Our patient was a 39-year-old gravida 2 para 1 (G2P1) Caucasian woman who presented to our emergency department at 10 weeks gestation with acute onset of a throbbing occipital and right-sided headache. Additional complaints included associated nausea, vomiting, and hyperacusis. Her headache was severe, occurred within minutes of sitting or standing, but was relieved by recumbency. She denied fever or other infectious complaints and there was no recent history of trauma. This pregnancy had been otherwise uncomplicated and a first trimester ultrasound had confirmed a viable singleton intrauterine pregnancy.
An evaluation in the emergency department resulted in a presumptive diagnosis of migraine headache and she was treated with intravenous hydration and narcotics after which she was discharged home.
She returned the following day with a recurrence of her symptoms and was again treated with IV fluids and antiemetics. The results of a computed tomography (CT) scan of her head were negative. A neurology consultation was obtained and a diagnosis of SIH or low-pressure headache made on the basis that headache worsened within fifteen minutes of sitting or standing and was relieved with recumbency, with associated nausea, vomiting and hyperacusis [].
A magnetic resonance imaging (MRI) scan was deferred due to concerns of gadolinium use in pregnancy. Complete bed rest with IV hydration and caffeine were prescribed by the neurologist for SIH. After 10 days of continuous therapy, our patient had not improved and remained unable to sit or stand without recurrence of her headache within minutes. Nausea and vomiting would ensue if she remained upright.
Prednisone was initiated at 80mg daily (for a 55kg patient) and within four hours our patient was able to sit upright without symptoms. The steroid was tapered down and discontinued over the next four weeks and our patient remained symptom-free subsequently.


The proband, a 1-day-old boy, was the first child of non-consanguineous, healthy 35 year-old parents. The couple had a past history of twice spontaneous abortions both occurred between 7 and 10 weeks of gestation, but product-of-conception (POC) samples were not analyzed. The cytogenetic analyses of the couple preformed at another hospital revealed apparent normal karyotypes. This pregnancy was uneventful, and there was no prenatal exposure to teratogens. However, the prenatal ultrasound examination showed an increased nuchal translucency (4.0 mm) at 12+ weeks of gestation. Taking into account of the advanced maternal age as well, interventional prenatal diagnosis was referred to the couple. After understanding detailed information about sampling procedures, the risk of fetal mortality and the limitations of the testing, the couple decided to receive an amniocentesis at 18 weeks of gestation for further diagnosis. Amniotic fluid cells were cultured in situ and their karyotypes were analyzed by using G-banding technique
[], the cytogenetics revealed a apparently normal karyotype 46,XY (Figure
).
Following ultrasound examinations showed an increased size in dimensions of biparietal diameter and abdominal circumference, fetal cerebral ventriculomegaly, increased nuchal folder, polyhydramnios. However, given their past history of spontaneous abortions, the couple was eager to have children, and since the cytogenetic analysis result of this fetus was negative, they decided to continue the pregnancy. The proband was born at 39 weeks and 2 days of gestation by vaginal delivery. His birth weight was 2,688 g (25th centile), length was 47.5 cm (25th centile), and head circumference was 33.5 cm (75th centile). Apgar scores of the infant were 8 at 1 min and 8 at 5 min. Notable physical features included skull joint separation, single transverse palmar crease on both hands, craniofacial dysmorphism including round face, low-set and dysplastic ears (Figure
). Ultrasonic tests of brain/abdomen and cardiovascular examination were postponed according to the parents of the affected infant.
Peripheral blood samples were obtained from the proband and his parents for cytogenetic analyses. Sample collection procedures were approved by Guangdong Women and Children Hospital Institutional Review Board and Ethics Committee of Guangzhou Medical College, China. The family gave their written informed consent. Peripheral blood samples were cultured for 72 hours in RPMI medium, after that metaphase chromosomes were analyzed by the standard G-banding technique.
The cytogenetic analysis of the peripheral blood sample from the proband initially revealed a possible chromosome 18p deletion, but the breakpoint and the deletion region were difficult to determine with the limited resolution of chromosome banding technique (Figure
).
Genomic DNA from the proband was isolated from the whole blood by standard procedures using Fuji DNA Blood Mini kit. Array-based CGH analysis was performed using Agilent’s 8 × 60 K commercial arrays (Agilent Technologies, CA, USA), which consist of 60,000 oligonucleotide probes and evaluate the whole genome with an effective backbone resolution of roughly 50 Kb. 500 ng of experimental and gender-matched reference DNAs (Promega, Madison, WI) were digested with Alu I and Rsa I restriction endonucleases (Promega) and fluorescently labeled with cyanine 3-dUTP and cyanine 5-dUTP respectively. Labeled experimental and reference DNAs were purified, combined, denatured, pre-annealed, and hybridized to the microarrays in a rotating oven (20 rpm) at 65°C for 24 hours. The data was analyzed with Agilent Genomic Workbench Lite Edition 6.5.0.18 software (Agilent Technologies). Aberrations were identified using the Agilent Genomic Workbench Lite software via the Aberration Detection Method-2 algorithm with a sensitivity threshold of 6.0 and a data filter that rejected aberrations that did not include at least five probes with a log2 set of 0.25. All quality control metrics passed.
As shown in Figure
, a combination of 18p deletion and 7q duplication was identified in the proband by array-CGH analysis. A deletion spanning approximately 14 Mb was detected at 18p11.32-p11.21, with the deleted base pair coordinate ranging from 4,316 to 14,216,904 (hg18). Array-based CGH analysis also identified a duplication of about 11.2 Mb that involving the 7q36.1- q36.3 region, with distal breakpoint falling between 147,580,628 bp (last duplicated oligomer) and 158,781,397 bp (first normal oligomer).
The array-CGH analysis results of the proband highly indicated that the unbalanced translocation could be inherited from a balanced translocation carrier parent. To trace the origin of the translocation, cytogenetic analyses were provided to the proband’s parents, even though they had received cytogenetic analyses before at another hospital and revealed apparent normal karyotypes. With the guidance of array-based CGH results of the proband, the cytogenetic analyses revealed an abnormal karyotype [46,XY, t(7;18) (q36; p11.2)] of the proband’s father (Figure
), and a normal karyotype [46,XX] of the proband’s mother. The cytogenetics suggested that the father of the proband was a carrier of the balanced translocation.


The patient was a 24-year-old female weighing 70 kg, with mandibular trauma as a result of a car accident without any loss of consciousness after the accident. Five days after the accident, the patient decided to undergo an open reduction and fixation surgery for the right mandibular angle fracture at Imam Khomeini hospital, Ahvaz, Iran. She had no history of any previous diseases except a history of an abortion under general anesthesia 6 years ago performed without any complications. The patient’s physical examination had no abnormal findings except paresthesia of the inferior lip, tenderness and edema in her right mandibular angle, forehead and scalp tenderness on the right side with no evident fracture. All nodes in the maxillofacial area except for the mandible itself were normal. There were no occlusion and the maximum jaw opening was 10 mm. The patient had a class II airway according to the Mallampati classification. As per the regulations of the maxillofacial ward, any patient with car accident should undergo a pre-operational neurosurgical consultation. Permission for performing the surgical procedure under general anesthesia was obtained from the patientduring the neurosurgical consultation. The laboratory analysis data were all in the normal acceptable ranges.
At 8:30 am, a general anesthesia was induced using 2 mg midazolam, 150 µg fentanyl, 100 mg lidocaine, 0.5 mg atropine, 300 mg thiopental sodium and 100 mg succinylcholine. Then the patient was intubated using a size 7.5 nasotracheal tube and 40 mg atracurium was administered for muscular relaxation. Tetracycline 1% ophthalmic ointment (Sina Darou, Tehran, Iran) was applied to the eyes, to keep the eyes shut during the operation. Anesthesia was maintained by infusion of 100-200 µg/kg/min propofol, 0.1 µg/kg/min remifentanil and 50% N2O- 50% O2. The patient underwent mechanical respiration and the monitoring included an electrocardiogram, noninvasive check of blood pressure and pulse oximetry implicated during the anesthesia. During the operation, the patient received 2000 mL of ringer's serum while the volume of bleeding was 100 mL and the patient released 150 mL urine. To maintain hemostasis, the surgeon locally injected 5 mL of 2% lidocaine with epinephrine 1:100000 after aspiration, into the right mandibular angle. After intraoral vestibular incision in mandibular angle area, displaced angle fracture was reduced and rigid fixation was performed using 2 four-hole miniplates at the external oblique ridge bythe Champy technique. After irrigation suturing with absorbable material was performed, the surgery and anesthesia were performed without any complications. At the end of the operation,the left pupil was completely dilated without any reaction to light while the right pupil was 3 mm with normal reaction to light. To reverse the muscular relaxation, 3.5 mg neostigmine and 1 mg atropine were administrated. To rule out intracranial hemorrhages and related eye and optic nerve pathologies, consultation with neurosurgery (in another hospital) and ophthalmology (in the same hospital) services was performed. After extubation, the patient was transferred to the recovery room 2 hours and 20 minutes after the induction of anesthesia, being conscious and oriented with a fairly general state without any complaint of blurred vision. The report of the ophthalmology consultation was as follows: Marcusgunn was negative; the dilated eye was reactive to light, the cornea and the anterior chamber were transparent, the retina vessels had normal appearance, the disc and the capsule were normal without any bleeding, and the lens was normal. Two hours and 10 minutes after ophthalmologic consultation, the patient was transferred to another hospital for neurosurgery consultation. At this point the diameter of the left pupil was 5 mm and the right pupil was 3 mm both being reactive to light. The neurosurgery team performed a brain computed tomography (CT) scan for the patient, the results of which were normal. In the neurosurgery consultation report, it was indicated that the examination of the cranial nerves was normal, the eyes movements were normal, the diameter of the right and the left pupils were respectively 3 mm and 4 mm, and both of them were reactive to light. The patient was returned to the hospital 3 hours and 50 minutes later when the left pupil mydriasis was completely resolved, being in fair general health with stable vital signs. The patient examination was normal days after.


