Selection of Patients for Treatment of Brain Arteriovenous Malformations by the Transvenous Approach: Relationship with Venous Anatomy and Risk of Hemorrhagic Complications.

BACKGROUND AND PURPOSE: Intracranial hemorrhage represents a severe complication of brain arteriovenous malformation treatment. The aim of this cohort was to report the rate of hemorrhagic complications after transvenous endovascular embolization and analyze the potential angioarchitectural risk factors as well as clinical outcomes. MATERIALS AND METHODS: During an 11-year period, 57 patients underwent transvenous endovascular embolization. All cases of hemorrhagic complications were identified. We analyzed the following variables: sex, age, hemorrhagic presentation, Spetzler-Martin grade, size of the AVM before the transvenous treatment, number of venous collectors, pattern of drainage, presence of dilated veins, and technical aspects. Univariate and multivariate multiple regression analyses were performed to evaluate the potential risk factors for procedure-related hemorrhagic complications. RESULTS: Hemorrhagic complications (either intraprocedural or periprocedural) unrelated to a perforation due to micronavigation occurred in 8 (14.0%) procedures. Significant (mRS > 2) and persistent neurologic deficits were present in 2 (3.5%) patients at 6-month control. Larger nidi, especially >3 cm (P = .03), and a larger number of venous collectors have shown a statistically significant correlation with hemorrhagic complications. Only the number of venous collectors was identified as an independent predictor of hemorrhagic complications in the multivariate analysis (OR, 8.7; 95% confidence interval, 2.2-58.2) (P = .006). CONCLUSIONS: Larger nidus sizes and an increased number of venous collectors may increase the risk of hemorrhagic complications when implementing transvenous endovascular treatment of AVMs. The technique is effective and promising, especially with small nidi and single venous collectors.

Bromelain's penetration into the blood and sinonasal mucosa in patients with chronic rhinosinusitis.

SUMMARY: The aim of this research is to investigate penetration of Bromelain into sinonasal mucosa in patients with chronic rhinosinusitis (CRS) versus a control group. Bromelain is derived from pineapple (Ananas comosus) and has various pharmacological effects. 40 patients (20 patients and 20 controls) were enrolled in the study. Bromelain 500 mg tablet twice daily was administered for 30 days. We scored bromelain presence in turbinate and ethmoid mucosas and in the serum of both the groups. Bromelain has an excellent distribution from blood to rhinosinusal mucosa. Its diffusion ability may allow the use of bromelain as an anti-inflammatory agent in paranasal sinus pathologies.

Influence of Carotid Siphon Anatomy on Brain Aneurysm Presentation.

BACKGROUND AND PURPOSE: Intracranial aneurysm is a devastating disease of complex etiology that is not fully understood. The purpose of this study was to assess the implications of carotid siphon anatomy for the formation and development of intracranial aneurysms. MATERIALS AND METHODS: Between January 2007 and May 2015, lateral view digital subtraction angiographic images of 692 consecutive patients with intracranial aneurysms treated in our department of interventional neuroradiology were reviewed and had their angles measured. Data on the location, presentation, and size of the lesions were collected and evaluated by multivariate analysis in relation to the measured angles. RESULTS: Of 692 aneurysms, 225 (32.51%) ruptured and 467 (67.49%) unruptured, 218 (31.50%) were in the carotid siphon and 474 (68.50%) were distal to the siphon, and the mean aneurysm size was 7.99 ± 6.95 mm. Multivariate analysis showed an association between angles of >15.40° and rupture (P = .005), postsiphon location (P = .034), and aneurysm size of >1.001 mm (P = .015). Multivariate analysis also showed that every 1-year increase in patient age produced an increase of 1.002 mm in aneurysm size (P = .015). CONCLUSIONS: There was a significant independent direct relation of greater anterior knee angle with intracranial aneurysms located distal to the carotid siphon, larger aneurysms, and greater risk of rupture. These findings may be associated with the hemodynamic interactions of blood flow and the curvature of the carotid siphon.

Middle Cerebral Artery Bifurcation Aneurysms Treated by Extrasaccular Flow Diverters: Midterm Angiographic Evolution and Clinical Outcome.

