany) sealer using lateral condensation technique ().
Subsequently, patient was referred to restorative department for their final restoration. After six months, patient had no clinical symptoms and complete clinical and radiographic resolution was seen ().


A 50-year-old woman presented to the Breast Unit of Sant’ Anna and San Sebastiano Hospital of Caserta, Italy, after becoming aware of a non-tender lump in the median areolar area of her right breast. She first noticed the mass one month previously. During this period, she did not have any pain or discharge from the nipple. Further, she had no family history of malignancy, including breast cancer. She was in antihypertensive therapy.
She had never undergone any radiation and hormone replacement therapy. On physical examination, the patient had a demarcated, mobile, firm and fast-growing mass in her right breast.
The mass was not tender, approximately 4 cm in diameter, and was detected in the median areolar area of the right breast. There was no clinical evidence of regional lymphadenopathy.
Mammography revealed an opaque and ovoid lesion occupying the median equatorial region of the right breast; this lesion was 35 mm in diameter, with regular margins, moderate intensity and homogeneous density; there was no evidence of defined focus of pathological calcification (Figure ). Ultrasonography revealed a bulky, firm, hypoechoic lesion, with blurred and irregular margins, richly vascularized on color Doppler, with high speed systolic flow. This mass was 45 mm in diameter, and referred to as a heteroplastic lesion. There was no evidence of lymphadenopathy.
Ultrasound-guided fine needle aspiration on the lesion showed epithelioid and spindle cells, which were positive only to the immunohistochemical staining for vimentin and so we suspected a mesenchymal lesion.
An ultrasound-guided core needle biopsy performed subsequently showed connective tissue, including cells similar to those already present in the needle aspirate and there were many multinuclear osteoclast-like giant cells. The immunohistochemical staining confirmed the mesenchymal nature of the lesion (positivity for vimentin), but did not indicate clearly a specific histotype for the actin, CD34 and S100 protein negativity.
Preoperative examination consisted of a complete blood count, serum kidney and liver function, thyroid function test, and tests for the levels of several hormones related to the development of gynecomastia, including estrogen, testosterone, prolactin and gonadotrophic hormones as well as cancer markers (CEA, CA 15–3, CA 125). Ultrasound (US) of the abdomen failed to document any abnormalities. An isotope bone scan did not reveal any abnormal uptake. All results were within the normal limits.
The patient underwent total mastectomy without axillary lymph node dissection, awaiting histology.
Macroscopic examination of the specimen, measuring 19 × 15 × 8 cm and including the normal nipple, revealed a grayish, apparently delimited nodular lesion, measuring 10 cm in diameter, with cystic-necrotic and few hemorrhagic areas. The lesion was 0.5 cm away from the fascia and 1 cm away from the skin; furthermore, another grayish nodular lesion measuring 1.5 cm was in the subcutaneous tissue.
Microscopic examination of the sections from the specimen showed nodular proliferation of pleomorphic-spindle-shaped and ovoid cells, with connective tissue septa, mixed with many multinuclear osteoclast-like giant cells that did not show, mainly, malignant features (Figures a-b; Figure a, b).
Necrotic areas and abnormal mitosis were identified. Immunohistochemical stainings for Cytokeratin Pan (Figure a), Cytokeratin 7-8-18-19, EMA (epithelial membrane antigen), S100 protein, SMA (smooth muscle actin) and CD34 were negative; immunohistochemical staining for vimentin was positive (Figure b). Mitotic activity was observed with a high proliferation index, assessed with Ki67. Moreover, in the surrounding parenchymal component, there were multiple foci of intraductal carcinoma, evaluated with immunohistochemical staining for muscle actin and collagen IV. The lesion was contained within the margins of excision.
The histological and immunohistochemical findings established the diagnosis of undifferentiated pleomorphic sarcoma with osteoclast-like giant cells of the breast.
The patient was monitored after the operation and we did not consider that adjuvant treatment was necessary in the presence of adequate local control and in the absence of metastatic spread of the disease. Follow-up mammography has been satisfactory to date, and she remained well without tumor recurrence at 15 months.


A 7-year-old male child was referred to molecular cytogenetic analysis, because of intellectual disability and facial dysmorphisms. He was born at 39 weeks of gestation to a 25-year-old mother and 28-year-old father. The couple is healthy and unrelated, having a history of a previous first trimester miscarriage. The pregnancy was reported to be complicated by hypertension during the third trimester. He was delivered vaginally. Neonatal measurements were as follows: birth weight was 2.9 kg (10th centile), and length was 49 cm (25th centile). At the age of one week, feeding problems (feeding intolerance and food refusal) were noted. Physical examination made at the age of 7 years showed microretrognathia, hypertelorism, upslanting palpebral fissures, prominent eyes, broad nasal bridge, low set ears, and low frontal hairline. Mild intellectual disability and speech delay were noticed.
Cytogenetic analysis was performed by GTG-banding according to standard procedures. Thirty metaphase plates were studied at a resolution higher than 550 bands. Detectable karyotype abnormalities were not found.
High-resolution metaphase CGH was performed according to previously described protocols of DNA labeling, hybridization, and detection [, ]. The use of this technique has suggested the presence of a deletion in 20q11.2 ().
Array CGH was done using the customized human genomic microarrays (slightly modified Constitutional Chip 4.0) containing about 5000 human BAC/PAC clones (Human BAC Array-System, Perkin Elmer, USA) achieving a resolution of 0.3–1 Mb for the whole genome scan. Technical performance of array CGH (DNA labeling, hybridization, detection, and data analysis) was made according to previously described protocols [, , ] and to manufacturers' instructions. Array CGH has revealed an interstitial deletion in 20q11.21 spanning from 29,392,835 to 32,017,043 (confirmed by four BAC probes: RP5-1018D12, RP5-836N17, RP5-1085F17, and RP5-1125A11 in two reverse assays). The minimal deletion size was estimated to be about 2.6 Mb ().
To get further insights into understanding of the phenotypic outcome, we evaluated the deleted region by NCBI Build 37.1 () and UCSC Genome Browser () as previously described []. The deletion resulted in the loss of 68 genes, among which 23 genes are listed in OMIM (). Among the latter, five genes are disease causing: COX4I2 (exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis/OMIM: 612714), MYLK2 (cardiomyopathy, hypertrophic, midventricular, and digenic/OMIM: 192600), ASXL1 (Bohring-Opitz syndrome/OMIM: 605039 and myelodysplastic syndrome, somatic/OMIM: 614286), DNMT3B (immunodeficiency-centromeric instability-facial anomalies syndrome 1 or ICF syndrome/OMIM: 242860), and SNTA1 (long QT syndrome 12/OMIM: 612955). It is noteworthy, that no similar cases are indexed in DECIPHER (database of unbalanced chromosome aberrations ) and benign genome variations (retrieved from Database of Genomic Variants ) mapped to this genomic region involve DNMT3B ().