The first patient was a 26-year-old male farmer, brought to the emergency room 3 hours after intentional ingestion of 100 mL of monocrotophos (organophosphorus compound). He was conscious and oriented with a heart rate of 56/minute and blood pressure of 110/60 mm Hg. His pupils were pinpointed and he had fasciculations. Examination of chest revealed bibasal fine crackles. Gastric lavage was administered and he was started on infusion of atropine sulfate titrated according to clinical response. In view of diaphragmatic weakness, he was intubated and ventilated. His investigations showed haemoglobin of 13.5 g% with normal leucocyte and platelet counts. Renal and liver functions were normal. Serum cholinesterase levels were low (650 U/L; normal: 3500–8500 U/L). After 6 hours of hospitalization, he started passing black colored urine (). We evaluated this uncommon manifestation and found no evidence of haemoglobin or myoglobin in the urine. Besides, creatine phosphokinase levels were found to be normal, ruling out the possibility of rhabdomyolysis. The patient developed ventilator associated pneumonia on the 3rd day. Endotracheal aspirate culture showed MRSA, which responded to clindamycin. Patient was weaned off ventilatory support on day 6. Discoloration of urine resolved over a period of 8 days and patient was discharged with no further complications.


The second patient, a 39-year-old male diabetic, was admitted to the intensive care unit following consumption of 25 mL of ethion, 8 hours prior to hospitalization. He had already received gastric lavage and 10 mg of atropine from a primary care hospital. On examination, he had a heart rate of 98/min and blood pressure of 120/70 mm Hg with 4 × 4 mm pupils bilaterally reacting to light. His chest was clear and neurologic examination was normal. Over the next 3 hours he developed weakness of the neck flexors and respiratory muscle weakness. He was mechanically ventilated and started on atropine. His baseline investigations were normal except for hyperglycemia and a low serum cholinesterase (970 U/L). On the 2nd day, his urine showed blackish discoloration without any reduction in hourly output (). In this patient too, workup for intravascular hemolysis and rhabdomyolysis turned negative. The patient was successfully weaned off the ventilator by day 7 and his urine became clear over the next 24 hours.


DA, a 47-year-old right-handed woman with 13 years of education, who worked as town employee, received the diagnosis of relapsing remitting MS at the age of 32, with the postulated onset of the disease at 12 years. She has a familial history of inflammatory bowel disease, but no previous or concomitant diseases were reported. Her last relapse goes back to the age of 35 and during the last 10 years she has gradually developed progressive paraparesis and bladder dysfunction, suggesting a secondary progressive MS. Moreover, at the age of 47 she developed a focal epilepsy secondary to MS cortical lesions. The patient's expanded disability status score (EDSS) at the time of referral was 6.5; concomitant medications were baclofen and levetiracetam.
DA was referred for neuropsychological evaluation because of intermittent and bizarre writing disorders (i.e., at times her right hand would not respond or would write letters or digits different from intended ones). During the initial interview she described additional peculiar behaviors of her left hand frequently interfering with the activity of the other hand; for example, when she was opening a door or drawer with her right hand, she simultaneously pushed it shut with the left hand; on other occasions, she would open her pocket with the right hand but immediately her left hand would close it, or when choosing from the closet a pullover to dress, instead of taking the preferred one, sometimes she would find her left hand getting another, even from a different shelf. These behaviors did not always occur in the same situations and her left hand usually cooperated well with the right. She also reported occasional inability to move either the left or right hand at will during a task. Thus, her symptoms suggested the presence of alien hand signs, in particular of diagonistic dyspraxia,the core symptom of the “callosal variant.” It was also expected to detect additional signs, typical of interhemispheric disconnection, on neuropsychological testing, such as difficulty in writing with the nondominant hand, left hand apraxia, dominant hand constructional apraxia, and tactile anomia [].


A 20-year-old woman presents with chronic dyspnea on exertion and exercise intolerance that was attributed to and treated as presumed exercise-induced asthma since childhood. She experienced worsening left-sided chest heaviness and was subsequently referred to our institute. She has no coronary risk factors and no family history of premature coronary artery disease or congenital heart condition. Physical examination was normal except a subtle continuous murmur at apex and lower right sternal border. ECG showed sinus rhythm without ST or T wave changes (Supplemental Figure 1 available at doi:10.1155/2012/471759). Chest X-ray showed no cardiomegaly (Supplemental Figure 2). Serial cardiac enzymes were negative. In the light of cardiac murmur, an echocardiogram was obtained and revealed anomalous coronary arteries with a large left coronary artery to main pulmonary artery fistula. There was mild left ventricular enlargement with preserved left ventricular contractile function and an ejection fraction of 65%. The appearance of the left ventricle and left atrium was consistent with a systemic to pulmonary vascular shunt with increased stroke volumes in the left heart. There were no structural abnormalities of the aortic, mitral, tricuspid, or pulmonic valves, and there was very mild mitral regurgitation by Doppler. A subsequent cardiac catheterization confirmed the diagnosis of ALCAPA with retrograde filling through collaterals arising from an enlarged right coronary artery (12 mm) (), pronounced left-to-right shunting from the left main coronary artery into the left main pulmonary artery trunk; and the right coronary artery gives rise to collaterals to a large left anterior descending artery which has ectasia in its proximal segment into a smaller circumflex artery. The patient underwent surgical treatment by the creation of a pulmonary artery tube graft from the aorta to the left coronary artery and reconstruction of the main pulmonary artery with a bovine pericardial patch. She had no major complications or ischemic symptoms 18 months after operation. A follow-up echocardiogram at that time showed normalized stroke volume and left atrial and ventricular size secondary to reversed left-to-right shunt, preserved LV EF at 55%, and absence of valvular abnormalities.


In September 2004, a 24-year-old male presented with progressive dyspnea on exertion, paroxysmal atrial fibrillation, malaise, and peripheral eosinophilia. Initial evaluation showed a left atrial mass and a separate mass adherent to the mitral valve for which the patient underwent surgical resection and mechanical mitral valve replacement. The diagnosis of noninfectious hypereosinophilic granulomatous disease was made by histopathologic evaluation. The patient underwent treatment with imatinib mesylate and a 5-month steroid course, which eventually led to complete resolution of eosinophilia, residual masses, and symptoms.
In December of 2009, the patient presented to an outside facility with fevers, night sweats, and weight loss and was diagnosed with subacute mechanical valve endocarditis from Streptococcus viridians. TTE noted multiple large vegetations at the four and five o'clock positions of the mechanical valve. The patient underwent a second mitral valve replacement using a 29 mm St. Jude mechanical valve, with a cross-clamp time of 85 minutes and total bypass time of 132 minutes. Intra-operative TEE was performed without mention of aortic valve injury or regurgitation. Pathology review of the prosthetic valve vegetations showed focal necrosis with fibrinous exudates without prominent eosinophilia. A two-day postoperative TTE report noted new mild to moderate aortic insufficiency. His postoperative course was significant for atrial flutter and mild congestive heart failure symptoms. He was discharged on appropriate heart failure therapy and neurohormonal blockade.
The patient's condition continued to deteriorate, and he presented to our institution 2 months after the second operation with NYHA Class III decompensated heart failure. Repeat echocardiography revealed an overall preserved ejection fraction of 45%–55%; however, a new finding of severe aortic regurgitation was noted ().
TEE also demonstrated a large regurgitant jet originating from the non-coronary and left coronary cusps concerning for valve perforation ().
For better visualization, a cardiac gated CT scan was done, which confirmed a 4-5 mm perforation of the aortic valve non-coronary cusp ().
Given extensive scarring from his recent surgical procedures, the patient underwent a trial of optimal medical management for the ensuing 4 months. Despite these efforts, he did not recover and was referred for surgical correction requiring a third sternotomy. Operative evaluation revealed a misplaced prolene suture used in closure of the transseptal surgical approach which perforated the non-coronary cusp. The defect was repaired with a pledgeted subannular stitch to reapproximate the leaflet. Intra-operative TEE demonstrated aortic and tricuspid valve competence, without stenosis or insufficiency. Postoperatively the patient made an excellent recovery.


GP shows evidence of neuronal differentiation, also supported by cell positivity for several neuroendocrine (ND) markers.
In this case, a 48-year-old caucasian man was referred to our Institution after recurrent upper GI bleeding with melena. The patient reported a four month history of intermittent coffee ground stools, fatigue and weight loss. Clinical examination was uneventful and the patient was hemodinamically stable with 8.4 g/dl value of Haemoglobin and a Hematocrit of 28%. Iron deficiency was also present. No history of previous pathologies was reported. Pan-colonoscopy was negative and a standard gastroscopy had been performed at another Institution, revealing a 4 cm bulky mass of the distal duodenum. Gastroscopy was repeated in our institution with pediatric instrument to have a better evaluation of the mass. The lesion, located in the 4th duodenal portion, was included in the duodenal wall and covered with normal mucosa with a bleeding surface. Multiple biopsies were performed but the results were inconclusive.
A CT-scan was also performed, revealing a thickening of the 4th portion of the duodenal wall and non-lymphadenopathies.
The patient underwent an exploratory laparotomy with segmental resection of the 4th portion of the duodenum and the first jejunal loop. An end to end anastomosis between the 4th duodenal portion and the jejunum was carried out. The patient was discharged on the 6th post-operative day after an uneventful course.
Twenty-four months after surgery, the patient was diagnosed disease free.
Macroscopically the surgical specimen showed a polypoid lesion, covered with smooth mucosa with microerosion area, of 4 cm × 4 cm × 3 cm. All tumor samples were stained with H/E (hematoxilin/eosin). IHC stains were then performed.
Under microscopic observation the tumor was composed of epithelioid cell nests, areas of spindle cells and scattered ganglion cells (Figure ). The neoplastic proliferation affected submucosal layers up to the lamina propria and was covered with duodenal mucosa devoid of morphological abnormalities, with focal areas of erosion of the epithelial layer.
The panel of immunohistochemical markers used showed a negative cellular reaction for cytokeratin (CK) 7 (Dako, OVTL 12/30, 1: 200), CK20 (Dako, Ks20.8, 1:50), CDX2 (Dako, DAK-CDX2, 1:50) and CD117 (Dako, CD117, 1:50). A low positive cellular reaction was present for Vimentin (NeoMarkers, Westinghouse, California, D9, 1:1000.), S100 (Dako, 1:3000), Chromogranin A (Dako, A0430, 1:1500
 and Somatostatin (Abcam, ab103790, 1:200) while a strong positive cellular reaction was detected for Synaptophysin (Dako,1:3000), CD56 (Dako, 123C3, 1:50) and NSE (Dako, BBS/NC/VI-H14, 1:100) (Figure ).
The final histological examination revealed a GP tumor.
After histological diagnosis, we evaluated the expression by IHC of NeuroD1 marker with primary antibody against human NeuroD1(Abcam, ab60704,1:200) for one hour of incubation. The sections were rinsed in TBS and incubated for 20 min with Novocastra Biotinylated Secondary Antibody (RE7103), a biotin-coniugated secondary antibody formulation that recognize mouse and rabbit immunoglobulins.
The sections were then rinsed in TBS and incubated for 20 min with Novocastra Streptavidin-HRP (RE104). Peroxidase reactivity was visualized using a 3,3′-diaminobenzidine (DAB).
IHC staining of Neuro D1 was scored as follows: - , if < 5% of tumor cells were stained; +, if there were focal, weak tumor cells staining; ++, if there were moderate tumor cells staining; +++, if there were marked tumor cells staining.
NeuroD1 showed a marked positivity (+++), (Figure ) mostly cytoplasmic, especially in ganglion and epithelioid cells.
Finally, for gene expression analysis, total RNA was isolated from a frozen biopsy of the tumor stored in our Institutional Bio-Bank, using RNeasy Mini Kit (Qiagen GmbH, Hilden, Germany) following the manufacturer’s instructions. The sample was treated with RNase-free DNase (Qiagen GmbH, Hilde, Germany) to prevent amplification of genomic DNA. A total of 1 mg RNA was subjected to cDNA synthesis. Quantitative Real Time -PCR (qRT PCR) was performed in a Light Cycler system (Roche Molecular Biochemicals, Mannheim, Germany) using specific TaqMan Gene Expression Assays for human NeuroD1 (Real Time Designer Assay cod. 05583055001, Roche Molecular Biochemicals).
qRT PCR analysis showed NeuroD1 over-expression compared to other cancer samples used as controls (Figure ).


