A 26-year-old woman presented with progressive shortness of breath. Her past medical history was notable for asthma diagnosed at age 3, hearing loss at age 23 (that was not fully worked up) and hypertension at age 24. Ten months prior to admission, her blood pressure was 143/91 mmHg, and urine dipstick detected large protein and blood, but she was lost to follow up. The family history was significant for asthma and hypertension in her mother, type II diabetes mellitus in her father and asthma in her brother; her sister was healthy.
On admission, she was afebrile, blood pressure was 191/125 mmHg and the physical examination was otherwise unremarkable; fundoscopy was not performed. Urine analysis detected 25–50 non-dysmorphic RBCs/HPF, 5–10 WBCs/HPF,100 mg/dl protein, positive leukocyte esterase, and numerous “muddy brown casts”. Relevant laboratory results were white blood cell count 7.2× 109/L, hemoglobin of 8.9 g/dL, platelet count 73,000/μL, BUN 71 mg/dL, and serum creatinine 10.11 mg/dL. Other studies include AST 34 u/L, ALT 36 u/L, haptoglobin 10 mg/dl (low), and LDH 2331 u/L (very high). Occasional schistocytes were seen on peripheral smear and ADAMTS13 was normal. Serological studies were normal including C3 (138), C4 (37.2), ANA (neg), anti-MPO (< 0.2), anti-PR3 (< 0.2), anti-GBM antibodies (< 0.1), hepatitis B, hepatitis C, HIV, and serum and urine immunoelectrophoresis. Chest x-ray showed pulmonary congestion and kidneys were echogenic on ultrasound. The patient was started on hemodialysis and a kidney biopsy was performed.
The light microscopy sample had only 2 glomeruli and they had circumferential cellular crescents (Fig. a) and compressed capillary loops. Prominent tubular atrophy and interstitial fibrosis was seen with sparse interstitial inflammation and a few interstitial foam cells. The interlobular arteries and arterioles were mostly well preserved, but one arteriole had endothelial swelling, karryorrhexis and fibrin thrombus (Fig. b). No vasculitis was identified. Immunofluorescence revealed one glomerulus (also with crescent) and segmental granular C3 (1+; scale 0–4). No staining was seen with IgG, IgA, IgM, C1q, κ and λ. Three glomeruli, again with crescents, were available for ultrastructural examination. In addition to the extravasated fibrin and basement membrane rupture, focal endothelial cell damage was apparent with expansion of the subendothelial space by electron lucent material. Several capillary loops had basement membrane irregularities and multi-lamination of lamina densa (Fig. c). No electron dense deposits were identified and podocytes overlying these compressed capillary loops displayed prominent foot process effacement.
The biopsy findings were most compatible with crescentic glomerulonephritis without extrarenal manifestations. Occasional arterioles had histological features of TMA. The glomerular basement membrane changes raised concern for Alport syndrome (AS), but due to the paucity of tissue sample, type IV collagen staining could not be performed. Given the suboptimal sample and concern for systemic TMA and AS, a second biopsy was performed 3 weeks after admission.
Eighteen glomeruli were sampled for light microscopy and three were globally sclerosed. Cellular/fibrocellular crescents were seen in 8 glomeruli with one fibrous crescent. Fibrin thrombi were identified in two glomeruli (Fig. d). Several other glomeruli had ischemic changes and the tubular atrophy and interstitial fibrosis involved over 80% of the cortex. Clusters of interstitial foam cells were seen throughout the cortex. Several cross sections of interlobular arteries and arterioles had intimal edema, fibrinoid necrosis, and concentric thickening of the wall; no vasculitis was identified (Fig. e). Immunofluorescence was negative. On ultrastructural examination of 3 ischemic glomeruli, extensive endothelial cell injury was seen with subendothelial electron lucent material; prominent mesangiolysis was also present (Fig. f). Lamina densa lamellation was again seen. Additional immunofluorescence was performed for type IV collagen α2, α3 and α5 chains (Fig. g-i). Alpha2 staining was normal, indicative of good antigen preservation. However, α3 was completely absent in both glomeruli and tubules, and α5 lacked staining along the glomerular basement membranes but had intact staining along Bowman’s capsules and distal tubular basement membranes.
Both kidney biopsies were stained for C4d (rabbit polyclonal, cat. no. 04-B1-RC4D, Biomedica, Austria, 1/20 dilution) and C5b-9 (mouse monoclonal, cat.no. M0777, DAKO, Denmark, 1/10 dilution). Intimal and medial staining was seen with both C4d and C5b-9 in arterioles affected by thrombotic microangiopathy. Glomerular staining was seen in crescents and sclerosed segments, albeit more strongly with C5b-9 (Fig. ). In addition, C5b-9 staining was seen in patchy peritubular capillaries and interstitium.
Both kidney biopsies demonstrate crescentic glomerulonephritis, with increased chronicity on the second biopsy. In addition, there was acute and subacute TMA, better visualized on second biopsy. A sequencing of 12 aHUS-related genes was performed using a database of over 400 aHUS-associated mutations, disease-associated polymorphisms, benign polymorphisms and other known variants of undetermined significance (Machoan Diagnostics, Oakland, CA). Our patient was negative for the large CFHR1-CFHR3 homozygous deletion associated with CFH auto-antibodies. However, she had a heterozygous missense variant (c.1246 A > C, p.lle416Leu) in exon 11 of CFI, reported in aHUS [, ]. A heterozygous missense variant (c.136C > T, p. Pro46Ser) in exon 2 of CFHR5, reported in dense deposit disease was also noted []. A heterozygous polymorphism (IVS9–78 G > A) within an intron in MCP/CD46 was present and there were also 5 SNPs near and within MCP/CD46 that comprised a haplotype, also associated with increased risk for aHUS [].
The clinical, laboratory and genetic findings indicate a diagnosis of aHUS coexistent with glomerular crescents seen on biopsy. The interstitial foam cells on light microscopy (in the absence of chronic nephrotic proteinuria), basement membrane abnormalities on electron microscopy and abnormal immunofluorescence for α3 and α5 chains of type IV collagen support a diagnosis of AS, that likely contributed to the underlying chronic kidney disease. The immunofluorescence pattern of α3 and α5 staining suggests a α3 gene mutation with autosomal recessive inheritance. A genetic analysis for AS was suggested.
The patient was treated on admission with pulse methylprednisolone followed by oral prednisone. Daily plasmapheresis was initiated, but was discontinued after a few days once the ADAMTS13 levels were found to be normal. Cytoxan was administrated after the first biopsy results. Eculizumab therapy was initiated after the second biopsy and she continued to receive it every 2 weeks at her 8-month follow up. Her kidney function remains poor requiring maintenance hemodialysis.


A routine urine test of a 19-month-old male infant showed urine protein ++ and occult blood. Twenty-four-hour protein excretion was 1340 mg/24 h. Serum albumin was 39.3 g/l. Twenty days later, he was sent to our hospital for diagnosis and his urine protein and occult blood were tested in our ward; results were still positive. No other symptoms and abnormal laboratory examination results were found. Pregnancy and birth were normal and term. No known family member had shown similar symptoms, including his mother. The urine protein tested by electrophoresis analysis also showed LMW proteins (Table ), mainly RBP, α1-microglobulin, and β2-microglobulin. However, the urine calcium to creatinine ratio was in the normal range (0.236). Renal biopsy was not performed. Instead, NGS was directly used for screening for Dent disease. A hemizygotic mutation (c. A815G, p.Y272C) was found in the exon of the CLCN5 gene(ChrX:49850995), which has also been reported in another two Dent 1 case (, ). The same mutation was detected in his mother. Two months later, calcium to creatinine ratio was tested in the child showing 0.608 in a spot sample, which also reached the standard of hypercalciuria.
Table outlines the clinical characteristics of the two boys with Dent disease 1. Serum creatinine was measured using an enzymatic method and renal function was calculated using the modified Schwartz formula.


