A 23 year old woman was referred by her general dental practitioner to the Department of Endodontics, Health Science Institute, Faculdades Unidas do Norte de Minas (FUNORTE), with the chief complaint of spontaneous pain in her right posterior maxilla for 3 days. The patient medical history was unremarkable and non-contributory. A clinical examination revealed extensive restoration in the maxillary right first molar, which was tender to percussion. Palpation of the buccal and palatal aspect of the tooth did not reveal any tenderness. The tooth was not mobile and periodontal probing around the tooth was within physiological limits. Vitality testing of the involved tooth with Endo Ice (Coltene/Whaledent GmbH+ Co. KG, Langenau, Germany) caused an intense lingering pain. A preoperative radiograph revealed restoration approaching the pulp space (). From the clinical and radiographic findings, a diagnosis of symptomatic irreversible pulpitis with symptomatic apical periodontitis was made, and endodontic treatment was suggested to the patient. The patient's consent form was obtained.
The radiographic evaluation of the involved tooth did not indicate any variation in the canal anatomy (). The tooth was anesthetized using 1.8 mL 2% lidocaine with 1:100,000 epinephrine (DFL, Rio de Janeiro, Brazil). Then rubber dam isolation was performed and endodontic access cavity was established using high-speed diamond round and Endo-Z burs (Dentsply Maillefer, Konstanz, Germany). Clinical examination revealed three canal openings in the mesiobuccal root, two in the distobuccal root, and one in the palatal root ().
In order to evaluate this unusual morphology, the patient underwent cone beam computed tomographic (CBCT) examination. An informed consent was obtained from the patient, and a CBCT scan of the maxilla was performed (Eagle 3D CBCT unit, Dabi Atlante, São Paulo, Brazil). The involved tooth was focused, and the morphology was obtained in transverse, axial, and sagittal sections of 0.5 mm thickness. CBCT scan slices revealed seven canals: three mesiobuccal (MB1, MB2, and MB3), two distobuccal (DB1 and DB2), and two palatal (P1 and P2) canals in the right maxillary first molar (). Surprisingly, in the palatal root, a Vertucci's type VI configuration (two separate canals leaving the pulp chamber, merging in the body of the root, and re-devising short of the apex to exit as two distinct canals) was found ().
At the second appointment, the tooth was anesthetized using 1.8 mL 2% lidocaine with 1:100,000 epinephrine (DFL), cleaning and shaping was performed under rubber dam isolation using R25 Reciproc file (VDW, Munich, Germany) used in a reciprocating with slow in-and-out pecking motion according to the manufacturer's instructions, and continuous irrigation with 2.5% sodium hypochlorite solution and 17% EDTA and bidistilled water as the final irrigant. The canals were dried with absorbent paper points (VDW), and were then obturated with the single-cone obturating technique using complementing gutta-percha points (VDW) in each canal and AH Plus sealer (Dentsply Maillefer) ().
The tooth was then restored with a composite resin core (Filtek Z350, 3M ESPE, St. Paul, MN, USA). The patient was advised of a full-coverage porcelain crown, and the tooth was asymptomatic during the follow-up period of 1 year ().


A 44-year-old male presented with a 3-month history of atypical chest pain, palpitation, and exertional dyspnea. Cardiac auscultation revealed a Grade III/IV to-and-fro murmur. Electrocardiography showed normal sinus rhythm.
Transthoracic echocardiography (TTE) revealed an aneurysm of the noncoronary cusp of sinus of Valsalva rupturing into the RA. Transesophageal echocardiography (TEE) and three-dimensional (3D) images were taken before the procedure. In the midesophageal right ventricle (RV) inflow view, they clearly showed ruptured sinus of Valsalva [RSOV] into RA.
The procedure was performed under general anesthesia with TEE guidance. Seldinger technique was used to achieve percutaneous access to the right femoral artery (RFA) and vein so that two hemostatic sheaths were inserted. Intravenous heparin (200 IU/kg) and cefazolin were given.
From RFA approach, right and left heart pressures and saturations were obtained, and aortic root angiography was performed. The RSOV was measured at its aortic end as well as at the rupture site on TEE. RSOV was tried crossing with terumo wire under real time-TEE guidance. However, we were not able to pass through RSOV. Hence, we took use of 3D imaging available in our TEE machine and tried passing terumo wire across RSOV and position in SVC under the guidance of midesophageal aortic valve long axis at 120° and other real time-3D video images and Aortography, and we succeeded in passing the guide wire across RSOV. It was then snared from venous end, and an arteriovenous loop was established. The defect was measured 5.5 mm at its aortic end as measured by TEE and 8 mm when measured in 3D images. According to the measurement in the 3DTEE and aortogram, a patent ductus arteriosus (PDA) occluder 2–4 mm larger than the narrowest diameter of the ruptured site was chosen to close most of the lesions. An 8F PDA delivery sheath then placed in the descending aorta and 10 mm × 8 mm RSOV PDA occluder device (life tech) was placed in the sac of RSOV noncoronary cusp after checking for aortic regurgitation (AR). The entire assembly was pulled back until the disk blocked the aortic end of the ruptured site without slipping into the aneurysm.
TEE images and aortogram after releasing of the device showed minimal residual shunt across RSOV and no AR. Subsequent echocardiography (echo) next day showed no residual flow [ and Video –].


A 32-year-old male presented with a 2-year history of symptomatic floaters in the right eye. He had previously been seen elsewhere for the same problem and had received neodymium-doped yttrium aluminum garnet laser vitreolysis for the right eye. This was done on 3 occasions. He did not improve with this therapy. Best-corrected visual acuity (BCVA) was 20/20 in both eyes upon presentation.


A 21-year-old male presented with a 5-year history of symptomatic floaters in the left eye. Upon presentation, BCVA was 20/20 in both eyes. No treatment had previously been performed for the floaters.


A 28-year-old female presented with a 1-year history of symptomatic floaters in the right eye. BCVA was 24/20 in both eyes upon presentation. She had previously been subjected to LASIK surgery for both eyes and vitrectomy for floaters (retrobulbar anesthesia) for the left eye. No treatment for the floaters in the right eye had previously been performed.
Examination showed vitreous opacity in the patients presented. The diagnosis of symptomatic vitreous opacity was made. Details of the preoperative characteristics of these patients are presented in Table .
The conditions were explained to the patients, and the option of watchful waiting was offered. Vitrectomy was discussed, including potential risks and benefits. They agreed to proceed with surgery. It was felt that with full pupil dilation and with an indirect wide-angle viewing system, most of the vitreous could be removed without scleral indentation. Therefore, it was felt that topical anesthesia would be safe. 27-gauge sutureless three-port pars plana vitrectomy surgeries with topical anesthesia were performed.
At the beginning of this surgery, topical proparacaine hydrochloric (0.5% Alcaine: Alcon, TX, USA) was instilled 3 times in 5-min intervals. Standard three-port cannulae (Constellation; Alcon, Inc., Fort Worth, TX, USA) in the superior-nasal, superior-temporal, and inferior-temporal were established. The central and peripheral vitreous was removed without performing posterior vitreous detachment, and the total duration of the surgery was approximately 8–10 min. All surgical procedures were performed by the same surgeon (R.H.W.). The patients did not experience pain during surgery. No intraoperative anesthesia supplementation or postoperative analgesics were required.
At postoperative day 7, the intraocular pressure and BCVA were almost recovered to that on the preoperative day. All these patients reported that their floaters had disappeared. They enunciated a high level of satisfaction both with the procedure and the outcome. At postoperative month 3, the BCVA were all the same as on the preoperative day. Furthermore, no postoperative complications occurred in these patients (Table ).


A 67-year-old female presented for a 1-day history of left upper quadrant abdominal pain. She described the pain as moderate, sharp, and radiating to her left shoulder. There was no history of fever, chills, abnormal bowel movements, nausea, or vomiting. Her past medical history was remarkable for cirrhosis secondary to primary biliary cirrhosis complicated by hepatic encephalopathy and ascites. She denied recent trauma, previous miscarriage, deep vein thrombosis, or embolic disease. Medications included furosemide, spironolactone, rifaximin, lactulose, ursodiol, and lansoprazole. She had no known allergies. Physical examination was normal apart from epigastric and left upper quadrant tenderness. No ascites was noted. Laboratory results on admission were comparable to previous routine blood draws done 2 months earlier and were the following: hemoglobin 10.3 g/dL, hematocrit 32%, platelet count 55 ×103/μL, white blood cell count 9.1 ×103/μL, international normalized ratio 1.5, aspartate aminotransferase 39 IU/L, alanine aminotransferase 35 IU/L, alkaline phosphatase 151 IU/L, total bilirubin 2 mg/dL, total protein 5.6 g/dL, and albumin 2.3 g/dL. EKG, chest X-ray, and cardiac enzymes were all within normal range.
Computed tomography (CT) scan of the abdomen with contrast revealed cirrhotic morphology of the liver, large varices in the right lower quadrant, and numerous wedge-shaped areas of hypoenhancement extending to the periphery of the spleen concerning for splenic infarcts (Fig. ).
Doppler ultrasound of the spleen confirmed the presence of infarcts with preserved flow within the main splenic artery. Further evaluations were performed to rule out other secondary causes of spontaneous splenic infarcts including a hypercoagulable workup, autoimmune disease markers, and an echocardiogram. All were unremarkable.
The patient was treated with conservative management and analgesia. She reported progressive improvement over the next few weeks. Follow-up at 2 months showed consistent resolution of her clinical symptoms and signs. A repeat CT scan of the abdomen showed stable splenic infarcts.