We report a case of trastuzumab-associated cardiotoxicity, initially manifesting as an acute coronary syndrome (ACS), in a 59-year-old male with metastatic adenocarcinoma of the esophagus. The patient was diagnosed in October 2010 (20 months prior to his ACS admission). His initial treatment involved cisplatin, 5-fluorouracil, and radiation followed by esophagogastrectomy and bilateral myotomy. Progression of his disease was noted the following year in April 2012. He was initiated on FOLFOX (folinic acid, fluorouracil, and oxaliplatin) and trastuzumab for HER2-positive disease. The FOLFOX was given every two weeks and the trastuzumab every three weeks.
Immediately following his third trastuzumab infusion, he developed chest tightness, shortness of breath, and nausea. An EKG demonstrated new anterolateral T-wave inversions (). Significant laboratory data included an initial troponin I of <0.006 ng/mL (normal 0.000–0.040 ng/mL) and a hemoglobin of 11.7 g/dL. He was transferred to a tertiary level medical center coronary care unit where his cardiac biomarkers remained negative (peak troponin I 0.007 ng/mL). An echocardiogram demonstrated new anterior and anteroseptal wall motion abnormalities () and an ejection fraction of 40%. He was begun on standard cardiac medications, including a beta blocker. A cardiac catheterization demonstrated mild nonobstructive coronary artery disease with wall motion abnormalities on the left ventriculogram, consistent with findings on the echocardiogram. The decision was made to hold treatment with trastuzumab until his left ventricular function improved. However, followup echocardiograms (four and ten weeks after cardiac hospitalization) demonstrated persistent left ventricular dysfunction with ejection fractions of 40%. Of note, serial echocardiograms prior to and during chemotherapy all demonstrated normal left ventricular systolic function.


A twenty-five year old Caucasian female was admitted acutely with right iliac fossa (RIF) pain and maximal tenderness over McBurney's point. Past medical history included sciatica and cervical intraepithelial neoplasia grade III. There was no previous surgical history of note.
Admission blood tests revealed a haemoglobin of 136 g/L (range 135–160 g/L), white cell count of 16.69 × 109/L (4.0–11.0 × 109/L), neutrophil count of 11.51 × 109/L (2.0–7.5 × 109), a serum amylase of 16 iu/L (25–125 iu/L), and a C-reactive protein (CRP) of 194 mg/L (0–5 mg/L). Serum liver and renal function tests on admission and were within normal reference range. Working diagnosis was acute appendicitis and the patient underwent an emergency laparoscopic appendicectomy.


A previously fit and healthy 21-year-old female presented to the psychiatric services with uncharacteristic behaviour. She was noted to be extremely anxious, with repetitive phrases and evidence of disordered thought. She was admitted to a psychiatric hospital and treated for acute psychosis. However, her care was transferred to the acute medical services following the development of acute dystonia of the face, tongue, and symmetrical jerking movements of the limbs. This progressed over the next 48 hours to what appeared to be atypical generalised seizures while still maintaining some degree of volitional control, with a documented Glasgow Coma Scale between 3 and 11. Autonomic dysfunction was also evident with hyperpyrexia and varying tachycardia.
She was intubated and ventilated for airway protection. CT imaging was unremarkable, and an EEG, although was encephalopathic, did not show status epilepticus. CSF was not pleocytic with normal biochemistry. Initially, she was treated for atypical status epilepticus with propofol, phenytoin, and midazolam; however, ongoing seizure-like activity and orofacial dyskinesia were noted with no EEG correlate.
A provisional diagnosis of NMDA receptor encephalitis was made by the neurology team, and although a serum anti-NMDA receptor antibody assay was negative, treatment with methylprednisolone was commenced. The main clinical problem for the ICU team was managing her profound dyskinesia and agitation without acquiring iatrogenic complications such as ventilator-associated pneumonia, central line-associated infections, rhabdomyolysis, venous thrombosis, and propofol infusion syndrome while managing her dyskinesia and awaiting the response to immunotherapy.
Despite multiple adjuvant sedation regimes (in addition to propofol and alfentanil) including benzodiazepines, clonidine, dexmedetomidine, and risperidone, she remained either completely anaesthetised or unmanageable from distressing orofacial dyskinesia (tongue protrusion, drooling, and chewing), agitation, and coughing. Occasionally, she was responsive and able to follow one step commands but was never lucid. She developed early flexion contractures of her arms and legs, and peripheral access was not possible.
Over the course of her two month admission, she developed a probable ventilator-associated pneumonia and central line infection (both recognised early and treated successfully).
Although a serum anti-NMDA receptor antibody assay was negative, a subsequent CSF anti-NMDA receptor antibody test was positive, and immunotherapy in the form of sequential steroids, immunoglobulins, and plasmapheresis was instituted. It took over two months to be completed, and there were no initial signs of response: she remained as described previously. A tracheostomy was performed following a failed attempt at extubation (primarily due to laryngeal oedema).
Several days after the final plasmapheresis session, levetiracetam and a ketamine infusion (20 mg/hour) were commenced. The commencement of the ketamine coincided with a dramatic improvement in her clinical state: within a few hours there was no more orofacial dyskinesia, and she was lucid for the first time since admission.
She was successfully decannulated two days later and discharged to a level 1 environment later that week. She remained on 20 mg per hour of intravenous ketamine on discharge from ICU, and this was tapered off over the course of two weeks with no clear relapse in symptoms.
She has made an excellent recovery and has no lasting neurological deficit. Interestingly, she has no recollection of the events in intensive care, a finding commonly seen in NMDA receptor encephalitis.


A 79-year-old woman was admitted to the emergency department of Peking Union Medical College Hospital complaining of severe abdominal pain with unknown causes for 4 hours. The pain got worse after 2 hours with an acute hypotension (blood pressure drop from 106/79 mmHg to 61/44 mmHg), heart rate elevation (from 80 beats/min to 100 beats/min) and blunted. Laboratory investigation noted a decrease of hemoglobin from 119 g/dL to 62 g/dL in half an hour. Emergent computed tomographic angiography (CTA) showed the presence of a very tortuously ruptured AAA that now was 10.33 cm in diameter with a 90° neck angle (Figure A). The rupture, which extended from 2.5 cm below the opening of bilateral renal arteries down to the celiac artery and elongated to both common iliac arteries, involved the inferior mesenteric artery. Although the two iliac arteries were unobstructed with a 2.1 cm and 1.8 cm diameter of the right and left respectively, the right iliac artery was severely tortuous with a ‘S’ appearance (Figure B and C).
Previous medical history was normal except that she had a hypertension for more than 10 years with a maximum blood pressure of 160/90 mmHg, and was diagnosed of AAA by CTA with a maximum diameter of 6 cm in 2009. She refused to follow up because of no abdominal symptoms since then. She had no surgical history. Given the age of the patient and the emergent status, an endovascular approach was conducted despite the hostile neck. The time of door-to-cath lab was about 70 minutes. After local anesthesia, a 6-F, 11 cm-long introducer sheath (Cordis, Johnson & Johnson, NJ, USA) was placed percutaneously through the left groin for the diagnostic angiography, which confirmed the existence of an unfavorable aneurysm inferior to the renal artery (Figure A and Additional file : Movie S1). An 18-F, 30-cm-long sheath (W.L. Gore & Associates, Flagstaff, AZ, USA) was introduced and a 28-12-160-mm Excluder aortic main body (W.L. Gore &Associates) was deployed below the origin of the bilateral renal arteries (Additional file : Movie S2). Another 18-F, 30-cm-long sheath (W.L. Gore & Associates, Flagstaff, AZ, USA) was used, and two iliac legs of 20–120 and 20–100 (W.L. Gore & Associates, Flagstaff, AZ, USA) were placed superior to the opening of the right hypogastric respectively.
The guidewire was hard to enter the iliac leg due to the severely tortuous right iliac artery (Additional file : Movie S3), and therefore balloon-assisted technique was designed. The balloon was deployed in the proximal part of the main body and then inflated, thus keep the stiff wire in place which allowing the positioning of the guidewire (Figure B and Additional file : Movie S4).
In order to avoid the type Ib endoleak, we deployed a 26–30 cuff above the bifurcation of the iliac artery (W.L. Gore & Associates, Flagstaff, AZ, USA) (Figure C). A 20–140 iliac leg was placed above the bifurcation of the left iliac artery (Figure D). The stent-grafts were dilated using balloons (CODA, COOK, USA). The following angiography showed a severe Ia endoleak in the proximal neck (Figure E and Additional file : Movie S5), and therefore, a 32–4.0 Cuff (W.L. Gore & Associates, Flagstaff, AZ, USA) was deployed distal to opening of the left renal artery with off-the-shelf solution [] (Figure F).
Final angiography confirmed successful sealing of the rAAA with continued perfusion of both celiac and right renal arteries, and the aortic body pulsation disappeared accordingly (Figure G, H and Additional file : Movie S6). The patient had an uneventful recovery and was discharged home after 6 days. She is well and symptom-free 6 months later. Follow-up CT at 6 months demonstrated fluent celiac and bilateral renal arteries (Figure ).