A 35-year-old Caucasian female patient presented to her local emergency department in November 2016 with a chief complaint of neck pain. The patient had a past medical history significant for Hodgkin lymphoma diagnosed in 1998 following excision of a neck mass at age 16. She underwent chemotherapy and mantle field radiation in 1998. The radiation targeted lymph nodes in the neck, axilla, and behind the sternum in order to encompass the nodal basin of her cancer and the common lymph node drainage areas. The patient denied any history of radiation to her face. She reported remission at the time of presentation for this complaint of neck pain and was not following with anyone for her history of HL. She had no notable past surgical history. Menarche was at age 13 and she gave birth to one child at age 18. The patient’s family history was unremarkable with the exception of ovarian cancer in her maternal great aunt. There was no family history of breast or thyroid cancer. The patient was a previous smoker, quitting after about 10 years of use. No drug or alcohol use was recorded.
In the emergency department, a neck CT revealed a subcutaneous mass over the mid-clavicle, a breast mass, and multiple nodules in the thyroid gland with the largest nodule measuring 1.5 × 1.6 × 2.0 cm. The breast mass had dimensions of 2.6 × 4.0 × 4.9 cm by ultrasound. The patient was instructed to follow-up in breast and thyroid clinics for these findings.
The patient followed the emergency department’s recommendations and was examined by a surgical oncologist. In the breast clinic, she stated that the large right upper-outer quadrant breast mass had been present for 1 year. She was unsure how long the mass overlying the clavicle had been present, as it had been asymptomatic. On physical examination, the patient appeared well developed and well nourished. Respiratory, abdominal, musculoskeletal, and cardiovascular systems were normal. An 8.0 cm mass was located in the upper-outer quadrant of the right breast centered at the 10:00 axis about two fingerbreadths on the nipple border. Nipples were normal bilaterally. There was no cervical, supraclavicular, or axillary lymphadenopathy. Directly overlying the clavicle about two fingerbreadths medial to the mid-clavicular line was a 0.6 cm mobile mass within the skin. It was not associated with any regional lymphadenopathy. Laboratory workup was negative and unremarkable.
The patient underwent a bilateral mammogram in December 2016, followed by ultrasound-guided core biopsy of the breast mass. Initial core biopsy performed at an outside institution of the right breast mass came back as fibrocystic change. The outside biopsy was not reviewed at our institution. Based on a high level of clinical suspicion, additional imaging and a repeat biopsy were performed at our institution in January 2017. The repeat biopsy of the right upper-outer quadrant breast mass showed a phyllodes tumor. Pathology results described a fibroepithelial lesion with hypercellular stroma, mild-moderate stromal cytologic atypia, increased stromal mitotic activity (4-5/10 HPF), and focal areas suggestive of phyllodes architecture. The nature of the margins (pushing or infiltrative) could not be determined from the biopsy material. MRI showed the phyllodes tumor in the right breast measuring 4.7 cm. An excisional biopsy of the clavicular mass was done in a separate operation. The biopsy result was a cutaneous adnexal adenocarcinoma with eccrine differentiation. Surgical excision was recommended for both the breast and clavicular masses (Figures and ).
The patient also followed up in thyroid clinic for the multinodular goiter seen on her CT scan of the neck in the emergency department. Review of systems in the thyroid clinic was negative for change in voice or positional dyspnea but was significant for difficulty swallowing that started roughly 3 months prior. The patient also had pain in the right lower neck. She described the pain as constant, with an intensity of 5/10, and alleviated by acetaminophen. Ultrasound revealed three complex nodules with the largest in the left lobe measuring 1.3 × 1.8 × 2.5 cm, and other smaller nodules. The patient was diagnosed with multinodular goiter at this time. Two nodules met criteria for FNA. Cytology for both nodules was benign. The patient elected to defer any intervention and did not continue to follow-up.
In early March 2017, the patient underwent wide local excision of the phyllodes tumor, wide local excision of the cutaneous adnexal adenocarcinoma and right axillary sentinel lymph node biopsy, and concurrent post-reduction bilateral oncoplastic reconstruction. Surgery entailed intra-dermal injections of Tc99m-filtered sulfur colloid 1-2 cm from the margins of the lesion located over the right clavicle. Lymphoscintigraphy revealed uptake in two right axillary nodes. Once in the operating room, a standard axillary incision was made and 2 “hot” and blue lymph nodes were identified and removed. The cutaneous adnexal adenocarcinoma was then resected with a 1.5 cm margin which created a 4 × 10 cm ellipse. A lumpectomy was performed through predesigned incisions to ensure a cosmetically favorable closure for the phyllodes tumor in the right upper-outer breast. After removal, the plastic surgery team completed a bilateral breast tissue rearrangement and left breast reduction for symmetry. All aspects of the operation went smoothly, and the patient recovered uneventfully.
Pathology confirmed a phyllodes tumor measuring 4.1 cm in greatest diameter and clear margins. The phyllodes tumor pathology showed a circumscribed border, mild to moderate stromal cellularity, mild stromal cytologic atypia, and a mitotic rate of 4-5/10 HPF. Necrosis and malignant heterologous elements or stromal overgrowth were not identified. Overall, features were consistent with a benign phyllodes tumor (Figure ).
The adnexal neoplasm in the right chest was resected with negative surgical margins, and 0 of 2 nodes were positive for metastatic disease. The pathology report noted the presence of mitotic figures and rare atypical mitotic figures, favoring the diagnosis of a malignant adnexal neoplasm. The report adds that since the breast is a modified sweat gland, it is impossible to distinguish a primary cutaneous adnexal neoplasm from a primary breast neoplasm based on histologic features and that no immunoperoxidase stains can distinguish these two entities.
On her first postoperative clinic visit, the patient was recovering well. Her incisions were clean, dry and intact without erythema, drainage, hematoma or seroma. The patient has since continued to follow-up and has not experienced any complication or recurrence. She is recommended to follow-up annually.


The patient is a 78-year-old man referred to our department for splenomegaly seen on abdominal computed tomography (CT) scan. Eight years previously, the patient underwent extended thymectomy and postoperative radiation therapy for a thymoma (WHO classification, AB type; Masaoka classification/TNM classification, stage II) with subsequent follow-up. Five years after resection, a low density, isolated nodule in the spleen was seen on CT scan. Although follow-up continued for three years thereafter, the lesion was noted to continually increase in size, and the patient was then referred for further examination and treatment.
The patient underwent appendectomy for acute appendicitis at the age of 23 years, treatment for hypertension since he was 61 years old, extended thymectomy at age 71 years, and laparoscopic left hemicolectomy for cancer of the descending colon (stage I) at age of 73 years of age. The remainder of the history and physical examination were unremarkable, except for healed surgical scars from the previous thymectomy and the laparoscopic left hemicolectomy. Laboratory studies showed no abnormalities. Serum tumor marker levels were within normal limits (CEA 1.9 ng/ml, CA19–9 12 U/ml, SCC 1.5 ng/ml, CYFRA 2.0 ng/ml, PSA 1.29 ng/ml).
CT scan showed a sharply circumscribed 50 mm tumor slightly hypodense and heterogeneous enhancing lesion in the spleen with no intraperitoneal lymphadenopathy (Fig. ). On Magnetic Resonance Imaging (MRI), T2-weighted images, the tumor had high intensity, equivalent to or slightly lower than that on T1-weighted images, and no decrease on diffusion-weighted images. The tumor was multinodular and had a low-signal spoke-wheel sign in the margin, enhanced gradually on the dynamic study (Fig. ). Follow-up CT scan showed the tumor gradually increased in size over three years. On positron emission tomography (PET)-CT, the tumor had relatively low accumulation (Fig. ).
Based on these diagnostic imaging studies, we considered metastatic thymoma, hemangioma or lymphangioma with bleeding and organization, and sclerosing angiomatoid nodular transformation in the differential diagnosis. Surgical resection was then recommended to the patient and undertaken. The lesion was visually confirmed intraoperatively. No extracapsular invasion was observed. A laparoscopic splenectomy without lymphadenectomy was performed.
Pathological examination showed that the spleen was 12 × 7 × 6 cm in size. A lobulated medullary tumor was seen, 6 × 5 × 4.5 cm in size, yellow-brown in color on cut surface (Fig. ). The capsular structure of the spleen was maintained. Histologically, spindle to slightly epithelioid-shaped cells homogeneous in size with abundant nuclear divisions were growing in a medullary manner with blood vessels. The lesion was morphologically similar to the previously resected thymoma (Fig. ). Pancytokeratin and p63 were positive, while CD5 and c-Kit were negative histochemically. Vascular endothelium markers (CD31/CD34/factor VIII) were negative. TdT-positive lymphocytes were not discovered on immunostaining. Based on its histological appearance, the splenic mass was unlikely to be a primary splenic tumor or related to a hematological disease. The lesion was not consistent with a metastasis from the previous colon cancer. The histological appearance of the tumor was similar to the previously resected thymoma, and the final pathological diagnosis was metastatic thymoma (Fig. ).
The patient is now three years status post resection of the spleen and is followed every three months. He is in good condition without recurrence or any other symptoms.


A 16-year-old boy without systemic disease had come to our attention in October 2012 with a diagnosis of bilateral JOAG and high myopia (− 8.0D). Although he was treated with dorzolamide 2%, latanoprost 0.005%, brimonidine 0.2%/timolol 0.5% fixed combination, and oral acetazolamide 500 mg/day at another hospital, his IOP was approximately 25 mmHg and was poorly controlled in both eyes by full medication. Several months before this visit, he had ceased treatment with anti-glaucoma medication. His BCVA was 20/20 in both eyes in 2012, though it gradually deteriorated to 20/400 in both eyes in 2017. Gonioscopy revealed a normal iridocorneal angle; pachymetric measurements were 611 μm in the right eye and 614 μm in the left eye. The axial length of the right eye was 27.56 mm and that of the left eye was 27.46 mm. Fundoscopic examination revealed bilateral enlarged disc cupping of the optic nerves with sectorial excavation and reduction of the neural rim in the left eye (Fig. ). Optical coherence tomography angiography (OCTA) revealed retinal nerve fiber layer (RNFL) thinning over the temporal upper and lower quadrants and nasal upper quadrant of the right eye and RNFL thinning at the temporal quadrant and nasal upper quadrant of the left eye (Fig. ). The vascularity of the peripapillary capillaries was 43.6% in the right eye and 49.15% in the left eye. Both eyes revealed a decrease in the sectoral division of the temporal regions (Fig. ). A VF of 30–2 Swedish interactive thresholding algorithm standard (30–2 SITA standard) was characterized by progressive central scotoma in both eyes (Fig. ). Due to the presence of bilateral progressive central scotoma, further examinations were arranged. The electroretinogram (ERG) result was subnormal in both eyes, and there were more decreased amplitudes in the right eye than there were in the left eye. However, no obvious implicit time delay was noted. The pattern visual evoked potential (VEP) and pattern ERG showed extinguished responses in both eyes (Fig. ). A brain MRI revealed an incidental finding of a 0.8 mm non-enhancing nodule in the pituitary gland. Furthermore, the genetic test revealed an ND4 m11778G > A mtDNA mutation, which is pathognomonic for LHON. High-dose ubidecarenone (240 mg/day) was prescribed by the neurologist. However, under high-dose ubidecarenone therapy, the patient’s IOP was still poorly controlled and his visual acuity gradually decreased to less than 20/400 in both eyes after one year of ubidecarenone treatment.


A 15-year-old boy, the first younger brother of Patient 1 who was diagnosed with bilateral JOAG in 2010, attended our clinic in October 2012. He denied having systemic disease, but he had a family history of glaucoma and LHON (Fig. ). After taking medication, including dorzolamide 2%/timolol 0.5% fixed combination, latanoprost 0.005%, and brimonidine 0.15%, IOP was controlled in both eyes. His BCVA of both eyes remained at 20/20 during the follow-up period. Gonioscopy revealed a normal iridocorneal angle, and the pachymetric measurements were 592 μm in both eyes. Fundoscopic examination revealed bilateral mildly paled optic disc with enlarged cupping and reduction of the neural rim in both eyes (Fig. ). OCTA revealed RNFL thinning at the nasal upper quadrant of the left eye (Fig. ). The VF (30–2 SITA standard) was normal in both eyes during the follow-up period. The pattern VEP showed no delay, and the pattern ERG revealed decreased N95 amplitudes in both eyes (Fig. ). The genetic test revealed an ND4 m11778G > A mtDNA mutation, which is pathognomonic for LHON. High-dose ubidecarenone(240 mg/day) was prescribed as well. During the course of high-dose ubidecarenone treatment, the patient’s IOP, visual acuity, and visual field remain stable.


A 35-year-old man without systemic disease first attended our clinic in August 2004 for bilateral JOAG. He denied having a family history of glaucoma, but his uncle had been diagnosed with LHON. When he was undergoing therapy with timolol 0.5%, his IOP was approximately 20 mmHg in both eyes. His BCVA gradually decreased from 20/200 in both eyes in 2006 to counting fingers at 25-30 cm in both eyes in 2016. Gonioscopy revealed a normal iridocorneal angle; pachymetric measurements were 561 μm in the right eye and 563 μm in the left eye. Fundoscopic examination revealed paled optic disc with enlarged disc cupping of the optic nerves with sectorial excavation and reduction of the neural rim in both eyes (Fig. ). OCTA disclosed diffuse RNFL thinning and a decreased peripapillary vascularity in both eyes (Fig. ). The VF (30–2 SITA standard) was characterized by progressive central scotoma in both eyes. The ERG was subnormal in both eyes, and the pattern ERG revealed decreased N95 amplitudes in both eyes (Fig. ). The genetic test revealed an ND4 m11778G > A mtDNA mutation, which is pathognomonic for LHON.