BACKGROUND AND PURPOSE: Flow diverters have been increasingly used lately in off-label, distal intracranial aneurysm treatments. Our aim was to evaluate the effectiveness of flow diverters in the treatment of middle cerebral artery bifurcation aneurysms and to analyze midterm angiographic patterns of regional flow modifications for safety and clinical outcomes. MATERIALS AND METHODS: Consecutive patients treated from January 2010 to December 2014 by the authors by using endovascular flow-diverting stents for MCA bifurcation aneurysms were evaluated retrospectively with prospectively maintained data. All patients had been followed for at least 12 months after treatment, with at least 2 control angiograms; regional flow-related angiographic modifications were registered by using a new angiographic outcome scale for flow diverters. Data were analyzed with emphasis on procedure-related events, angiographic results, and clinical outcome. RESULTS: Fifty-eight patients were included in the study, with 63 MCA bifurcation aneurysms; 13 of these were large and giant. Pretreatment mRS was 0 for 12 patients (20.7%), 1 for 41 (70.7%), and 2 for 5 patients (8.6%). Six-month control revealed mRS 0-2 for 57 (98.3%) patients and 3 for 1 (1.7%) patient. Procedure-related morbidity and mortality were 8.6% (5/58) and 0%, respectively. From 95% of still circulating immediate postprocedure angiographic outcomes, 68% progressed to aneurysm occlusion at 6 months and 95%, to occlusion at 12 months, with a 0% aneurysm rupture rate. CONCLUSIONS: Flow diverters seem to be an effective treatment alternative for complex MCA bifurcation aneurysms, with reasonable complication rates. Longer angiographic follow-ups are needed to assess the morphologic outcome; immediate subtotal occlusions do not seem to be related to rupture.

Evaluation of Neoadjuvant Radiochemotherapy Response (RCT) in Squamous Esophageal Cancer (ESC) and Implications in Therapeutic Conduct.

The multidisciplinary approach in ESC emerged as a result of efforts to maximize the treatment outcome of this disease.Surgical approach as the only therapeutic option is not always followed by a good distance survival. A concomitant neoadjuvant radiochemotherapy in ESC may result in a favourable outcome for responding patients, reducing the size of the tumor and the degree of lymph node damage increasing resectability and the R0 resection rate, improving prognosis. For non-responding patients or if the disease continues to progress under RCT therapy, the surgical time is delayed, adverse effects of radiochemotherapy are added and postoperative morbidity and mortality are increased. The imaging methods for the assessment of response have only limited value and metabolic response; only FDG-PET manages to come close to pathological response. Determining the response degree is very important for the establishment of the surgical conduct: planned or necessity surgery, or non-surgical palliative therapy.

Giant Esophageal GIST: Diagnostic and Therapeutic Challenge - Case Report.

GIST are rare mesenchymal tumors of the digestive tract (less than 1% of the digestive tract neoplasia). Of these, less than 1% are found in the esophagus. Surgery is the main treatment of GIST and is supported by targeted therapy with tyrosine kinase inhibitors like imatinibmesylate. We present the case of a female patient of 51 years, admitted in our clinic for a bulky tumor in the posterior mediastinum, diagnosed after investigations performed for fatigue for the great efforts. Clinical examination was unspecific. Chest X-ray and thoraco-abdominal CT identified a widening of the mediastinum through a posterior mediastinal tumor mass, determining a deviation to the left of the thoracic esophagus without causing not abledysphagia or respiratory symptoms. It was decided surgery by thoracotomy in V right intercostal space and total excision of the tumor was performed. Histopathology examination confirmed the preoperative suspicion of esophageal GIST. Prognosis is reserved, the risk of relapse is very high given the fact that the tumor was extracted fragmented. Currently the patient is under treatment with imatinib mesylate and entered into clinical and imaging follow-up program, according to clinical guidelines.

Clinical and therapeutic considerations of GIST.

Gastrointestinal stromal tumors (GIST) are rare tumors of the digestive tract, with an incidence of about 1.5 per 100,000/year. Clinical features may vary depending on location, size and aggressiveness. The diagnosis is confirmed by immunohistochemistry tests that identify CD 117 or DOG1 (typical receptors/markers for most GISTs) at the level of biopsy specimen. The treatment of localized GIST is based primarily on the surgery, while for metastatic GIST the targeted therapy with tyrosine kinase inhibitors represents the current standard. The neoadjuvant and adjuvant therapy indications guided and depending on genetic analysis included in the diagnostic and treatment algorithm as well as the strategy for cases surveillance are listed in the journal. All these data obtained from the literature have been integrated in a practical experience of 19 cases of GIST, operated in the clinic in the last 10 years for which we have proposed an adapted diagnostic algorithm.

Prognostic significance of KRAS gene mutations in colorectal cancer--preliminary study.