A 45-year-old Caucasian man was admitted to the Accident and Emergency Department of our hospital after presenting with a two-week history of progressive walk impairment associated with paresthesias around his mouth and the fingers on his right hand. The most remarkable features of his medical history were the presence of type 2 diabetes (recently diagnosed), dislipemia, high blood pressure and morbid obesity (body mass index: 41.3).
A medical examination showed a lower limb paresis (grade 3/5), which was more prominent in dorsal flexion of both feet, an absence of reflexes and a loss of superficial sensitivity in his left limb. The presence of enlarged lymph nodes in the cervical area was also evident; they were variable in size (some of them of more than 1cm) and mobile. Furthermore, a large scalp mass was identified in the parietal-occipital area; it was stuck to the skull, had an irregular shape, a tough texture, and palpation was not painful. Apart from these findings, the presence of a bilateral gynecomastia and a hyperpigmentation of the skin, mostly of the areoles, were noteworthy.
An electromyography (EMG) test was performed to better determine the neurological symptoms. The EMG showed a motor-dominant polyneuropathy with demyelinating features in his lower limbs. The administration of steroids only partially improved his neurological symptoms.
A cranial computed tomography (CT) scan was performed and showed a mass in the scalp with intense underlying bone erosion (Figure ). The mass was in contact with the posterior part of the sagittal sinus, but did not invade it. There were no signs of brain damage or infiltration and the tumor presented intense vascularization, mainly from vessels of the external carotid artery (ECA). A magnetic resonance imaging (MRI) scan could not be performed because of our patient’s high body weight. A whole-body CT scan was carried out and revealed adenopathies in the cervical area, mediastinum and retroperitoneum. Splenomegaly was also identified.
His laboratory test results showed a significant increase of immunoglobulin G (IgG) with a clear peak in the proteinogram, increase of lambda and kappa light chains in serum and high levels of vascular endothelial growth factor (VEGF) (Table ). No Bence Jones proteinuria was identified. A bone marrow biopsy showed reactive changes and intense plasmocytosis and pathological analysis of one of the cervical lymph nodes showed reactive changes with peripheral follicular proliferation, hyalinization of the vessels and the presence of plasma cells (Figure d). These findings were compatible with Castleman’s disease. Serological tests for human herpes virus-8 (HHV-8) and human immunodeficiency virus (HIV) infection were performed, with negative results, because of the association between Castleman’s disease and these viral infections [,]. Castleman’s disease occurs in about 11 to 30% of patients with POEMS syndrome [].
The decision was taken to surgically remove the parietal-occipital mass, with a previous embolization of the main arteries feeding the tumor in order to avoid excessive bleeding during surgery. The patient was operated on under general anesthesia. We performed a circular craniectomy around the tumor and a complete excision of the lesion by dissecting its adherences with the dura mater, which did not seem to be damaged (Figure a and 2b). A titanium mesh was placed in the osseous defect.
Pathological analyses concluded that the tumor was a well-differentiated plasmocytoma with expression of CD38, IgG and lambda light chain (Figure c). A bone marrow biopsy showed reactive changes with intense plamocytosis.
Subsequently, according to the definitive pathological results, dexamethasone pulse therapy was initiated (three pulses per month of 20mg/day for four days) and the patient also received radiotherapy to the skull to complete the treatment, with an accumulated dose of 50Gy in the surgical field.
As mentioned above, his neurological status improved slightly with the initial prescription of steroids, but neurological deficits recovered progressively after surgery. The rest of the POEMS features also improved after surgery and even more so when steroids and radiotherapy were initiated (two weeks after surgery).
Apart from his clinical status, his response to treatment was evaluated with positron emission tomography (PET), which was performed two months after the last steroid pulse. It showed a complete resolution of adenopathies in the different areas and no abnormal activity was identified in the skull. Moreover, vascular endothelial growth factor (VEGF) and lambda chain serum levels normalized progressively. During the 18-month follow-up, there have not been any clinical or laboratory abnormalities to indicate a recurrence of the disease. No complications related to the surgical procedure were reported (Figure ).


A 27-year-old female patient, who experienced upper abdominal pain and progressive hepatoma for 4 years, was diagnosed with a giant hepatic hemangioma. The patient showed mild jaundice, abdominal fullness, and abdominal varicose veins on presentation. Laboratory examination showed a hemoglobin level of 81 g/L and a platelet count of 95 × 109/L. Blood biochemistry showed total bilirubin concentration of 1.34 mg/dL, alanine aminotransferase concentration of 10 U/L, and creatinine level of 0.44 mg/dL. The coagulation tests showed a prothrombin time (PT) of 15.4 seconds, activated partial thromboplastin time of 35 seconds, fibrinogen concentration of 4.2 g/L, and fibrinogen degradation product tests were negative. An abdominal CT scan indicated the presence of low-density areas in both the liver lobes, occupying the entire abdominal cavity without rupture (Figure ). The recipient was further examined and this revealed a hemangioma occupying the entire abdominal cavity, measuring approximately 50 × 40 × 25 cm in size (Figure ).
Surgery was performed on September 1, 2007. The donor was the patient’s 55-year-old father. Preoperative evaluation showed that the graft-to-recipient weight ratio (GRWR) was 1.46% and the remnant liver volume (RLV) of the donor was 47%. During surgery, the liver was not mobilized and rotated to prevent the risk of hemangioma rupture. We ligated the portal canal and blocked the upper and lower blood supply to the liver, and then resected the recipient’s liver and simultaneously preserved the donor’s inferior vena cava. A hepatic occlusion clamp was used to control the blood flow to the liver from the inferior vena cava. End-to-end anastomosis was performed in order to join the recipient’s right hepatic vein and the donor’s right hepatic vein. The diameter of the V8 segment vein was 0.3 cm. We dealt with the inferior mesenteric vein by bridging the inferior vena cava to avoid congestion of the V8 segment vein (Figures and ). End-to-end anastomosis was also performed between the donor and recipient’s right branch of the portal vein, as well as for the donor’s and recipient’s common hepatic veins. The hepatic artery, portal vein, and bile duct was resected using the anterior approach. The portal vein was cut using the 55-mm cutting stapler (Johnson & Johnson) to avoid the effects of using a surgical clamp on the portal vein. In situ incision of the coronary ligament and deltoid ligament was performed to separate the hepatogastric ligament for the left side of the liver. Finally, 3 to 5 hepatic segment veins were ligated and incised along the hepatic inferior vena cava in the centripetal direction and the diseased liver was resected without moving the right liver lobe with retention of the retro-hepatic inferior vena cava.
A variation in the donor’s bile duct was observed and dealt with surgically. The right anterior branch was connected to the left hepatic duct, which was clearly visible on bile duct radiography of the graft (Figure ). The right anterior branch and the posterior branch were anastomosed to a single orifice.
The surgery was performed successfully without the transfusion of any blood products. The donor’s surgical time was approximately 3 hours and 10 minutes (the time spent on hepatectomy was 2 hours, excluding the initial abdominal entry and subsequent closure) and that of the recipient was approximately 4 and a half hours. The patient recovered gradually after operation without experiencing any infection or any vascular or biliary complications. She was discharged 20 days after surgery.
Postoperative pathology showed that the surface of the removed liver was an abnormal color ranging from gray-red to gray-yellow. A cross-sectional sample that was obtained was also gray-yellow in color. The entire liver comprised of tumorous tissue, with little normal hepatic tissue remaining. A giant hepatic cavernous hemangioma was diagnosed. The immunity class showed CD34 (+).
A liver biopsy 12 months after the operation confirmed an acute rejection reaction with a Buffer score of 9, but the patient recovered with methylprednisolone treatment. The second episode of rejection occurred at 17 months with a Buffer score of 7 and was treated by increasing the tacrolimus dosage and concentration. The patient currently remains healthy, and the graft is fully functional.


A 9-year-old intact female Lhasa Apso dog presented to the animal hospital for mild lethargy and anorexia. No significant changes were detected by complete blood count (CBC) and serum chemistry. A hyperplastic uterus was identified on radiologic imaging, and a closed pyometra was suspected; thus, ovariohysterectomy (OHE) was performed. On gross appearance, the right ovary had multiple follicular cysts, and the connected uterine horn showed mild endometrial hyperplasia.
The resected ovary and uterus were fixed in 10% neutral buffered formalin, embedded in paraffin, and processed routinely with haematoxylin and eosin (HE) stain. For immunophenotyping of lymphocytes, immunohistochemical analysis was performed using the Vectastain® Elite ABC-Peroxidase kita according to the manufacturer’s instructions. Rabbit monoclonal anti-CD3b (1:100) and mouse monoclonal anti-CD79ac (1:200) were used as primary antibodies. The antibody reaction was visualised using diaminobenzidine peroxidase substrate (DAB).d The sections were counterstained with Mayer’s haematoxylin, dehydrated, and mounted.
In HE stain, the uterine horn showed massive infiltration of basophilic cells, and the disappearance of endometrial glands with moderate haemorrhage was noted. The basophilic infiltrates partially invaded the muscular layer (Figure ). Under higher magnification, the round basophilic cells were identified as medium-sized lymphocytes with a moderate nuclear:cytoplasmic (N:C) ratio and multiple prominent nucleoli (Figure ). Previously reported descriptions supporting a marginal zone (MZ) B-cell origin include neoplastic cells possessing a relatively abundant amount of cytoplasm, a low N:C ratio, eccentric nuclei, and distinct nucleoli []. The neoplastic cells in this case displayed strong immunoreactivity for CD79a (Figure ) and a negative reaction for CD3 (data not shown), indicating a lymphoma of B-cell origin.
The patient recovered after OHE, and no additional occurrence or systemic metastasis of lymphoma was found.


