Cauda equina neuroendocrine tumor: a report of three cases and review of the literature with focus on differential diagnosis and postoperative management.

INTRODUCTION: Cauda equina neuroendocrine tumors (CENETs), previously described as cauda equina paragangliomas (PGLs) are rare and well-vascularized benign entities which can be often misdiagnosed with other intradural tumors more common in this anatomical site, such as ependymomas and neurinomas. We describe three cases of CENETs observed at our institution with particular focus on differential diagnosis and postoperative management. Since the lack of guidelines, we performed a literature review to identify factors that can predict recurrence and influence postoperative decision making. CASE REPORT AND LITERATURE REVIEW: We report on three patients, two of them presenting with a clinical history of lower back pain and sciatica. In all cases magnetic resonance imaging (MRI) of the lumbosacral spine with and without Gd-DTPA revealed an intradural lesion with strong contrast enhancement, first described as atypical ependymoma or schwannoma. A complete tumor resection was achieved in all cases, the histopathological diagnosis classified the tumors as CENETs. In our literature review, a total of 688 articles were screened and 162 patients were included. Patients demographic data, clinical symptoms, resection and recurrence were recorded. DISCUSSION: Differential diagnosis between CENETs and other more common tumors affecting cauda equina region, such as ependymomas or schwannomas (neurinomas), is still very challenging. Due to the lack of specific clinical or radiological characteristics, a correct preoperative diagnosis is almost impossible. With this paper we want to point out that CENETs must be considered in the differential diagnosis, most of all in case of entities with atypical radiological features. According to the literature, tumor recurrence after gross total resection is unlikely, while a long-term follow-up is recommended in case of subtotal resection or local aggressive behavior.

[Update on diagnostics and microsurgical treatment of vestibular schwannoma]. / Vestibularisschwannome ­ ein Update zu Krankheitsbild und mikrochirurgischer Behandlung.

Vestibular schwannomas are primary benign tumors of the cerebellopontine angle originating either from the superior or the inferior vestibular nerve. Hearing deterioration is the leading symptom, which is why the widespread name for this tumor is acoustic neuroma. Due to the widespread availability of magnetic resonance imaging (MRI), the diagnosis of vestibular schwannoma is frequently made in an early stage of the disease. In these cases a wait and scan policy is recommended. If the tumor grows, the therapeutic options are stereotactic radiotherapy or microsurgical tumor operation. Young patient age, functional hearing ability, persistent dizziness, cystic tumor consistence and large space-occupying tumor size are in favor of surgery via the retrosigmoid, transmeatal approach. In experienced hands excellent results in terms of functional preservation of the facial nerve and the cochlear nerve and radical tumor resection can be obtained.

Pelvic exenteration as ultimate ratio for gynecologic cancers: single-center analyses of 37 cases.

BACKGROUND: Pelvic exenterations are a last resort procedure for advanced gynecologic malignancies with elevated risks in terms of patients' morbidity. METHODS: This single-center analysis reports surgical details, outcome and survival of all patients treated with exenteration for non-ovarian gynecologic malignancies at our university hospital during a 13-year time period. We collected data regarding patients and tumor characteristics, surgical procedures, peri- and postoperative management, transfusions, complications, and analyzed the impact on survival outcomes. RESULTS: We identified 37 patients between 2005 and 2013 with primary or relapsed cervical cancer (59.5%), vulvar cancer (24.3%) or endometrial cancer (16.2%). Median age was 60 years and most patients (73%) had squamous cell carcinomas. Median progression-free survival was 26.2 months and median overall survival was 49.9 months. The 5-year survival rates were 34.4% for progression-free survival and 46.4% for overall survival. There were no significant differences in progression-free survival and overall survival with regard to disease entity. Patients with tumor at the resection margins (R1) had a nearly significantly worse progression-free survival (median: 28.5 vs. 7.3 months, HR 2.59, 95% CI 0.98-6.88, p = 0.056) and a significantly worse overall survival (median: not reached vs. 10.9 months, HR 4.04, 95% CI 1.40-11.64, p = 0.010) compared to patients with complete tumor resection (R0). In addition, patients without lymphovascular space invasion had a significantly better progression-free survival (p = 0.017) and overall survival (p = 0.034) then patients with lymphovascular space invasion. We observed complications in 14 patients (37.8%), 10 of those were classified as Clavien-Dindo 3 or 4. There was a trend to worse progression-free survival in patients that suffered complications (p = 0.052). Median total amount of transfused blood products was 4 (range 0-20). CONCLUSION: Pelvic exenteration is a procedure that provides substantial progression-free survival and overall survival improvement and-in selected patients-can even achieve cure in otherwise hopeless clinical situations. Patients need to be offered earnest counseling for sufficient informed consent with realistic expectations what to expect.