The patient was a 9-yr-old Iranian girl presenting to the Pediatric Emergency Room of Moosavi Hospital, Zanjan, Iran in January 2017, with sudden onset of headache and recurrent vomiting, ataxia and history of 3 consecutive days of fever and malaise. There were left eye ptosis and decrement of left nasolabial fold in patient’s face. The patient had tremor and truncal ataxia. The force of the extremities and deep tendon reflexes were normal in physical examination. Her heart rate was 110 min, blood pressure 90/60 mm Hg and temperature 38.2 °C. The patient’s weight was 21 kg and had 133 cm height and head circumference was 52 cm. The patient had no history of head trauma.
An informed consent was obtained from her parents in order to publish data as a case report without publishing her name. Ethics Committee of the university approved the study.
Diagnostic focus and assessment:
The patient underwent a brain CT scan without contrast in first day of admission preceded by CBC, diff, BUN, Cr, Na, K, Arterial blood gas sampling (ABG) and Urine analysis. On the second day, brain magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) with flair, T1, T2 and DWI sequences and also EEG were ordered, then lumbar puncture with 3 samples was carried out. About 48 h after the MRI the patient became aggressive and had severe headache, nausea and vomiting plus ataxia and delirium, then the patient transferred to PICU and we decided to order the second CT scan and after the results, we asked for urgent neurosurgery consultation and the patient was prepared for brain surgery. The day after surgery the patient underwent brain CT scan without contrast again and laboratory tests were repeated. The patient underwent the last brain CT scan without contrast on thirteenth day and also had an EEG on the same day. We also did a portable echocardiography plus electrocardiography to determine presence of any PFO or ASD or any cardiac problems.
Therapeutic focus and assessment: The patient presented with sudden onset of headache and recurrent vomiting, ataxia, and history of 3 consecutive days of fever and malaise. Our first clinical suspicion was cerebellitis or post infectious ataxia () so we ordered intravenous ceftriaxone, intravenous pantoprazole, and ondansetron for two days. We also ordered acyclovir ampule plus dexamethasone ampule for the patient and after the brain MRI results that were consistent with cerebellar infarction aspirin tablet was prescribed for the patient. On the fourth day (48 h after) because of the patient’s severe headache, intravenous acetaminophen was administered and dexamethasone was held and the patient was transferred to pediatric intensive care unit (PICU) and intravenous phenytoin ampule plus vancomycin ampule were prescribed. After the brain CT, because of obstructive hydrocephaly arising from cytotoxic edema mannitol and dexamethasone ampule were ordered for the patient and the patient became ready for the brain surgery. The next day after the surgery and inserting a drain in the left lateral ventricle, mannitol was discontinued. The day after, phenytoin ampule was held and Diamox tablet (acetazolamide) was ordered. Physiotherapy and occupational therapy of the left extremities begun for the patient and because of constipation lactulose syrup were ordered.
Follow-up and outcomes
The first EEG report was mildly abnormal due to some spike and wave discharges (Figure 2 Left) and in the last EEG report, there were some background attenuations without epileptiform activity (Figure 2 Right). The patient had a lumbar puncture with normal result. The first and the last laboratory data are as follows ()
The urine analysis result was normal. The HPLC Amino Acid profile was normal except lower than normal range of arginine (26.8) and higher than normal range of alanine (148.0). We also obtained an Arterial Blood Gas sample from the patient that was normal (Table 1). The echocardiography and electrocardiography results both were normal. Findings on the first brain CT scan were a dim hypodensity in the left cerebellar hemisphere accompanied by a mild generalized ventriculomegaly ( Left). The MRV’s result was also normal ( Right). In the MRI report, there were abnormal low T1 and high T2 signal intensity in left cerebellar hemisphere involving superior and middle cerebellar peduncles in the same side as well ( Right , Middle), restriction was noted in this region. DWI findings were consistent with cerebellar infarction in this region ( Left). On the second brain CT scan that was 48 h after the MRI, there was an intense hypodensity arising from cytotoxic edema in the left cerebellar hemisphere with concomitant cortical entanglement exerted pressure on fourth ventricle and had resulted in hydrocephaly, severe ventriculomegaly was also seen in the CT scan ( Left) . On the third brain CT which was after the patient’s surgery, there were evidence of craniotomy in occipital bone on the left side and hemispherectomy of the left hemisphere of the cerebellum, the drain in the left lateral ventricle was in its appropriate position ( Middle). The last brain CT scan had no new findings and the drain was extracted from the brain ( Right). Pathology result of surgical biopsy of brain tissue was cerebellar tissue with small foci of hemorrhage accompanied by presence of vascular malformation, most probably venous angioma.
After 5 months the force of the extremities was normal and the ataxia was completely disappeared. The patient now goes to school and has no problems in daily life activities. The patient is now under treatment with an aspirin 80 mg tablet daily.


A 56-year-old Caucasian man with severe AS (valve area 0.81 cm2, mean gradient 54 mmHg), high Society of Thoracic Surgeons (STS) score (> 8), moderate chronic obstructive pulmonary disease with forced expiratory volume in 1 second (FEV1) of 1.9 L at 53% of predicted, Crohn’s disease (on immunosuppressive therapy), hypertension, and non-obstructive coronary artery disease presented for a TAVR procedure under monitored anesthesia care. An echocardiogram and subsequent left ventricular hemodynamic study completed as part of the preoperative evaluation showed symmetric, concentric left ventricular hypertrophy with no left ventricular outflow gradient. His early intraoperative course was unremarkable. Following successful deployment of the transcatheter valve and cessation of rapid ventricular pacing at 180 beats per minute, he became hypotensive, tachycardic, and short of breath. Despite escalating doses of phenylephrine, ephedrine, vasopressin, norepinephrine, and epinephrine, he remained profoundly hypotensive and unresponsive. He continued to decompensate and developed acute pulmonary edema, requiring oral suctioning and rapid sequence intubation. Given his deterioration immediately following rapid pacing and valve deployment with poor response to epinephrine, an LVOT obstruction was considered, but other etiologies were included in the differential (Table ). Consequently, inotropic medications were ceased and rate-control and afterload-increasing medications (esmolol, phenylephrine) were prioritized with marked improvement in symptoms. An expedited intraoperative transesophageal echocardiography (TEE) assessment confirmed the presence of hypertrophic cardiomyopathy pathology causing LVOT obstruction with associated mitral valve systolic anterior motion, as shown by the “hockey sticking” of the anterior mitral valve leaflet into the LVOT in Fig. a. The physiologic consequence of this decompensation is clearly represented in Fig. b, showing a near obliteration of flow across the LVOT. The initial peak gradient across the LVOT obstruction reached 70 mmHg, and we considered performing an urgent septal alcohol ablation in the event that the gradient remained refractory to our attempts at medical management. Beta blockade with metoprolol was titrated for rate control, a phenylephrine infusion was started to maintain systemic vascular resistance, and fluid resuscitation to achieve euvolemia was guided by TEE. This resulted in a significant improvement of the LVOT obstruction (peak gradient of 25 mmHg, mean of 13 mmHg) as shown in Fig. a and b. Intubated, paralyzed, and showing stable vital signs, our patient was transported without external pacing to the intensive care unit. Subsequent arterial blood gas was normal with improving respiratory status.
He was mechanically ventilated, sedated, and remained on a phenylephrine infusion until postoperative day (POD) 1 when he became responsive. A transthoracic echocardiogram showed moderate to severe concentric left ventricular hypertrophy, normal left ventricle (LV) systolic function, ejection fraction of 60%, and a normally functioning prosthetic valve with peak gradient of 27 mmHg and mean systolic gradient of 10 mmHg. An overlying LVOT gradient of 40 mmHg that was late peaking was also observed. He was weaned from vasopressor medications and extubated on POD 2. He was ambulatory and able to move to the ward on POD 4, and was discharged on POD 5. Post-discharge, his LVOT gradient gradually increased again and his HOCM was deemed refractory to medical management. Eight months after his TAVR, he received an alcohol ablation which successfully relieved the LVOT obstruction.


A 40-year-old woman, 90 kg, was admitted to the Intensive Care Unit of University of Campania “L. Vanvitelli” from an outlying hospital because of an intubation-related tracheal lesion. The intubation has been necessary for the removal of right vocal cord using direct suspension microlaringoscopy (SDML) with CO2 laser. The patient showed severe subcutaneous emphysema extended from the chest up to the neck and head. She was affected by dyspnea, with 50% inspired oxygen through the Venturi mask. Blood pressure (BP) was 150/95 mmHg, mean arterial pressure (MAP) 113 mmHg, heart rate (HR) was 120 bpm, and peripheral oxygen saturation (SpO2) was 93%. The neck and chest CT (computerized axial tomography) scan showed “a 4-cm length lesion into the right posterolateral wall of the trachea in correspondence with the fourth dorsal vertebra, about 37 mm from carena; pneumomediastinum; diffuse signs of subcutaneous and perimuscular emphysema were visible, from the chest till to the neck to the head; and normal expansion of lung areas.” (Fig. ). The patient was, immediately, carried to the operating theater for a diagnostic bronchoscopy and for the endoscopic suture with fibrin glue. We decided to manage the airway using an LMA positioned in deep sedation. Sedation was induced using propofol 4 mg/kg/h and fentanyl 1 μg/kg. We also administered 0.5 mg/kg of intravenous lidocaine to blunt laryngeal reflexes. We conducted the anesthesia by mean of spontaneous breathing with oxygen supplement throughout manual breathing circuit. The patient was placed in extended neck position. The blood pressure monitoring was executed by left radial artery catheterization and pulse oximetry on the other side. Heart rate and end expiratory CO2 (ETCO2) were also monitored. The flexible bronchoscope was introduced through the LMA (Fig. ). Intraoperative monitoring: the thoracic surgeon first of all confirmed the tracheal lesion and then sutured it with 6 ml of fibrin glue. The procedure lasted about 30 min. During the procedure, all the hemodynamic parameters were stable. At the end, the patient was awakened in the operating room and moved to the Intensive Care Unit spontaneously breathing with 50% inspired oxygen through the Venturi mask. Forty-eight hours after the surgery, a chest and neck CT scan was made. It showed the resolution of pneumomediastinum and subcutaneous emphysema, and so the patient was transferred to the thoracic surgery ward and 72 h after the surgery she was discharged. She came back 15 days after the surgery and for a diagnostic flexible bronchoscopy that showed a complete resolution of the tracheal rupture.