OBJECTIVE: The prognostic significance of KRAS gene mutations, evaluated by using two methods in patients with colorectal cancer (CRC). MATERIAL AND METHODS: Retrospective study involving 58 patients diagnosed with CRC and treated between 2003 and 2010 in the General and Esophageal Surgery Clinic of "Sf. Maria" Hospital, Bucharest. The macroscopic and microscopic examination of the resected specimens was also processed for genetic analysis in NIRDPBS, where KRAS status was determined by using two methods: PCR-RFLP and pyrosequencing. RESULTS: The clinical and biological parameters of the patients were assessed for 72 months in average. A relapse in 21 patients and a 5-year survival rate of 79.3% was discovered. The genetic analyses of KRAS gene found mutations in 22 cases (45.3%): 17 cases had mutations in codon 12, 5 cases in codon 13. The survival rate analyses of patients with wild KRAS gene compared with the patients carrying the mutation on codon 12 /13 revealed a superposition of the survival curve. The statistical analysis based on the TNM stage revealed different survival curves in stage I and II, shorter survival period in patients with KRAS mutation on codon 13 than in those with wild type gene (stage I--p_value=0.015; stage II--p_value=0.000). CONCLUSIONS: It was not found that KRAS gene status had any prognostic significance. Nevertheless, for stage I and II patients, the mutation found on codon 13 determined a statistic significant shorter survival rate than for those with wild type. The results obtained by using the pyrosequencing method for the determination of KRAS gene status proved that it represented a reliable and reproducible method.

Are HMGB1 protein expression and secretion markers of upper airways inflammatory diseases?

Taking into account the mechanisms at the origin of the airways inflammatory pathologies, our attention has been recently addressed to the study of HMGB1, a protein belonging to the group of alarmins. Alarmins are those molecules which in homeostatic conditions carry out specific metabolic and/or structural functions; furthermore, after a direct trauma or an infection, these molecules are released in the extracellular milieu becoming there activators of the innate immunity and powerful inflammatory factors. In a previous research we found in patients affected with chronic rhinosinusitis with/without nasal polyposis (CRSwNP) an increased expression of this protein in the nucleus of nasal mucosa epithelial cells. HMGB1 was overexpressed also as focal subepithelial infiltration and in the inflammatory cells of patients in comparison with controls. These results suggested a possible pathogenetic role of HMGB1 in CRSwNP. The aim of the present study was to investigate if the expression and localization (nuclear, cytoplasmic and extracellular) of the HMGB1 protein-cytokine is somehow related to the severity and complexity of the histological and clinical picture. We noticed values which have around statistical significance between nuclear HMGB1 and eosinophils infiltrate (p=0.0607) and between nuclear HMGB1 and inflammatory infiltrate (P=0.0524). Even more significant was the correlation between extra-cellular HMGB1 expression and the presence of allergic-hyper reactive conditions such as asthma, allergic rhinitis, NSADs intolerance, antibiotic allergy. HMGB1 was significantly more expressed in the nucleus (p=0.0499) and in the intercellular space (p=0.0380) in allergic patients than in non-allergic subjects and as extra-cellular infiltrate in patients with NSADs intolerance (p=0.0022). These results confirm the role of HMGB1 in the pathogenesis of chronic rhinosinusitis with/without nasal polyposis; besides the higher extra-cellular expression in patients with a more severe clinical and inflammatory picture and the presence of associated co-morbidities suggests to seek for new compounds: these compounds, decreasing the extra-cellular release of this alarmin through a scavenger mechanism, could keep under control the inflammatory process without interfering with the nuclear transcriptional messengers.

Solitary ganglioneuromatosis of the descending colon, presenting as giant retroperitoneal tumour.

Ganglioneuroma (GN) is a benign neoplasia of the autonomous nervous system, colonic GN is uncommon in adults. There are three subgroups: polypoid GN, ganglioneuromatous polyposis and diffuse ganglioneuromatosis. Ganglioneuromatosis is highly-associated to neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia type 2b (MEN2B). A 68-year-old female, with a discrete retarded emission of stools, was admitted for a large tumor in the left flank; CT scan, urography and barium enema demonstrated a large retroperitoneal mass, presumed as sarcoma. Open surgery discovered a 16 10 11 cm solid and encapsulated tumor, attached to the retroperitoneal descending colon, with no macroscopic mucosal involvement; the pathologic diagnosis of the resected specimen (en-bloc tumorectomy with limited colectomy) was intramural colonic ganglio-neuromatosis. Anamnesis, physical examination and complete endoscopic explorations showed no evidence of personal bearing or familial aggregation of genetic syndromes. In adults, association of transmural ganglioneuromatosis to NF1 or MEN2B is not mandatory; presentation often mimics obstructive carcinoma and positive diagnosis is provided by pathological examination of the resected specimen. In this peculiar case, the loose tissue of the retroperitoneal space favoured a slow development of intramural ganglioneuromatosis, presenting as a gigantic retroperitoneal mass with no radiological evidence of its colonic origin.