Posterior fossa meningioma with invasion of the internal acoustic canal.

BACKGROUND: To evaluate the significance for outcome of meningioma invasion into the internal auditory canal (IAC) in posterior fossa meningiomas. METHODS: From April 2005 to September 2015, 174 posterior fossa meningiomas have been surgically treated in our Institution. Careful analysis of preoperative MRI depicted in 63 cases (36%) meningioma invasion into the IAC. A retrospective analysis was done of clinical and radiological presentation, surgical findings, outcome, and relevant prognostic factors in order to stratify the risk of complication and evaluate the surgical outcome. RESULTS: Gross total resection was achieved in 67% of patients. There was no mortality. CSF leak occurred in 5%. Postoperative moderately severe (HB 4) and severe dysfunction (HB 5) of the facial nerve was observed in 5% of patients. In 17 patients (27%), IAC was opened. Deterioration of facial function occurred in 24% of patients, hearing loss in 12%, and CSF leak in 6%. In 46 patients (73%), IAC was not opened. Deterioration of facial function occurred in 43% of patients, hearing loss in 13%, and CSF leak in 4%. Opening the IAC, a GTR was achieved in 82% while, without opening, in 61% of patients. CONCLUSIONS: Meningiomas of the posterior fossa may in one-third of the cases invade the IAC. Opening of the IAC in these cases was a crucial step for increasing the GTR. Despite the minimal increased risk of transient CSF leak, IAC opening was not associated with an increased risk of facial palsy or hearing loss in comparison to non-opening the IAC.

Foramen magnum meningioma: The midline suboccipital subtonsillar approach.

OBJECTIVES: Foramen magnum meningiomas (FMMs) represent a technical challenge even for experienced neurosurgeons, because they grow in close contact with osteoarticular, nervous, and vascular structures that cannot be sacrificed or retracted during surgery. Our goal is to present our experience with 24 cases of surgically resected foramen magnum meningiomas used the midline suboccipital subtonsillar approach and discussed the present risks associated with the treatment of this condition. PATIENTS AND METHODS: We retrospectively reviewed all patients who underwent surgery treatment for foramen magnum meningiomas operated on between August 2005 and July 2013. A total of 24 cases were included. Data regarding age, sex, symptoms and sign types, locations, surgical aspects, postoperative new deficits, and follow-up are presented. RESULTS: There were 18 female and 6 male patients (mean age: 52 years). The symptom among most patients (14 patients) was cervico-occipital pain, dysphagia and gait unsteadiness in five, and paresthesia of the upper limbs in four. Total removal of the tumor was achieved in 20 patients, subtotal in two, and partial resection in four patients. Two patients had permanent deficits. Follow-up was 45.6 months (range, 6 months to 8 years), there was no recurrence among tumors totally removed but 1 patient of regrowth among the cases with subtotal removal. CONCLUSIONS: Our experience confirmed that the midline suboccipital subtonsillar approach was accurate in safely removing anterior, anterolateral, and posterior FMMs. There was no significant postoperative complication in the remainder of the patientes, and their conditions improved after surgery.

Do T1a breast cancers profit from adjuvant systemic therapy? A multicenter retrospective cohort study of 325 T1a-patients.