A 59-year-old male who used to work as a stone miner for 10 years complained of chest distress and dyspnea for months and worsened 3 days before admission. Symptoms were aggravated either after activities or lying flat. He had no chest pain, hemoptysis, fevers, chills, night sweats and his vital signs were stable before admission. Patient reported a smoking history of 30 years. Rales or wheezes were not heard during auscultation.
Initial investigations including chest X-ray and CT found a 25×33 mm nodule in the right upper lung and diffused small nodules throughout the lung (Figure ). The chest CT also demonstrated thickened and restricted pericardium (Figure ). CT guided biopsy of the 25×33 cm lung nodule was performed and pathology demonstrated fibrous tissue hyperplasia and hyaline changes with carbon deposits and chronic inflammatory cell infiltration (Figure ), which were definite pathologic evidences of silicosis. No tuberculosis bacilli were found in the tissues. We then had this patient screened for TB (tuberculosis) antibodies, T-spot.TB and PPD skin test. However, none of these TB screens were positive.
The patient, diagnosed with silicosis and constrictive pericarditis, was then transferred to surgery department for pericardium decortication. The surgery went successfully. Pathology of the excised pericardium showed granular and fibrous tissue hyperplasia and negative fast acid staining (Figure ). Patient was well recovered from previous dyspnea and chest distress and discharged afterwards. He remained very well and reported no similar symptoms during our follow-ups. Follow-up chest X-rays did not show any enlargement of the 25×33 mm nodule in the right upper lung.


A 38-year-old male presented to the emergency room at Santa Maria della Misericordia Perugia, Italy, with a 12-hour history of abdominal pain associated with fever (38.2°C). The patient reported the acute onset of abdominal cramps mainly localized in the hypogastrium and left iliac fossa; neither alterations of bowel transit nor nausea and vomiting were reported. The patient’s personal and family history were negative for neoplastic disease, and pathological anamnesis revealed untreated allergic asthma and hypertension. Clinical examination revealed diffuse abdominal tenderness elicited on deep palpation of the lower quadrants and positive Blumberg sign. Blood tests showed neutrophil leukocytosis (11,060 white blood cell count, 81% neutrophils). Abdominal ultrasonography was normal, while X-ray showed air-fluid levels of the small bowel on the right flank.
A few hours after admission, the patient’s clinical conditions suddenly worsened with exacerbation of the abdominal pain. The patient consequently underwent emergency diagnostic laparoscopy. The intraoperative finding was a peritoneal purulent fluid collection with a large sigmoidal abscess, due to a perforated diverticulitis on the mesenteric bowel side. Laparotomic conversion was requested by the septic condition and resection of the sigmoid colon with prophylactic appendectomy was performed. Careful exploration of the abdominal content revealed MD, located approximately 50 cm above the ileocaecal valve, which was also prophylactically removed. Finally, a ghost ileostomy was created by collecting (without externalizing) the ileum to the abdominal wall, approximately 70 cm above the ileocaecal valve.
The pathologic examination of the specimen showed sigmoid diverticular disease, complicated by acute diverticulitis and fibrinopurulent peritonitis, scleroatrophic appendix and the presence of reactive mesothelial cells in the peritoneal fluid, in the absence of atypia. A carcinoid tumor was found in the submucosa of the MD, locally invading the mucosa but not the muscular layer on a ground of fibrinopurulent serositis.
This well-differentiated neuroendocrine tumor (measuring 1.25 mm on the histological section) was located at the level of the diverticular body. Immunohistochemistry was performed, revealing chromogranin positive, synaptophysin positive and a Ki-67 (MIB-1) proliferation index of less than 1% (Figure
). According to the diameter of the tumor, simple diverticulectomy without bowel resection was considered adequate treatment.
The postoperative course was regular and the patient was discharged in good clinical condition on the 12th postoperative day. A computed tomography (CT) scan was subsequently performed and excluded metastatic dissemination. To date, the follow-up of the patient has been 3 years, and there has been no evidence of recurrence or metastatic disease.
MD is the most common congenital disease of the gastrointestinal tract, affecting approximately 2% of the population
[,]. Although described in 1598 by Fabricus Hildanus as an anatomic variant, in 1809, Johann Meckel was the first to produce a detailed description on the subject.
MD is the most common true diverticulum of the gastrointestinal tract. It is localized approximately 45 to 60 cm proximal to the ileocaecal valve on the antimesenteric side, on the projection of the terminal branch of the superior mesenteric artery (SMA), which represents the rotational axis of the fetal gut
[]. With regards to pathogenesis, MD is the result of incomplete obliteration of the vitelline duct between the 5th and 8th week of gestation
[], which may also rarely evolve as a fistula or a fibrous band
[]. MD may contain areas of ectopic mucosa, mainly of gastric type, or be the site of development for various proliferative lesions, including benign tumors such as leiomyomas and lipomas, malignancies such as malignant sarcomas and adenocarcinomas, or more commonly carcinoid tumors
[].
In most cases, MD is not symptomatic and diagnosis is accidental during a laparotomy or laparoscopy performed for other reasons (as in our case), or during radiographic study of the small bowel, but most frequently it is an autoptic finding
[]. The estimated average complication risk of patients with MD ranges between 2% and 4%
[,], and appears to be inversely proportional to age: 4 to 5% under 2 years, 1% at 40 years and almost 0% at 70 years
[].
The most common complications of MD include intestinal obstruction (22 to 50%) and gastrointestinal bleeding (11.8%), and is often related to the presence of ectopic mucosa and inflammatory complications (20%). Less common presentations are associated with Littré’s hernia (anecdotal), fistula (1.7%) or as a consequence of neoplastic degeneration (3.2%).
MD-associated tumors occur in approximately one-third of carcinoid cases (33%)
[], and other histological types include adenocarcinomas, pancreatic carcinomas, intraductal papillary mucinous adenomas of the ectopic pancreas, gastrointestinal stromal tumors (GISTs), leiomyosarcomas, lymphomas, lipomas, adenomyomas and villous adenomas. Carcinoid neuroendocrine tumors originate from enterochromaffin cells, which are probably originally located in the neural crest, and represent the most common primary tumor of the small intestine.
In 1907, Oberdorfer coined the term carcinoid to describe a type of neoplasm that, considering the benign characteristics, could be distinguished from cancer. In 1914, Gosset and Masson detected the affinity of carcinoid cells for silver salts. Carcinoids can theoretically occur in any anatomical region, but are most commonly found in the appendix, with the ileum being the second most affected site, usually in its last 60 cm. These tumors can secrete various hormones, the most important of which are serotonin and substance P. They may have malignant behavior but usually show a low aggressiveness, being asymptomatic in 70 to 80% of cases
[]. Symptoms of intestinal carcinoid tumors can be periodic abdominal pain, gastrointestinal bleeding and obstruction, or by the typical carcinoid syndrome (10 to 20%) with acute episodes of skin flushing, diarrhea, asthma attacks, hepatomegaly and development of cardiac lesions. Carcinoid syndrome, supported by serotonin secretion, occurs in 45% of patients with massive liver metastasis and in 10 to 20% of patients affected by carcinoid of the MD. Because of the non-specificity of symptoms, especially in the early phase, the average time between the onset of symptoms and diagnosis varies from 2 to 20 years
[]. Therefore, half of patients present a disseminated disease at the time of diagnosis
[].
Since both MD and carcinoid tumors are rare clinical entities, the occurrence of a carcinoid tumor on a MD is even more uncommon. Considering the limited dimension of the MD, it should be noted that it has the highest incidence of carcinoid transformation per cm2 of mucosal surface
[]. Modlin et al.
[]reported that approximately 0.48 to 0.74% of all carcinoids occur in the MD.
The association between carcinoid tumors and MD seems, in fact, validated by a common embryological origin, arising from incorrect interactions between the neural crest and endoderm
[]. The average age of appearance of a carcinoid on a MD is 55 years, with an incidence 2.5 times higher in men than women
[]. Until 1988, 52 cases of carcinoid in MD had been described
[], and in 1997 a review identified 111 cases
[]. Currently, the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, the authoritative source of information on incidence and survival of cancer in the US, has reported 121 cases
[].
Carcinoids localized in the appendix or in the colon usually have a lower aggressive behavior than those with bronchial and small bowel origin. As demonstrated by Moyan[], MD-associated carcinoids have a similar immunophenotype of small bowel carcinoids and consequently a comparable biological behavior. The clinical presentation is closely related to the disease stage: lesions smaller than 10 mm with intact muscle layers are rarely symptomatic, whereas those with more aggressive local characteristics are frequently associated with local and systemic signs and symptoms.
According to Moertel et al., carcinoid tumors smaller than 1 cm have an incidence of 2% of metastasis, whereas lesions with a size between 1 and 2 cm metastasize in 50% of cases, and those larger than 2 cm metastasize in 80% of cases
[]. Much higher rates have been detected by Thompson[], who demonstrated an incidence of metastasis of 18% for lesions smaller than 1 cm and 85% for lesions between 1 and 2 cm. The liver is the most commonly affected organ, with a 5-year survival of approximately 30% in patients with hepatic metastases; lung and bone metastases are less frequent. Metastases are twice as common in women than men, most likely because of hormonal factors. According to their ability to early metastasize, carcinoid tumors of MD should be considered as relatively aggressive. Therefore, according to some published studies, resection of the adjacent ileal segment and corresponding mesentery is recommended for tumors larger than 5 mm
[].
In more than 70% of cases, carcinoids originate at the distal extremity of the MD
[]. In our case, however, the tumor was localized in the middle third of the diverticulum.
The excision of MD is of course required in the case of symptoms, regardless of age, while for asymptomatic diverticula the most appropriate treatment to adopt is controversial. According to the majority of published studies, the incidental finding of a MD in children is an indication for surgical resection, while many others advise prophylactic excision of the MD in pediatric age, especially for young infants; however, the strategy to be followed in the case of MD in adults divides the experts
[-].
Despite the availability of many publications on the management of an incidental finding of MD, with more than 600 publications in the last ten years, most are case reports and prospective or randomized studies, which can hardly be realized because of the rarity of the condition. Many centers report their own experience and often disagree on epidemiology, but especially on surgical indications; and, to date, the strategy to be followed in the case of MD in adults is not yet unanimous. In 1976, Soltero and Bill collected 202 cases of complicated MD that underwent emergency surgical treatment[]. They calculated that the risk of developing complications in MD carriers was 4.2% at birth, with a progressive decrease to zero with older age. Considering that literature-reported mortality was 6 to 7% for complicated MD surgery compared to zero for elective diverticulectomy, and that associated morbidity was 11.1% and 8.9%, respectively, Soltero and Bill argued that surgical resection at birth (when the incidence of complications is greater) in 400 patients could have saved one life (mortality 6%), but would have been responsible for 36 cases of associated morbidity (morbidity 8.9%). In adulthood, with decreasing risk of complications, 800 prophylactic resections would be necessary to prevent one death. For this reason, they stated that in the absence of specific risk factors, the high risk of postoperative complications together with the low incidence of diverticulum-related complications does not justify the removal of an incidentally diagnosed MD (Table
).
In contrast, Cullen et al., in a review published in 1994, supported prophylactic diverticulectomy
[]. A higher lifetime risk of complications was calculated as 6.4%, making prophylactic resection advisable before the age of 80 years. Diverticulectomies performed for MD complications carried an operative mortality and morbidity of 2% and 12%, with a cumulative risk of long-term postoperative complications of 7%, and an operative mortality and morbidity for incidental diverticulectomies of 1 to 2% and 2%, respectively. They concluded that prophylactic surgical excision of MD is indicated at any age, especially before 80 years of age (Table
).
A more recent review by Zani et al. focused on the differences in terms of early and late complications in 2,975 incidentally detected MD cases, comparing patients treated conservatively with those who underwent resection[]. The result was a significantly higher incidence of complications in patients undergoing prophylactic diverticulectomy (5.3%), compared to untreated MD (1.3%). According to this review, the number of prophylactic diverticulectomies to perform in order to prevent one death was estimated to be 758 in childhood, 771 between 45 and 65 years of age, 911 between 65 and 75 years of age, and 1,111 in older patients. Therefore, Zani et al. supported the theory of a conservative approach (Table
).
Park et al. instead proposed a more accurate selection of MD carriers, with the aim of only submitting patients to surgery with a higher risk of complications
[]. Taking into account the frequency of some characteristics associated to symptomatic diverticula, such as age, gender, length and presence of ectopic tissue, Park et al. recommended the resection of MD in males, in patients younger than 50 years, in the presence of a diverticulum longer than 2 cm and with visible anatomical changes. According to this theory, the simultaneous presence of all four features would be associated with an expected complication rate of 70%, and the finding of three, two or one of the aforementioned criteria would correspond to a risk of 42%, 25% and 17%, respectively.
It is important to note that most of the available data refer to retrospective studies, in which patients had undergone laparotomic diverticulectomies. The advent of laparoscopy, which allows a comprehensive exploration of the abdominal cavity with a minimally invasive technique, while enabling the tangential resection with an endostapler in a quick and safe manner, could modify the indications for surgery
[].
A recent review by Thirunavukarasu et al. examined the controversy of elective resection of MD, focusing on the relative risk of malignant transformation
[]. They analyzed epidemiology, incidence, stage at first diagnosis and survival in 163 cases of MD carcinoids and 6,214 cases originating from the ileum. They argued that, given the low but increasing incidence of MD malignant transformation (1.44 per 10 million inhabitants) and its enhancement with age, together with an estimated risk of MD transformation of 70 times higher than all other ileal locations, incidental MD is best treated with resection. Our own experience confirms this strategy, considering that the excision of an incidentally found MD resulted in early detection of a carcinoid tumor with subsequent prevention of its spread.
Obviously, once a carcinoid on MD is diagnosed, treatment should be adapted according to disease stage. Simple MD excision is considered adequate by most of the studies in the case of lesions of less than 10 mm in size
[,], while according to others it is sufficient only for those smaller than 5 mm
[]. For larger lesions, resection of the ileal tract and the corresponding mesentery is generally recommended.
The presence of secondary lymphatic or hepatic dissemination is not considered as a contraindication to surgery, which should include the treatment of hepatic metastases
[].
Residual disease is managed through administration of chemotherapy associated with symptomatic inhibition therapy with octreotide acetate (Sandostatin® LAR; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA). Five-year survival ranges around 75%
[] for patients with bowel circumscribed disease, while for patients with lymphatic or hepatic involvement it decreases to 50% and 20%, respectively
[].