A 65-year-old Caucasian woman presented in March 2007 with a 3-month history of painless left-sided cervical lymphadenopathy. She denied any associated fevers, chills, loss of weight, dyspnea, dysphagia, or any other symptoms. The patient's surgical history was pertinent for a completely resected stage IA melanoma over the left shoulder 16 years before this presentation. Physical exam revealed enlarged and non-tender cervical and axillary lymph nodes without splenomegaly. A skin survey did not reveal any new nevi or concerning lesions. A complete blood picture showed a white blood cell count of 14.7 × 103/μL, an absolute lymphocyte count of 7.35 × 103/μL, hemoglobin of 13.8 g/dL, a platelet count of 258 × 103/μL, and lactate dehydrogenase of 291 U/L. Flow cytometry of the peripheral blood demonstrated a monoclonal lymphocyte population expressing CD5, CD19, CD20, CD24, CD43, and CD52 with lambda light chain restriction and no increase in CD34-positive blasts. The cells were negative for CD38 and ZAP-70. Based on the above findings, the patient was diagnosed with Rai Stage I CLL and placed under observation.
Two years after her initial diagnosis, the patient presented with progressive dyspnea, associated with pleuritic chest pain and a 20 lbs weight loss over a period of 3 months. Physical examination revealed increased axillary and cervical lymphadenopathy and decreased breath sounds over the right lung. Chest X-ray revealed a large right-sided pleural effusion (Fig. ). White blood cell count was noted to be 53.4 × 103/μL, and she had an absolute lymphocyte count of 40.7 × 103/μL. The pleural fluid analysis was consistent with an exudative effusion, with increased atypical lymphocytes. Flow cytometry demonstrated a 12% clonal population consistent with the pleural involvement of CLL. The majority of the lymphocytes were CD4+ T-lymphocytes (CD4:CD8 in a ratio of 15: 1), but polymerase chain reaction failed to show any clonal T-cell receptor-γ or T-cell receptor-β gene rearrangements.
Secondary to rapid reaccumulation of pleural fluid, increasing lymphadenopathy, and rapid doubling time of lymphocyte count, the decision to treat symptomatic CLL was made. Chemotherapy with pentostatin, cyclophosphamide, and rituximab did not result in any meaningful clinical response. As the patient's pleural effusion was refractory to CLL treatment, video-assisted thoracoscopic surgery was performed, which demonstrated diffuse nodular thickening of both visceral and parietal layers of the pleura (Fig. ). A biopsy of these lesions revealed enlarged cells with an increased nuclear-cytoplasmic ratio and pleomorphic nuclei with occasional cherry red nucleoli (Fig. ). Immunohistochemistry studies demonstrated positive staining with HMB-45 (Fig. ) and S-100 protein. Electron microscopy revealed type II melanosomes with cross-striated lattice in an enclosed membrane (Fig. ), type III melanosomes with increased deposition of electron-dense melanin, and type IV melanosomes with highly electron-dense melanin (Fig. ). Based on the above findings, a diagnosis of malignant melanoma was made. Computed tomography of the chest revealed extensive lobulated tumor lining the entirety of the right parietal pleural surface without any evidence of parenchymal involvement. The patient's medical condition rapidly declined, and she ultimately succumbed to death before initiation of any therapy.


A 42-year-old premenopausal, G3P3-stage woman presented with serious pelvic pain and polymenorrhagic haemorrhage. Upon specular vaginal examination, the vulva and vagina were normal, and no suspicious cervical lesion was observed. A mobile solid, ca. 10 × 10-cm mass was evident upon bimanual examination of the left adnexa. Transvaginal ultrasonography revealed a 106 × 113-mm cystic mass mimicking an endometrioma; the unilocular cyst yielded diffuse homogeneous ground-glass echoes (Fig. ). Pelvic computed tomography revealed a 118 × 78 × 85-mm septate cystic lesion characterised by high lipid content, nodular components, and focal wall calcification (Fig. ). Only the levels of CA-125 (49.8 U/mL) and CA-19,9 (42.1 U/mL) were elevated. Exploratory laparotomy was performed. The uterus, right adnexa, and ovary were normal; no malignant ascites or peritoneal spread of a malignant tumour was apparent, but a mobile 10-cm-diameter mass was evident in the left adnexa. The mass was not adherent to other pelvic organs. Left salpingo-ovariectomy was performed, and the mass subjected to frozen sectioning (Fig. ). The pathologist reported that the mass could not be defined as either malignant or benign; we thus ceased operating, awaiting a final pathology report. No pre- or postoperative complication developed; the patient was discharged.
One month later, the final pathology report confirmed that a squamous cell carcinoma and a malignant fibrous histiocytoma had developed in a mature cystic teratoma. We performed a repeat laparotomy; 40–50 mL of ascites was aspirated, and the wash cytology was sampled. On the left side, the sigmoid colon, left ureter, and bladder were conglomerated. Pararectal and paravesical fossae were identified, and we performed total abdominal hysterectomy, right salpingo-ovariectomy, tumourectomy, and bilateral pelvic and para-aortic lymph node dissection. About 0.5 cm of tumour were not removed on the left ureter to avoid damage. A drainage tube was inserted, and the abdominal incision closed. The patient was hospitalised for 4 days, but no complication was observed pre- or postoperatively.
On gross examination, the mass was enclosed and contained greasy material including keratin and hair; haemorrhagic areas were evident in the cystic region. Microscopically, an irregularly thickened necrotic area was apparent. Stratified squamous epithelium, skin cells, cartilage tissue, and ciliated bronchioles epithelium were demonstrated. A well-differentiated squamous cell carcinoma appears to arise from benign squamous epithelium (Fig. , Fig. ). The cells formed strands, cords, and nests and exhibited pleomorphic hyperchromatic nuclei, eosinophilic cytoplasm, and focal keratinisation. Squamous cell carcinoma showed pancytokeratin and P63 positivity. Mature adipose tissue and a ciliated columnar epithelium surrounded the cyst walls. Multinucleated giant cells, scattered cells that were polygonal-to-spindle-like in shape (and markedly pleomorphic in their characteristics), and unusual tumour cells were evident (Fig. , Fig. ). Multiple atypical mitotic figures and a significant multinucleated giant cell reaction were apparent. The tumour cells were negative for desmin, smooth muscle actin, and myogenin, but positive for CD68 (Fig. ). These features were consistent with a diagnosis of a malignant fibrous histiocytoma and squamous cell carcinoma, arising from a mature cystic teratoma. The two components were spatially separated.
The 2-week follow-up visit was uncomplicated, but the 2-cm abdominal incision gap lay only 5 cm below the umbilicus. Two stitches were placed. After the 1-month follow-up, the patient was referred to our medical oncology department because no complications were evident. Platin-based chemotherapy was scheduled. At the 3-month follow-up, the patient complained of serous flow through the area of secondary suturing. A plastic surgeon was consulted. Positron emission tomography-CT was performed; a 6-cm-thick metastatic area was observed near the incision; this had spread to the musculus rectalis facia. The abdominal incision was enlarged, a skin biopsy was taken, and skin-thickness grafting performed. The pathology report on the skin sample revealed metastasis of the squamous cell carcinoma. At the 1-year follow-up, the patient remains alive.


A 47-year-old gentleman presented to our urology outpatient department with 2 days history of insertion of an iron ring into his penis. He further revealed that it was put by himself with an expectation to increase the hardness of his penis for better sexual pleasure, and he manipulated at home to remove without success. On examination, an edematous and swollen penis was found with a thick and hard metal iron ring (wheel bearing) at the base of it []. Other physical examinations were normal. All maneuvers such as pulling out, sliding to remove the ring after lubrication, and cutting by hacksaw were unsuccessful. Later on, it was easily cut into two pieces in 10 min by micromotor (Marathon-3 serial no 0809, Sae Yang Co) with wheel shape bur which is used as a dental instrument without any kind of anesthesia [Figures –]. The skin entrapped underneath was protected by a metal blade to avoid injury. The area was continuously irrigated by cold saline to prevent from thermal injury generated during the procedure. Penile edema was significantly decreased, and he was discharged on next day. On follow-up after 7 days, his penis was healthy with normal erections [].


A 46-year-old man underwent ureteroscopy treatment for his right vesicoureteral junction stone. His preoperative urine analysis showed negative for leukocyte and nitrite. Intraoperatively, the procedure was completed in 1 h without any complication. Ureteral stent was inserted. Two days postoperatively, he complained of frequency, dysuria, suprapubic pain, and fever. Despite initial treatment with antibiotics, the symptoms did not diminish. He started to notice a rapid deterioration in the vision of his right eye in the following 2 days. The affected eye was also painful, red, and swollen. He is a known case of diabetes mellitus and hypertension.
On examination, his best-corrected visual acuity was 6/60 for the right eye and 6/6 for the left eye. There was associated lid swelling and conjunctival injection, with reduced red reflex. Fundus examination of the right eye showed vitreous haze secondary to vitritis, deep yellow subretinal lesion with fluffy edges, “string of pearls” abscess, and swollen optic discs. There was no retinitis or vasculitis noted []. The left eye examination was unremarkable.
His urine and ureteric stent culture grew Candida albicans, which was sensitive to amphotericin B, voriconazole, fluconazole, and caspofungin. Blood sample and vitreous tapping were negative. He was also given intravitreal amphotericin B 5 mcg in 0.1 ml and intravitreal voriconazole 100 mcg in 0.1 ml. He was initially treated with intravenous (IV) amphotericin B and IV fluconazole. IV amphotericin B was changed to intravitreal injection due to nephrotoxicity. IV fluconazole was substituted with tablet voriconazole. Repeat urine samples were clear after 1 week.
Due to nonclearing vitritis, he underwent transscleral pars plana vitrectomy (TPPV) after 1 month, with intravitreal injections of amphotericin B, vancomycin, and ceftriaxone. Second TPPV and phacoemulsification, with intraocular lens implant, were performed after 3 weeks. He was followed up in the eye clinic. One month after the second operation, the best-corrected visual acuity of his right eye was 6/60.