UNLABELLED: Small tumor size (≤5 mm, T1a) carries an excellent prognosis. Controversy exists over the extent of the variety of treatment approaches. We therefore explored the effect of adjuvant systemic therapy (AST) on recurrence free survival (RFS) and overall survival (OAS) for the group of T1a-tumors. METHODS: The multicenter study population included 9625 early breast cancer patients, diagnosed between 1992 and 2008. 5196 patients were T1 (54.0 %) and 325 of these patients (3.4 %) were T1a. RESULTS: Compared to patients with AST RFS and OAS were significantly worse for patients who did not receive AST (RFS: p = 0.001; OAS: p = 0.021). Even N0-T1a-patients (n = 279) significantly profited from AST (RFS: p = 0.001; OAS: p = 0.006). Patients with at least one poor prognostic factor (HR-, HER2+, N1 or G3) without AST also showed a significantly worse outcome (RFS: p = 0.026; OAS: p = 0.024) compared to pT1a-patients with AST. Consensus guidelines state that the prognosis of patients with T1a that are N0 is uncertain even if HER2 is amplified or overexpressed. In our study nodal-negative (N0) T1a-patients (n = 279) without AST showed a significantly worse RFS (p = 0.001), and a significantly worse OAS (p = 0.006) compared to those patients with AST. In multivariate analysis even after adjusting by age, grading, hormonal receptor status, HER2/neu-status and nodal status T1a-patients without AST were associated with a significantly worse RFS resp. OAS compared to patient with AST (RFS: p = 0.002; OAS: p = 0.007). CONCLUSIONS: There is an association between AST and improved RFS or OAS for breast cancer patients with T1a tumors.

Therapeutic potential of larval excretory/secretory proteins of the pig whipworm Trichuris suis in allergic disease.

BACKGROUND: Gastrointestinal nematodes are currently being evaluated as a novel therapeutic in the treatment of chronic human inflammatory disorders, due to their unique ability to induce immunoregulatory pathways in their hosts. In particular, administration of ova from the pig whipworm Trichuris suis (T. suis; TSO) has been proposed for the treatment of allergic, inflammatory and autoimmune disorders. Despite these advances, the biological pathways through which TSO therapy modulates the host immune system in the context of human disease remain undefined. METHODS: We characterized the dominant proteins present in the excretory/secretory (E/S) products of first-stage (L1) T. suis larvae (Ts E/S) using LC-MS/MS analysis and examined the immunosuppressive properties of whole larval Ts E/S in vitro and in a murine model of allergic airway disease. RESULTS: Administration of larval Ts E/S proteins in vivo during the allergen sensitization phase was sufficient to suppress airway hyperreactivity, bronchiolar inflammatory infiltrate and allergen-specific IgE production. Three proteins in larval Ts E/S were unambiguously identified. The immunomodulatory function of larval Ts E/S was found to be partially dependent on the immunoregulatory cytokine IL-10. CONCLUSIONS: Taken together, these data demonstrate that the released proteins of larval T. suis have significant immunomodulatory capacities and efficiently dampen allergic airway hyperreactivity. Thus, the therapeutic potential of defined larval E/S proteins should be exploited for the treatment of human allergic disorders.

Maximizing the extent of resection and survival benefit of patients in glioblastoma surgery: high-field iMRI versus conventional and 5-ALA-assisted surgery.

AIMS: A safe total resection followed by adjuvant chemoradiotherapy should be the primary goal in the treatment of glioblastomas (GBMs) to enable patients the longest survival possible. 5-aminolevulinic acid (5-ALA)- and intraoperative MRI (iMRI)-assisted surgery, have been shown in prospective randomized trials to significantly improve the extent of resection (EOR) and subsequently survival of patients with GBMs. No direct comparison of surgical results between both techniques has been published to date. We analyzed the additional value of iMRI in glioblastoma surgery compared to conventional surgery with and without 5-ALA. METHODS: Residual tumor volumes, clinical parameters and 6-month progression-free survival (6M-PFS) rates after GBM resection were analyzed retrospectively for 117 patients after conventional, 5-ALA and iMRI-assisted surgery. RESULTS: Mean residual tumor volume (range) after iMRI-assisted surgery [0.5 (0.0-4.7) cm(3)] was significantly smaller compared to the residual tumor volume after 5-ALA-guided surgery [1.9 (0.0-13.2) cm(3); p = .022], which again was significantly smaller than in conventional white-light surgery [4.7 (0.0-30.6) cm(3); p = .007]. Total resections were significantly more common in iMRI- (74%) than in 5-ALA-assisted (46%, p = .05) or white-light surgery (13%, p = .03). Improvement of the EOR by using iMRI was safely achievable as peri- and postoperative morbidities were comparable between cohorts. Total resections increased 6M-PFS from 32% to 45%. CONCLUSIONS: Analysis of residual tumor volumes, total resections and neurological outcomes demonstrate that iMRI may be significantly superior to 5-ALA and white-light surgery for glioblastomas at comparable peri- and postoperative morbidities. Longer 6M-PFS was observed in patients with total resections.