A 53-year-old woman, 125 kg weight, 175 cm tall, body mass index (BMI) 40.8 kg/m2, was admitted to the Intensive Care Unit of University of Campania “L. Vanvitelli” from a nearby hospital because of an iatrogenic intubation-related tracheal lesion. The intubation has been necessary in order to perform anesthesia for a laparoscopic sleeve gastrectomy. The patient was affected also by hypertension and hypercholesterolemia. She arrived with an orotracheal tube (size 7.0 mm reinforced) and in assisted ventilation through manual breathing circuit. She presented a severe subcutaneous emphysema from the chest till to the neck to the head. The hemodynamic parameters were not too stable (BP 180/100 mmHg, MAP 127 mmHg, HR 130 bpm, SpO2 97%). A diagnostic fibrobronchoscopy was immediately performed. It showed a 2-cm lesion of pars membranacea in subglottic region. During fibrobronchoscopy, the orotracheal tube was changed with a 6.0-mm-size tube, positioned distally the lesion and before the carena. A chest radiograph was made, and pneumomediastinum and subcutaneous emphysema were confirmed. The patient was thus carried to the operating room. We decided to anesthetize the patient with propofol 6 mg/kg/h and fentanyl 2 μg/kg. We also administered 0.5 mg/kg of intravenous lidocaine to blunt laryngeal reflexes. The neuromuscular blockage was achieved with rocuronium bromide 0.6 mg/kg. During the procedure, protective mechanical ventilation was set up (tidal volume 6 ml/kg, positive end expiratory pressure (Peep) 5 mmHg, FiO2 50% respiratory rate 15). The patient was placed in extended neck position. The blood pressure monitoring was done by left radial artery catheterization and pulse oximetry on the other side. Heart rate and ETCO2 were also monitored. The flexible bronchoscope was introduced next to the lesion and before the tube cuff. The thoracic surgeon first of all confirmed the tracheal lesion, and then, he sutured it with 5 ml of fibrin glue. At the end of the surgery, the patient was awakened and extubated and then she was carried to the Intensive Care Unit for postoperative monitoring in spontaneous breathing with 50% inspired oxygen through the Venturi mask. Forty-eight hours after the surgery, esophageal X-ray was taken to exclude an esophageal lesion and to check the sleeve gastrectomy and eventually the nasogastric tube was removed. Seventy-two hours after the surgery, there was a notable reduction of subcutaneous emphysema and good hemodynamics. Consequently, the patient was moved to the thoracic surgery ward.


A 63-year-old woman, weighing 60 kg, 165 cm tall, with BMI of 22 kg/m2 was admitted to the Intensive Care Unit of University of Campania “L. Vanvitelli” from a regional hospital because of an iatrogenic tracheal lesion probably due to the removal of a neoplasm that was involving the epiglottis and vocal cords. At the end of the surgery, during the patient’s awakening, hemoptysis showed up with dyspnea and a fibrobronchoscopy had to be made that showed a lesion on the right bronchus. Excluding the right lung, a double-lumen tube (Robertshaw 37F) was positioned in order to reduce the air leak and protect the airway from bleeding and then the patient was carried to the Intensive Care Unit of University of Campania “L. Vanvitelli”. The patient was suffering from hypertension. She was affected by subcutaneous emphysema from the chest to the neck and the head; thus, a right chest drainage was positioned because of pneumothorax. The blood gas analysis showed respiratory acidosis with hypoxia (partial pressure of oxygen (PaO2) 75 mmHg) and hypercapnia (partial pressure of carbon dioxide (PCO2) 60 mmHg). The patient was connected to a mechanical ventilator (FiO2 65%, Peep 5, tidal volume 4 ml/kg, inspiratory/expiratory ratio 1/2.5). A flexible fibrobronchoscopy was taken that showed a lesion of the right bronchus 4 cm distal the carena. A chest X-ray demonstrated emphysema of the chest wall and neck, pneumomediastinum, and bilateral pleural effusion. The patient was transferred to the operating room in order to proceed with the operative bronchoscopy. We decided to manage the airway by removing the double-lumen tube and positioning a small size single lumen tube (5.5) into the left bronchus in anesthesia with propofol 6 mg/kg/h and fentanyl 2 μg/kg. The neuromuscular blockage was achieved by rocuronium bromide 0.6 mg/kg. We also administered 0.5 mg/kg of intravenous lidocaine to blunt laryngeal reflexes. During the procedure, the mechanical ventilation was started (tidal volume 4 ml/kg, Peep 5, FiO2 50%, respiratory rate 18). The flexible bronchoscope was introduced beside the orotracheal tube next to the lesion, and the thoracic surgeon sutured the bronchus lesion with 5 ml of fibrin glue. After the surgery, the patient was carried to the intensive care unit without changing either the tube or the mechanical ventilation (tidal volume 4 ml/kg, Peep 5 mmHg, FiO2 50%, respiratory rate 18). Twelve hours after the surgery, a consultation with an otolaryngologist was asked for and a flexible videolaryngoscopy was taken which both confirmed edema and hyperemia of the larynx, glottis, and subglottic region. The extubation was not considered safe, the single-lung ventilation was no longer acceptable, and the normal double-lung ventilation could be detrimental to the bronchus suture. So we decided to practice a percutaneous tracheostomy (single-dilator percutaneous tracheostomy Ciaglia techniques), and at the end of the procedure, the mechanical ventilatory weaning both in analgosedation with remifentanil and in assisted ventilation (Peep 0, pressure support 8, FiO2 0, 45 tidal volume 500, respiratory rate 16) was carried out. Twenty-four hours after the surgery, the patient was freed from mechanical ventilation and put in spontaneous breathing by tracheostomy with oxygen supplement 5 l/min. Ninety-six hours after the surgery, there was a notable reduction of subcutaneous emphysema and good hemodynamics and so the patient was moved to the thoracic surgery ward. Eighteen days after the surgery, a new consultation with the otolaryngologist and a flexible videolaryngoscopy were carried out that showed the complete resolution of edema; hyperemia of the larynx, glottis, and subglottic region; and normal mobilization of the vocal cords and so the tracheostomy tube was removed, and the day after, the patient was discharged from the hospital.


A 54-year-old male who had a left hemisphere ischemic stroke 2 years ago was recruited. The participant had limited voluntary motion in the arm and hand with significant muscle atrophy but had no cognitive impairments. The average ratio of the subject's maximum finger forces between hands was 0.076, and the subject's Chedoke-McMaster Stroke Assessment hand score was 2, both indicating severe impairment. A 35-year-old male participant was also recruited as a neurologically-intact control subject for comparison. This study was carried out in accordance with the recommendations of the Institutional Review Board (IRB) of the University of North Carolina at Chapel Hill with written informed consent from the subject. The subject gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the local IRB. Additional written informed consent was obtained from the subject for the publication of this case report.


A 52-year-old man was admitted to our institute due to a history of chronic cough, dysphagia and an abnormal chest radiographic finding. A chest x-ray and computed tomographic angiography scan (CTA) revealed an ARSA behind the esophagus with about 5.6-cm sized proximal descending aortic aneurysm (Fig. a). The esophagus was clearly compressed by the ARSA (Fig. b), likely causing the dysphagia. Both carotid arteries had a common origin. Because of his progressive symptoms and large fusiform thoracic aneurysm, we planned the hybrid repair for simultaneous relief of ARSA causing dysphagia and thoracic aneurysm. First, an ARSA to the right carotid artery transposition with a proximal ligation of the ARSA along distal to the right vertebral and mammary arteries was performed via the right supraclavicular incision (Fig. c). One hour later, we performed a thoracic endovascular aortic repair (TEVAR), deploying of a thoracic endovascular covered stent graft (Valiant™ thoracic stent graft with the Captivia™ delivery system) in the descending thoracic aorta with the coverage of the origin of the ARSA and the proximal descending thoracic aneurysm. The postoperative recovery was uneventful. The follow-up thoracic CTA revealed no endoleak, no graft migration, and complete exclusion of the ARSA and aneurysm. The right carotid to subclavian artery re-routing was showed to be excellent structural integrity and normal flow patterns with well-preserved right vertebral artery and right upper limb flow (Fig. ). He was asymptomatic with complete resolution of his cough and dysphagia.


The male infant was born to a 23 year-old primi-gravida mother. Pregnancy was uneventful, fetal urinary tract appeared normal on ultrasound, the mother’s medical history was negative for any medication as was family history for renal or cardiovascular disease. While amniotic fluid volume seemed normal on routine ultrasound examinations, anhydramnios of unknown origin was observed at 32 weeks of gestation. No signs of tear or leak in the amniotic membrane were detected. Anhydramnios and pathological umbilical blood flow led to Caesarean section at 34 + 0 weeks of gestation. Birthweight was 2515 g (66th percentile), head circumference 31 cm (24th percentile), APGAR scores 9 at 5′ and 10 at 10 min, umbilical cord artery pH 7.35. The anterior fontanelle was wide and the infant showed features of Potter-sequence with contractures of wrist and ankle joints as well as epicanthus. He also presented with distinct general edema.
After good postnatal adaptation, the infant needed mechanical ventilation due to respiratory distress caused by a spontaneous right-sided pneumothorax at the age of 1 h. He quickly stabilized after nasotracheal intubation and placement of a chest tube. Neither signs of pulmonary hypoplasia nor pulmonary hypertension were evident from chest x-ray or echocardiography (see Fig. a and b). Pre- and postductal oxygen saturation monitoring did not show any significant difference, ventilatory support was minimal (SIMV-mode, PIP 13 mbar, FiO2 0,25) and the patient had no signs of surfactant deficiency.
During the first day of life, he developed severe arterial hypotension (mean arterial blood pressure around 30 mmHg, below 10th percentile []) and consecutive renal failure and anuria (no urinary output for 36 h, serum creatinine 1,98 mg/dl, blood urea nitrogen (BUN) 120 mg/dl) which poorly responded to fluid boluses, catecholamine therapy (dobutamine, noradrenaline and epinephrine), furosemide and hydrocortisone therapy. Sepsis, cystic kidney disease and connatal nephrotic syndrome were ruled out. The cortisol level was normal. Echocardiography revealed good biventricular function without signs of pulmonary hypertension.
After 36 h, vasopressin therapy was initiated with excellent response at doses of 0,001 IE/kg/min; blood pressure stabilized with consecutive onset of diuresis almost immediately after starting of vasopressin (see Fig. ). Initially elevated creatinine and blood urea nitrogen normalized with the onset of diuresis. Weaning of vasopressin, however, was difficult due to rapid deterioration of blood pressure and urinary output and could not be discontinued for the next three weeks. Oligohydramnios, refractory arterial hypotension, renal failure with normal renal ultrasound was highly suggestive of renal tubular dysgenesis. On the fourth day of life, the patient suffered from a spontaneous gastric perforation, which was surgically treated without complications (see Fig. ). On the 21st day of life, hyperkalemia needed to be treated with repetitive doses of furosemide. As renal tubular dysgenesis was suspected, endocrinological assessment was performed on day 12. It revealed an excessively high active renin concentration > 330 ng/l (normal 6.3 to 149 ng/l), a low concentration of ACE < 8 U/l (normal 8.3 to 21.4 U/l) and hypoaldosteronism (aldosterone < 37 ng/l, normal 73–425 ng/l). As this is a common finding in RTD, we established a fludrocortisone therapy resulting in stable electrolytes and bicarbonate. The infant required a gastric tube due to poor feeding until the 6th week of life. He was discharged at the age of 7 weeks.
Mutational analysis of the ACE gene showed a novel compound hyterozygous mutation. C.5303 + 1G > A has been described before and impairs splicing of pre-mRNA of ACE []. The other mutation was c.1487G > A and has not been reported before in RTD. Therefore, we present a patient with a novel compound hyterozygous constellation of RTD.
The patient is now 17 months of age and has been re-admitted several times for dehydration due to poor feeding in times of respiratory infection. Whenever fludrocortisone therapy was discontinued due to non-compliance, the patient developed hyperkalemia and rise of creatine levels. Currently he is suffering from stage 2 chronic renal disease with a GFR of 60 ml/min/1,73m2 (normal > 90 ml/min/1,73m2). Renal ultrasound shows increased echogenicity but no enlargement of the kidneys. With reestablished fludrocortisone therapy and sodium bicarbonate substitution electrolytes and blood urea nitrogen are normal, serum creatinine and cystatine C only slightly elevated (Creatinine 0,45 mg/dl, cystatine C 1,43 mg/l). Blood pressure is on the 50th percentile. Cognitive and psychomotor development are age-appropriate.