A 31-year-old primigravida in her 36 weeks of gestation came to our hospital with sudden dizziness, three episodes of seizure within 20 minutes followed by unconsciousness. Seizure was generalized tonic-clonic seizure (GTCS) type and each lasted for approximately 15 second. She was known case of gestational hypertension under medication of tablet Labetalol 5 mg daily. At presentation her blood pressure was 170/110 mm of Hg pulse rate 138/minute, bilateral pedal oedema with fetal heart sound 142/min. Immediately Injection Diazepam 10 mg and Magnesium sulphate 5 gm. Bolus dose followed by 2 gm. Over 40 minutes in i/v infusion was given. Patient was admitted and shifted to obstetrics Intensive Care Unit (ICU) with diagnosis of eclampsia and differential diagnosis of intracranial hemorrhage, PRES. Biochemical and laboratory tests were unremarkable except with 3+ proteinuria on urine deep stick test. Patient had recurrent seizure in ICU so, and urgent CT was advised. CT head showed low density shadow on bilateral parietal lobe, high density shadow near the top of the cerebral sulcus (shown in ). So with respect to the CT findings and clinical presentation, RPLS was diagnosed and prompt caesarian section was done without any complication. Post operatively patient had no episodes of seizures and blood pressure was controlled with medication. Repeat CT scan of head on 7th day of postoperative showed disappearance of low density and high density shadows. She was discharged after one week, with oral antihypertensive medication, and patient had no recurrences of symptoms after 2 months of discharge.


A 24-year old male thalassaemic patient presented electively with a history of a right-sided abdominal mass on self-examination, with no other complaints. A magnetic resonance image of the abdomen was requested, which revealed a 20 cm mass arising in the right suprarenal region, which was suspected to be a malignant adrenal tumour. Investigations revealed no evidence of adrenal dysfunction. The Patient was optimized for surgery in keeping with haematological recommendations and prepared and consented for removal of the right suprarenal mass.
A Chevron incision was made to provide adequate access. At surgery, a giant highly vascularized tumour was excised from the right suprarenal region. There was an easily dissectible plane around the mass and its blood supply originated from a short pedicle from the aorta and inferior vena cava. There was no evidence of invasion into the surrounding structures. The patients' primary spleen and other intra-abdominal organs were otherwise normal in anatomy and size.
Histological examination revealed this mass to be normal splenic tissue with a small central area of infarction and no evidence of malignancy noted (Figures , , , and ).


A 59-year-old woman presented with a positive fecal occult blood test. She had no family history of FAP. She had had a colonoscopy at a clinic, and at that time she was diagnosed with type2 colon cancer at the sigmoid colon. She then underwent a laparoscopy-assisted sigmoidectomy. The pathological examination revealed five lesions that were colon cancer.
Two years later, she had a colonoscopy and was diagnosed with aFAP. A depressed lesion was detected at the transverse colon; colorectal cancer was suspected. And then, she received an operation. According to the pathological examination, this lesion was early colon cancer, type0 IIa+IIc, 12 × 9 mm, adenocarcinoma (tub1), SM3 (pSM: 1750 μm), ly1, v1, pN0 ().


A 65-year-old woman was under observation at her clinic after being diagnosed with FAP. A total colorectomy was recommended, but she refused it and was followedup every six months. A lesion was eventually detected that suggested colorectal cancer at the sigmoid colon. The lesion was IIa+IIc type colon cancer, and the endoscopic diagnosis was submucosal-invasive cancer.
A pathological examination indicated that the lesion was advanced colon cancer, type0 IIa+IIc, 11 × 7 mm, adenocarcinoma (tub2), pMP, ly2, v1, pN1, pPM0 (68 mm), pDM0 (93 mm). No adenoma component was observed in this lesion ().


A 78-year-old man presented blood feces and was introduced to our institution. A colonoscopy revealed a IIa+IIc lesion at the transverse colon, and the diagnosis of FAP was made. Because the patient declined to undergo surgery, an endoscopic membrane resection was performed. The pathological examination showed that the lesion was well-differentiated adenocarcinoma that had invaded the submucosal layer ().


A 54-year-old female patient, with unremarkable past medical history except hypertension and depression, was admitted to our department because daily fever up to 39 °C associated with rigors and notice of a palpable painful mass in her right axilla. She reported no previous close animal contact or injury.
On admission, the patient’s vital signs were 38.9 °C, HR 92 bpm, RR 14 b/min BP 130/85 mmHg. Oxygen saturation breathing ambient air was 97%. Physical examination revealed a 5 cm painless mass in the right axilla, palpable liver 3 cm below the right costal margin and just palpable spleen below the left costal margin.
Initial laboratory evaluation showed WBC count 13.2 × 109/L, with predominant neutrophils (82%), hematocrit 28.4% hemoglobin 9.2 g/dL (MCV = 80 and MCH = 26) and platelet count 587 × 109/L. Prothrombin and partial thromboplastin times were normal and d-dimers were increased at 1.20 μg/mL. The blood biochemical test results including serum angiotensin converting enzyme were normal except of increased serum globulins at 3.7 g/dL. Protein electrophoresis was normal. Serum CRP was increased at 17.5 mg/dL, ESR at 130 mm/h, fibrinogen at 808 mg/dL and ferritin at 336 mg/dL. Thyroid function tests were normal. Urinalysis and 24-hour urinary calcium and protein excretion were unrevealing. Electrocardiogram, chest X-ray, echocardiogram and arterial blood gas were also normal. A detailed ophthalmologic examination including slit lamp eye examination, fundoscopy, Rose Bengal and Schirmer’s tests was unrevealing.
A full body CT scan revealed enlarged lymph nodes in the right axillary, mediastinal () and retroperitoneal region, most with a hypodense center, and hepatosplenomegaly with multiple hypodense splenic and hepatic lesions (). There was no evidence of lung parenchymal disease, pleural or pericardial effusions or ascites, whilst the vascular perfusion of abdominal organs was normal. A dual phase hepatic CT scan showed a diffuse heterogeneity in hepatic arterial perfusion with multiple hypodense lesions not enhancing in arterial face. A Gallium-67 scan showed increased radiotracer uptake in right axillary, mediastinal and retroperitoneal lymph nodes and in the right hepatic lobe and the spleen. An 18F-FDG PET/CT scan showed multiple foci of increased metabolic activity in the lymph nodes of the right axillary and subcarinal regions, in the right hepatic lobe and the spleen. A performed digital mammography was unrevealing.
All sets of blood cultures (at least six), urine and stool cultures were negative. Antibodies for hepatitis A, B, C, coxsackie, echo, herpes simplex virus, Epstein-Barr, cytomegalovirus, human immunodeficiency virus, human T-lymphotropic virus-1 and -2, Yersinia enterocolitica Entamoeba histolytica, Bartonella henselae, Francisella tularensis Leishmania donovani, Coxiella burnetii and Rickettsia coronii were negative. Wright and RPR tests as well as the tuberculin skin test were also negative.
The patient underwent upper and lower gastrointestinal tract endoscopies, which detected no pathology. A bronchoscopy was also performed without pathologic findings, whilst examination of bronchoalveolar lavage with Gram and Ziehl-Neelsen stains, cultures, polymerase chain reaction for mycobacterium tuberculosis and cytology were unrevealing. The CD4:CD8 ratio in the bronchoalveolar lavage was normal.
A full immunologic screening with rheumatoid factor, antinuclear antibodies, antibodies to double-stranded DNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, anti-Jo-1, anti-Scl-70, anti-histones, anti-mitochondrial antibodies, anti-smooth muscle antibodies, cytoplasmic-antineutrophil cytoplasmic antibody (ANCA), perinuclear-ANCA, anti-transglutaminase, anti-cardiolipin, and lupus anticoagulant was negative. Serum complement and levels of immunoglobulins (Igs; IgA, IgG, IgM, IgE, IgD) were normal. The results of genetic testing for mutation of the familial Mediterranean fever gene (M694V, V726A, M694I, M680I, and E148Q) were negative. In addition, the results of a full tumor marker profile were also normal.
The patient underwent surgical excision of the enlarged right axillary lymph nodes for microbiological and histological examination. Histology revealed a granulomatous lymphadenitis with central suppurative necrosis (). Gram, Giemsa, Ziehl-Neelsen, Grocott methenamine silver stains for detection of common bacteria, mycobacteria and fungi were all negative. Immunohistochemical studies for lymphoproliferative disease was unrevealing. In addition, lymph node was examined with PCR for mycobacterium tuberculosis, atypical mycobacteria (africanum I/II, microti, carnetti, bovis, avium complex), fungi and Bartonella hensellae, in addition to application of culture techniques, without detection of any pathogen. A CT-scan-guided liver biopsy was performed in hepatic hypodense lesions, which demonstrated the presence of hepatic histiocytic granulomas (). A gastrocnemius muscle biopsy was also performed without identification of sarcoid granulomas.
The peripheral blood film showed no evidence of lymphoproliferative disorders. Bone marrow biopsy and immunophenotypic analysis revealed no pathologic findings. Peripheral blood immunophenotypic analysis revealed T-lymphopenia. Beta -2 microglobulin levels, serum and urine kappa and lambda light chains and urine Bence-Jones protein test were unrevealing.
The patient had been initially empirically treated with antimicrobial therapy consistent of ciprofloxacin and clindamycin without disease control. During hospitalization episodic disease flares characterized by SIRS and spikes of increased markers of inflammation were recorded, which were treated with step up of antimicrobial therapy to cover potential intra-hospital pathogens (linezolide - meropenem) and hydrocortisone 50 mg qid. After completion of the above described extensive diagnostic work-up which demonstrated no evidence of an infectious etiology of our patient’s symptoms, we decided to administer corticosteroids (32 mg methylprednisolone) as a therapeutic trial. The patient presented an immediate improvement after institution of this therapy becoming afebrile and with normalization of serum inflammatory markers. She entered a very slow corticosteroid tapering scheme (reduction of 2 mg of methylprednisolone every month) with close clinicolaboratory follow up and she presented gradual resolution of lymphadenopathy. However, the disease relapsed with reappearance of fever, lymphadenopathy and increased inflammatory markers, when methylprednisolone dose was reduced below 10 mg/d. Methylprednisolone dose was again increased to 16 mg/d with immediate response of fever and gradual resolution of lymphadenopathy, followed by slow tapering of corticosteroids. Unfortunately, a second relapse occurred again with methylprednisolone dose reduction below 10 mg/d. A trial of a non-steroidal anti-inflammatory agent (ibuprofen 800 mg daily) added in methylprednisolone treatment, which was again raised to 16 mg/d, failed to prevent a new disease flare with methylprednisolone dose reduction below 10 mg/d. After this third disease relapse, anakinra (100 mg of daily) was added concurrently with methylprednisolone dose escalation in 16 mg daily. The patient was treated with 16 mg/d of methylprednisolone for two months and entered a slow corticosteroid tapering scheme (reduction of 2 mg of prednisolone every month). She is currently treated with 6 mg/d of methylprednisolone and is free of symptoms with resolution of lymphadenopathy, and absence of radiotracer Gallium-67 up-take. The hypodense hepatic and splenic lesions are still discernible on contrast CT imaging; however, a repeated CT-guided biopsy of liver lesions detected no granulomas but only evidence of pericentral and pericellular fibrosis. Liver function tests are within normal limits.