Molecular factors and criteria for predicting the response to neoadjuvant treatment in patients with esophageal squamous cell carcinoma (ESCC) -- responder/non-responder.

UNLABELLED: Regarding the mortality causes, esophageal squamous cell carcinoma (ESCC) is on the 7th place in the US and the 6th place in the world, with 5 year overall survival rate of 14%, which is still modest in comparison to other digestive neoplasia. Multiples strategies were involved to improve this percentage, associating surgical procedures and chemo- and radio- oncologic therapies. The distant results showed sensitive improvement, after introduction of multimodality neoadjuvant therapies. MATERIAL AND METHOD: Fifty-seven patients diagnosed with ESCC were evaluated between 2006 and 2010, male preponderance (77%), average age of 55. A multimodality therapeutic protocol was used: first - radio-chemotherapy (RCT), second - surgery and/or third - chemo- or radiotherapy. Four weeks post RCT all patients were evaluated to determine the response to neoadjuvant treatment followed by surgery - esophageal resection. Histopathological (HP) and immunohistochemical (IHC) analysis of the pathological specimens were performed in order to identify the molecular predictors with responsive or non responsive character; the studied markers were p53 (Dako 1:50), Ki-67 (Biogenex, 1:20), c-erbB-2 (Dako, 1:250). Based on these results, the working model used to determine the response to neoadjuvant therapy was tumor regression grade (TRG). RESULTS: After HP and IHC examination, the patients were included in two groups: responders and non responders (tumor cells > 10%). Complete neoplasia sterilization was achieved in 5 of the patients. CONCLUSIONS: We are able to state that the identification of potential predictive markers along with HP and IHC results represents a great perspective alternative in the ESCC therapy outcome. The detection of molecular type aggressiveness of the neoplastic process allows therapeutic orientation or guidance to certain therapy sequences or even to specific molecular targeted treatments.

[Gastrointestinal stromal tumor (GIST)--medical rarities?]. / Tumora stromala gastrointestinala (GIST) o raritate medicala?

Although their overall incidence is low, GISTs are distinctive subgroup of gastrointestinal mesenchymal tumors which express CD117 or platelet derived growth factor receptor alpha (PDGFRA). Considered as rare digestive cancers, tumors like schwannomas, neurofibromas, gastrointestinal leiomiomas are now reclassified as GIST based on immunohistochemistry studies. GIST are more frequent in stomach (40-70%), small bowel (20-40%), colon (5-15%), meanwhile locations such as mesentery, omentum, retro peritoneum in less of 5%. 10 GIST patients were surgically managed during 2004-2009. 5 gastric and 5 small bowel GIST. Most with symptomatic disease: palpable tumor, abdominal pain, anemia, fatigue, superior digestive hemorrhage or occlusion. Imagistic diagnosis consisted of: barium swallow, abdominal sonography, CT and PET-CT. Confirmation was made by hystopathological exam and immunohistochemistry. All patients had more or less wide surgical resections. For some patients there was also a specific adjuvant treatment. All patients survived after surgery. The principle of surgery for GIST is RO resection of the tumor. Tumor rupture or R1 resection of the primary tumor has a negative impact on disease free survival. Some patients (great volume tumors, R1 or R2 resection) had adjuvant treatment. Imatinib mesylate and derivates showed a significant improvement of recurrence free survival with one condition: permanent treatment. Surgery remains the mainstay of treatment in patients with localized, resectable GIST. Recurrence rate of 17-21% and 5 years survival rate of 48-70%, even in resectable GIST, impose an adjuvant treatment.

[Cholangiocarcinoma of the distal bile duct--case presentation]. / Adenocarcinom de coledoc distal--prezentare de caz.

Cholangiocarcinoma is a rare disease (0.15-0.16% in the general population). We present the case of a man, 64 years old, who was admitted to our clinic for emergency with intense jaundice, abdominal pain in the supra-umbilical region. Laboratory analysis revealed elevated total bilirubin (23.5 mg/dl), with predominant direct bilirubin and an increased serum level of alkaline phosphatase and GGT, AST, ALT. The abdominal CT shows an tumor infiltrating distal bile duct, with important dilatation of proximal biliary tree and enlarged retro pancreatic lymph node (8 mm). The first therapeutic procedure was an surgical exploration of the abdomen to asses the resectability of the tumor and an internal biliary drainage colecisto-gastrostomy to allow improving of patient's biological and clinical state and a latter radical operation, after remission of jaundice. After a month we performed cephalic duodenopancreatectomy. Pathology result: moderately differentiated adenocarcinoma of intestinal type (G2) pT2NOMO (stage II). The postoperative evolution was favorable encumbered by a small pancreatic fistula healed by conservative method.