Patient 2 was an 11-year-old girl who had complex CHD and entered our Department of Cardiothoracic Surgery for surgical correction. She was the first child of a healthy non-consanguineous parent. She was born at full term with a weight of 3,150 g (50th centile) and a height of 50 cm (50th centile). She had severe cyanotic heart disease (double outlet right ventricle, DORV and a large 20 mm VSD). Preaxial ploydactyly was observed in the right hand (Figure ) and was surgically removed at the age of two years. Clinical evaluation revealed dysmorphic features, including facial asymmetry, microcephaly with sparse eyebrow, a large nasal tip, a long midface with a large mouth and crowding teeth. The last examination was performed at the age of 12 years. She weighed 30 kg (10th centile) with a height of 150 cm (50th centile). Neurological assessment showed normal intelligence, however with some behavioral disorders such as hyperactivity.


A 74-year-old Caucasian woman was referred to our gynecology clinic for suspected pyometra. She was obese, diabetic and hypertensive. Outpatient hysteroscopy revealed a thickened white endometrium and pyometra. A pipelle endometrial sample was taken and sent for histology.
Three days later, she presented to the accident and emergency department feeling unwell, with profuse foul-smelling vaginal discharge and bleeding per rectum. She was admitted and started on intravenous antibiotics for suspected uterine sepsis.
The pipelle biopsy showed pus cells only. Her carcinoembryonic antigen (CEA) level was normal and CA-125 slightly raised at 73. Vaginal swabs showed no pathogens. As the clinical picture was highly suggestive of endometrial cancer, a magnetic resonance imaging (MRI) scan was performed, which revealed pyometra but no obvious tumor.
A repeat hysteroscopy was done under general anaesthetic and drainage of pyometra was performed. About 50ml of pus was drained and an endometrial biopsy was taken. Pus culture showed mixed anerobic growth and the repeat endometrial biopsy revealed acute on chronic endometritis. She improved clinically with intravenous antibiotics and was discharged home.
She presented 10 days later to the accident and emergency department with a history of collapse, acute abdominal pain, diarrhoea, vomiting and bleeding per rectum. A contrast computed tomography (CT) scan of the abdomen requested by the general surgeons was unremarkable. A sigmoidoscopy and colonoscopy revealed significant diverticular disease with prominent thickened folds. She improved with conservative management.
She presented to the surgical team three months later with acute abdominal pain. A CT scan was repeated, which revealed an inflamed thick-walled sigmoid colon that tracked down to the uterus (a colouterine fistula). Our patient underwent laparotomy where a large diverticular mass was seen perforating into the uterus (a colouterine fistula) and adherent to its posterior wall. Pus was draining through the vagina. A Hartmann’s operation with total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed.
She made a slow but complete recovery. At follow-up six months later she was asymptomatic. Our patient is now deceased but her death occurred due to a cause unrelated to the condition mentioned.


The patient was a 67-year-old male who presented with dry persistent cough for approximately one month. He was hospitalized for worsening dyspnea, cough, and clinical deterioration. Computerized tomography (CT) scan of the chest and abdomen showed a large right pleural effusion, a right renal mass, and multiple lung and liver nodules. The patient underwent a CT-guided biopsy of one of the lung nodules to establish a definite diagnosis. Pathological and immunohistochemical analyses were consistent with renal cell carcinoma of clear cell histology.
He was treated with sunitinib 50 mg orally daily for 4 weeks on a 6-week cycle. He experienced a rapid clinical response with improvement of respiratory symptoms. A restaging CT scan of the chest after cycle 1 of treatment showed evidence of necrosis of multiple lung nodules indicating at least stable disease.
He presented to the emergency department with complaints of headache and amaurosis 19 days after starting cycle 2 of treatment on previous schedule and dosing. His blood pressure was elevated at 180/100 mmHg despite no previous documented hypertension to that moment. On physical exam, he was found to be disoriented. Lateral nystagmus and visual field defect were appreciated. The remainder of the neurologic examination was normal.
Magnetic resonance imaging (MRI) of the central nervous system showed edema like increased T2 and fluid-attenuated inversion recovery (FLAIR) sequence uptake on parietal occipital white matter bilaterally (Figures and ).
Sunitinib was stopped. Intravenous benzodiazepine and anticonvulsants were started. Antihypertensives were given in an attempt to control blood pressure levels.
The patient gradually improved over the course of several weeks after discontinuation of sunitinib. The medication was not restarted given concerns of recurring side effects. After resolution of symptoms, second-line therapy with sorafenib was initiated with no clinical benefit.


A 48-year-old Asian female was seen because of radicular pain over the right hemithorax, and progressive dyspnea for 5 days. She was diagnosed with neurofibromatosis type I more than 10 years prior, and also had a moderate thoracic vertebral deformity. The patient was confined to bed or chair for more than 50% of her waking hours. Chest plain radiography showed a right, huge cystic lesion (21 × 11 cm) and marked kyphoscoliosis of the thoracic spine (Figure A). Magnetic resonance imaging (MRI) revealed widening of the right 4th, 5th, and 6th neuroforeman (Figure B). After discussion with the patient, a decision was made to perform thoracoscopic cystoperitoneal shunt implantation instead of total extirpation through a thoracotomy and laminectomy.
The patient was placed in the left semi-decubitus position and one lung ventilation was begun after induction of general anesthesia. A 30° thoracoscope was placed at the 9th intercostal space in the mid-axillary line. Two 5-mm accessory ports were placed at the 6th intercostal space in the anterior and posterior axillary line, respectively. Under thoracoscopic guidance, a small incision was made at the dependent part of the meningocele, and a purse-string was placed around the incision. A catheter was inserted into the meningocele, and the purse-string suture was tied tightly to avoid migration (Figure C). Another 2 cm abdominal incision was created superior to the umbilicus, and a peritoneal catheter was inserted into the peritoneal cavity.
Her symptoms of dyspnea improved gradually, and at 3 months postoperatively chest radiograph showed marked regression of the intrathoracic meningocele (Figure D). At 9 months postoperatively, the patient experienced shortness of breath, and chest plain radiograph revealed a right massive pleural effusion (Figure A). A diagnosis of cystoperitoneal shunt dysfunction was considered, and thoracoscopic surgery was arranged.
The patient was positioned in a lateral decubitus position opposite to side of the lesion after induction of general anesthesia and double-lumen endotracheal intubation. A thoracoscope was placed at the 9th intercostal space in the mid-axillary line. A 5-mm accessory port was placed at the 6th intercostal space in the anterior axillary line, and another 5-mm accessory port was placed at the same intercostal space in the posterior axillary line. Thoracoscopic visualization revealed a massive pleural effusion of approximately 2,000 mL and dislocation of cystoperitoneal shunt (Figure B). The tip of cystoperitoneal shunt was located in the pleural space, not in the meningocele. The cystoperitoneal shunt was removed, and intrathoracic meningocele plication with 3–0 Prolene suture under thoracoscopic guidance was performed. After plication, the meningocele was reduced to a small mass of soft tissue (Figure C). Multiple suture with non-absorbable filaments were placed to maintain the shape of cyst. Her shortness of breath improved significantly after surgery, and chest radiograph at 2 months postoperatively showed a marked improvement in lung volume (Figure D).