Our patient, a 44-year-old Caucasian German man working as a soldier, had no known history of neurological disorders or internal diseases apart from a febrile convulsion of unknown origin during childhood, and hypertension that had been treated with a combination of hydrochlorothiazide and lisinopril (Acercomp®, AstraZeneca, Wedel, Germany) during the two months preceding the seizure. Our patient denied any history of drug or alcohol misuse. He had received multiple pre-deployment vaccinations over a brief period of time. These vaccinations were given in addition to a primary immunization series against MMR, DPT, TBE, hepatitis A and hepatitis B, which he had completed the previous year. Our patient received the following vaccinations: first, a rabies vaccine and vaccines against abdominal typhus, yellow fever and meningococcal meningitis were administered. The second rabies vaccine followed one week later. Our patient received his first dose of JEV after a further week, followed by a third rabies vaccine and the second JEV after two weeks. He received his third dose of JEV four weeks after the previous vaccination and had his first seizure one day later. He was admitted to the Department of Neurology at the Hospital of Guestrow where he underwent several examinations. Temporarily elevated blood pressure levels were detected during 24-hour blood pressure monitoring. Magnetic resonance imaging (MRI) results were affected by artifacts. Of note, in his documented medical history during military service (25 years) there had been no craniocerebral injury. No pathological changes were revealed by the results of any of the following investigative procedures: electroencephalography ([EEG]: α-EEG (frequency: 10-Hz base rhythm), no epilepsy), 24-hour electrocardiography (ECG), lumbar puncture (color: clear, white blood cell count: 1, lactate: 1.58mmol/L, protein content: 371mg/L, no IgG), Lyme disease testing, sleep-deprived EEG and a Schellong test. Laboratory study results revealed elevated creatine kinase levels and myoglobin levels. Since this was the first time our patient had experienced a seizure and no pathological changes were detected, no regular medications were given. Three months later, our patient received a dose of TBE vaccine. Later on the same day, he had a second seizure and was again referred to the Neurological Department at the Hospital of Guestrow. Since our patient refused to be admitted to the hospital, no further diagnostic tests were performed. He was subsequently treated as an out-patient in the Department of Neurology at the German Armed Forces Hospital in Hamburg. Four weeks later he reported a further seizure. On the same day, drug therapy was started using 600mg of extended-release valproate, which was later replaced by 100mg/day of topiramate (Janssen-Cilag, Neuss, Germany). Control EEGs (α-EEG, no epilepsy) did not reveal any pathological changes. In addition, our patient was instructed to discontinue physically strenuous work. Ten weeks later he again had a seizure. Laboratory test results showed that the topiramate concentration was below a therapeutic level. On account of its diuretic effect, the hydrochlorothiazide-containing drug (Acercomp®) was considered to be the likely cause of the low topiramate level. For this reason, it was recommended that the drug be discontinued and the topiramate dose be increased to 125mg/day. However, as Acercomp® had been prescribed for the treatment of our patient’s hypertension and had been well tolerated, it was continued; topiramate was increased to 125mg/day. Control EEGs (α-EEG, no epilepsy) did not reveal any pathological findings. Two months later, our patient had a further epileptic seizure. Neither an EEG nor computed tomography scan demonstrated any abnormal changes. The dose of topiramate was increased to 200mg/day. After a further six weeks, the next seizure occurred. For the first time, EEG results demonstrated the presence of epileptiform abnormalities in the frontotemporal region. Topiramate was replaced by 100mg/day of lamotrigine. Further control EEGs revealed no pathological changes. At six and 18 weeks later, our patient had further seizures, even though his lamotrigine dose had been increased to 200mg/day. In order to obtain artifact-free MRI studies, a small piece of metal located subcutaneously was removed. Subsequent MRI scans detected no pathological changes that could explain the patient's recurrent seizures (i.e., there was no abnormal enhancement of contrast medium and there were no abnormal hippocampal structural changes. Incidental findings of a right central semiovale scar and cystic formation in the right frontal area were noted). His lamotrigine dose was increased to 300mg/day.
Six weeks later our patient was vaccinated against influenza. No complications were observed. However, at six and 12 weeks later the patient again experienced seizures. Treatment with levetiracetam (Keppra®, UCB Pharma, Brussels, Belgium) at a dose of 2000 mg/day was initiated by the Department of Neurology at the University of Rostock Hospital. The levetiracetam dose was given in addition to lamotrigine. Further diagnostic tests were performed in the Department of Neurology at the University of Greifswald Hospital. For diagnostic purposes, all medications were discontinued. This, however, did not induce a seizure. All test results were unremarkable. Lamotrigine was then discontinued and the dose of levetiracetam was increased to 3000mg/day. The occurrence of seizures has subsequently reduced to one to three per year since then.