A 68-year-old male undergoing a routine colonoscopy was found to have multiple TAs measuring 5-8 mm, including one in ascending colon with surrounding ulcerated, irregular and slightly raised mucosa (Figure ) which was also biopsied. Under microscopic examination, an infiltrating poorly-differentiated malignant tumor was identified in the ulcerated lesion in close vicinity with an overlying TA. The tumor demonstrated pathological findings suggestive of a high-grade malignancy such as increased mitotic figures and apoptosis. The differential diagnosis included a poorly-differentiated adenocarcinoma, medullary carcinoma, NEC, high-grade lymphoma and sarcoma. Immunohistochemical studies performed on formalin-fixed paraffin-embedded tissue sections revealed positive staining for keratin Cam5.2, neuroendocrine markers synaptophysin and chromogranin but negative for lymphoma (LCA/CD45), colorectal adenocarcinoma (CDX2, CK20, CK7), lung adenocarcinoma (TTF-1) and prostatic adenocarcinoma (PSA) markers. A diagnosis of high-grade NEC large cell type with associated TA was rendered. Further evaluation by computed tomography (CT) and magnetic resonance imaging (MRI) for tumor staging revealed no metastatic disease or lymphadenopathy. Three months after the biopsy, the patient underwent laparoscopic right hemicolectomy. A 3-cm umbilicated tumor mass was identified in the proximal ascending colon with slightly raised border and central ulceration (Figure ). The tumor was grossly and microscopically seen invading into and through the muscularis propria into subserosal soft tissue, but not the serosa. The microscopic examination revealed solid sheets and nests of high-grade tumor cells with medium to large-sized vesicular nuclei and prominent nucleoli as well as prominent lymphocytic infiltration; a pattern morphologically consistent with the large-cell variant of high-grade NEC (Figure and B). Moreover, the residual overlying TA is again identified in the raised mucosal surface with no high-grade dysplasia (Figure ). In addition to the classic morphology of a high-grade large-cell neuroendocrine carcinoma, the diagnosis was confirmed using immunohistochemical studies showing positive staining of the tumor cells for synaptophysin and chromogranin (Figure and B). The number of mitotic figures [up to 77/10 high power fields (hpf)], the presence of focal tumor necrosis and the Ki-67 proliferation index of 75% (Figure ) confirmed the stratification as a high-grade NEC. Mutational analysis studies indicated that the NEC tumor cells expressed wild type BRAF and KRAS in addition to intact expression of mismatch repair proteins (MLH1, MSH2, PMS2 and MSH6) and therefore negative screening for Lynch syndrome. Immunohistochemical studies showed strong and diffuse positive staining for CAM5.2 and nuclear staining for β-catenin in the NEC tumor cells and TA (Figure , E and F), indicating both components are related. No regional lymph node metastases were noted in 24 examined lymph nodes. According to the American Joint Committee on Cancer Staging Manual, 7th edition, the tumor is staged as pT3, pN0, pMx. The patient received adjuvant chemotherapy with cisplatin/etoposides for three cycles and has not shown any recurrence. The patient will be followed up for a year to detect recurrence.
We described a clinical scenario of a 68-year-old male patient who was found to have a mixed high-grade large cell NEC with an overlying TA discovered during routine colonoscopic screening in absence of clinical symptoms. The invasive large cell NEC was located underneath the TA, deeply involving the muscularis propria, without liver or distant metastatic disease or lymph nodes involvement at the time of primary tumor resection. The patient received postsurgical chemotherapy due to the high-grade nature of the carcinoma. As of the time of the article preparation, no recurrence was identified. Long-term follow up will be necessary to report any potential recurrence. We suspect that the clinical outcome will be shaped by the behavior of the clinically predominant tumor, which is neuroendocrine tumor in the present case.
The sequence of adenoma to adenocarcinoma in colorectal cancer is well established and both are believed to originate from the same precursor cells. A mixed or collision tumor is composed of both adenocarcinoma and NEC. The notion that the two malignancies as well as the TA originate from common multipotent stem cells simultaneously differentiating into glandular and neuroendocrine lineages is likely and plausible. However, when a TA is mixed with a high-grade NEC, their association becomes less clear. Following the examination of genome-wide loss of heterozygosity, it was proposed that the common genetics of the glandular and neuroendocrine components indicate origin from a single precursor[]. This suggests that the two components of mixed tumors arise from multi-potential stem cells and show bi-phenotypic differentiation after carcinogenesis is initiated[,]. An alternative hypothesis is that mixed tumors are a neuroendocrine phenotype of dedifferentiated tubular adenocarcinoma[]. Certain cases are reported of cecum and rectosigmoid collision adenocarcinoma and neuroendocrine tumors which were found to metastasize to lymph nodes as juxtaposed glandular and neuroendocrine components[,]. Likewise, a case of collision tumor located in transverse colon (adenocarcinoma and large-cell NEC) presented three years after resection with a retroperitoneal metastasis with 50% NEC and 50% adenocarcinoma[]. These latter examples support the counter argument against the double primaries theory.
Poorly differentiated NEC may lose their intestinal differentiation and show negative immunostaining for CK20 and CDX2 as in our case. However, we found CK20 and CDX2 to be positive in the TA component as expected. The dedifferentiation and/or loss of intestinal differentiation may be a late event.
The current case presented as an ulcerative mass in the right colon, with TA (30% of the mass) juxtaposed with NEC (70% of the mass). In a review of 67 previously reported cases and 23 new cases, mixed neoplasms were found to present as a polypoid growth (57%), mass (30%) and ulcerating lesion (9%). The glandular component varied from adenoma (17%) to adenoma with well- or moderately-differentiated adenocarcinoma (35%), or adenoma with poorly-differentiated adenocarcinoma (48%). Furthermore, 56% of mixed colo-rectal tumors arise in the right colon with the tumors being 58% collision tumors (two distinct neoplastic components), 42% composite (i.e., intermixed neoplastic components) and less than 1% amphicrine (where individual cells demonstrate both exocrine and endocrine features) and with mean age of presentation of 61.9[]. Nevertheless, mixed neoplasms have also been reported in various locations like the gallbladder[], pancreatic ampulla[], stomach[] and cecum[]. Based on the WHO 2010 classification, the neuroendocrine component in the present case is G3 based on the mitotic count of 77/10 hpf and the Ki-67 index of 75%, which far exceed the 20/10 hpf and 20% proliferation index, respectively used to grade NECs.
The patient under study has not presented with symptoms suggestive of carcinoid syndrome. Whereas many neuroendocrine tumors present with secretory syndromes characterized by flushing, diarrhea, wheezes, sweating, palpitations and right-sided heart valve lesions, gastrointestinal neuroendocrine tumors are less likely to present with carcinoid syndrome[]. Serum chromogranin A elevation can be detected in patient with neuroendocrine tumor in the absence of carcinoid syndromes.
The large cell NEC is a poorly-differentiated neoplasm that is quite and belongs to the poorest prognostic subgroup among primary colorectal cancers. In a study of 6495 patients with colorectal cancer, only 0.65% had NEC and only 0.2% had large cell NEC. Despite its rarity, it is important to differentiate colorectal NEC from other tumor types because patients may benefit from alternative cytotoxic chemotherapy[]. In this regard, unlike the colorectal adenocarcinoma, large cell NEC is managed primarily with platinum based chemotherapy such as cisplatin/etoposide and cisplatin/irinotecan. Based on various studies, the median survival rate for patients with colorectal NEC is between 5 and 11 mo with one-year survival rate between 10% and 15%. Patients with colorectal large cell neuroendocrine carcinoma were found an overall median survival of 9.4 mo[].
Well-differentiated neuroendocrine tumors (also known as carcinoid) or microcarcinoid tumor nests had been reported in association with colonic tubular or tubulovillous adenoma. Those neuroendocrine components are well-differentiated either forming tumor nodules or scattered in the lamina propria within the adenoma lesion[,]. High-grade NECs arising in association with tubulovillous or tubular adenoma have only been seen in a handful of cases[-]. Whereas more than 50% of cases were found to have liver, bone or nodal metastasis at the time of diagnosis even when the tumor was microscopic, some primary tumors showed invasion limited to the muscularis mucosa. Therefore, colorectal NECs tend to behave aggressively and the prognosis is extremely poor with survival lasting a few months. Our case represents a unique situation where the presence of a TA warranted a polypectomy and endoscopic evaluation led to the adjacent ulcerated mucosa to be noticed and biopsied. In other words, the contiguity of the NEC to the TA allowed for early diagnosis of the otherwise asymptomatic NEC. Being aware of this association bears practical implication where it can be conducive to the early and correct diagnosis of high-grade tumor such as the NEC in the current case, and avoiding overlooking other fragments distinct from the adenoma.
Another implication to be born in mind is that superficial biopsy specimens may not provide the adequate representation of underlying neuroendocrine tumor found in the mixed tumor. Even when present in the biopsy sample, pathologists must be vigilant of the possibility of a mixed tumor and resist the tendency to diagnose an adenoma before careful inspection of the tissue for additional lesions. The overlying large TA or tubulovillous adenomas may mask a deep invasive tumor, making it imperative to collect adequate and deep tissue samples. Furthermore, surgical pathologist must also be aware of the differential diagnosis of poorly differentiated neoplasms that may involve an adenoma. This includes poorly-differentiated adenocarcinoma, medullary carcinoma, high-grade neuroendocrine carcinoma and lymphoma. Because the prognosis and management varies significantly amongst these entities, careful attention must be paid to the morphology of the tumor cells and general architecture. In addition, a panel of immunohistochemical stains that includes neuroendocrine, lymphocytic and adenocarcinoma markers and DNA mismatch repair enzyme screening should be considered to use for rendering the correct diagnosis.


An 84-year-old female presented in hospital with abdominal pain, itching and cholestasis.
Clinical examination confirmed abdominal pain. Blood were counts normal with glutamic oxaloacetic transaminase 56UI/L (Normal range (nr) 40-45 U/L), glutamic pyruvic transaminase 46 UI/L (nr 5-35 U/L), alkaline phosphatase 241 UI/L (nr 55-142 U/L), Lactate Dehydrogenase 256Mu/Ml (nr 122-222 U/L), total bilirubin 1.48 mg/dL (nr 0.3-1.0 mg/dL).
Endoscopic retrograde cholangiopancreatography (ERCP) revealed a mass involving the entire thickness of the duodenal wall mid-portion with extension of 12 mm without ampulla of Vater involvement. Findings were confirmed by contrast-enhanced computed tomography (CT) which did not detect any nodal metastases. Biopsy findings were duodenal adenocarcinoma which was staged cT3N0M0 (AJCC Cancer Staging Manual 7th edition)[].
As surgery and systemic chemotherapy were excluded because of age and comorbidities (high blood pressure and ischaemic heart disease) the patient was not investigated further. Instead of palliative support we opted for radical treatment with EBRT. To visualize the lesion a CT without contrast medium was performed after having inserted a metal stent and a clip about 0.5 cm below the distal margin during a repeated ERCP.
CT images were acquired with 0.25 cm slice thickness and transmitted to the Pinnacle3 TPS V9.8. One radiation oncologist (VL) contoured the clinical target volume (CTV), i.e., the diseased duodenal tract. CTV was expanded 5 mm in all directions except for the cranial and caudal which were expanded 7 mm to provide the planning target volume (PTV). The radiation oncologist contoured the liver and kidneys as OARs.
The HT plan was generated using the Tomotherapy HD System commercial planning software. The dose prescription was 46.2 Gy to PTV in 21 fractions.
HT provided good PTV coverage as shown in Table . Table showed dosimetric results for the OARs, which were markedly lower than pre-defined dose constraints.
Treatment was associated with G2 acute abdominal toxicity (diarrhoea), as defined by CTCAE 3.0 criteria.
Follow-up included a clinical examination and complete blood work-up every three months, and abdominal ultrasound or CT scans every six months.
After 22-mo follow-up, the patient is alive and well, in complete remission without late side effects.


An 11-year-old male child presented with conus-cauda syndrome of 1-year duration. He presented with weakness in both lower limbs and difficulty in walking with the involvement of bladder and bowel. On examination, he had proximal muscle weakness, bilateral foot drop with sacral sensory loss. His ankle reflexes were sluggish and plantars were mute. He had no neurocutaneous markers. His magnetic resonance imaging [] of the spine revealed intramedullary tumor opposite D11–D12 vertebra, hyperintense on T1-weighted images with well-defined areas of hypointensity. There was a syrinx noted higher above, at D8–D9 level. On T2-weighted images, calcification was seen (hypo), and on contrast images, the lesion was partially coalescing and intensely enhancing. A provisional diagnosis of ependymoma, astrocytoma, or a calcified tuberculoma was made.
He underwent D10–D12 laminotomy and near total excision of the tumor. The tumor was relatively avascular grayish-white, firm with well-defined plane of cleavage. It had calcification superiorly, and xanthocromic thick mucinous material was seen with in the tumor. As dense adhesions were noted at the superior pole, complete excision was not possible. Interestingly, histopathological examination [] of the tumor specimen revealed round hyalinized mass with entrapped nerve roots, with a few anterior horn cell containing lipofuscin. Large foamy histiocytes, reticulin-rich Schwannian fibrillary stroma, and calcification were noted. No giant cells or granulomas were seen and stains for acid-fast bacilli and fungal hyphae were negative. Immunohistochemistry was positive for S-100 (spindle cells) and CD-68 (foamy histiocytes). A diagnosis of xanthomatous schwannoma was made. Patient's postoperative course was uneventful. He was recovering well at 6 months follow-up.