A 47-year-old premenopausal Caucasian woman presented in December 2009 during a multidisciplinary tumour board for nonpalpable lesions. Mammography revealed microcalcifications and gentle densities suspicious for invasion in the area of 6 × 8.6 cm in her left breast (Figure ). An ultrasound showed indistinct hypoechoic lesions with posterior acoustic shadows. A core biopsy revealed high grade DCIS with calcifications. Due to the extensive microcalcifications, the patient was recommended to undergo a mastectomy and immediate breast reconstruction with expander implant. The surgery was performed on 23 March 2010. The mastectomy specimen weighed 238 g and measured 13 × 12 × 3 cm. Grossly, in the upper lateral quadrant of the breast a suspicious area was found. The suspicious focus measured around 2 cm in the largest diameter and consisted of somewhat harder yellow-whitish tissue of granular appearance. In the other parts, the breast tissue was mainly fatty without macroscopically suspicious changes. Careful sampling of the suspicious area and surrounding parenchyma was performed. Altogether, 12 tissue blocks were taken from that area. Besides, one paraffin block was taken from each quadrant and central part of the breast. Microscopic examination revealed massive, high grade DCIS with multiple foci of microinvasion that measured up to 0.1 mm in the largest diameter. Deeper sections from the paraffin blocks with microinvasion were also performed, but no invasive focus ≥1 mm was found. DCIS was located mainly in the upper lateral quadrant but multicentric foci of DCIS were present in all breast quadrants. The dimension of the DCIS was approximately 8 cm. Surgical margins were free (the basal margin was 6 mm). Tumour cells were negative for oestrogen (expressed in less than 1% of cells) and progesterone receptors (0%). Testing for HER2 status was not performed. In the pathologist’s opinion, the invasive clusters were too small for a reliable determination of HER2 status. Isolated tumour cells were found in the two sentinel lymph nodes. No adjuvant systemic therapy was recommended. The patient was regularly checked by a plastic surgeon from March to June 2010. In the meantime, filling of the expander implant with saline was performed. In June 2010 the patient went back to her work. On 23 September 2010, the replacement of the temporary implant for the permanent silicone prosthesis was performed. Blood count, electrolytes, urea and creatinine were in a normal range at that time. Laboratory liver function tests were not performed. She was examined for the last time by the plastic surgeon on 11 October 2010 when the sutures were removed and the wearing of an elastic bra was recommended. On 23 November 2010, the patient was referred to our institution after having been hospitalised for two weeks in a regional hospital due to the general deterioration of her health. Upon referral, she was icteric and in Eastern Cooperative Oncology Group performance status 3. Laboratory tests revealed leucocytosis, hypercalcaemia, deterioration of the liver and renal function and elevated tumour markers. Laboratory results upon referral were: leukocytes 14.8 × 109/L, haemoglobin 121 g/L, platelets 167 × 109/L, creatinine 145 μmol/L, urea 12 mmol/L, calcium 3.78 mmol/l, alkaline phosphatase 7 μkat/L, gama glutamil transferase 14 μkat/L, total bilirubin 95 μmol/L, direct bilirubin 84 μmol/L, aspartate transaminase 8.7 μkat/L, alanine transaminase 1.9 μkat/L, lactate dehydrogenase 7.9 μkat/L, albumins 26 g/L, C-reactive protein 69 mg/L, procalcitonin 4.1 μg/L, carcinoembryonic antigen 37000 μg/L, CA 15–3 432 kU/L and ammonium ion 187 μmol/L. An abdominal ultrasound was performed and showed ascites and an enlarged liver with diffuse lesions suspicious for metastases. A sample of ascites was sent for cytopathological examination. No malignant cells were found in the specimen. The hepatorenal failure progressed rapidly and the patient died on 29 November 2010. An autopsy was performed.In the autopsy a massive and diffuse infiltration of the liver with breast cancer metastases was found (Figure A). On immunohistochemical staining, tumour cells were negative for oestrogen and progesterone receptors and highly positive for HER2 (Figure B). The fluorescent in situ hybridization deoxyribonucleic acid probes score was over 10 (Figure C).
We report a highly aggressive course of DCISM in a premenopausal woman. She was treated with a mastectomy, sentinel lymph node biopsy and immediate breast reconstruction with implant. Tumour cells in microinvasive foci were hormone receptor negative and of unknown HER2 status. The sentinel lymph nodes showed no macrometastases but isolated tumour cells. The patient received no adjuvant systemic therapy. Eight months after the surgery she died from hepatic failure without her previously known breast cancer progressing. The autopsy revealed diffuse liver metastases with HER2-positive and hormone receptor negative breast cancer.
Despite the increasing incidence of DCIS as a consequence of widespread use of screening mammography, the incidence of DCISM remains low and accounts for around 1% of all breast cancers []. In general, the prognosis of DCISM is good and thought to be intermediate between pure DCIS and an early stage invasive cancer (T1a). Only a few reports present the local and distant recurrence rate and long-term outcome of patients with DCISM [,,,]. The heterogeneous definitions of microinvasion that were used in the past make clinical outcomes difficult to compare. In studies in which the current American Joint Committee on Cancer definition of microinvasion was used, the 5-year local relapse rate was between 0% and 3% and 5-year distant relapse free survival almost 100% [,,]. The worst distant relapse free survival was reported by Parikh et al. In a group of 72 patients the 10-year distant relapse free survival was 97.9% [].
We are currently still lacking a reliable test to accurately predict outcomes. Among prognostic factors for the outcome in DCISM, the number of microinvasive foci, metastases to the sentinel lymph node, high Ki-67, negative oestrogen receptor status, and HER2 overexpression were found [,]. The number of microinvasive foci is probably higher in more extensive DCIS. The size and extent of DCIS lesions are often only an estimate []. Quantifying the size of a DCIS lesion is difficult and precise measurement is often impossible. Still, an estimation of the DCIS size is clinically very important. According to the College of American Pathologists guidelines for examining specimens from patients with DCIS, microscopic examination of the entire area affected by DCIS is recommended but is very often impractical if DCIS is larger than 4 (even 2) cm []. In such a case, there is always a possibility of undetected areas of invasion if the area affected by DCIS is not completely examined. As well, smaller invasive foci could be missed because they can be present deeper in that part of the paraffin block that was not histologically examined. It is difficult for the pathologist to find all possible foci of microinvasion in very extensive DCIS. The multifocality of microinvasive disease is in correlation with positive sentinel nodes [,].
In invasive breast cancer, axillary lymph node metastases are the most powerful prognostic factor for relapse and survival. The risk of sentinel lymph node metastases among patients with DCISM has been reported to be between 0 and 20% []. It is crucial to identify a very small subset of microinvasive cancer patients with macrometastases, which could benefit from adjuvant systemic therapy []. In case of a positive sentinel node, an axillary dissection should be performed [,,]. In case of positive axillary nodes, adjuvant systemic therapy with tamoxifen in hormone receptor positive tumours, and with chemotherapy in hormone receptor negative tumours could be offered. In invasive breast cancer, micrometastases but not isolated tumour cells were associated with additional positive nodes upon axillary dissection and with distant recurrence []. Most authors agree that a sentinel node biopsy should be performed although some believe it could be omitted due to a low rate of positivity [,]. The outcome is generally very good with few local and even fewer distant relapses [,]. At present, the significance of lymph node micro- or macrometastatic disease on overall survival in DCISM is unclear and needs to be ascertained with further studies. Colleoni et al. reported increased Ki-67 as a significant prognostic factor for disease free survival in DCISM [].
HER2 overexpression was present in 77% of locally relapsed tumours after breast-conserving therapy for DCIS (with or without radiation therapy in European Organisation for Research and Treatment of Cancer trial 10853) []. A clinical implication of HER2 status in DCIS is unclear. On the contrary, HER2 overexpression in even small invasive cancers is correlated with poor prognosis. Roses et al. found HER2 status to be a predictor for the transition from in situ to invasive breast cancer []. However, there are some technical constraints on HER2 testing as a certain volume/number of malignant cells in a cluster should be found for reliable testing. One of the on-going trials in HER2-positive DCIS involves the testing of a single application of neoadjuvant trastuzumab in <1 cm DCIS before surgery. The second trial is a phase III National Surgical Adjuvant Breast and Bowel Project B43 trial comparing adjuvant radiotherapy with or without two doses of adjuvant trastuzumab in HER2-positive DCIS after breast-conserving surgery []. There are also promising results of clinical studies with HER2-pulsed autologous dendritic cell vaccine administered before surgical resection of high-risk HER2-positive DCIS [,]. The results of those trials will hopefully show more insights into the biology of HER2-positive DCIS and DCISM.
Mori et al. evaluated almost 400 tumour specimens of patients who were diagnosed with either DCIS, DCISM or T1a breast cancer. The comedo type and ER negative/HER2-positive type were found more frequently in DCISM than in either DCIS or T1a tumours. The co-expression of HER2 and 14.3.3 zeta could be important since HER2 overexpression plays a role in the process of first invasion and 14.3.3. zeta in the reduction of cell adhesion [].
Our patient had many potential risk factors for relapse. She had a very extensive DCIS in the whole breast with more than one microinvasive focus within DCIS. DCIS was of a comedo subtype. She had no micro- or macrometastases but isolated tumour cells were present in the sentinel lymph node, which suggested a more aggressive disease. Tumour cells were negative for oestrogen and progesterone receptors. HER2 status was not determined due to an unreliable result determined on a scant sample. The patient received no adjuvant systemic therapy. The number of invasive foci and the extent of DCIS could be very suspicious of many microinvasive foci. In that specific case, we did not consult a pathologist for the additional counting of invasive foci. Following this case, the general practice at our institution has changed. If a pathologist finds more than 5 microinvasive foci (where the sum of the sizes is at least 5 mm) we discuss adjuvant chemotherapy with the patient.