CR is a 34-year-old female with CF homozygous for the F508del mutation whose sputum cultures had been positive for both Ps. aeruginosa and S. aureus for many years. Her CF was complicated by allergic bronchopulmonary aspergillosis (ABPA), marked seasonal allergies, and asthma. Her treatment regimen consisted of alternate day prednisone (20 mg), alternate week omalizumab (300 mg), itraconazole 100 mg bid, fluticasone 110 mcg/puff, 2 puffs bid, and azithromycin 500 mg orally every Monday-Wednesday-Friday. She chose not to use inhaled 7% hypertonic saline, rhDNase, or inhaled tobramycin. She used chest physiotherapy intermittently.
The patient was in her usual state of health (baseline FVC at 99% predicted and FEV1 at 85% predicted) until she developed intermittent, left-sided sharp chest pain at rest. She denied fever, hemoptysis, numbness, diaphoresis, paresthesias, left arm pain, or abdominal discomfort. The pain was worsened with cough. Upon admission to the hospital, a chest radiograph was consistent with a left pleural effusion and consolidation in the left mid and lower zones. There were also new inflammatory changes in the right mid zone.
The patient started on intravenous tobramycin and imipenem to treat the organisms known to be in her sputum. Despite appropriate therapy, on hospital day number 3, the patient developed increased respiratory distress and a temperature elevation to 39.4°C. A repeat chest X-ray film demonstrated a significant increase in the left pleural effusion and consolidation in the left lower lobe (). A 6-French pigtail catheter was placed under ultrasound guidance on hospital day number 4, and pleural fluid was sent for microbiology culture. Pleural fluid analysis revealed a pleural fluid pH = 6.61, glucose < 5 mg/dL, LDH = 4531 IU/L, and total protein = 3.9 g/dL. Serology obtained at the time of the catheter placement revealed a total protein level =4.4 g/dL. There was no available serum LDH. A CT scan of the chest revealed a large partly loculated left pleural effusion with marked subcutaneous emphysema and pneumomediastinum (). The pleural fluid culture was positive initially for S. aureus, and vancomycin was added to her antibiotic regimen. Subsequently, Ps. aeruginosa was also isolated from the pleural fluid. The patient underwent a second ultrasound-guided insertion of an 8-French pigtail catheter on hospital day number 5. Because of limited drainage, 10 milligrams of tissue plasminogen activator (tPA) mixed into 100 mL of normal saline were instilled into one of the chest tubes on both hospital days number 6 and number 7 with a resultant marked increase in fluid drainage. Her respiratory status improved significantly following this drainage. Serial chest-imaging studies performed throughout the hospitalization revealed improvement of the pleural fluid collection and subcutaneous emphysema. The pleural catheters were removed on hospital days 9 and 11, respectively, and she was ultimately discharged in stable condition in room air on day 15. She received an 18-day course of cefepime and 28-day course of inhaled tobramycin at home.
The patient was seen in pulmonary clinic 2 weeks after her hospital discharge where she was found to have an FVC of 90% predicted and FEV1 of 73% predicted, which were slightly below her baseline pulmonary function. A chest radiograph revealed near complete resolution of the left pleural effusion with minimal fluid remaining (). Two months following her hospital discharge, the patient felt markedly improved, and her pulmonary function (FVC of 98% predicted and FEV1 of 79% predicted) was returning toward her baseline.


In November 2005, in a 58-year-old male patient an adenocarcinoma of the lung was diagnosed and he underwent multimodal treatment including resection of the upper pulmonary lobe and adjuvant chemotherapy. Nine months later (July 2006), a follow-up MRI revealed a contrast-enhancing solitary lesion in the left frontal brain, highly suggestive for a brain metastasis originating from adenocarcinoma of the lung (Figure ). The lesion was treated by linear accelerator (LINAC) based SRS (tumor volume, 0.6 ml; surface dose, 20 Gy; isodose level, 65%) [,]. Follow-up MRI after 3 months (Figure ) showed a decrease of contrast enhancement > 50% of the treated lesion (partial response according to the Macdonald criteria []) as well as a new enhancing lesion also suggestive for a metastasis in the left temporal lobe (Figure ), which was also treated with LINAC based SRS (tumor volume, 1.2 ml; surface dose, 20 Gy; isodose level, 65%). The subsequent MRI performed in December 2006 showed complete remission of both metastases (images not shown).
Thirty-seven months after SRS of the left temporal metastasis, a new contrast-enhancing lesion with perifocal edema was detected in the area of applied irradiation (Figure ). Due to further progression of size in the follow-up MRI one month later (tumor volume, 2.8 ml), the lesion was highly suspicious for local tumor recurrence. In order to differentiate local tumor recurrence from radiation-induced changes, a stereotactic biopsy was performed. Histological assessment revealed a radiation-induced necrosis. Tumor cells were completely absent. The diagnosis of a radiation-induced necrosis was additionally confirmed by the clinical and radiological course. In follow-up MR imaging, the contrast enhancement vanished completely (Figure ).
Fifty-eight months after SRS of the left frontal metastasis, we observed a recurrence of contrast enhancement (tumor volume, 1.8 ml) within the area of applied irradiation accompanied by a hyperintensity in the FLAIR-weighted MRI (Figure , ). For further evaluation of this lesion, PWI MRI, MRS, and 11C-methyl-L-methionine (MET) PET was performed.
In detail, PWI MRI revealed a perfusion deficit with low mean transit time and low relative cerebral blood volume (rCBV), which was corresponding to the signal alterations on the FLAIR-weighted image (Figure ). Areas with increased rCBV, however, could not be clearly identified within the perfusion deficit. Furthermore, diagnostic information of MRS was heavily influenced by artifacts and was therefore inconclusive (Figure ). It should be noted that most probably due to the patient’s unusual large frontal sinus adjacent to the left frontal lesion, the diagnostic value of PWI MRI, and MRS might have been negatively influenced. MET PET imaging of the suspicious left frontal lesion revealed a mean tumor-to-brain ratio of 1.40 (normalized against the gray matter of the unaffected right frontal cortex) (Figure ). It has been previously demonstrated that a mean threshold of at least 1.41 or 1.42 has the best diagnostic accuracy for the identification of recurrent brain metastasis [,]. Accordingly, the tumor-to-brain ratio of 1.40 was suggestive for radiation-induced necrosis. Nevertheless, the ratio of 1.40 was very close to the thresholds for diagnosis of recurrent metastasis (1.41 and 1.42, respectively) and MR imaging findings were not helpful. We therefore decided to perform a stereotactic biopsy for histological evaluation of the suspicious left frontal lesion. According to our previously reported protocol, a stereotactic 125I brachytherapy (SBT) after intraoperative verification of tumor within the same surgical procedure was planned [,]. Intraoperatively, histological findings were consistent with radiation necrosis (Figure ). Thus, SBT was not performed.
Follow-up MRI after 74 months showed a decrease of contrast enhancement (Figure ). During the complete course of the disease, the patient was asymptomatic and had no neurological deficit. Furthermore, there were no clinical signs for systemic disease progression.