Comparing the outcome between multicentric and multifocal breast cancer: what is the impact on survival, and is there a role for guideline-adherent adjuvant therapy? A retrospective multicenter cohort study of 8,935 patients.

Multifocal (MF) and multicentric (MC) breast cancers have been comprehensively studied, and their outcomes have been compared with unifocal (UF) tumors. We attempted to answer the following questions: (1) Does MF/MC presentation influence the outcome concerning BC mortality?, (2) Is there an impact of guideline-adherent adjuvant treatment in these BC subtypes?, and (3)What is the influence of guideline violations concerning surgery (breast-conserving surgery versus mastectomy) on the survival of MF/MC BC patients? Between 1992 and 2008, we retrospectively analyzed 8,935 breast cancer patients from 17 participating breast cancer centers within the BRENDA study group. Of 8,935 breast cancer patients, 7,073 (79.2 %) had UF tumors, 1,398 (15.6 %) had MF tumors, and 464 (5.2 %) had MC tumors. RFS was significantly worse for MF/MC BC patients compared to patients with UF tumors (MF p = 0.007; MC p = 0.019). OAS was significantly worse for MC patients but not for MF patients compared to patients with UF tumors (MF p = 0.321; MC p = 0.001). Guideline adherence was significantly lower in patients with MF (n = 580; 41.5 %) and MC (n = 204; 44.0 %) compared to patients with UF (n = 3,871; 54.7 %) (p < 0.001) tumors. Guideline violations were associated with a highly significant deterioration in survival throughout all subgroups except for MC, with respect to RFS and OAS. For 100 %-guideline-adherent patients, we could not find any significant differences in RFS and OAS after adjusting by nodal status, grade, and tumor size. Furthermore, we could not find any significant differences in RFS and OAS in patients with MF or MC stratified by breast-conserving therapy (BCT lumpectomy and radiation therapy) and mastectomy. There is a strong association between improved RFS and OAS in patients with MF/MZ BC. There are no significant differences in RFS and OAS for patients with breast-conserving therapy or mastectomy.

[Modern surgery of meningiomas affecting anterior visual pathways]. / Moderne Meningeomchirurgie im Bereich der vorderen Sehbahn.

Meningiomas are the most common form of primary intracranial tumors. If the anterior visual pathways are affected clinical visual compromise, visual field defects, oculomotor nerve disturbances or propotosis are predominant. Meningiomas of the anterior visual pathway remain therapeutically challenging due to the direct anatomical relationship to the circulus arteriosus cerebri, the cavernous sinus and cranial nerves. The therapy of choice is microsurgical resection. In many cases a curative approach can be achieved with modern surgical techniques and simultaneously maintaining patient quality of life. Problematic are cases in which resection would be associated with the risk of clinical impairment and in these cases radiotherapy is an important therapeutic option. In cases involving complex invasiveness an interdisciplinary treatment to control local clinical symptoms is favored.

Does Non-Placement of a Drain in Breast Surgery Increase the Rate of Complications and Revisions?

Purpose: Although surgical therapy for breast cancer has become less radical, intrasurgical placement of drains and the use of compression bandages is still standard practice. However, evidence for the clinical benefit of wound drains is controversial, and use of drains is associated with increased pain and longer hospital stays. This raises the question whether, given the latest surgical techniques, wound drainage is still medically necessary. Material and Method: A retrospective analysis was done of patients with breast cancer treated surgically between January 2009 and April 2012 in the Breast Centre Hohenlohe (n = 573). Complication rates and revision following surgery with and without placement of wound drains were compared for patients who had breast-conserving surgery (n = 425) and patients who underwent mastectomy (n = 148). Results: The baseline characteristics (age, number of resected lymph nodes, numbers of patients who had sentinel lymph node resection, tumour characteristics, receptor status and affected side) were comparable for the investigated patient groups. The overall rate of complications was 4 %. There was no significant difference with regard to complication rates after surgery with and without placement of wound drains between the group of patients with breast-conserving surgery and the group of patients with mastectomy (p = 0.68 and p = 0.54, respectively). Conclusion: Our data indicate that non-placement of a wound drain does not influence complication or revision rates after breast-conserving surgery or mastectomy.

T2 and DWI in pilocytic and pilomyxoid astrocytoma with pathologic correlation.