[Adenoid cystic carcinoma of the breast--two case reports]. / Carcinom adenoid chistic mamar--prezentare a doua cazuri.

Adenoid cystic carcinoma is a rare type of breast carcinoma with a good prognosis. It represents less than 0,1% of breast carcinomas. We present two cases of adenoid cystic carcinoma diagnosed in the Surgical Department of Coltea Hospital in the last 3 years. The first case is a 66 years old patient with a breast tumor that has clinical and imagistic features compatible with a benign diagnosis. The frozen sections established the diagnosis of adenoid cystic carcinoma, confirmed by histopathologic examination of paraffin embedded tissue and immunohistochemistry. The second case is a 68 years old patient with a breast tumor located in the central quadrant of the left breast, with skin infiltration. Preoperatory fine needle aspiration is sugestive of a papillary tumor, so the cytologic exam cannot establish malignancy. The frozen sections established the diagnosis of ductal invasive carcinoma and histopathologic examination of paraffin embedded tissue and immunohistochemistry established the diagnosis of adenoid cystic carcinoma associated with ductal invasive carcinoma grade I and adenomyoepitelioma. The cytology had a false papillary aspect, in fact there was amorphous material contained in pseudoluminal spaces. In both cases the treatment was surgical resection with tumor excision and free resection margins. In the second case lymphadenectomy was also performed.

[Difficulties in diagnosis and surgical treatment of a giant retroperitoneal lipoma]. / Probleme de diagnostic si de tactica chirurgicaa ridicate de un lipom retroperitoneal gigant.

Primary retroperitoneal tumors are relatively rare and the histological characters vary. We present the case of a retroperitoneal lipoma in a 51-year-old male patient, whose main complain was enlarging of the abdomen in the last 2 months. The CT of the abdomen and pelvis revealed a giant retroperitoneal tumor. The patient suffered a surgical intervention that revealed a giant retroperitoneal tumor, 40/35 cm, weighting 14 Kg. The pathology exam established the diagnosis: retroperitoneal lipoma with areas of necrosis and lipogranulomatosis. The postoperative evolution was simple.

Pheochromocytoma--from endocrinologist to surgeon.

We report the case an asymptomatic patient who underwent left adrenalectomy for a incidentally discovered large, cystic adrenal tumor. The patient presented no hypertension before or during the intervention. The hystopatological exam revealed a pheochromocytoma, with signs suggesting malignancy. One year after the surgery, the patient is still asymptomatic, the metanephrine levels are normal, and the 1231-metaiodobenzylguanidine scintigraphy showed no metastases. The indications and limits of laparoscopic adrenalectomy are presented.

The role of p53, PCNA and Ki-67 as outcome predictors in the treatment of laryngeal cancer.

The aim of our study was to determine the importance of p53, PCNA and Ki-67, evaluated by immunohistochemistry, in the treatment and prediction of the laryngeal carcinoma. Out of a total of 319 patients with laryngeal carcinoma that underwent surgery in our department between 1999 and 2007, we performed a retrospective study on 71 cases who benefited by immunohistochemical guidance before the beginning of the treatment. All these patients have been followed-up two to five years after surgery. The values of p53, PCNA and Ki-67 are strongly correlated with the histological grading, by means of descriptive statistics (confidence level 95%); the mean values of these three markers corresponding to each HP grade. A highly statistical significant positive correlation (r = 0.84, p < 0.001 ) between the values of p53 and PCNA was observed. The values of p53, PCNA and Ki-67 in the patients from this study are strongly correlated with the absence of the loco-regional lymph node metastases, by means of descriptive statistics (confidence level 95%). Ki-67 only is correlated significantly to the presence of lymphatic metastases in the regional lymph nodes (stage N1, N2 or N3 TNM). P53 and PCNA are not correlated significantly with the presence of the metastases in the regional lymph nodes.

MR imaging-based decision in thrombolytic therapy for stroke on awakening: report of 2 cases.

Patients with stroke on awakening are denied the potential benefit of thrombolysis on the grounds that the onset time is unknown. Relying on clinical and MR imaging to indicate the most appropriate treatment could be more rational. We report 2 cases of stroke with unknown onset time. In both cases, anamnesis and MR imaging indicated that we might still be within 6 hours from stroke onset, with salvageable tissue. Arterial recanalization was successfully performed in both cases.