A 13-year-old male presented to us with fever (acute in onset, mild to moderate grade and associated with mild chills) since last 10 days followed by gradually progressive sensory motor paraparesis with urinary incontinence since last 4 days. He was then hospitalized with weakness remaining static for one day and then progressed and involved both upper limbs within 24 hours. Examination showed LMN type sensory motor quadriparesis with only flickering of contraction present in all the limbs; planter was downgoing bilaterally. The patient was febrile with other systemic and general examinations showing no significant abnormality. After one day of quadriparesis, patient developed acute onset altered sensorium preceded by drowsiness and headache which was diffuse and bursting in nature. No significant past and family history and similar episode were previous noted.
Now examination showed a Glasgow Coma Scale of E1M1V1 and patient was deeply comatose. On the basis of this history and examination we put the diagnosis of ascending myelitis of viral origin and did investigation accordingly. As the patient belongs to an endemic region, differential diagnosis of JE was kept too. All routine investigations were within normal limit. We did CSF which revealed total leucocyte count of 42 cells/cmm with lymphocytic predominance and slight elevation of protein and normal sugar along with elevated IgM titres against JE virus. Brain MRI showed bilateral basal ganglia that were grossly swollen with vasogenic edema tracking along internal capsule and midbrain. Adjacent ventrolateral thalamus and internal capsule also show mild abnormal intensities (Figures , , and ). Spinal screening shows abnormal cord intensities in entire cord with gross edema in cervical and conus region (Figures and ). Electrophysiological study was suggestive of preganglionic axonal involvement of upper limb and lower limb. Diagnosis of ascending myelitis and encephalitis due to JE virus was established. We started the patient on conservative treatment with intravenous methyl prednisolone for 5 days and rest treatment was symptomatic. Patient started to show improvement in the form of moving limbs and staring. Patient regained full consciousness after 2 week and was discharged and asked to be followed up in OPD. He regained near normal power at 3 months in followup but hesitancy, dysarthria, and slowness of movement persisted. This is one of the rare cases of JE which causes ascending myelitis (ATM).


A 79-year-old man with no notable medical or surgical history presented with a four-day-long history of distending pain in the right side of the abdomen. There was no palpable mass and no guarding or rebound tenderness was observed. Ultrasound showed a pathologic mass, 4 cm in diameter in the right side of the abdomen and the echo of the normal appendix was not displayed. Biochemistry laboratory results were within normal range. At surgery, a smooth mass was noted at the base of the appendix that continued into the cecum at the ileocecal junction. The tumor was not observed to be involved with the appendix, which, up to the base, was hard and encapsulated with no adhesions to the surrounding tissue. The frozen section of the mass was consistent with appendiceal cystadenoma. An appendectomy was performed. When the specimens were cut yellowish jelly-like mucinous material was observed (). The patient was discharged 7 days after surgery without discomfort and was followed up at 4 months. The patient has had no recurrence so far.


A 70-year-old woman was in good health until a large abdominal mass was detected in her right lower quadrant upon routine physical examination. Physical and laboratory examinations were within the normal range, but the patient had a raised carcinoembryonic antigen (CEA) level of 6.64 ng/ml. Ultrasound found a pathologic mass, which was consistent with appendiceal mucocele. The patient underwent a diagnostic laparoscopy. Intraoperatively, dense adhesions were not encountered in the right lower quadrant, but the capsule wall ruptured with an outflow of yellowish jelly-like mucus (). The patient received an irrigation of the peritoneal cavity instead of chemotherapy or hyperthermic chemotherapy. Ascites were observed in the abdominal drainage following surgery. The volume of drainage was assessed. There was 10 ml of yellowish mucus on day 5 after surgery, which increased to 15 ml on day 7. It was clean on day 18 after surgery and the patient was discharged. Sonography revealed seroperitoneum with maximum depth of ∼31 mm liquid anechoic area during the patient’s hospitalization. Few mucin-producing epithelial cells were found in the ascites on cytology. Biochemistry laboratory results of ascites revealed that Rivalta’s test was positive and a clinical diagnosis of PMP ascites type was made (). At the last clinic visit, the patient reported with the chief complaint of abdominal distension. The patient’s abdomen was again enlarged and seroperitoneum was obtained again on sonographic studies. The patients refused to receive an ultraphonic guided puncture and was discharged after certain symptomatic approaches were performed.


A 73-year-old female presented with a 1-month history of a distended abdomen, without nausea and vomiting. A computed tomography (CT) scan was obtained and revealed abnormal appendix enhancement, which was partially thickened at the surface of the liver and peritoneum. At this point, surgical options were discussed and the patient underwent diagnostic laparoscopy. Operative findings included diffusely light yellow nodules located at the surface of the liver and peritoneum without ascites (). There was a firm and irregular suspicious looking tumor measuring ∼2×2 cm at the end of appendix (), suspected to be an appendiceal cystadenoma after man-made rupture. A section of the epiploic appendices with nodules located was cut and intraoperative histopathologic examination was performed. This demonstrated non-necrotizing granuloma which was considered to be the same as the diffusely light yellow nodules located at the surface of the liver and peritoneum. There was little mucous membrane epithelium in the nodule on histopathologic examination, thus immunohistochemical methods were impossible. ( and ). The medical team considered that a diagnosis of intestinal tuberculosis could not be eliminated, requiring medical therapy rather than surgery. In accordance with the wishes of the patient’s family, an appendectomy was not performed, even though a test for acid-fast bacilli was negative. A PPD skin test was inconclusive. After further investigation of the patient’s history, an ultrasound demonstrated a dilated and fluid filled appendix. The clinical diagnosis was ascites and low-grade appendiceal mucinous neoplasm. After 3 days of symptomatic approaches the patient improved and symptoms disappeared. The patient and her family refused to accept further checks and left the hospital. The patient remained healthy for 7 months with no treatment, but then had signs of bloating again. According to the history and clinical presentation, this case matched the diagnosis of PMP. The symptoms persisted but the patient’s family did not consent to further surgery due to her age and general condition. She was discharged for follow-up.