A 64-year-old healthy man presented with a 10-year history of a painless exophytic lesion on his inner right leg, treated at home by repeated curettage. The patient was asymptomatic and had no significant medical or surgical history. Physical examination revealed an exophytic ulcerated mass, adhered to deep planes, of 6.5 cm greater dimension in the inner part of the lower right leg. A swollen subcutaneous mass in the right groin was also present, clinically suggestive of positive lymph nodes.
The lesion was surgically removed with a 1-cm margin and closed with a split-thickness skin graft. The histopathological study showed a nodular proliferation of basaloid cells from the dermis to subcutaneous fat tissue, with poor circumscription. The lesion was ulcerated, and revealed an invasive tumor containing irregular nests (Fig. ). The central part showed the transition of basaloid cells into shadow cells. The anaplastic basaloid cells in the periphery were proliferating with numerous mitoses, and exhibited an infiltrative growth with extensive areas of necrosis. The tumoral nests were surrounded by dense desmoplastic stroma, containing a variable amount of inflammatory infiltrate composed mainly of lymphocytes (Fig. ). The surgical margins on microscopic examination were negative.
A lymph node dissection of the groin was performed on a second surgery. Lymph nodes showed complete effacement of the nodal architecture and proliferation of monomorphic large cells with oval or cleaved nucleus, with vesicular chromatin and several nucleoli. Immunophenotypic analysis demonstrated CD20-, CD79α-, BCL-6- and BCL-2-positive cells, confirming the diagnosis of diffuse large B-cell lymphoma (DLBCL). The remainder of the parenchyma constituted a mixed population of B and T cells of normal appearance.
Positron emission tomography–computed tomography (PET-TC) and bone marrow biopsy revealed no systemic disease.
The patient was treated with R-CHOP chemotherapy for his lymphoma. After 10 months of treatment, his general condition was good; no abnormalities were found on clinical examination, and there was no evidence of any disease on the last PET-CT. Clinical examination was also scheduled by his dermatologist every 6 months.
Informed consent was obtained from all patients for being included in the study.


A 73-year-old male presented to the emergency department after sustaining a ground-level fall due to a syncopal episode. He was experiencing some neck pain. He had no weakness in the upper or lower extremities. He had no numbness and was ambulating with no difficulty. Per the emergency department protocol, a computed tomography (CT) scan of the head and cervical spine was performed. Cervical spine CT demonstrated DISH from C2 to T2 and a minimally displaced type 2 odontoid fracture (). There was initial concern whether the fracture is acute or chronic. However, since he was having pain and was neurologically intact, he was offered nonoperative management consisting of a hard cervical collar. At 2-year follow-up, the patient was experiencing mild neck pain. Radiographs and CT of the cervical spine demonstrated a stable fracture nonunion of the odontoid fracture (). After discussing nonoperative versus operative options, the patient and treatment team elected to continue with nonoperative management.


The patient was a 19-year-old woman who was born with a scalp defect. The defect healed after conservative wound management early in her life. She had no specific medical history and no signs of neuropsychiatric problems. Neither her parents nor brothers had dermatologic or systemic problems.
She first visited our clinic for evaluation of her scalp lesion 10 years ago, when she was nine years old. The scalp lesion had been replaced by fibrotic tissue and appeared to be an atrophic alopecic patch (). Examination of skin biopsy specimens from the scalp showed an irregularly thickened epidermis, atrophic dermis with upward extension of the subcutaneous tissue, and mild fibrotic changes and loss of periadnexal structures (). A diagnosis of aplasia cutis congenita was made based on clinical and histologic features.
During the 10 years after her last visit, atrophic and nodular skin changes on the right side of the trunk and limbs began to appear and become progressively more prominent, while the syndactyly of the right fourth and fifth toes, which had not been identified previously, was negatively influencing her quality of life. Thus, the patient returned to our clinic and a complete physical examination of the body was performed. We identified multiple, variously sized, and well-demarcated atrophic patches that were mostly confined to the right trunk and leg (). Some lesions appeared as brown or yellow protruding masses, and were accompanied by deposited and herniated fat tissue. The atrophic patches and protruding masses were arranged in a linear fashion following Blaschko's line. We observed only a few atrophic patches on the patient's left leg. We also noted the syndactyly of the right fourth and fifth toes ().
A skin biopsy from the right calf revealed prominent dermal atrophy and extension of subcutaneous fat toward the upper dermis (). Focal dermal hypoplasia, also known as Goltz syndrome, was diagnosed on the basis of clinical and histologic findings. Because most of the skin lesions were confined to the right side of the body, the focal dermal hypoplasia in this case was identified as the almost unilateral form.
Because the patient complained of discomfort from syndactyly of her right fourth and fifth toes, we referred her to the Department of Plastic and Reconstructive Surgery to surgically manage this condition.


A 25-year-old gravida 2, para 1, abortion 0, woman presented with 5 weeks pregnancy. She earlier had a home delivery where the baby had severe birth asphyxia and did not survive. She was found to be normotensive, had a normal glucose challenge test, and was B Rh-negative. ICT was found to be negative. On inquiry, she revealed that anti-D immunoglobulin had not been given to her in the last delivery. She was prescribed tablet folic acid 5 mg and was followed up with regular antenatal checkups. At 28+ weeks of pregnancy, her ICT was found to be positive in a dilution of 1:64. She was called for a Doppler sonography and reported at 31+ weeks of pregnancy. The peak systolic velocity (PSV) of middle cerebral artery (MCA) was found to be 45 cm/s, corresponding to 1.0 mean of median (MOM). She was monitored with measurements of PSV of MCA every fortnightly and PSV remained below 1.3 MOM till 35 weeks of pregnancy [].
She was administered short-course betamethasone to prevent hyaline membrane disease, and elective induction of labor was performed at 36+ weeks pregnancy.
A 2.25 kg male baby was delivered vaginally with a good Apgar score. The baby was O Rh-positive with hemoglobin 13.2 g. Cord blood bilirubin was 2.21 mg/dl and direct Coombs test was positive. At 24 h of birth, the bilirubin was still 3.20 mg/dl. Since significant hyperbilirubinemia did not occur, the baby thus was discharged.


A 31-year-old woman presented with 7 weeks pregnancy. She was G8 P4 A3, i.e., gravida 8 para 4, abortions 3, with one female alive issue. Her first pregnancy was uncomplicated, but the baby died at 4 years of age. In the second pregnancy, a preterm delivery occurred and baby died because of jaundice and brain damage. The third pregnancy was a preterm twin delivery and the twins did not survive. In the fourth pregnancy, a female baby was delivered at 34 weeks but survived after two exchange transfusions. Thereafter, the woman had three consecutive pregnancy losses between 6 weeks and 5 months. Antepartum hemorrhage, hypertension, and congenital anomalies were not associated with these pregnancies. On examination, her blood pressure was 110/90 mmHg and she weighed 60 kg. On investigation, her blood group was B Rh-negative, hemoglobin 11 g%, glucose challenge test by O’ Sullivan method showed blood sugar to be 120 mg%, thyroid-stimulating hormone 0.31 mIU/ml, and anticardiolipin antibody and β2 glycoprotein were in the normal range. The ICT was negative.
The woman was started on folic acid, low dose aspirin 75 mg, and micronized vaginal progesterone 200 mcg by vaginal route daily. A viability scan showed 7 weeks viable fetus with no associated uterine anomaly or myoma. After 13 weeks pregnancy, the patient was started with iron with folic acid and calcium tablets. An anomaly scan at 17 weeks revealed a healthy fetus and 40 mm cervical length.
However, at 23 weeks, as ICT was repeated, it was found to be strongly positive, the ICT titer being 1:2038.
She accessed us with the report after 3 weeks at 26 weeks 6 days gestation on October 20, 2015.
The patient was sent for an ultrasound examination and a Doppler study. PSV of MCA was measured. The PSV-MCA at 27 weeks was 37 mm/s and its MOM was 1.29. The patient was monitored with measurements of PSV of MCA every 2 weeks []. The values of PSV were plotted on the nomogram proposed by Moise to know the MOM and thus judge the degree of anemia[] []. Considering the very high ICT titer, the bad obstetric history suggesting Rh isoimmunization (neonatal hyperbilirubinemia and history of exchange transfusions in earlier births), IVIG was decided upon to improve neonatal outcome.
IVIG 5 g was first administered to her at 27 weeks of pregnancy. IVIG 5 g was repeated at 29 weeks and 31 weeks of pregnancy after PSV-MCA was determined and found to be < 1.29 MOM, i.e., zone C (normal hematocrit zone) [].
Hence, a total of three doses of IVIG were given at 2 weekly intervals. At 33 weeks, as the cervical length became 30 mm and imminent preterm labor was evident, short-course betamethasone was administered consisting of 12 mg in two doses at an interval of 24 h.
Preterm vaginal delivery occurred on December 20, 2015, at 34 weeks 2 days gestation.
A male baby weighing 2.5 kg was delivered with a good Apgar score and the baby was shifted to neonatal care unit. The baby was B Rh-positive, cord blood hemoglobin was 14 mg%, bilirubin was 6.5 g%, and direct Coombs test was positive. The serum bilirubin rose to 11 g% 6 h after birth when an exchange transfusion was performed. A dose of IVIG, 1 g/kg body weight was administered to the neonate. A repeat exchange transfusion was performed at 24 h after birth when serum bilirubin became 17 mg%. Another dose of IVIG was also repeated after 24 h of the first dose. Thereafter, the serum bilirubin started decreasing and the baby slowly recovered. At 1 month of age, the infant has normal tone and normal reflexes. At 6 months of age, the baby has normal milestones with no neurological deficit.


A 28-year-old Filipino gentleman mechanical engineer without any medical problem admitted to our hospital on 16th of February 2016 with complains of numbness and weakness in lower limbs when he woke up for urination at around 3:00 am on the day of admission which started distally symmetrically and progressed proximally and gradually involved the upper limbs in the same pattern, the proximal muscles were affected more severely than distal muscles, became bed bound in over 3 h when he was brought to emergency room (ER) by his roommate. He took large amount of cookies and soft drink at dinner time which triggered this crisis. Past history of weakness of both lower limbs was present in the year 2011 which was recovered fully without any motor sequelae and remained asymptomatic till the day of admission.
On physical examination revealed a healthy male with regular pulse and normal blood pressure with fine tremor on out stretched hands and proptosis of left eye with no palpable goiter. Cardiovascular, pulmonary, and abdominal examinations were unremarkable. The neurological examination revealed cranial nerves intact with upper and lower limbs power was grade 0/5 and decreased to absent deep tendon reflexes with intact sensation.
In ER initial potassium level was 1.6 mmoL/L and electrocardiogram () shows features of hypokalemia, i.e., ST depression, U-wave, and high QRS Voltage. An initial diagnosis of hypokalemia periodic paralysis was kept and intravenous potassium 20 mEq/L along with oral replacement was started following which limb weakness improved in 24 h. His thyroid-stimulating hormone was 0.009 µIU/L (normal 0.55-4.78), T4 was 44.2 pmol/L (normal 12-22) and T3 was 14.9 pmol/L (normal 4.35-6.85), and together with left eye exophthalmos, which were consistent with thyrotoxicosis. Patient was started on propranolol 40 mg BID and Carbimazole 20 mg/day and discharged on the third day with final diagnosis of TPP secondary to Graves’ disease.