A 69-year-old man presented to the outpatient clinic of the Department of Breast Surgery at the Shiga General Hospital (Moriyama, Shiga, Japan) with a lump in his left breast in the 1990s. Physical examination revealed a mass measuring > 6 cm without skin invasion in the upper-lateral region as well as axillary lymph node swelling. The patient had a history of diabetes, hyper tension, cerebral infarction, and brain schwannoma controlled by oral glimepiride 0.5 mg, nifedipine 40 mg, and aspirin 100 mg. He had no remarkable family history.
Ultrasonography showed a breast mass and right-sided axillary lymph node swelling. A core needle biopsy was performed, and the tumor was diagnosed as a high histological grade invasive ductal carcinoma. It was ER-positive, PgR-negative, HER2-negative and AR-positive (detected by anti-AR rabbit monoclonal antibody SP107; Roche tissue diagnostics, Ltd.); the Ki-67 labeling index was 10% (Fig. ). The tumor was radiologically classified as cT3N3M0, stage IIIC disease (Union for International Cancer Control-TNM classification, 8th edition) [].
Preoperative chemotherapy was not performed at the time; thus, a mastectomy and axillary dissection were performed. The final histological diagnosis was pt3n3a (36/39) M0, stage IIIC disease. Postoperative chemotherapy with epirubicin 40 mg/body with 5-fluorouracil (5-FU) 500 mg/body every 2 weeks plus oral cyclophosphamide 100 mg daily (CEF) was administered. After 2 cycles of the chemotherapy, computed tomography (CT) revealed pleural metastasis in his right lung. Anti-estrogen therapy with high-dose toremifene (TOR) 120 mg b.i.d and oral 5-FU, doxifluridine (5’DFUR) 1200 mg was administered as first-line therapy for metastatic breast cancer.
Two years after the recurrence, the patient complained of frequent urination. Radiological and histological examinations revealed that he had cT3N0M0, stage III primary prostate cancer (Fig. ) with a prostate-specific antigen (PSA) level of 40.5 ng/mL. He underwent radiation therapy at a dose of 66.0 Gy/33 fractions as local control to treat the prostate cancer. After radiotherapy, the prostate cancer therapy was temporarily suspended, and the watchful waiting approach was taken. Breast cancer therapy with high-dose TOR was continued since breast cancer control was good. Six months later, the PSA level increased from 3.7 ng/mL to 18.0 ng/mL. Oral estramustine phosphate sodium hydrate (Estracyt®) 626.8 mg was administered daily because this drug remains specifically in prostate cancer tissue and is not contraindicated in patients with breast cancer. The PSA level immediately decreased to within the normal range (3.7 ng/mL), and Estracyt® as well as TOR were continued for 3 years until the patient experienced a deep vein thrombosis in his right leg related to the endocrine therapy, while the antiplatelet therapy was ongoing.
TOR was stopped but Estracyt® was continued for symptomatic disease control. A CT scan revealed liver metastasis from the breast cancer after the patient stopped the breast cancer therapy. Estracyt® was changed to the non-steroidal anti-androgen agent, Casodex® as the second-line endocrine therapy for the prostate cancer and a luteinizing hormone-releasing hormone (LHRH) agonist as third-line treatment; however, the patient died due to breast cancer progression 5 years after the diagnosis of prostate cancer (Fig. ).
We retrospectively reviewed the medical records of 1431 patients with breast cancer who underwent breast cancer therapy at the Shiga General Hospital between 1998 and 2017. The retrospective review of the medical records was approved by the appropriate ethics review board, and the study complied with the tenets of the Declaration of Helsinki. Of all patients, 8 (0.6%) were men; they were diagnosed with primary breast cancer histologically. Table shows the clinicopathological characteristics of the patients with MBC.


A 28-year-old primigravida woman was referred to our hospital for the evaluation of a suspected fetal cranial abnormality at 17 weeks of gestation. There was an unremarkable medical history and family history and no history of drugs or substance abuse. 2D ultrasound images (Voluson E8; GE Medical Systems, Zipf, Austria) revealed the absence of calvarium with deformed brain tissue directly exposed to the amniotic cavity, suggestive of exencephaly (). The fetal spine also showed the absence of vertebral posterior elements with splaying of the lamina at the thoracic level (). The lower limbs appeared to be fused in fixed extension with two femora and two tibiae (); however, we were not able to identify whether there were one or two feet. The fetal kidneys and urinary bladder were visualized as normal, and the amniotic fluid was normal. Color Doppler showed a single umbilical artery. 3D rendering images using 4D ultrasound with HDlive mode clearly revealed the absence of calvarium with deformed and degenerated brain tissues, consistent with exencephaly (). The spine also showed extensive clefts in the posterior part of the fetal vertebrae from the upper cervical region to the sacrum (). These findings were consistent with those of craniospinal rachischisis totalis (anencephaly with rachischisis totalis). The lower extremities were completely fused, and the feet were fused with the heels, which were immobile (). Absence of the right upper limb was also identified (). Thus, the diagnosis of sirenomelia with anencephaly, rachischisis totalis, and absence of the right upper limb was made prenatally.
The parents were informed about the findings and the associated poor prognosis; they then opted for termination of pregnancy, which was performed at 18 weeks of gestation. External examination of the fetus revealed anencephaly with craniorachischisis totalis (), fused lower limbs (), nine toes with a fused bilateral thumb (), absence of the right upper limb () and external genitalia, and imperforate anus, almost coinciding with the observation on the 3D sonographic rendering images. The autopsy imaging by radiography demonstrated complete rachischisis (). The single lower limb contained two femora and two tibiae with some metatarsals and phalanges ().


A 42-year-old man with a history of ulcerative colitis was referred to the surgical department by the gastroenterologist, after finding a lesion in the anal canal during follow-up colonoscopy (). The patient was monitored by the gastroenterology team for his ulcerative colitis and was being treated with biological factors.
The patient complained of periodic anal pain, discomfort, and rectal bleeding during defecation, which started approximately 6 months earlier. On physical examination, he had an unremarkable abdominal exam. On digital and anoscopic examinations, there were third degree prolapsed hemorrhoids and an ulcerated, soft lesion on top of the 3 o'clock hemorrhoid. Colonoscopy revealed no additional findings from the rest of the rectum and colon. No biopsy was taken during colonoscopy due to the location of the lesion. Consequently, a surgical biopsy of the anal lesion was performed under local anesthesia, as a day case, without any complications. Histopathological examination showed lymphangioma of the anal canal.
A wide excision of the lesion under general anesthesia followed (). The new histopathological examination revealed total excision of the lymphangioma, which was a round lesion measuring about 1.5 cm in radius and had at least 0.7 cm of distance from the closest margins of the specimen (). Immunohistochemistry was positive for CD31 and D2-40 and negative for CD34 (Figures and ). At the end of the first postoperative month, full wound healing was accomplished with no signs of recurrence.


Our patient was born at 33 weeks of gestation by cesarean section to a 36-year-old gravida 3, para 2 woman after a prenatal diagnosis of left CDH (31 weeks' gestation). Postnatal chest X-rays confirmed the left CDH, with the liver in the thorax. Initial echocardiogram revealed only a small patent ductus arteriosus. There were no signs of PH at this time. At 24 hours of life, she underwent surgical repair of a huge diaphragmatic defect (type D according to the CDH Study Group staging system)
that required a silastic patch closure. Weaning from mechanical ventilation was achieved on postoperative day (POD) 4, but 3 days later she was reintubated for recurrent respiratory distress. Respiratory support was finally stopped on POD 26, and she was discharged home on POD 58. Predischarge echocardiography was unremarkable. The infancy was uneventful and the quality of life was excellent. She underwent periodic follow-up visits that revealed gastroesophageal reflux (GER) and initial mild scoliosis. At the age of 10, she was admitted for abdominal pain, vomiting, and dyspnea, and GER disease and severe PH were diagnosed. Heart ultrasound showed an estimated systolic right ventricular pressure of 130 mm Hg, with a systolic blood pressure of 100/50 mm Hg. Medical treatment for PH was initiated, including sildenafil, bosentan, and furosemide. Since PH progressively worsened despite maximal medical treatment, leading to end-stage respiratory failure, at the age of 14, she was listed for H-Ltx, and 3 months later she received the new organs. Postoperative course was characterized by short-term complications such as severe central venous line-related infections, massive pleural effusion and ascites, and delayed complications, including CDH recurrence with intestinal obstruction, requiring laparotomy and ileostomy formation. In addition, she suffered from recurrent respiratory infections, severe malnutrition, and drug-induced diabetes, significantly impacting her quality of life. With aging, scoliosis and GER also aggravated, requiring posterior vertebral arthrodesis and Nissen's fundoplication at 16 years of age. At 17 years of age, she developed a further episode of pneumonia-related respiratory failure and required a tracheostomy for multiple failed attempts of extubation. Bronchiolitis obliterans deteriorated her respiratory function, and the same year she was relisted for Ltx and underwent her second bipulmonary transplantation.
Despite the second transplant, her general conditions rapidly deteriorated, she developed chronic lung rejection, and she eventually died at the age of 18, 4 and 1.5 years after the first and the second Ltx, respectively.