A 44-year-old Peruvian woman, who had immigrated to Japan 20 years earlier, presented with postprandial upper abdominal pain of four months duration. She was found to have a gallbladder stone, which might have been the cause of her epigastralgia. Her past medical history was unremarkable except for a left renal stone. She had been pregnant three times and given birth to three children. On physical examination, there were no remarkable findings. As to laboratory tests, levels of aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), glutamyl transferase and total bilirubin were within normal ranges. Ultrasonography showed a few strongly echoic stones but there was no gallbladder wall thickening. Neither intra- nor extra-hepatic bile ducts were dilated. Routine preoperative computed tomography (CT) revealed a series of tortuous collateral veins at the liver hilum, irregularly surrounding the gallbladder from the neck to the fundus (Figure a, b). The extra-hepatic portal vein was occluded at the level of the spleno-portal junction (Figure c, d). There were no evidence of hypertrophy of the left liver, splenomegaly or ascites, suggesting that she was not cirrhotic. To check the anatomy of the biliary tract, we performed magnetic resonance imaging, which confirmed discontinuity of the common bile duct. This finding was assumed to have resulted from surrounding collateral vessels rather than a bile duct stone. Our diagnosis was symptomatic cholecystitis with CTPV. After being fully informed of her options, she provided consent to undergo surgery.
We considered SILS to be feasible because the cavernous vessels were not close to Calot’s triangle, and most ran from the middle to the left side of the hepatoduodenal ligament and liver hilum. Two distended collateral veins flowed extra-hepatically to the edge of the posterior segment of the liver. We were determined that these vessels could be sacrificed during the surgical procedure.
The operation was performed under general anesthesia, starting with a trans-umbilical incision. The peritoneal cavity was entered employing the open method, and a LAP PROTECTOR (HAKKO CO.,LTD. NAGANO,JAPAN, TM) was then inserted with EZ ACCESS (HAKKO). There were three holes, for two 5 mm ports and one 12 mm port. A flexible laparoscope (Olympus, Tokyo, Japan, TM) and two operating forceps were used. The pneumoperitoneum was set at 8 mmHg. Suture suspension of the gallbladder was not adopted. The courses of the cavernous vessels surrounded the neck of the gallbladder (Figure a). We first approached the cystic duct, with an assistant holding the neck of the gallbladder at the ventral position. Fragile cavernous vessels were encountered in this area, such that we kept the cystic duct together with these vessels. During the entire procedure, this process caused the most bleeding. Pulling the cystic duct out together with collateral vessels, employing a silk suture, we detached the cystic duct and the neck of the gallbladder from Calot’s triangle (Figure b). The cystic artery was ligated and transected near the neck of the gallbladder. After confirming the common bile duct, the cystic duct was ligated and clipped. There was bile oozing from the stump of the cystic duct, which was treated by ligation. The remaining surgical procedures were carried out with little difficulty. Hematoma was removed as extensively as possible, and no intra-peritoneal drainage was applied. Total operating time was 132 minutes and blood loss was 370 grams.
The patient was quite well postoperatively, with slightly increased AST (134 U/l), ALT (109 U/l) and ALP (188 U/l) on postoperative day 1, which decreased to 53, 78 and 181, respectively, the next day. Postoperative CT revealed that two extra-hepatic meandering vessels had been sacrificed but there were no hepatic perfusion abnormalities. She was uneventfully discharged on postoperative day 2. The liver enzymes dropped within normal ranges and she was asymptomatic on her last outpatient day of postoperative day 8.


A 52-year-old woman (gravida 6, para 1) presented to the gynecology clinic at Guro Hospital, College of Medicine, Korea University, with a complaint of low abdominal pain. In addition to low abdominal pain, the patient had experienced low back pain, urinary frequency, and tenesmus for approximately 1 year. She had undergone myomectomy 2 years previously in China.
The patient’s menses had ceased at the age of 50. She had no complaints of vaginal bleeding or low abdominal distension. She has never undergone a cervical screening test. On pelvic examination, the cervix was found to be small, and no specific abnormalities were observed. On physical examination, a hard mass with an irregular surface was palpable. A Pap smear and a HC2 test were performed. The Pap smear result was a low-grade squamous intraepithelial lesion, and The HC2 test result was negative for high-risk human papillomavirus. Transvaginal ultrasonography examination revealed an approximately 11-cm mixed echogenic solid mass of the left adnexa, which strongly suggested the presence of a malignant tumor (Figure ). However, serum CA 125 (6.9 U/mL), CA 19–9 (10.8 U/mL), CEA (<0.5 ng/mL), AFP (2.5 ng/mL), and beta-hCG (2.3 mIU/mL) levels were not elevated. The findings of chest radiography, mammography, and breast sonography were normal. An endoscopic examination of the stomach and colon showed no evidence of metastasis. However, colonoscopic evaluation was unsuccessful because of stenosis of the lumen, and the rectal mucosa protruded into the lumen, probably because of extrinsic compression by the pelvic mass. Pelvic MRI and CT of the abdomen and pelvis revealed an approximately 12.4-cm heterogeneous solid mass occupying the entire pelvis and a portion of the lower abdominal cavity. This mass also showed internal degeneration and hemorrhagic change, findings strongly suggestive of a primary ovarian malignancy (Figure ). The mass was abutted to the posterior sigmoid colon, whereas the presence of direct invasion was indeterminate. The uterus displayed an approximately 1-cm well-defined mass that was suggestive of leiomyoma, but both ovaries were not delineated. On 18F-FDG PET/CT, a large pelvic mass with heterogeneous metabolism was identified, suggesting the presence of a malignant mass (Figure ). No specific finding suggestive of metastasis was observed.
Explorative laparotomy with a supraumbilical incision was performed. A large mass with a longest diameter of approximately 20 cm was identified. This mass was located in the cul-de-sac and was densely adhered to the rectum, retroperitoneal surface, and posterior uterine body. The uterus and both ovaries and tubes were normal on gross appearance. A portion of the mass was subjected to frozen examination, and the result was a mesenchymal tumor originating from the gastrointestinal tract, such as a gastrointestinal stromal tumor. We then performed supracervical hysterectomy and bilateral salpingo-oophorectomy. After the completion of gynecologic surgery, a surgical team from the department of colorectal surgery subsequently performed anterior resection of the colon and appendectomy. The operation was uneventful, and the patient was transferred to the department of colorectal surgery after the operation.
Histopathological analysis of the full specimen revealed a grade 3 leiomyosarcoma, 22 × 17 × 6 cm3 in size, with free mucosal resection margins. The mitotic count was ≥20 per 10 high-power fields, and an area of necrosis was identified. The tumor cells had characteristically elongated, pleomorphic, and blunt-ended nuclei and eosinophilic to pale cytoplasm (Figure ). On immunohistochemical staining, the tumor cells were positive for smooth muscle actin, desmin, and CD99 but negative for S-100 protein and CD34, consistent with a diagnosis of rectal leiomyosarcoma. The resected appendix also showed the presence of a metastatic leiomyosarcoma. The uterus and both adnexa were free of metastasis. Postoperatively, the patient underwent adjuvant chemotherapy with cyclophosphamide, vincristine, and doxorubicin.


This study is approved by the Research Ethics Board of the Montreal Children's Hospital and exempted from a full review.
A 15-year-old girl presented with a painless submucosal nodule on the anterior right side of the floor of the mouth measuring 0.8 cm in the largest dimension for an unknown duration (). The patient had no other signs or symptoms.
Her past medical history included acute lymphoblastic leukemia (ALL), diagnosed at the age of 2 years requiring irradiation followed by bone marrow transplant. She has been in remission ever since. She also has a history of multiple acquired nevi which have been biopsied and returned benign.
An incisional biopsy was attempted to make the final diagnosis. The pathology report showed cellular NTK. A completion surgery was then performed.
There has been no sign of recurrence after 8 months of followup.


A 62-year-old male with past medical history of type 2 DM (DM-2) and hypertension of 20 years presented to our emergency room with progressive dyspnea that had worsened gradually over the last three months. He was being treated in another facility with questionable diagnosis of congestive heart failure with incomplete response to diuretic therapy. There was no history of chest pain, cough, orthopnea, or paroxysmal nocturnal dyspnea. He was a nonsmoker and had used alcohol occasionally. There was no recent viral or flu-like illness. On careful questioning, he complained of difficulty in walking and weakness in his legs. The patient denied any back pain, fever, weight loss, bladder involvement, or pain and paresthesias in his extremities. Neurological examination revealed bilateral symmetric muscle weakness with power of 4/5 in upper proximal and distal extremities and 3/5 in lower proximal and distal extremities. There was no ptosis or gaze paresis. Cranial nerves I–XII were grossly intact. There was no evidence of atrophy of the hand muscles and fasciculations. Sensory exam revealed decreased pinprick sensation distal part of extremities. Deep tendon reflexes were graded one in both upper and lower extremities. His blood pressure on admission was 161/106 mm Hg. A fasting blood glucose done at emergency room triage was 229 mg/dL. The clinical and functional examinations did not correlate with the severity of dyspnea. Arterial blood gas (ABG) revealed respiratory insufficiency (pO2 of 60 mm Hg, pCO2 of 58 mm Hg, and SaO2 of 89%).