A 51-year-old man began experiencing back pain in May 2014. Myelofibrosis was suspected because of the significant signal change in the spinal body on magnetic resonance imaging (MRI) and dry-tap bone marrow aspiration. He did not have a Janus Kinase 2 (JAK2) mutation.
The patient was administered analgesic agents for 4 months until blood examination showed a worsening of anemia, emergence of nucleated erythrocytes, and a left shift of leukocytes. Adenocarcinoma (well-to-moderately differentiated) was observed in a bone marrow biopsy specimen obtained in September 2014. A subsequent colonoscopy revealed a circumferential diffuse infiltrative lesion in the rectum (Ra-Rb) causing a narrowing of the lumen; a biopsy showed poorly differentiated adenocarcinoma. Imaging examinations (computed tomography [CT], MRI, and positron-emission tomography-CT) at the time of the onset of back pain had not shown any suspicious lesions, but reexamination in September and October showed a rectal tumor with multiple metastatic lesions (bone, liver, left pararenal gland, peritoneum, and pleura; ); the cancer was diagnosed as clinical stage T4N0M1 (Union for International Cancer Control, 7th edition).
The patient underwent ureteral stenting for hydroneph-rosis due to ureteral stricture, as well as emergency surgical decompression and colostomy for colon obstruction caused by the primary tumor and severe peritoneal metastasis. The patient’s condition deteriorated most severely on postoperative day (POD) 3; his Eastern Cooperative Oncology Group performance status (PS) was 3, and he experienced a recurrent fever >39°C due to rhabdomyolysis, sepsis, and the neoplasm. Blood tests at POD 3 showed prothrombin time-international normalized ratio (PT-INR) 1.65 (6.8 s prolonged), fibrin and fibrinogen degradation product (FDP) 73.5 mg/L, creatine kinase (CK) 15.45 µkat/L (925 U/L), lactate dehydrogenase (LDH) 61.71 µkat/L (3,695 U/L), C-reactive protein (CRP) 313.91 nmol/L (32.96 mg/dL), procalcitonin 1.81 µg/L, white blood cell (WBC) count 13.05×109/L, hemoglobin 65 g/L, and platelet count 114×109/L. DIC treatment (including recombinant human thrombomodulin), antibacterial and antifungal agents, and red blood cell transfusion, improved the patient’s blood test results as follows: PT-INR 1.39 (4.7 s prolonged), FDP 44.5 mg/L, CK 1.95 µkat/L (117 U/L), LDH 6.03 µkat/L (361 U/L), CRP 118.38 nmol/L (12.43 mg/dL), WBC 5.76×109/L, hemoglobin 85 g/L, and platelet count 114×109/L. However, his eligibility for chemotherapy remained uncertain. Surgery was deemed to be the principal cause of rhabdomyolysis, and recurrent fever was eventually diagnosed as neoplastic fever after no bacterial growth was observed in culture tests. Prompt relief from pyrexia was achieved with naproxen.
We administered chemotherapy in the form of infusional 5-fluorouracil (5-FU) plus levoleucovorin. Details of the chemotherapy regimens are shown in . CT after two cycles of chemotherapy showed progressive disease with worsening liver metastasis (). Despite disease progression, the patient’s PS score had improved to 2 owing to the amelioration of rhabdomyolysis and recurrent fever. Additionally, molecular testing at this time showed no KRAS mutation. Thus, he was administered modified FOLFOX6 combined with anti-EGFR antibody therapy as a second-line therapy. CT after two cycles showed a partial response; his primary lesion and liver metastasis shrank, and pleural effusion and ascites decreased (). Furthermore, his PS score improved to 1, leukoerythroblastosis disappeared, and red blood cell transfusion was no longer required because his anemia improved. Moreover, his tumor markers normalized, as shown in . Observed adverse events (per the Common Terminology Criteria for Adverse Events version 4.0) were as follows: rash (grade 2), paronychia (grade 2), peripheral neuropathy (grade 2), fatigue (grade 2), neutrophil count decrease (grade 3), anemia (grade 3), platelet count decrease (grade 2), and hypomagnesemia (grade 1). We switched the anti-EGFR antibody from panitumumab to cetuximab owing to the development of a rash; we did not wish to discontinue anti-EGFR antibody therapy outright.
The patient performed well for 20 cycles (10.8 months) until CT showed worsening of the primary lesion and liver metastases. The patient then received FOLFIRI plus bevacizumab as a third-line therapy; response lasted for nine cycles (4.8 months) until bone marrow metastasis progressed and leukoerythroblastosis and anemia relapsed, necessitating red blood cell transfusion. He died following the progression of the left pararenal gland metastasis, impairment of renal function, and uncontrollable hemorrhage 22.7 months after diagnosis and 16.6 months after commencing first-line therapy.
The patient’s next of kin provided written informed consent for the publication of this case report.


A 14-year-old male, presented with complaints of sudden reddish discoloration of urine 5 days back followed by yellowing of eyes and skin, nausea, and vomiting associated with feeds. This was preceded by an episode of high-grade fever. At presentation, his vitals were normal. He was afebrile. Severe pallor, as well as icterus, was present. There was no palpable organomegaly. On routine investigation, he was anemic (hemoglobin 4.9 g%) with thrombocytopenia (platelets 97,000). Total leukocyte counts were normal. Renal functions were deranged with a serum creatinine of 4.27 and blood urea of 116.8. His total bilirubin was 5.3 with an indirect component of 4.1. Kidney sizes were normal with raised cortical echogenicity and a normal renal Doppler study. Serum lactate dehydrogenase levels were raised at 2944 IU/L. A peripheral blood smear revealed dimorphic anemia with thrombocytopenia with polymorphonuclear leukocytosis with abundant schistocytes and tear drop cells suggestive of hemolytic uremic syndrome with a reticulocyte count of 30%. Urine analysis showed granular and hyaline casts and strongly positive test for hemosiderin. Urine output was adequate. Anti-nuclear antibodies were absent with low complement 3 (C3) and normal C4 levels. Anti-complement factor H (CFH) antibodies were found to be significantly raised at 2043 AU/ml. A diagnosis of aHUS was made. He was initiated on plasma exchange with 7 initial daily cycles and a total of 16 cycles titrated to clinical response. His renal and liver functions normalized by the 12th cycle. Anti-CFH antibodies were repeated and found to have decreased to 191.07 AU/ml. Peripheral smear showed a complete absence of schistocytes with urine negative for hemosiderin. He later developed sudden onset severe headache followed by loss of vision progressing to generalized tonic–clonic seizures and status epilepticus. Blood pressure was increased at 200/140 mmHg. He was intubated and later successfully weaned off mechanical ventilation. A magnetic resonance imaging (MRI) brain revealed posterior reversible encephalopathy with altered signal intensity in a subcortical white matter of the bilateral parietal, occipital, posterior temporal lobes and cerebellar hemispheres []. He subsequently developed three more episodes of status epilepticus with posterior reversible encephalopathy. Blood pressure control was achieved using nifedipine, labetalol, and telmisartan. Seizures were controlled on phenytoin, levetiracetam, and clobazam. Severe skin rashes developed almost 2 months into admission: Centripetal in development with mucosal involvement and was diagnosed as Steven–Johnson syndrome []. Phenytoin was withheld and the lesions resolved. He was started on further immunosuppression with steroids and azathioprine and discharged on day 91 of admission in complete clinical and hematological remission.


A 44-year-old man with medical history of alcohol dependence with recurrent attacks of acute pancreatitis came to the emergency department complaining of persistent non-bloody, greenish vomiting associated with epigastric and left upper quadrant pain for 3 days. Patient admitted to drinking alcohol daily for about 20 years. Patient had pertinent history of an episode of alcohol-induced acute pancreatitis 10 days prior to this index admission with amylase and lipase levels of 91 and 189 U/L, respectively. Patient was hemodynamically stable at the time of admission. Physical exam was consistent with epigastric and left upper quadrant tenderness without guarding or rigidity. Laboratory studies revealed a hematocrit of 43%, leukocyte count of 10.3 × 109/L (71% neutrophils), lipase of 163 U/L, amylase of 90 U/L and creatinine of 2.7 mg/dL (baseline of 0.5mg/dL). Ultrasound (US) of abdomen did not reveal gallstones but showed mild hepatomegaly and hepatic steatosis. Computerized tomography (CT) scan of abdomen revealed changes in pancreas consistent with acute pancreatitis along with distended stomach and duodenum raising concern for obstruction at the proximal jejunum ( and ) from surrounding edema/inflammation. Patient was admitted with an impression of alcohol-induced severe acute pancreatitis with acute kidney injury and small bowel obstruction. Patient was started on aggressive intravenous hydration with lactated Ringer’s solution and metoclopramide as needed for nausea and vomiting. Electrolytes were replenished as appropriate. Surgeons recommended conservative management with periodic gastric suctioning via a nasogastric tube connected to low wall suction. Patient continued to have abdominal pain with nausea and vomiting over the next 2 days with worsening of leukocyte count and renal function (creatinine trended up to 4.9 mg/dL). Patient had no bowel movements during this period. Patient was also noted to have metabolic alkalosis with a pH of 7.62. Patient was switched to intravenous normal saline given the metabolic alkalosis likely from vomiting.
Magnetic resonance cholangiopancreatography (MRCP) was also performed. MRCP revealed changes consistent with acute pancreatitis with no intra-luminal common bile duct (CBD) or pancreatic duct (PD) pathology. Patient was continued on aggressive intravenous hydration with clinical improvement and complete resolution of small bowel obstruction within next 4 days. Patient was eventually started on oral diet which he tolerated well. Patient was discharged home with extensive counseling on importance of alcohol abstinence.


A 55-year-old male patient was admitted to our emergency department with right flank tenderness preceding 4-6 hours. He had no dysuria, hematuria, fever, nausea, or vomiting. Except for the right flank tenderness and 3/6 systolic murmur at the cardiac apex, his physical examination and hemodynamic parameters were normal. His medical history was remarkable for non-ischemic dilated cardiomyopathy, which was diagnosed by coronary angiography (CAG) and cardiac catheterization in another clinic 2 days ago, and the drugs in use were carvedilol, ramipril, furosemide, and acetylsalicylic acid. The abdominal x-ray, urinary ultrasonography (US), and laboratory analysis were all normal. Only mild microscopic hematuria was detected. The patient was clinically diagnosed with renal colic, treated with analgesics, and then discharged home for further ambulatory urologic investigation. A few hours later, the patient returned to the emergency department with severe right flank pain. On contrast-enhanced computed tomography (CECT), performed for persistent flank pain, to rule out nephrolithiasis and CAG complications, such as retroperitoneal hematoma, a hypodense, non-enhancing, wedge-shaped area in the right kidney, which was compatible with renal infarction, was seen (). Globally systolic dysfunction (ejection fraction: 35%), mild-moderate mitral insufficiency, dilated left chamber without thrombi or vegetation, and multiple self-terminating atrial fibrillation (AF) episodes compatible with paroxysmal AF were detected on transthoracic echocardiography and 24-hour Holter monitoring, respectively. CHA2DS2-VASc and HAS-BLED scores were calculated as 3 and 2, respectively. Dabigatran (150 mg, b.i.d.), analgesics, and hydration were initiated. In 5 days, he recovered and was discharged home on dabigatran. On the control CECT scan performed 1 month later, reperfusion and contrast enhancement were seen at the previously hypodense renal infarct area ().