A 10-year-old girl first noted a swollen left knee and underwent repeated arthrocentesis. At age 13, she underwent arthroscopic surgery and was diagnosed with benign TGCT. She subsequently underwent numerous synovectomies to treat local recurrences and radiation therapy to her left knee joint at age 15. Ultimately, her disease spread to her upper calf and posterior thigh. At age 32, her upper calf lesion was resected, and the tumor in her posterior thigh was treated with radiation. At age 34, swelling of an inguinal lymph node was noted and fine needle aspiration was consistent with malignant TGCT. Other staging scans revealed a pelvic mass and a sub-centimeter pulmonary nodule. Her disease remained stable after four cycles of doxorubicin/ifosfamide and she subsequently received gemcitabine/docetaxel as well as radiation therapy to her pelvis with stable disease for three months. She underwent left-sided above the knee amputation and excision of the intrapelvic masses. Eight months later, enlarging pulmonary nodules were resected. She was treated with sirolimus (rapamycin) and remained disease-free for eight months until a pulmonary nodule and two inguinal masses were noted. In 2007, at age 37, she was referred to our hospital and treated with sorafenib for four months with mixed response. She subsequently began on sunitinib 37.5 mg daily. Interval restaging scans showed no evidence of progressive disease for 15 months. She had significant interval progression of a right-sided pelvic mass while she temporarily stopped sunitinib in the perioperative setting of resection of painful metastatic nodules near the amputation stump (Fig. a, b, and c). Given that the drug had a significant role of controlling the disease, her sunitinib was restarted in combination with sirolimus (rapamycin). Her disease was under good control for eight additional months until she had progressive disease in the pelvis and underwent hemipelvectomy. She died of the disease at age of 39, six years after the malignant transformation.


A 53-year-old man was diagnosed with malignant TGCT after undergoing resection of a soft tissue tumor in the right proximal rectus femoris muscle. He underwent adjuvant radiation therapy but developed a local recurrence and underwent another wide resection five months after the initial wide resection. One year after the initial wide resection, he developed further progression of his tumor in the thigh and repeat staging evaluation revealed involvement of a right inguinal lymph node and bilateral small pulmonary nodules (Fig. d, and e). He was enrolled in a clinical study with sorafenib (NCT00330421); however, he was taken off study after a month because of dramatic disease progression in the lungs (Fig. f) as well as in the thigh. The patient died of disease 20 months after diagnosis.


A 55-year old woman presented with an enlarging mass in the posterior aspect of her right knee. The initial MRI revealed an extensive soft tissue lesion in the calf with fluid levels present (Fig. g, and h). Biopsy was consistent with a benign diffuse-type TGCT. Three months after she underwent resection of the mass in the posterior popliteal fossa, she developed a local recurrence (Fig. i). Above-knee amputation followed the second resection of the recurrent tumor whose pathology revealed malignant transformation. CT scans two months later revealed metastases to the right inguinal nodes and the lung (Fig. j, and k). She subsequently began imatinib, but treatment was terminated because of progressive disease. Four cycles of doxorubicin/ifosfamide demonstrated partial response, resulting in disappearance of pulmonary nodules and significant decrease in size of inguinal nodules (Fig. l). She was enrolled in two clinical trials of investigational mTOR inhibitor or placebo and of an investigational PI3K/mTOR inhibitor, neither of which provided significant clinical benefit by the time of first follow-up CT. She then completed two cycles of liposomal doxorubicin, with no clinical benefit. She was subsequently treated with two cycles of ifosfamide and palliative radiation to her leg, resulting in marked response of the tumor in the thigh, but progressive disease systemically. Her disease then showed partial response to gemcitabine/docetaxel for five months before developing progressive disease in the lungs. She died of the disease 23 months after the diagnosis of malignant TGCT.


A 46-year-old woman presented with a 10-cm mass involving the right psoas muscle, the gluteal muscles, and the iliac bone. A CT scan at presentation demonstrated sub-centimeter pulmonary nodules, in addition to the pelvic mass. The CT-guided biopsy was consistent with malignant TGCT. Cytogenetic studies demonstrated an unbalanced t (1;2) translocation. Because of severe pain in her right hip, she underwent palliative radiation therapy (54 Gy) to her right pelvis, which dramatically improved her intractable pain. Her disease remained stable after four cycles of doxorubicin/ifosfamide. She enrolled in a clinical trial of nilotinib for TGCT (NCT01207492) but progressed after 1 month. She was then treated with gemcitabine/docetaxel without clinical benefit, and she died of the disease nine months after diagnosis.


A 44-year-old man first noted a mass in the vastus medialis. A biopsy demonstrated a diagnosis of benign diffuse-type TGCT (Fig. p). The patient elected to follow a course of observation. Three years later, he noted an increase in the size of the mass and subsequently underwent a marginal excision of the tumor. Pathology was consistent with malignant TGCT with positive margins (Fig. q). Staging CT revealed multiple pulmonary metastases. The patient subsequently participated in a blinded clinical trial of doxorubicin with an investigational drug or placebo and developed a partial response; he completed 6 cycles before electing to stop chemotherapy. He later developed metastatic disease to the subcutaneous tissue, pleura, liver, mesentery, bones, and sacral nerve roots and was treated with palliative radiation to the spine with concurrent paclitaxel, which failed to control his disease. Subsequent gemcitabine/vinorelbine provided no clinical benefit, and he died of disease 17 months after diagnosis of malignant TGCT.


A 54-year-old man noted progressive discomfort and swelling in his left knee. Resection of the lesion revealed benign diffuse-type TGCT. Despite resection, he developed rapid recurrence within weeks. Given the aggressive nature of the recurrent tumor, the patient was treated with two cycles of doxorubicin/ifosfamide in a neoadjuvant setting that was stopped for progression of disease, and he then underwent above-knee amputation. Pathology confirmed multifocal malignant transformation of TGCT. One year after amputation, he developed painless inguinal lymphadenopathy from metastatic TGCT. Six months later he developed malaise, dyspnea on exertion, nonproductive cough, and night sweats. Chest CT demonstrated a left sided pleural mass which was confirmed as metastatic malignant TGCT by biopsy. PET-CT revealed several pulmonary nodules, a focal hypermetabolic lesion in the L3 vertebral body, and a rapidly progressing pleural lesion. Systemic treatment with imatinib showed mixed response, with resolution of FDG avidity of the bulk of the mass but development a new hypermetabolic component invading his chest wall. He received palliative radiation to this mass and then initiated pazopanib but within one week developed symptomatic progression and entered hospice care. He died 3 years after initial diagnosis, 2 years after diagnosis of malignant TGCT, and 13 months after he developed metastatic disease.


A 9-year-old male patient accompanied by his mother sought dental assistance complaining of a palatal swelling. The lesion was painless and had initially been observed 5 months earlier. The medical history was noncontributory.
The intraoral physical examination revealed a 10x5 mm, ill-delimited, firm and sessile nodule, located in the palatal mucosa of the left central incisor (Fig. A,B). The overlying mucosa was intact and normal in color. Buccoversion of the adjacent teeth was observed, but no mobility or other periodontal alterations.
Panoramic, occlusal and periapical radiographs did not show alterations in the area adjacent to the lesion (Fig. A-C). A cone beam computed tomography (CBCT) exam also revealed no related bone alterations, but show a slight soft tissue swelling located in the palatal mucosa of the left maxillary central incisor (Fig. D).
The main diagnosis hypotheses included fibrous hyperplasia, peripheral ossifying fibroma, pyogenic granuloma and peripheral giant cell granuloma. An excisional biopsy was performed under local anesthesia. During the lesion’s surgical removal, no superficial bone resorption was observed. Grossly, a cyst-like structure was observed adhered to the oral mucosa. The sample was sent to a Pathology Laboratory.
The histological examination revealed an oral mucosa fragment covered by a stratified squamous keratinized epithelium showing areas of hyperplasia (Fig. A). A cystic lesion was observed adhered to the deeper lamina propria (Fig. A-D). The cystic capsule, formed by dense fibrous connective tissue, was lined by an ameloblastoma-like epithelium (Fig. E). The basal layer cells of this lining epithelium were cubic or columnar, showing reversed polarity and hyperchromatic nuclei, disposed in palisade. The cells of the suprabasal layers were sometimes loosely arranged. Enlarged epithelial cells with eosinophilic cytoplasm and no nucleus (ghost cells) were sporadically found in the lining epithelium (Fig. E,F) and abundantly observed in the cyst lumen (Fig. C,G). Calcification of ghost cells was also observed (Fig. C-F). Juxtaepithelial dentinoid could be seen in the cyst capsule (Fig. E). Moreover, soft and hard dental tissue resembling a developing odontoma were observed in the cyst wall (Fig. C,H).
The diagnosis of peripheral COC was established. In a follow-up visit two months after the excisional biopsy, the area was adequately healed (Fig. C). One year after the surgical removal, no recurrence was observed (Fig. D). The patient has been disease-free for 5 years. Informed consent has been obtained by the patient.


A 16-year-old man with no systemic diseases, resident of the city of São Lourenço, Rio Grande do Sul, Brazil, sought a dental surgeon for the endodontic treatment of the tooth 47. Radiographs were requested in December 2004 and was observed a well delimited unilocular lesion associated with impacted tooth 48 (Fig. ). The man was referred to a specialist in oral and maxillofacial surgery in the city of Pelotas, RS, before endodontic treatment.
The marsupialization of the lesion and an incisional biopsy was performed and histologic analysis revealed dentigerous cyst. Three months later the endodontic treatment of the tooth 47 was made. After nine months, the lesion was completely removed and the biopsy was sent for histopathological analysis in Center of Diagnosis of Diseases of the Mouth, Federal University of Pelotas, Brazil (CDDB-FO / UFPEL). Histologic analysis revealed unycistic mural ameloblastoma (Fig. A-C). Approximately 3 months after tooth 48 extraction and total removal of the lesion, it was possible to observe a mineralize d aspect compatible with the normal repair process of the region. Patient was followed up every 12 months. The tooth 47 was extracted. Currently, the patient is clinically healthy. In panoramic x-rays at 5 (Fig. A) and 13 years (Fig. B) after diagnosis it is possible to observe evidence of bone repair.