A 51-year-old North African man presented with a 1-month history of fluctuating jaundice with pale stools and dark urine, right upper quadrant pain, and intermittent vomiting. His past medical history included neurosyphilis for approximately 8 years. A physical examination revealed little upper abdominal quadrant tenderness. Biochemistry demonstrated elevated bilirubin, alkaline phosphatase and γ-glutamyl transpeptidase levels, and leukocytosis. Ultrasound and magnetic resonance imaging showed a complete stop at the biliary bifurcation compatible with a Klatskin tumor associated to common bile duct stones (Figure
). Endoscopic retrograde cholangiography revealed dilated intrahepatic ducts and common bile duct above multiple polylobed filling defects. These findings were mainly suggestive of multiple impacted stones of his common bile duct, cholangiocarcinoma, or hemobilia. After an endoscopic sphincterotomy, a balloon sweep retrieved friable, polypoid soft tissue from his bile ducts (Figure
). Two biliary plastic stents were placed. Histology of the tissue demonstrated papillary adenomatous proliferation showing high-grade dysplasia; the patient was referred for surgical management. Laparoscopic exploration demonstrated a dilated common biliary duct. A transversal choledochotomy revealed a papillary polylobed mass (Figures
 and
). Common bile duct resection was performed with macroscopically safe margins and biliary reconstruction was achieved by Roux-en-Y hepaticojejunostomy.


A 9-year-old Hispanic boy with spina bifida, hydrocephalus status post-VP shunt with normal neurological cognitive function, and neurogenic bladder with ileovesicostomy was scheduled for bladder augmentation and revision of his urinary diversion. He was admitted to the hospital for preoperative bowel preparation consisting of polyethylene lavage (1400cc over 4 hours) via nasogastric feeding tube (NGT) with a kangaroo feeding pump. The NGT placement was confirmed with auscultation. Shortly after the infusion was begun, the patient developed significant coughing and gagging with small amount of emesis of clear fluid. The infusion was immediately stopped and a radiograph showed placement of the NG tube in the right lung. A review of the feeding pump revealed the patient had received a total of 283 mL of solution. The primary care provider and the pediatric and pulmonary services were notified and consulted.
Prior to the incident the patient's vitals were stable with a heart rate of 80 beats/minute, blood pressure 90/64 mm Hg, respiratory rate 18 breaths/minute, and oxygen saturation 100% in room air. When the infusion was stopped, the patient's vitals were mildly elevated with a heart rate of 126 beats/min, blood pressure 111/55 mm Hg, a respiratory rate 28 breaths/min, and oxygen saturation 93% in room air. On exam the patient had decreased breath sounds over the right lung field with no crackles or wheezing and did not appear to be in significant distress. A chest X-ray showed a right lower lobe aspiration pneumonitis (). IV clindamycin was begun and the patient was transferred to the Pediatric IMU (intermediate medical unit) for continuous cardiopulmonary monitoring with recommendations to start supplemental oxygen and intravenous steroids if his condition deteriorated. Overnight, the patient had an increase in tachypnea and his oxygen desaturated to 87–89% on room air. He subsequently received 2 liters of oxygen via nasal cannula to maintain oxygen saturations above 92% and IV Solu-Medrol was begun at a dose of 2 mg/kg/day. A subsequent X-ray was performed the following day that showed worsening of his pneumonitis though his PCO2 and pH remained within normal limits and he appeared clinically stable. Two days after the ingestion, the patient was transitioned to room air and his condition began to steadily improve. The patient was discharged 4 days after the infusion and a final chest X-ray obtained demonstrated complete resolution of pneumonitis ().


A kidney biopsy was performed in a 37-year-old man with chronic kidney disease stage 3 and Fabry disease was diagnosed, as previously described []. Besides the characteristic and specific features of Fabry disease, the biopsy disclosed remarkable and predominating findings consistent with advanced secondary focal and segmental glomerulosclerosis. Despite a wide pharmacological maintenance therapeutic intervention consisting of agalsidase beta for 24 months (Fabrazyme, Genzyme Corp., Cambridge MA), meprednisone 6 mg/day, valsartan 160 mg/day, and aliskiren 300 mg/day, proteinuria persisted between 2 and 2.8 g/day. Other medications included omeprazole 20 mg/day, aspirin 100 mg/day, and ergocalciferol 16800 IU/weekly. Low-sodium diet compliance was followed with urinary sodium excretion, achieving an average 24-hour sodium concentration of 40 mEq/day. Finally, amiloride 5 mg/day was added to this regime, and proteinuria decreased to 0.9 g/day for the last 6 months of follow-up. Noteworthy, antihypertensive drugs were added in a stepwise manner to avoid hypotensive episodes, which were not referred by the patient. The patient was started initially on valsartan 160 mg, followed by aliskiren 300 mg/day four weeks later. Amiloride 5 mg/day was finally prescribed one year later. No hyperkalemic events have been reported.


A 34-year-old woman visited our department with a chief complaint of masticatory dysfunction and incompetent lip seal. Representative values were SNA, +0.1 standard deviation (SD); SNB, −3.0 SD; SN-Pog, −3.3 SD; L1-Mp, 0.0 SD; interincisal angle, −0.9 SD; OB, +0.5 mm; and OJ, +9.0 mm. The cephalograms taken at each step are shown in and superimposed cephalometric tracing is provided in . The lower and upper second premolars had already been extracted at 11 years of age due to crowding. The precise treatment course with cephalograms has already been described previously [] and Cases 1 and 2 in the present study are the same as those in the previous one. Using advancement genioplasty, Pogonion (Pog) was moved 10.0 mm horizontally forward and 2.0 mm vertically upward. SN-Pog was improved to 4.3°. Bone was sufficiently augmented at the junction of the advanced segment and the anterior aspect of tooth-bearing segment. At this point, the L1-mandibular plane angle seemed to increase due to the change in reference line, because the mandibular plane angle was defined by the position of Go and Pog, and Pog was moved both anteriorly and superiorly by genioplasty. About 8 months later, segmental alveolar osteotomy was performed. The angle of the L1-mandibular plane was returned back to 92.9°, representing a more desirable value, and interincisal angle was improved from 115.5° to 123.1°. Preorthodontic treatment was performed for another 9 months, with no obvious cephalometric changes seen during this period (T3-T4). As the last step, two-jaw surgery was performed. The maxilla was separated into three pieces for coordinating the maxillary arch and ensuring suitable bilateral intercusp width against the mandibular arch. The maxilla was repositioned 2.0 mm superiorly and 2.0 mm posteriorly. The body of the mandible was advanced 3.0 mm at the vertical osteotomy line adjacent to the buccal groove of the left first molar on both sides by sagittal split ramus osteotomy. Postoperative orthodontic treatment was initiated 2 months after surgery and continued for 2 years to detail the occlusion. The overall active treatment time was 4 years. After debonding, a retainer was worn fulltime on both arches. Net movement of Pog was 12 mm horizontally forward and 1 mm upward, rotating 4.8° in SN-Pog. Net increases in mandibular plane angle and occlusal plane angle were 6.2° and 6.0° counterclockwise (T5), respectively. These data indicate that the position of Pog was greatly influenced by the counterclockwise rotation of the distal mandibular segment. All incisors were vital and no obvious recession was observed. Root resorption was never evident during treatment () nor was ankylosis seen. Pre- and posttreatment oral photographs are shown in . Significant improvement in facial appearance was achieved and the patient was able to close her lips more easily than before at rest and without conscious effort (). All cephalometric measurements made during treatment are listed on .


A 17-year-old girl presented with a chief complaint of a lack of interincisal contact, crowding of the mandibular incisors, and mandibular retrusion. She had a severe Class II skeletal relationship with a concave profile. No clicking, joint pain, or limitation of opening was found on initial examination. There was no apparent condylar absorption or shortening of the ramus height. Treatment course and our original distraction method have already been described elsewhere []. Briefly, the patient had a total arch discrepancy of −22 mm with retrognathia. The representative values were SNA, −3.4 SD; SNB, −4.5 SD; SN-Pog, −4.2 SD; L1-Mp, +0.5 SD; interincisal angle, −2.1 SD; OB, 2.0 mm; and OJ, 10.0 mm. The cephalograms taken at each step are shown in and superimposed cephalometric tracing is provided in . These measurements are listed in . The same maneuver as in Case 1 was adopted, with some modification because of the length deficiency of alveolar bone. After making a basal foundation by advancement genioplasty, 4 mm forward and 2 mm downward, tooth-borne distraction of the incisal segment was performed to elongate the perimeter and improve the axis of the incisors. The change clearly appeared as a difference in the lines of T3 and T4 on . After an 8-week consolidation period, orthodontic treatment was performed for another 22 months, and finally two-jaw surgery was performed after eliminating crowding of the anterior dentition. Substantial movement of Pog with proper incisor axis confirmed to the mandibular plane was achieved. The net increase in SN-Pog angle was 6.6° and Pog was moved 14 mm horizontally forward and 3 mm vertically downward. Postsurgical orthodontic treatment was started 2 months after surgery and continued for another 10 months. Desirable skeletal configuration was obtained with improvement of lip seal. All incisors were vital and no obvious recession was observed. Ankylosis was also not seen. However, subtle apical resorption of mandibular incisors was observed (). All cephalometric measurements during treatment are listed in . Crowding of the lower tooth was markedly improved with the axis correction (). Significant improvement in facial appearance was also achieved ().


A 21-year-old man with severe open bite and mandibular retrusion was referred to our department. Initial measurements were SNA, +0.7 SD; SNB, −2.0 SD; ANB, +4.0 SD; SN-Pog, −2.4 SD; interincisal angle, −2.4 SD; L1-Mp, +0.6 SD; OB, +4.8 mm; and OJ, +8.1 mm. The cephalograms taken at each step are shown in and superimposed cephalometric tracing is provided in . With the first genioplasty, Pog was advanced 9 mm horizontally forward and 1.2 mm vertically downward, and SN-Pog was improved to 3.1°. About 17 months later, segmental alveolar osteotomy was performed, and interincisal angle was improved by 9.0°. After completing preorthodontic treatment for another 1 year, two-jaw surgery was performed. Net linear movement of Pog was 20 mm forward and 3 mm upward with the help of counterclockwise rotation of the occlusal plane by 6.9°. Postsurgical orthodontic treatment was started 2 months after surgery and continued for 1 year to detail the occlusion. The net increase in SN-Pog was 7.0°. Alignment of lower incisors was performed without any obvious root resorption (). All incisors were vital and no obvious recession was observed. Ankylosis was also not seen. All cephalometric measurements during treatment are listed in . Intra- and extraoral photos are shown in Figures and , respectively.