A previously healthy 31-year-old man was admitted to our hospital presenting with recurrent unconsciousness accompany with right limbs convulsions for 12 days duration. Clinical manifestation showed recurrent unconsciousness, right limbs convulsions, aconuresis, or encopresis, which sustained 3 to 8 min. Subsequently the patient felt severe headache, and nausea after remission, and these symptoms could disappear after a rest within 24 h. He reported no blurred vision, slurred speech, physically disability, or limb's numbness. He has no history of infection and vaccination within 6 weeks, and he has no other medical history. His family has no hereditary diseases. The patient was a primary school teacher. He was not married and reported no recent sexual contacts or recreational drug use. He drank alcohol and smoked occasionally.
The physical and neurological examinations were unremarkable. Serum C-reactive protein (CRP) was 11.78 mg/L (normal range, 0–10), and erythrocyte sedimentation rate (ESR) was 18 mm/h (normal range, 0–15, Westergren method). Serum antineutrophil cytoplasmic antibody (ANCA), antinuclear antibodies (ANAs), rheumatoid factor (RF), antidouble-stranded DNA, cryoglobulins, and human immunodeficiency virus (HIV) testing were negative. Lumbar puncture showed the patient's intracranial pressure was 190 mm Hg (normal range, 80–180), and cerebrospinal fluid (CSF) protein was 0.48 g/L (normal range, 0–0.45). Additional testing of the CSF, including white blood cell (WBC), glucose, immunoglobulin G (IgG) index, oligoclonal bands (OB), and virus were negative. Other laboratory findings including complements 3 and 4 were within normal range, and no other clinically significant findings were noted.
A 24 h electroencephalogram (EEG) test showed that complex, low-moderate amplitude δ waves occurred frequently in the left temporal lobe, and θ waves were sporadic in other lobes. Brain computed tomography (CT) plain showed a hypodensity space-occupying lesion with surrounding edema in cortex and subcortical of the left temporal lobe, and white matter hemorrhages also could be seen (Fig. A). Brain magnetic resonance imaging (MRI) showed that the lesion was hyperintensity on fluid-attenuated inversion recovery (FLAIR) sequences (Fig. B). Brain magnetic resonance spectroscopy (MRS) showed that the metabolic peak of choline (Cho) within the lesion increased (Fig. C). Magnetic resonance angiography (MRA) suggested a complete occlusion in the third segment of the left middle cerebral artery (MCA) (Fig. D). An intensity change of the lesion on MRI T1, T2, diffusion-weighted imaging (DWI), and Gd-enhanced were showed in Fig. E–H, respectively. Mixed hyperintensity was presented on MRI T1 and T2 images, and hyperintensity was observed on DWI and Gd-enhanced images. Four weeks later, compared with previous images, the hyperintensity of the mass lesion was decreased on T1, T2, DWI, and Gd-enhanced images, respectively (Fig. I–L). A biopsy of leptomeningeal lesion before treatment was performed. Hematoxylin and eosin staining revealed a lymphocytic infiltrate targeting the vascular wall of a small muscular artery, with the intima hyperplasia and luminal stenosis (Fig. A). Immunohistochemical staining revealed a lot of T lymphocyte infiltrate within the lesion (Fig. B and C).
The patient was diagnosed with PACNS and epileptic seizure by biopsy and EEG. Intravenous pulse methylprednisolone 1 g daily was given for 3 days, and epileptic seizure symptoms quickly disappeared, subsequently oral prednisone was continued at high dose (1 mg/kg per d) for 4 weeks in combination with cyclophosphamide (CyP) 2 mg/kg per d for a total 6 months. Fortunately, the patient's condition was stable, and only mild memory impairment remained without adverse event 7 months later.


A 22-year-old man was admitted to our hospital with partial seizures and progressive declined cognitive for 5 months duration. Clinical manifestation showed Jacksonian epilepsy, first weakness in the right thumb, occasionally the corner of the mouth, and then marched over a few seconds to the entire right hand, feet or facial muscles, usually followed by right limbs’ paralysis for several hours. Meanwhile, the patient complained poor memory and mental disorders. He reported no loss of awareness. He has no brain injury or viral infections history such as HIV, hepatitis B and C, and his family has no hereditary diseases. His medications included the oxcarbazepine tablets (300 mg orally twice per day) and levetiracetam tablets (500 mg orally twice per day). The patient was a senior at university. He reported no history of recreational drug use, and he never drank alcohol and smoked.
The physical and neurological examinations were normal. Serum CRP was 10.52 mg/L (normal range, 0–10), and ESR was 22 mm/h (normal range, 0–15, Westergren method). Serum ANCA, ANA, RF, and HIV testing were negative. Lumbar puncture showed the patient's intracranial pressure was 210 mm Hg (normal range, 80–180), CSF protein was 0.85 g/L (normal range, 0–0.45), IgG index was 0.8 (normal range, 0–0.7), and albumin quotient was 11.5 × 10−3 (normal range, 0 to 7 × 10−3). Additional testing of the CSF including WBC, glucose, OB, and virus were negative. Other laboratory findings were within normal range, and no other clinically significant findings were noted.
A 24 h EEG test showed that low-moderate amplitude δ waves and θ waves arisen from the precentral gyrus area of the brain, which was an abnormal brain wave pattern that signified seizure activity. Brain CT plain showed a space-occupying mass lesion with surrounding edema in cortex and subcortical of the left temporal lobe (Fig. A). The mass lesion involving both white and gray matters was hypodensity on brain MRI T1 image, hyperintensity on MRI T2 image, and mild hyperintensity on MRI Gd-enhanced image (Fig. B–D). MRA detected a sever stenosis in the distal bifurcation of the left MCA (Fig. E). Fifty days later, CT and MRI showed that the volume and mass effect of the lesion decreased. The lesion were equidensity on brain CT plain, hypodensity on brain MRI T1 image, mild hyperintensity on MRI T2 image, no enhanced signal on MRI Gd-enhanced image, and mild hyperintensity on MRI FLAIR image (Fig. F–J). A biopsy of leptomeningeal lesion before treatment detected a transmural inflammation of the artery, with lymphocyte infiltration by hematoxylin and eosin staining (Fig. A). Immunohistochemical staining demonstrated T lymphocyte activation and no evidence of B lymphocyte within the lesion (Fig. B and C).
The patient was diagnosed with PACNS and epileptic seizure by biopsy and EEG. He was administered with methylprednisolone 1 g daily intravenously for 3 days, then tapered over 25 days to prednisone 30 mg daily by oral administration, and the treatment was maintained for 6 months duration. The patient was followed up, and most of symptoms were relieved in 50 days after corticosteroid therapy, including the intractable seizures, no adverse event was observed, and the patient was able to return to work again in spite of mild cognitive impairment.


In 2004, a 66-year-old man was diagnosed with a papillary grade 2 nonmetastatic right renal cancer and was treated with radical right nephrectomy. A nonspecific 10 mm-diameter tumor was detected on his left kidney, and hence, he was placed under close surveillance. In 2005, a partial left nephrectomy was performed but no pathological signs of malignancy could be evidenced. In 2006, the patient was diagnosed with a prostatic adenocarcinoma, and hence, a radical prostatectomy was performed without any complication. A few months later, multiple suspect left renal lesions were identified and a left radical nephrectomy was recommended by the multidisciplinary urologic board after meeting. Pathological analyses revealed a papillary renal cancer. The patient underwent hemodialysis 3 days a week (Monday, Wednesday and Friday) after bilateral complete nephrectomy and was closely monitored. Hemodialysis was performed between 2007 and 2010 without any complications. In 2010, a 70 mm local recurrence was diagnosed in the left renal fossa bed. Biopsies were performed, evidencing a recurrence of the papillary renal cancer. Since complete resection was impossible and in agreement with patient’s nephrologists, sunitinib was initiated in August 2010. For the first cycle, the smallest recommended dose of sunitinib was administered (ie, 37.5 mg/day). Sunitinib cycles consisted of 28 days on and 14 days off treatment. All along sunitinib administration, blood pressure was monitored weekly. He was considered to be stable and did not require treatment initiation.
Grade 3 vomiting occurred during all hemodialysis sessions performed following the first sunitinib initiation. Anticipatory nausea/vomiting was not suspected since the patient was not reported to be anxious and anxiolytic treatments did not decrease the symptoms. However, the 14 days treatment break was associated with a complete resolution of nausea and a related-to-sunitinib side effect was suspected.
Ondansetron was prescribed during the whole second cycle of sunitinib, but grade 1–2 vomiting during hemodialysis sessions was still reported. Digestive symptoms ceased again during the sunitinib off period.
Because of a grade 2 thrombocytopenia, the third cycle was delayed and the sunitinib dose was reduced to 25 mg/day. Despite the dose reduction and ondansetron systematic administration, grade 1 vomiting under hemodialysis was systematic during the sunitinib administration. Vomiting only stopped after sunitinib was replaced with another TT because of disease progression after three sunitinib cycles.


In 2008, a 69-year-old man was diagnosed with a nonmetastatic Fuhrman grade 3 left RCC. A radical left nephrectomy was performed, and the patient was monitored for 2 years without any other medical complications. No renal failure or electrolyte disorders were reported. In 2010, a metastatic progression was suspected on a systematic computed tomography scan, with lateral aortic nodes involvement and a left renal fossa tumor extended to the left colon and diaphragm. Sunitinib was initiated at 37.5 mg/day after biopsies confirmed a histology-proven metastatic RCC recurrence. The patient was treated with a 28-day on and 14-day off schedule. Plasma uric acid was normal at baseline. During the first cycle of this treatment, the patient presented his very first episode of gout attack located on a big toe. As it was reported to be normal in 30% of acute gout attacks if assessed immediately, the plasma uric acid concentration was assessed 15 days later, which was 81 mg/L (normal plasma uric acid concentration <70 mg/L). No concomitant renal failure, hemoglobin and/or hematocrit disorder, or concurrent medication intake other than sunitinib (acetylsalicylic acid, diuretics, pyrazinamide, ethambutol, etc.) were reported. Purine-rich food and alcohol were cutoff, but the patient did not consume much of them. Allopurinol (100 mg/day) was initiated before the second cycle of sunitinib without colchicine because interactions with sunitinib were feared. Two months later, during the fourth sunitinib cycle, the patient developed a similar acute gout attack without any identified triggering factor. Allopurinol dose was increased to maximum (300 mg/day), while sunitinib was maintained at 37.5 mg/day until progression. The patient kept sticking to his purine-depleted diet. Iterative gout attacks of lower intensity were still periodically reported during the following months under sunitinib therapy. After progression, a new line of treatment was initiated. Sunitinib discontinuation was followed by a total regression of gout attacks.