A 64-year-old woman with a past medical history of Grave’s disease presented to the hospital complaining of sudden onset of facial and bilateral arm swelling, as well as "bruising" in her neck, abdomen, and arms, all of which she developed over a few days. Further, the patient reported fatigue, neck tightness, and dyspnea on exertion. She denied any other symptoms and the remainder of the full review of systems, including weight loss, was negative. Social history was significant for 40 years of smoking. The patient was hemodynamically stable with good oxygenation on 2 L of oxygen by nasal cannula. Physical exam revealed swelling of the face, neck, and both arms, superficial varicosities on the neck, chest, back, and arms, as well as mild inspiratory stridor. Computed tomography angiography (CTA) of the thorax and neck showed a large central mediastinal mass occluding the pulmonary artery and extending into the right atrium, encasing the superior vena cava (SVC), abutting the trachea but not causing tracheal narrowing (A), as well as pulmonary emboli at the right lower lobe (B). Given the tobacco abuse history, lung cancer leading to SVC syndrome was suspected, although other malignancies such as lymphoma were in the differential. The patient was started on a heparin drip and the Pulmonary and Hematology-Oncology services were consulted, both of which agreed for the need for tissue diagnosis of the likely malignancy and rapid initiation of treatment.
A complicating factor in this patient’s care was her adamant belief that the swelling was an allergic reaction to one of the many over-the-counter herbal and homeopathic medications that she was taking to try to rid her body of the “flukes” which she claimed to have seen in her nasal secretions and stool. The patient soon moved on to express the belief that her mediastinal mass was caused by her parasites and demanded treatment for them rather than for the cancer. Review of this patient’s medical record did not yield any evidence for a documented psychiatric disorder or treatment thereof in the past. However, her significant other at bedside revealed that the patient had been preoccupied with the notion of having blood flukes for at least eight years.
After much discussion, the patient agreed upon undergoing biopsy of her mass as long as she was also tested and treated for the parasites. Fine needle aspiration of the right supraclavicular lymph node on day two of admission revealed metastatic small cell carcinoma. On that same day, the patient was transitioned to the ICU due to increasing oxygen requirements necessitating bilevel positive airway pressure ventilation. Radiation–Oncology was consulted and recommended starting radiation treatment; however, the patient was reluctant to do so until the final diagnostic confirmation of cancer on day four. Similarly, she stated that she would refuse to start chemotherapy until she could obtain a second opinion. Not surprisingly, the consulting services deemed it dangerous to postpone treatment initiation given the size and location of the mediastinal mass and the patient’s worsening respiratory status. Due to an enlarging pleural effusion, thoracentesis was performed on the right side on day five and the pleural fluid was negative for malignant cells. Further, a metastatic workup revealed a suspicious lesion at S1 on a nuclear medicine scan that was consistent with Paget’s disease as well as malignancy. An MRI brain scan could not differentiate between small vessel ischemic disease and a possible small metastatic lesion. In the meantime, ova and parasite studies of the patient’s stool, nasal secretions, and lymph node aspirate had returned negative, yet she remained adamant in her decision to refuse chemo-radiation until the parasites were treated. Although there was a plan for an Ethics consultation, it was postponed as the patient changed her mind and underwent the first chemotherapy cycle on days 8 (carboplatin), 9 and 10 (etoposide), and radiotherapy was started on day 10. Ethics was eventually consulted on day 10 and recommended avoiding treatment for unproven parasitosis. Repeat CTA of the thorax on day 12 demonstrated new pulmonary emboli in the left lower lobe, slight increase in the bilateral pleural effusions, and no significant change in the tumor burden. On day 14, the patient decided to change her code status from FULL CODE to DNR/DNI. On day 19, her blood pressure dropped and she required pressor support, was started on a five-day course of cefepime for neutropenic fever, as well as fludrocortisone and hydrocortisone for a few days until the shock resolved. Given her unstable state, further chemotherapy was not advisable. Another complicating factor in the patient’s care were her poor nutritional status, her repeated attempts to drink water despite the danger for aspiration, as well as her increasing agitation and lack of cooperation with the hospital staff. The use of anxiolytics provided only partial relief and the situation continued to escalate to the point where the patient started being verbally abusive to the medical personnel, was refusing medications, radiation therapy, and physical exams. Her respiratory status continued to worsen and she was often heard to voice her wish to die. Therefore, on day 34 a family meeting was held, during which the patient’s poor prognosis was discussed. Although at that time the patient did not wish to pursue comfort care, the prolonged drop in oxygen saturation later that evening was causing her so much discomfort that she decided to make the transition. The patient was pronounced at midnight, from cardiopulmonary failure. Up to the point of death, the patient maintained her belief that the primary cause of her symptoms was a parasitic infestation and that her diagnosis of carcinoma of the lung was “fake”.


A 57-year-old man presented to the cardiologist's office as a part of the preoperative evaluation before undergoing an ophthalmological surgery. He complained of shortness of breath and fatigue. The patient had a prior history of coronary stents and heart failure. Physical examination was unremarkable. Echocardiogram reported moderate dilation of the left ventricle and hypokinesis of the apical lateral wall and apical septal wall. Ejection fraction was reported to be 35-40% (). The patient was evaluated by a nuclear stress test which came out to be abnormal. The patient then underwent an invasive coronary angiography that showed a 70% eccentric obstruction of the proximal left anterior descending (LAD) artery and a 70% obstruction of the left circumflex artery as well with diffuse calcification. The right coronary artery (RCA) was believed to be anomalous (Figures and ). Cardiothoracic surgery evaluated the patient and coronary artery bypass graft was performed that identified intraoperatively an anomalous origin of RCA from the pulmonary artery which was then successfully reimplanted into the ascending aorta.


Patient One was a 30-year-old woman, American Society of Anesthesiologists (ASA) Classification I (weight, 64 kg; height, 168 cm) with no coexisting diseases. She was scheduled for arthroscopic shoulder surgery. Her preoperative shoulder mobility over the shoulder joint was limited to 120° with severe pain. The patient described acute relief of the pain in her shoulder and increased mobility after ESPB performed before the surgery started. She was treated surgically for arthroscopic acromioplasty and bursectomy. Her pain was recorded as 1/10 on NRS and needed no additional analgesia in the PACU. Her maximum dynamic pain score was 4/10 on NRS. Her 24-hour PCA tramadol consumption was 40 mg total.


Patient Two was a 65-year-old woman, ASA Class I (weight, 55 kg; height 165 cm) registered for a Neer Type 3 humeral fracture and surgical repair. She reported sudden pain relief after the application of ESPB. An open reduction and internal fixation via the anterolateral method was performed under general anaesthesia. In the PACU, she reported her pain as 2/10 on NRS with mobilization. At the 24-hour follow-up evaluation, she reported no pain score higher than 3/10 on NRS, and no rescue analgesic treatment was administered. Her total PCA consumption was 240 mg in 24 hours. Although her PCA consumption was high, she needed no fentanyl in the PACU nor additional diclofenac sodium and meperidine as rescue analgesia.


Patient Three was a 39-year-old woman, ASA Class I (weight, 55 kg; height, 165 cm) who presented for arthroscopic shoulder surgery. She had severe pain (8/10) on NRS with abduction-adduction at the shoulder and was not able to move over 30°. After ESPB, the patient was able to move her arm at the shoulder to approximately to 70° abduction without pain. She had acromioplasty and fibrous tissue resection in the shoulder joint including shoulder cap. In the PACU, her pain score was 8/10 on NRS, so she was given 50 µg fentanyl. Her PCA tramadol consumption was 240 mg in 24 hours. Despite the rescue analgesia treatment (IM diclofenac sodium, 75 mg and IV meperidine, 50 mg), her level of pain remained constant between 4/10 to 6/10 on NRS.


A 65-year-old female presented with fatigue, 20 lb weight loss, and intermittent painless jaundice. Initial laboratory investigations revealed an elevated bilirubin of 9.8 mg/dL (normal range 0.3–1.7), alkaline phosphatase of 977 U/L (normal 44–127), and carbohydrate antigen (CA) 19-9 of 267 U/mL (normal 0–37). Abdominal ultrasound revealed cholelithiasis with possible central biliary tree dilation. Endoscopic retrograde cholangiography (ERC) with sphincterotomy showed a malignant-appearing stricture in the common hepatic duct but yielded equivocal brushings and biopsies (). A laparoscopic cholecystectomy had been attempted at an outside institution but was aborted secondary to extensive inflammation in the porta hepatis, preventing visualization of the gallbladder. After referral to our institution, the patient underwent a repeat ERC and magnetic resonance cholangiopancreatography (MRCP) () with placement of bilateral 7F biliary stents. Again, duct brushings revealed only benign cells with fibrosis and inflammation. The differential diagnosis included primary gallbladder adenocarcinoma, hilar cholangiocarcinoma, and cholecystitis with extrinsic compression of the biliary tree (Mirizzi syndrome), and the decision was made to proceed with open exploration.
During open surgical exploration, the gallbladder was markedly inflamed with dense adhesions to the duodenum, without signs of disease dissemination. On dissection of the gallbladder, an obvious fistula was identified between the infundibulum of the gallbladder and the biliary bifurcation. Intraoperative frozen section analysis was negative for malignancy. After resection of the damaged extrahepatic bile ducts, separate right and left hepatic ducts remained. Reconstruction was performed with bilateral hepaticojejunostomies to a Roux-en-Y segment of the jejunum. Pathological analysis () of the surgical resection specimen revealed xanthogranulomatous cholecystitis with extensive fibrosis and inflammation (without dysplasia or malignancy), consistent with the Mirizzi syndrome. The patient recovered well and returned to her practice as a clinical psychologist.