The patient was an 84-year-old man, weighting 72 kg, who was hospitalized for open prostate surgery. In records, the patient was only complaining from exertional dyspnea, had no obvious cardiopulmonary problems, and did not mention using any specific drugs. In the conducted examination, pulmonary auscultation had no problems. Examination of abdomen and organs was normal, and only IV/VI systolic murmur and a thrill were heard in the aortic area. In order to evaluate the patient before the operation, blood tests, electrocardiogram, and echocardiogram were requested. The only positive point in the lab tests was prothrombin time (PT) = 15.6 sec. In the electrocardiogram (ECG), heart rate was 65 beats per minute, and the rhythm was regular; however, left axis deviation and left ventricle hypertrophy were observed. In echo, ejection fraction was 57%, severe hypertrophy of left ventricle, calcified and narrow aortic valve were reported; also, 52 mm Hg was reported for transvalvular aortic gradient; but, no functional and wall motion disorder was seen for left ventricle.
Vital signs of the patient before the induction were blood pressure of 150/90 mm Hg and heart rate of 60 beats per minute. For anesthetic induction with caution and low dose, 100 µg of fentanyl, 4 mg of pancuronium, and 80 mg of propofol were used. After tracheal intubation, in order to maintain anesthesia, a combination of propofol and remifentanil (200 mg + 500 µg) along with 50% oxygen and N2O was used. The rate of infusion was 0.2 µg/kg/min for remifentanil. After induction and beginning the infusion of remifentanil and propofol, the patient suffered from decreased heart rate (35–40 beats per minute) and decreased blood pressure (80/50 mm Hg); after a few moments, he experienced Mobitz II atrioventricular block (). To increase heart rate and sinus control, first, 0.5 mg atropine and then 10 mg ephedrine were injected; however, atrioventricular block was not modified (heart rate of about 40 beats per minute) despite increased blood pressure to 110/75 mm Hg. Then, infusion of remifentanil was stopped and propofol with rate of 50 µg/kg/min was used alone. After about 2-3 min, atrioventricular block and bradyarrhythmia were overcome (), and the patient's blood pressure was raised to 130/90 mm Hg. The patient had no hemodynamic problem during the operation, and recovery and was completely under control. He had a little restlessness during the recovery and improved after some minutes. Then, he was transferred to the ward in total awareness with blood pressure of 130/80 and heart rate of 62 beats per minute.


A 62-year-old male patient attended the outpatient department for endoscopic clarification of lower gastrointestinal bleeding haemorrhage. Since the patient had atrial fibrillation, he was on phenprocoumon. Colonoscopy revealed a circular exulcerating carcinoma located in the upper third of the rectum. Histological workup revealed an adenocarcinoma. Ultrasonography of the abdomen showed a number of virtually hypoechoic lesions compatible with liver metastases. Consequently, deep anterior rectal resection plus peritonectomy in the region of the posterior wall of the bladder combined with a descendorectostomy were performed to resolve a high-grade stenosis caused by the rectal carcinoma. Intraoperatively, peritoneal carcinomatosis was also found. The findings were categorized pathohistologically as pT4b, pN2 (5/28), L0, V1, pM1 (PER, HEP), and G2 (UICC Stage IV). The postoperative course was uneventful. Diffuse, nonresectable liver metastases and peritoneal carcinomatosis were diagnosed, and palliative treatment with combination chemotherapy comprising high-dose 5-FU and sodium folinic acid in the form of a 24 h infusion plus oxaliplatin every second week was scheduled [].
One day after receiving the first dose (5-FU 2.000 mg/m2, sodium folinic acid 500 mg/m2 combined with a previous application of oxaliplatin 85 mg/m2) the patient presented at our emergency unit with progressive dyspnoea and a subfebrile temperature (38.4°C). Laboratory markers of inflammation were elevated (leucocytes 12.400/μL (normal range: 4.000–10.000/μL), CRP 41 mg/L (normal range < 5 mg/L)). Empirical antibiotic treatment with ampicillin/sulbactam was initiated. At that time the conventional chest X-ray and the previous computerised tomography of the chest (obtained one month prior to the initiation of chemotherapy) were inconspicuous (). Nevertheless, the patient's condition continued to deteriorate. On the patient's third day in hospital, his antibiotic therapy was adjusted to piperacillin/sulbactam and ciprofloxacin. From the fifth day onwards, fluconazole was added. During the course of treatment, both the conventional X-ray and the CT scan of the chest revealed bilateral patchy consolidations of both lungs and low-grade pleural effusions (). After seven days, the patient was transferred to the intensive care unit with respiratory failure (O2-saturation 70%). Antibiotic treatment was continued, and noninvasive mechanical ventilation initiated. On the following day, however, the patient had to be intubated because of progressive respiratory distress (arterial blood gases: FiO2 0.55, paO2 36.2 mmHg, pCO2 46.7 mmHg, Horowitz-Index 65.8). Bronchoalveolar lavage was performed. Neither microbiological nor virological examinations revealed the presence of pathogens. Ten days after intubation, the patient's gas exchange parameters showed no signs of clinical improvement (arterial blood gases: FiO2 1.0, paO2 99 mmHg, pCO2 43.0 mmHg, Horowitz-Index 99). The laboratory markers of inflammation continued to increase (maximum values: leucocytes 15.500/μL (normal range: 4.000–10.000/μL), CRP 174 mg/L (normal range < 5 mg/L)). Antibiotic medication was temporarily discontinued, and thoracoscopic wedge resections were performed in all three right pulmonary lobes. Prior to the availability of the microbiological and histological results, antibiotic treatment with ceftazidime and fosfomycin was applied. Neither the Grocott nor the Ziehl-Neelsen or Auramine staining revealed evidence of bacterial or mycotic pathology. Both the mycobacterial PCR and the bacteriological cultures were negative. Repeated microbiological and viral examinations (bronchoalveolar lavage, bloodcultures, galactomannan assay, central venous catheter tip, urine, and legionella-antigens in the urine) all remained negative. No signs of systemic autoimmune disease were to be found. The histological findings revealed extensive granulomatous inflammation with no evidence of malignancy (). No eosinophilic infiltration, fibroinflammatory buds, or collagen bundles as evidence of a hypersensitivity reaction or pulmonary fibrosis were seen. Since a drug-induced lung reaction to chemotherapy was suspected, i.v. high-dose steroid treatment (initial application: 1 g prednisolone per day) was started. Within 36 hours, the gas exchange parameters improved, and the patient was extubated after 4 days on steroid treatment and 16 days on invasive mechanical ventilation. During the following days, intermittent noninvasive mechanical ventilation was gradually reduced and finally discontinued on the third postextubation day. The daily prednisolone dose was reduced to 70 mg after eight days, to 50 mg after 12 days, and finally tapered off over 3 weeks.
On discharging the patient from the inpatient department, we reevaluated his clinical condition and radiological findings and discussed his treatment options with him in detail. His general state of health (ECOG 1) and alimentary status were both good. A dihydropyrimidine-dehydrogenase deficiency, which is sometimes associated with high-grade 5-FU toxicity, was excluded. A CT scan of the chest 5 months after respiratory failure () showed virtually complete resolution with only slight residual subpleural scarring and pleural calcifications.
Finally, with the informed consent of the patient, we decided to implement palliative second-line treatment (5-FU and sodium folinic acid in the form of a 24 h infusion plus weekly irinotecan) []. All in all, the patient received three cycles of palliative second-line treatment, one cycle of palliative third-line treatment (5-FU and sodium folinic acid in the form of a 24 h infusion combined with weekly irinotecan and cetuximab), one cycle of palliative fourth-line treatment (5-FU and sodium folinic acid in the form of a 24 h infusion combined with irinotecan, and bevacizumab every two weeks), and finally additional internal radiotherapy (SIRT). The additional palliative treatment regimens were well tolerated, and no more serious toxic side effects occurred. Pulmonary symptoms did not reoccur. From initiation of palliative first-line treatment, the patient survived 21 months. He died of tumour-associated cardiocirculatory failure caused by progression of the liver metastases.