In 2010, a 68-year-old woman was diagnosed with an abdominal-metastatic grade 3 RCC. Following total nephrectomy, the patient was treated with sunitinib from March to June 2010. Due to poor hepatic tolerance and tumor progression, the patient was switched to everolimus. Unfortunately, in the months following the second-line treatment initiation, she was diagnosed with everolimus-related bilateral interstitial pneumonia, requesting for urgent everolimus discontinuation. A third-line treatment based on sorafenib was initiated in January 2011. Despite immediate grade 1 abdominal, facial and truncal rash, sorafenib was continued at 200 mg twice a day. Twelve days later, the patient reported grade 3 dysesthesia of the whole scalp, negatively affecting her quality of life. The differential diagnosis of migraine was rejected by neurologists, and first-line migraine treatments did not improve dysesthesia. Sorafenib was stopped 15 days after the onset of dysesthesia and when the symptoms intensified. Sorafenib discontinuation resulted in a complete dysesthesia resolution in the following days.


In 1998, a radical nephrectomy was performed on a 79-year-old man with an intent to cure nonmetastatic grade 2 RCC. Histology-proven metastatic progression was diagnosed in 2006, with a painful 50×50 mm lytic lesion of the left scapula. A palliative radiotherapy was successfully performed (39 Gy, 3 Gy/fraction) with significant pain relief. Because of the patient’s age, bevacizumab was initiated in monotherapy at a third of the recommended dose (ie, 5 mg/kg intravenously every 3 weeks instead of 10 mg/kg every 2 weeks). The patient was 88 years old at that time but was still in excellent condition. Bevacizumab could be continued for another 5 years with a perfect tolerance and good efficacy: Scapula metastasis was stable (43×38 mm) and painless. Bevacizumab was stopped in 2011, considering the extended absence of cancer progression. Six months later, an isolated progression of the scapula lesion was reported, with an increasing left shoulder pain and an increasing metastasis volume (50×60 mm). Bevacizumab was readministered in 2012 with a pain resolution, and tumor volume decreased in 9 weeks. To date, the patient is still alive with an excellent tolerance. Intermittent (“start-and-stop”) bevacizumab is continued with a clear on/off effect on pain relief.


A 25-year-old male complained of sore throat and fever with chills and rigors for 1 month, petechial hemorrhages for 20 days, and unexplained weight loss. He revealed a history of cigarette smoking (2–3/day). On examination, the patient had subconjunctival hemorrhage, petechiae, hepatosplenomegaly, and bilateral submandibular and cervical lymphadenopathy. His baseline investigations at the time of admission showed hemoglobin (Hb) – 7.5 g/dl, TLC – 301,000/µL, and platelet count (PLT) – 20,000/µL. The patient was diagnosed as a case of biphenotypic acute leukemia (myeloid/T-cell) based on flow cytometry and bone marrow biopsy (97% blasts). The patient was immediately started on intravenous hydration, antibiotics, and steroids for hyperleukocytosis.
On day 4, the patient developed altered sensorium and shortness of breath with further deterioration needing ventilator support. An increase in TLC (321,200/µL) was also noted. Emergency therapeutic leukapheresis was initiated. One blood volume (3.5 L) was processed, and 359 ml of ACD-A was used. The reduction in TLC was 156,200/µL (49%) []. No adverse events or procedure-related complications were reported. Postleukapheresis, the patient, was transfused with 1 unit of packed red blood cells (PRC) and 1 unit of PLT on cell separator (POCS) (23% reduction in PLT count) and was started on vincristine and daunomycin, followed by addition of L-Asparaginase (day + 2 postleukapheresis). The patient improved symptomatically and was gradually weaned of assisted ventilatory support. The patient was discharged on day 29 in hemodynamically stable condition. On follow-up (6 months), patient is asymptomatic and doing well.


A 28-year-old male, known case of chronic myeloid leukemia (CML) on dasatinib, complained of headache and vomiting for 2 days and was found to have high TLC (102,100/µL) on routine follow-up. Bone marrow biopsy revealed relapsed disease with blast crisis (96% blasts) for which two leukapheresis procedures were performed on consecutive days.
During the first procedure, one blood volume (2.5 L) was processed, whereas in the second, two blood volume (5 L) was processed, and a total of 542 ml of ACD-A was used. The reduction in TLC was 5200/µL (5%) after the first procedure and 18,100/µL (19%) after the second procedure []. Patient experienced mild symptoms of citrate toxicity during the first procedure, which was managed effectively with calcium infusion and fall in PLT count by 28,000/µL from baseline levels (41% reduction) was noted after the first procedure for, which patient was transfused with 1 unit of POCS. After the second procedure, patient was started on hydroxyurea and antitumor lysis therapy and was transfused with 1 unit of POCS. No induction chemotherapy given. The patient was discharged (day 18) on dasatinib and advised for further follow-up on an outpatient basis. On follow-up (3 months), the patient was asymptomatic and doing well. Subsequently, the patient was lost to follow-up.


A 69-year-old male, known diabetic, hypertensive, chronic kidney disease with anemia of chronic disorder, was admitted to our center with a history of irrelevant talks, distension of abdomen, and with high TLC (87,100/µL). On examination, hepatosplenomegaly was found. The patient was diagnosed as a case of myelodysplastic syndrome with myelofibrosis (Janus kinase-2 positive). On day 2, the patient developed difficulty in breathing for which oxygen support was given. Leukapheresis was planned to provide symptomatic relief. One blood volume (3 L) was processed, and 281 ml of ACD-A was used. The reduction in TLC was 32,900/µL (38%) []. A fall in PLT count by 17% from the baseline was noted; however, the patient was not transfused. There were no procedure-related complications. No induction chemotherapy given. The patient was discharged on day 4, on hydroxyurea and prednisolone with advice to follow-up on outpatient basis. One month postprocedure, patient was readmitted with history of passage of blood mixed with stool, fever, and weakness for 2 days and later, the patient succumbed due to internal bleeding and septic complications (day 40 after leukapheresis).


A 27-year-old male complained of weakness and headache for 2 months, conjunctival bleed, gum bleeding, epistaxis, and hematuria for 2 days. On examination, the patient had bilateral swelling of the eyes with severe ecchymotic patches all over the body. His baseline investigations at the time of admission showed Hb – 6 g/dL, TLC – 112,000/µL (neutrophils – 14%, lymphocytes – 8%, monocytes – 5%, and blasts – 52%), PLT – 12,000/µL, lactate dehydrogenase – 1530 U/L. The patient was diagnosed as a case of AML – M4 on the basis of flow cytometry and bone marrow biopsy. The patient was transfused with 6 units of random donor platelets (RDPs) in view of low PLT counts. Therapeutic leukapheresis was planned as a prophylactic procedure (day 0). One and half blood volume (5.3 L) was processed, and a total of 594 ml of ACD-A was used. The reduction in TLC was 94,200/µL (84%) []. The procedure was uneventful. The patient was transfused with 1 unit of PRC and 4 units of RDPs postleukapheresis. With gradual improvement in the general condition of patient and chemotherapy was started on day 6 (cytarabine and daunomycin). Following the first session of chemotherapy, patient developed persistent fever with hematuria. Blood culture revealed Gram-negative bacilli and antibiotics were started as per se nsitivity. On day 30, the patient succumbed due to septic complications.


A 22-year-old female followed since 2004 had symptoms of severe dysautonomia, including frequent syncope, severe headaches, and postural tachycardia. She had severe gastrointestinal symptoms of dysphagia, nausea, abdominal pains, and diarrhea (up to 15 times daily). She was wheelchair bound by her OI. Head up tilt table test (HUTT) before MSC infusion showed tachycardia up to 150 bpm with syncope and hypotension after 4 min of head up tilt. Extensive autoimmune evaluation showed positive antiglutamic acid decarboxylase, antiparietal cell and antifolate receptor antibodies, elevated serum cytokines, and antithyroid peroxidase antibodies. She was initially diagnosed with polyarticular juvenile idiopathic arthritis. She received multiple anti-inflammatory and immunosuppressive agents; however, her symptoms were only partially alleviated and she continued to medically deteriorate. Her maternal aunt had a similar clinical course and died in her early 30s while being treated at the NIH, Bethesda, MD. In September 2014, she received 5 million ASCs/kg by intravenous infusion. At subsequent bimonthly evaluations after ASC therapy, there was dramatic improvement of her multiple symptoms, particularly gastrointestinal complaints, headaches, syncope, and subjectively improved stamina. Her inflammatory biomarkers were repeated 3 months after ASC therapy and showed improvement. After ASC therapy, she completed 30 min of head up position with normal heart rate (HR) and blood pressure (BP) responses and improved sympathetic/parasympathetic tone depicted by fast Fourier mathematical analysis of HR and BP variability ().


A 7-year-old male was diagnosed with systemic juvenile idiopathic arthritis with polyarthritis. Magnetic resonance imaging of his knees and hips showed effusions. Multiple therapies included nonsteroidal anti-inflammatory agents and cytotoxic agents. Symptoms increased and he developed abdominal pain and diarrhea. At 5 years of age, he developed hypotension and tachycardia at upright posture with dizziness. Symptoms prevented attendance at school. His family elected ASC treatment and he received 5 million autologous ASCs/kg in September 2014. He presented to our center 3 months after his ASC therapy. OI symptoms, arthritic pain, and other symptoms improved such that anti-inflammatory and immune modulatory agents were discontinued and he completed 30 min of HUTT test with normal HR and BP responses and normal cerebral perfusion by near-infrared spectroscopy.


The patient was a 57-year-old Japanese male. He was a current smoker (20 cigarettes/day) and had smoked for 40 years. He began to experience coughing but did not seek treatment. Two months later, he consulted a family doctor for his cough; other symptoms, such as hemosputum, appetite loss, and body weight loss, were absent. Chest X-ray showed an abnormal shadow in the left hilum lesion (Fig. ). Chest computed tomography (CT) revealed a solid lung tumor in the left lower lobe. Pathological examination by bronchoscopy revealed squamous cell carcinoma. He was then referred to our hospital to receive surgery.
Contrast-enhanced CT showed that blood flow into the left inferior pulmonary vein could not be visualized; therefore, we assumed that the tumor was invading the inferior pulmonary vein to the LA (Fig. ). Positron emission tomography-CT showed that the lung tumor had very strong uptake, but fortunately, there was no abnormal uptake indicating a distant metastasis (Fig. ).
We considered complete resection, which would be possible under CPB if the tumor was invading the LA wall. After thoracotomy, we confirmed that the tumor had invaded the left upper lobe and left inferior pulmonary vein without pleural dissemination. The patient then underwent left pneumonectomy combined with LA resection under CPB and complete resection was achieved.
Samples of 7.5 mL blood were taken to evaluate CTC counts; one sample was taken from peripheral blood just before the surgery and the other sample was taken from the CPB circuit. The samples of blood were collected in CellSave tubes (Veridex LLC, Raritan, NJ, USA) and were used for CTC tests. CTCs were quantitatively evaluated using the CellSearch system. The CTC count was found to be 0 in both samples.
The postoperative course was uneventful, and there were no complications. The patient was discharged 14 days after the surgery. Pathological examination showed that the tumor had invaded the left upper lobe and left inferior pulmonary vein and hilum lymph node, indicating TNM stage T4N1M0. The patient received 6 courses of adjuvant chemotherapy (cisplatinum and docetaxel). The patient is doing well without tumor recurrence and distant metastases have not been observed for 8 years after the surgery.