A 71-year-old previously healthy female presented with 2 weeks of painless jaundice. Ultrasound evaluation showed dilation of the intrahepatic and extrahepatic bile ducts as well as an impacted calculus in the gallbladder neck. Computed tomography (CT) and MRCP () confirmed the dilation and revealed the common bile duct narrowing at the level of the impacted stone. Before referral to our institution, endoscopic retrograde cholangiopancreatography (ERCP) was performed with successful placement of a biliary endoprosthesis and resolution of her jaundice. In our clinic, the patient was without complaints and laboratory evaluation revealed a bilirubin of 1.7 mg/dL, an alkaline phosphatase of 226 U/L, and aspartate transaminase and alanine transaminase of 49 and 41 U/L, respectively, and both CA 19-9 and carcinoembryonic antigen (CEA) were within normal limits (). The differential diagnosis for this patient was identical to that noted in Case 1. The patient was scheduled for an open exploration—cholecystectomy, extrahepatic biliary resection, and Roux-en-Y hepaticojejunostomy.
On operative exploration, a gallstone was found impacted in the neck of the gallbladder. However, a dense mass was also found at the junction of the gallbladder and the bile duct, encasing the right hepatic artery and portal vein—intraoperative frozen section revealed adenocarcinoma. Given the presence of vascular encasement, the most effective palliative measure to drain the biliary tree was determined to be resection of the damaged and partially obstructed bile ducts and performance of a palliative hepaticojejunostomy bypass. Pathological analysis of the resected specimen revealed a moderately differentiated adenocarcinoma, involving the cystic and common hepatic ducts, perineural and angiolymphatic invasion, and metastatic carcinoma in one station 12 lymph node (). After recovery from surgery, the patient was treated with palliative chemoradiotherapy and she survived for an additional 12 months postoperatively.


A 70-year-old male with a history of smoking and long-standing diabetes presented with a 60 lb weight loss, fatigue, constipation, and painless jaundice. Initial MRCP showed significant intrahepatic and extrahepatic biliary ductal dilation. In addition, it also showed a dilated pancreatic duct and ill-defined hypoechoic mass within the head of the pancreas (). The patient underwent biliary stenting at the time of ERCP and a biopsy was performed through endoscopic ultrasound, which was concerning for malignancy. The patient was referred to our institution for further management. On arrival at our institution, the serum bilirubin and alkaline phosphatase had normalized to 1.1 mg/dL and 80 U/L, respectively. His CEA was within normal limits, but the serum CA 19-9 remained elevated at 184 from an initial value of 328 U/mL before his biliary stenting (). The differential diagnosis for this man was broad, similar to the previous two cases, but due to the distal bile duct obstruction and mass within the head of the pancreas, a primary pancreatic malignancy was strongly suspected.
The patient underwent operative exploration and was found not to have any evidence of disseminated disease. A firm mass was noted involving the head and uncinate process of the pancreas. He underwent a cholecystectomy and pylorus-preserving pancreaticoduodenectomy with standard reconstruction with an invagination pancreaticojejunostomy, hepaticojejunostomy, and end-to-side duodenojejunostomy. Pathological analysis revealed a successful R0 resection of a T3N1M0 moderately differentiated invasive pancreatic ductal adenocarcinoma, invading into the peripancreatic soft tissue, ampulla, duodenal wall, and bile duct (). The patient recovered well after the surgery and was discharged home on postoperative day 5. He is currently 6 weeks from his resection and has fully recovered.


A 71-year-old elderly woman was admitted to Shandong Sunshine Union Hospital, Shandong, China, on November 10, 2017, due to chest tightness and breathing shortness after activity for 1 year and coughing for 2 months. The patient began to have chest tightness and breathing shortness after general physical activity 1 year ago and coughing (dry coughs mainly) 2 months ago. A small amount of white sputum was noted after a severe cough, which was heavy at night and light in the daytime. The patient was diagnosed with “severe aortic stenosis” using color Doppler echocardiography at several hospitals, and was admitted to the aforementioned hospital with “severe aortic stenosis (bicuspid deformity) and left ventricular outflow tract stenosis,” which was confirmed using transthoracic echocardiography. The patient had a history of hypertension for 10 years and usually took antihypertensive drugs to control blood pressure. The physical examination revealed a clear respiratory sound of bilateral lungs without rhonchus and moist rales and a systolic 3/6 grade murmur in the third intercostals of the left border of sternum. The liver was not enlarged and had no swelling in both lower extremities. The laboratory examination of brain natriuretic peptide was normal. Transthoracic echocardiography showed asymmetric hypertrophy of the left ventricle with a maximum thickness of 20 mm, the diameter of the left ventricular outflow tract of 13 mm, and the anterior flow velocity of the aortic valve of 4.3 m/s. Cardiac MRI revealed myocardial hypertrophy, left ventricular outflow tract stenosis, aortic stenosis, and bicuspid deformity (Fig. ), indicating the requirement of aortic valve replacement and left ventricular outflow tract dredging.[ Intraoperative transesophageal echocardiography (Fig. ) showed aortic stenosis and left ventricular outflow tract stenosis. Surprisingly, the aortic valve was normal without stenosis or insufficiency, and the asymmetrically hypertrophic myocardium under the aortic valve caused left ventricular outflow tract stenosis. Therefore, the diagnosis was changed to hypertrophic obstructive cardiomyopathy. The Morrow procedure was performed to remove the hypertrophic myocardium from the left side of the middle point of the right coronary leaflet to the left coronary leaflet. After the operation, the transesophageal echocardiography examination revealed that the velocity of left ventricular outflow tract decreased to 2.6 m/s and the opening restriction of aortic valve had been corrected (Figure unreserved). Hypertrophic cardiomyocytes were found in the pathology. The conditions of left ventricular outflow tract and aortic valve were observed using echocardiography in the follow-ups 6 months and 1 year after the operation.


A 40-year-old Chinese male presented with a 3-day history of sudden vision loss in his right eye. He complained of a sudden onset foreign body sensation in the right eye when he was riding, and vision loss after rubbing. Eye examination showed best corrected visual acuity was no light perception (NLP) in the right eye and 20/40 in the left eye. Anterior segment examination of the right eye showed keratin precipitates+, aqueous flare++, and vitreous opacity. The right fundus examination revealed that the retina was gray, with edema as well as scattered dotted and flaky hemorrhagic foci (Fig. ). In addition, hyalocytes were visible in the left eye, without obvious abnormalities in the fundus (Fig. ). Fluorescein fundus angiography showed the following results: For the right eye, the arm-to-retinal circulation time was 19.54″, background fluorescence of the choroid in the early angiography was not uniform. At 21.10", the optic disc showed hyperfluorescence, with perfusion in some disc blood vessels. Until the late stage of angiography at 10′30.20″, perfusion was seen only in retinal arteries near the optic disc, but not in other retinal blood vessels. The optic disc showed hyperfluorescence, and hemorrhage was visible along the retinal veins, which blocked the fluorescence (Figs. and ). For the left eye, telangiectasia was visible in the optic disc, with leakage in the disc in the late stage of angiography (Fig. ). Auxiliary examination showed that erythrocyte sedimentation rate (ESR) was 50 mm/h and C-reactive protein (CRP) was 18 mg/L. There were no significant abnormalities in blood routine, antineutrophil cytoplasmic antibodies, anticardiolipin antibody, direct antiglobulin testing, Toxoplasma gondii infection, rubella virus, cytomegalovirus, and herpes simplex virus and immune examinations. Echocardiography, carotid duplex ultrasound, abdominal Doppler ultrasound, and chest computed tomography showed negative results. Past medical history revealed that the patient had complaints of recurrent oral ulcers and vulvar ulcers for 8 years, which recently worsened. The patient was diagnosed as Behcet disease at a local hospital and given long-term low-dose oral prednisone, but the recurrent symptoms persisted with a recent relapse. At our hospital, the patient was diagnosed as bilateral uveitis (obstructive retinal vasculitis in the right eye), and Behcet disease. He was given topical corticosteroids, and compound Tropicamide eye drops. The patient was also hospitalized in the Rheumatology Department, and received systemic infusion of methylprednisolone and cyclophosphamide. Two weeks later, his vision acuity of the left eye was 20/20 and that of the right eye was NLP. During the telephonic follow-up after 1 year, the patient reported 2 recurrent episodes of uveitis in the left eye, which improved after treatment at the local hospital.


A 31-year-old woman (gravida 4, para 1) was referred to our department from local hospital at 33rd weeks gestation with low fever and right-sided flank pain, which had lasted for nearly half a year and severely aggravated for 5 days. As the patient recalled, previous prenatal examinations in local hospital contributed the pain to kidney stones or uterine contractions without any further inspection. After local outpatient treatment with antibiotics, progesterone and Nonsteroidal Antiinflammatory Drugs (NSAIDs), she was admitted to our department as the pain aggravated. She denied any vomiting, hematochezia, or difficulty with urination.
Moderate iron deficiency anemia, occasional dyspepsia, and diarrhea were present during the whole gestation period. At the time of presentation, patient had no family history of gynecologic or CRC. Physical examination revealed right-sided abdominal pain on palpation and normal bowel sounds. Vital signs are normal. Body mass index 24.8. Obstetric examination showed no abnormalities. Initial laboratory results included a mildly elevated white cell count and hemoglobin 7.6 g/dL and a mean corpuscular hemoglobin 26.7 pg. Her serum potassium was 4.0 mmol/L. Liver function tests showed the serum albumin was 20 g/L. Urinalysis and routine excrement examination remained normal with no occult blood. Tumor markers serum carcinoembryonic antigen (CEA) was elevated to 70.68 ng/mL. Abdominal ultrasound showed a large heterogeneous cystic mass located below the hepatic flexure of colon. Considering the extremely low risk of radiation teratogenicity in late pregnancy, an abdominal CT scan without contrast was obtained, which revealed incrassation of the ascending colon wall and exudative change around it (Fig. ). Multiple pathologically enlarged abdominal lymph nodes were observed. No colonoscopy was performed considering the site of the lesion and the possibility to induce uterus contraction of premature delivery.
After a detailed discussion in a multidisciplinary medical team, a planned delivery by caesarean section and tumor resection during the same operative procedure was performed, following the induced fetal lung maturation by dexamethasone. Intraoperatively, a palpable tumor mass at the hepatic flexure of colon with a diameter of 15 cm was identified, with the right lobe of the liver and perirenal adipose tissue involved. Mucopurulent discharge could be found through the rupture on the necrotic mass. Further abdominal exploration revealed paracolic lymph nodes, intermediate lymph nodes, and middle lymph nodes pathologically enlarged, with none metastatic lesions on pancreas or duodenum. Both adnexa and the rest of the peritoneal cavity also appeared normal. A 1550-g live female infant with an Apgar score 10-10-10 was delivered at 33rd of gestation. A right hemicolectomy and ileostomy were performed right after the cesarean section. Tumor histology of frozen section confirmed the diagnosis of ulcerative adenocarcinoma of the ascending colon with a diameter of 10 cm. Final pathologic evaluation showed a grade-1 adenocarcinoma with negative lymph nodes (16/0), R0 resection, pT4b pN0 M0, and Dukes B stage. The postoperative course was uneventful while patient received chemotherapy with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) after recovery smoothly and got discharged 1 month after surgery. Patient showed no relapse or progression during the follow-up time of 2 years.
Written informed consent was obtained from the patient for publication of the present case report and any relevant images.