A 42-year-old male patient with noncontributory medical history was referred for endodontic treatment of the left first mandibular molar. The clinical examination of the tooth revealed no swelling or sinus tract and a slight response to percussion and palpation. The tooth did not respond to thermal or electric pulp tests. A periapical radiograph revealed a deep distal carie and a slight widening of the apical periodontal ligament in the distal and mesial roots (). Based on the clinical and radiographic findings, the diagnosis was established as a pulp necrosis. A treatment plan, including nonsurgical root canal therapy of tooth, was presented to the patient. The patient consented to the proposed treatment.
During the first session, local anesthesia was administered, and a rubber dam was applied. Upon access opening, four well-defined root canal orifices were located using an endodontic explorer (Odous, Belo Horizonte, MG, Brazil) on the pulpal floor, two orifices for the distal root, and two separate orifices for the mesial root. The subpulpal groove of the mesiobuccal root was located after removing the excess dentin using an ultrasonic device (Gnatus, Ribeirão Preto, SP, Brazil) with an ultrasonic tip (TU17; Trinity, São Paulo, SP, Brazil). The tip of the explorer attached in the middle mesial canal orifice, which was located closer to the mesiobuccal canal (). A 4.5× binocular loupe (Bio-Art Equipamentos Odontológicos, São Carlos, SP, Brazil) was used to facilitate this procedure. The radiograph taken to determine the working lengths showed three independent mesial canals (). All root canals were prepared in a crown-down method using ProFile Taper 04/06 rotary NiTi instruments (Maillefer-Dentsply, Ballaigues, Switzerland). Preparation was always performed under irrigation with 2.5% sodium hypochlorite solution followed by smear layer removal with a 14.3% EDTA solution (pH 7.2) for 3 minutes. Afterward, the root canal was dried with paper points and filled with calcium hydroxide paste (Calen, SS White, Rio de Janeiro, RJ, Brazil) using a lentulo spiral. The cavity entrance was closed with a noneugenol temporary filling material (Coltosol, Vigodent, Rio de Janeiro, RJ, Brazil).
The patient returned for a second appointment 10 days later. The temporary restoration was removed under local anesthesia and rubber dam. The root canals were irrigated with 2.5% sodium hypochlorite, and the intracanal dressing was removed, stirring with a size 15 K-file (Maillefer-Dentsply, Ballaigues, Switzerland), followed by a final rinse with a 14.3% EDTA. The canals were dried and filled with a zinc oxide-eugenol-based sealer (Endofill, Dentsply, Petrópolis, RJ, Brazil) and nonstandardized gutta-percha cones (Odous, Belo Horizonte, MG, Brazil) using cold lateral condensation. A temporary filling was placed and a postoperative radiograph was taken to assess the quality of obturation (). The patient was referred for appropriate coronal restoration.
The tooth was asymptomatic and functional after 4 years of followup. The patient was informed about the possibility of CBCT examination, which was unavailable at the time of the initiation of treatment. It was explained that CBCT could be useful to check three-dimensionally the endodontic treatment performed. Thus, CBCT images focused on tooth number 19 were obtained after informed consent of the patient. Axial () and sagittal () slices of 0.076 mm thickness using the CBCT scan (Kodak 9000 3D, Carestream Health, Inc., Rochester, NY, USA) revealed normal periapical status and three independent filled root canals in the mesial root. A three-dimensional rebuild performed from the CBCT images showed in detail the internal configuration of the all filled root canals ().


A 72-year-old man experienced persistent severe back pain after falling from a cultivator 3 months prior to presentation. He demonstrated a normal neurological exam but was unable to ambulate secondary to pain. Magnetic resonance imaging (MRI) demonstrated a collapsed L1 vertebrae, with T1 and T2-weighted sequences showing edema and an intervertebral cleft (IVC) in the central area of the fractured vertebral body (Fig. a). Based on the AO classification, he was having an incomplete osteoporotic burst fracture (AO type A3.1). BKP was performed with injection of about 4.0-mL polymethyl-methacrylate (PMMA) (Fig. b). Postoperatively, his back pain significantly improved. At the time of hospital discharge, 2 weeks after the first operation, he was able to walk without a cane. However, he developed progressive bilateral lower-extremity weakness about 1 month after BKP. Exacerbation of back pain was not observed. Neurological examination revealed weakness in both thighs and legs (MMT 2/3), numbness on the anterior thighs, and symmetrical hyporeflexia (modified Frankel classification C1). MRI of the spine did not reveal canal stenosis but radiograph demonstrated the cement was still contained within the vertebral body. However, lateral spine flexion–extension radiographs demonstrated instability, with discontinuity between the PMMA and the endplate of the treated vertebrae (Fig. a). Surgical intervention was performed by instrumented fusion from T10 to L2 without decompression (Fig. b). Three days postoperatively, motor exam improved to grade four bilaterally with resolution of the paresthesia. Four weeks postoperatively, the patient was able to walk with a T-cane (modified Frankel classification D2).


A 79-year-old man experienced persistent severe back pain after falling from the rear deck of a truck 2 months prior to presentation. The findings on neurological examination were within normal limits. MRI of the spine revealed collapse of the vertebral body with the formation of a cavitary lesion at the T12 level. A high signal on T2-weighted MRI revealed a fluid-filled intravertebral cleft, he was having an incomplete osteoporotic burst fractures (AO type A1.3). Because of his intractable back pain, which was not relieved by conservative treatment, BKP was performed. Approximately, 6.0-mL PMMA was injected into the vertebral body (Fig. ). Immediately after the operation, his back pain improved and he was able to walk without a cane. However, he developed progressive bilateral lower-extremity weakness at about 2 weeks after BKP. Neurological examination revealed right lower-extremity weakness (MMT 2/5), and symmetrical hyporeflexia (modified Frankel classification C2). Similar to case 1, MRI of the spine did not reveal canal stenosis, yet dynamic radiographs demonstrated instability with discontinuity between the PMMA and the endplate of the treated vertebrae (Fig. ). An instrumented fusion was performed between T9 and L2 without decompression (Fig. ). Postoperatively, the patient demonstrated gradual improvement in motor strength to a grade of 5/5 by 1 month (modified Frankel classification D3).