A 76-year-old Caucasian man with a family history of liver disease and polycystic liver disease, because of epigastric pain underwent an esophagogastroduodenoscopy showing stomach poorly distensible at the level of the body. A subsequent thoracic, abdominal, and pelvic contrast CT scan showed a rounded lesion, suprafluid-filled, with maximum transverse diameters of 62 mm × 35 mm in the middle mediastinum, at the level of subcarinal area, reported as a probable bronchogenic cyst — although it was not clear whether the lesion was intra- or extrapericardial []. Sequelae of calcific pericarditis were evident [ bottom]. The 3D CT reconstruction as virtual bronchoscopy showed a perfect airway patency, with no evidence of extrinsic compression [].
Given the central position of the lesion within the mediastinum as well as the symptoms of the patient, a spirometry and a fiberoptic bronchoscopy were performed, in order to complete an assessment in view of a possible surgical removal of the cyst. Both exams showed no pathological findings.
Therefore, echocardiography was performed for a complete functional diagnosis of the heart (intra-versus extrapericardial cyst localization) with transthoracic echocardiogram (TTE) and transesophageal approach (TEE), with both 2D and 3D technique using a Philips IE 33 echo equipment (Eindhoven, Best, Netherlands) and a X7-2T probe (Philips, Eindhoven, Best, Netherlands; purchased with a grant from Cassa di Risparmio di Puglia foundation). For a better evaluation of both the perfusion and the kinetics of the flows, contrast echocardiography was performed using ultrasound contrast SonoVue (Bracco Imaging SpA, Milan, Italy), administered in two boluses of 1 cc intravenously followed by 2 cc of saline solution. TEE displayed the presence of a large round cystic mass, 51 mm × 38 mm in diameters [, ]; the mass through 3D evaluation was located contiguous with the esophagus (located posterior to the cystic lesion), the left atrium (to the left of the lesion) and the aortic root/pulmonary trunk (located at the front of the lesion), as well as located intrapericardial. The cystic mass appeared to have a moderately echogenic content (more echogenic than blood and less echogenic compared to the myocardium), well-delineated limits, nonloculated cavity, thin, smooth, noncalcified walls, with no signs of echinococcosis [, ]. Compared to the aortic root, the lesion was in close proximity to the common trunk of the right coronary artery, which did not exert compression on (coronary flow showed normal velocity of 25 cm/s, without acceleration and with normal systo/diastolic ratio).
Moving blood was not observed within the lesion in color Doppler mode, even after reduction of the color scale []; moreover, ultrasound contrast agent arrival inside the cyst was not observed after intravenous infusion of SonoVue contrast agent [].
Due to the paucity of symptoms and to the definite imaging information of this intrapericardial cyst of nonvascular nature, due to pericardial cyst in an extremely unusual location, surgery was not performed. At follow-up of 1 month echocardiogram and 3 month CT scan the cyst appeared unchanged in dimensions.


A 79-year-old male presented to the emergency department with a confusional state characterized by clouded consciousness, disorientation in time and space, difficulty in speech and gait and mouth deviation to the right. He also showed dysarthria, right hemiparesis, hemi-hypoesthesia and Babinski sign, bilateral grasping-sign and a positive Epstein sign. He was a former heavy smoker, hypertensive and diabetic patient with a previous history of ischemic cardiomyopathy and prior vascular and cardiac surgery due to aneurysm of the abdominal aorta and myocardial infarction, respectively. A reduced breath sound on the right hemi-thorax was found at the chest examination while cardiac objectivity was unremarkable.
The electrocardiogram showed sinus rhythm with a heart rate of 65 beats/m,‘ some premature ventricular complex and left atrial enlargement. Chest X-ray revealed two nodular opacities on the right lung, the largest of which of 2.0 cm.
Owing to the neurological status, patient was immediately submitted to a noncontrast-enhanced computed tomography (CT) head scan demonstrating a large, but nonspecific cerebral edema in the right frontal, temporal and parietal lobe and then, referred to the Neurological Department of our institution.
A brain magnetic resonance imaging (MRI), a chest CT scan and a transthoracic echocardiogram (TTE) were quickly scheduled. This last identified a large, round-shaped mass, in the left atrium (LA), mobile during the cardiac cycle suspected to arise from left superior pulmonary vein. However, this approach failed to provide a full characterization of the lesion, comprehensive of size, morphology and spatial relationships with surrounding structures. Therefore, patient was immediately submitted to transesophageal echocardiogram (TEE). Through this examination we were able to:
Confirm that the mass came from the left superior pulmonary vein [], Evaluate its size (linear dimensions = 3.5 × 3.6 cm with a largest planimetric area of about 10 cm2) and morphology (inhomogeneous texture for the presence of anechogenic areas in the context of a hyperechogenic tissue [] and Rule out any hemodynamic consequence into the left cavities by color Doppler flow analysis.
On the 2nd day, after admission, the prearranged brain MRI showed one heterogeneous, hypointense lesion, at the frontal right lobe, with perilesional vasogenic edema and partial compression of right lateral ventricle. Furthermore, an area of altered signal with “finger-like” appearance in the right cerebellar hemisphere, compatible with neoplastic edema was also identified [Figure and ].
Due to the above-mentioned imaging findings from cerebral and cardiac evaluation and in relation to the presence of nodular opacities on chest X-ray, a metastatic lung cancer was suspected. Accordingly, patient underwent chest CT scan showing a solid mass in the left inferior pulmonary lobe, infiltrating the left pulmonary veins and left atrium []. Focal thickening of adjacent pleura was also seen and on parenchymal window, a pulmonary mass with maximum axial diameter of 57 mm was identified. Therefore, a starting diagnosis of lung cancer with brain metastases and intracavitary heart dissemination through the left superior pulmonary vein was made. However, to achieve a definitive diagnosis from histology, patient was scheduled for a biopsy of pulmonary lesions but, unfortunately, he suddenly died before we can conclude the diagnostic procedures.


A 6-year-old male child presented in the emergency with high grade intermittent fever and erythematous rashes all over the face along with loss of appetite and weight for two weeks. Before being admitted in our hospital, he had received oral drugs prescribed on the line of lower respiratory tract infection. There was no history of peripheral intravenous cannulation, instrumentation, and blood transfusion. On arrival, he was conscious, febrile, dyspneic, pale, irritable with generalized lymphadenopathy, mild abdominal distension, and pedal edema. His temperature was 104°F, pulse was 140 per min, regular, blood pressure was 100/60 mm Hg and respiratory rate was 30 per min. At the admission, examination of cardiovascular system revealed no significant finding. Lung examination was suggestive of left side collapse consolidation-pneumonic. He was also having 4-cm soft, non-tender hepatomegaly. Neurological examination including fundus evaluation was normal. A working diagnosis of prolonged pyrexia due to left-sided pneumonia with anemia and congestive cardiac failure was made, and the possibilities of typhoid fever and malaria were also entertained. Blood, urine, and sputum cultures were taken. Empirical antibiotic therapy and supportive therapy were started along with diuretics.
Blood investigations revealed parameters suggestive of infective pathology. Peripheral smear showed normocytic hypochronic anemia with neurophilia and moderate thrombocytopenia and mild shift to left pattern. Malarial parasites were absent in smear. Widal test was also found to be negative. Urine microscopy was normal and urine cultures were sterile. ECG was within normal limits and chest X-ray showed left lower lobe pneumonic patch with left sided mild pleural effusion. Spikes of 103°F continued despite of intravenous antibiotics. On 2nd day, repeat thorough examination of cardiovascular system revealed faint systolic murmur with a tumor plop. Blood culture yielded growth of Staphylococcus aureus and antibiotics were changed according to sensitivity. Due to auscultatory tumor plop finding, transthoracic 2D echocardiography was done, and it showed large echodense heterogeneous mass (suspected vegetation) attached to tricuspid valve apparatus [Figures and ], mild to moderate tricuspid regurgitation (TR) with moderate pulmonary artery hypertension (PAP, 45 mm/Hg) []. Echocardiography revealed no predisposing condition in heart or pre-existing abnormalities of the any cardiac valve.
Repeat two blood cultures sent on 2nd hospital day also grew S. aureus. After due consent of the parents, the child was taken up for surgery. Midline sternotomy was done and under cardiopulmonary bypass. The right atrium was opened and the tricuspid valve was examined. Two vegetations were found attached to anterior leaflet measuring 2.5 × 2.0 sq.cm and posterior leaflet measuring 2.0 × 1.5 sq.cm []. Both masses were excised followed by reconstruction of posterior leaflet taking care to preserve the native valve. Modified DeVega annuloplasty done and competency of tricuspid valve was examined. The patient was weaned off from cardio pulmonary bypass gradually. Later, there was complete clinical symptomatic resolution with smooth postoperative recovery. We treated our patient with ceftriaxone/Cefixime for 6 weeks. Postoperative 2D echocardiogram revealed trivial tricuspid regurgitation, no visible mass or vegetation in the right atrium. Histopathological report shows acute fibrinous inflammation with focal suppuration and many bacterial colonies confirming of infective endocarditis (IE) in the tricuspid valve.


A 42-year-old male presented in emergency with history of sudden onset palpitations and chest discomfort. Half an hour before presentation in the emergency department, the patient was doing his normal routine work in kitchen garden where he was bitten by a flock of wasps over his head, back, and arms. He developed sudden pain and redness at the site of wasp bites. Thereby, he applied some oil as a home remedial measure to the local site. After about 15 min of the wasp bite, he experienced palpitations and chest discomfort which was sudden in onset and but persistent. He described them as fast and regular thumping in the chest that he had never experienced before. The episode was not associated with loss of consciousness, sweating, or chest pain. Within half an hour of the episode, he presented to the emergency department of our hospital. He also had one episode of vomiting while coming to hospital. He had no history of ischemic heart disease, hypertension, diabetes, and any other autoimmune disease. The patient was not taking any herbal or allopathic medications. On examination, patient was conscious, well oriented to time, place, and person. His pulse was 180/min regular, blood pressure of 164/86 mmHg, respiratory rate of 16/min, and oxygen saturation of 98% at room air. He was anxious and restless. His cardiovascular examination was normal except for tachycardia. His electrocardiography was done which showed wide QRS tachycardia with loss of P waves fitting into sustained VT of right bundle branch block type according to the Brugada criteria for VT (as shown in ). The patient was given a slow intravenous bolus of injection amiodarone 150 mg after which tachycardia improved and rhythm became sinus. The patient was put on tablet metoprolol 25 mg twice a day. The patient was also given injection chlorpheniramine and dexamethasone followed by tablet cetirizine 10 mg in once a day. Patient was kept for observation for next 48 h during which his vitals gradually improved. Transthoracic echo was normal with no regional wall motion abnormalities and normal ejection fraction. Serial electrocardiograms were normal. Further investigations such as electrophysiological studies, cardiac magnetic resonance imaging (MRI) were planned, but the patient refused for the same. The patient was discharged in satisfactory condition.