OBJECTIVE: To quantify and compare T2 signal and apparent diffusion coefficient (ADC) in pilocytic and pilomyxoid astrocytoma (PA and PMA) and correlate results with myxoid content. METHODS: Echo-planar diffusion weighted images (DWI) and standard magnetic resonance imaging (MRI) findings were reviewed retrospectively in patients with PA (n=34) and PMA (n=8). Regions of interest (ROIs) were drawn on ADC maps within tumor parts with lowest ADC values. Apparent diffusion coefficient values in tumor were normalized to those in cerebrospinal fluid (ADC/CSF). The ratio of T2 signal intensity in solid tumor parts to CSF (T2/CSF) was registered. Myxoid matrix was histologically quantified retrospectively in 8 PMAs and 17 PAs and correlated with imaging findings. RESULTS: Mean ADC/CSF for PA and PMA was 0.53±0.10 and 0.69±0.10 (p<0.01). Mean T2/CSF for PA and PMA was 0.78±0.19 and 0.93±0.09 (p<0.01). Mean proportion of myxoid tumor matrix in PA was 50% (range, 10-100%) and 93% (range, 90-100%) in PMA (p=0.004). Eight patients (32%; all PA) had less than 50% myxoid content and 17 (68%; 8 PA; 9 PMA) had more. There was positive correlation of ADC/CSF, T2/CSF and ADC (r2=0.61, 0.65 and 0.60 respectively) and significant difference between the groups with more and less than 50% myxoid content (p=0.01 for ADC/CSF and T2/CSF and p=0.02 for ADC). CONCLUSIONS: General imaging features of PA and PMA are non-specific, ADC values and T2 signal intensity are generally higher in the latter, reflecting the proportion of myxoid matrix in these tumors.

Pituicytoma in a patient with Cushing's disease: case report and review of the literature.

Pituicytoma is an exceptionally rare low-grade glioma (WHO grade I) of the neurohypophysis and infundibulum. We are reporting the case of a 48-year-old man who presented with severe Cushing's syndrome. Endocrinological evaluation unequivocally confirmed pituitary-dependent Cushing's syndrome (=Cushing's disease). Cranial MR-imaging displayed a conspicuous area in the dorsal and basal pituitary gland and a minimal bulging of the pituitary gland paramedian of the pituitary stalk on the right side. Transsphenoidal inspection revealed a small tumor in the basal and dorsal pituitary gland. Surprisingly, the definite postoperative histopathological diagnosis of the removed tumor was pituicytoma and not pituitary adenoma. Hence, the microadenoma responsible for Cushing's disease was not yet removed and persistent hypercortisolism necessitated transsphenoidal re-operation. During re-operation, hemihypophysectomy was performed on the right side. The non-tumorous specimen of the adeno-hypophysis showed signs of Crooke's hyalinization consistent with Cushing's disease. Undetectable postoperative ACTH- and cortisol levels provided clear evidence that the underlying ACTH-source was successfully removed during re-operation. Coincidence of pituicytoma and pituitary-dependent Cushing's disease has not previously been reported.

Venous air embolism and intracardiac thrombus after pressurized fibrin glue during liver surgery.

After segmental liver resection, a fibrin glue aerosol was used to stop diffuse bleeding from the liver resection site. Immediately after pressurized administration, severe hypotension and bradycardia occurred, requiring cardiopulmonary resuscitation and inotropic support. Transoesophageal echocardiography demonstrated air in both ventricles deriving from the inferior vena cava; contractility of both ventricles was markedly reduced. In addition, a 3 cm floating thrombus was detected in the right ventricle. This case demonstrates that sprayed fibrin glue can cause life-threatening air embolism and intracardiac thrombus formation in liver surgery.

Use of STAT1 inhibitors in the treatment of brain I/R injury and neurodegenerative diseases.

In the etiology of brain injury associated to ischemia/reperfusion (I/R) and neurodegenerative diseases, a critical involvement of excessive activation of signal transducer and activator of transcription 1 (STAT1) and successive induction of iNOS expression has widely been evidenced. Any compound capable to down-regulate STAT1 activation seems to represent a new, promising anti-inflammatory drug. Among plant compounds, only a few have shown to possess anti-STAT1 activity. Among them, epigallocatechin-3-gallate (EGCG), the main polyphenol present in green tea leaves, efficiently protects heart from I/R injury and this action is strictly correlated to its anti-STAT1 property. Hyperforin, the non-polyphenolic compound present in St. John's wort, attenuates β-cell death induced by interferon-γ (IFN-γ) by strongly down-regulating STAT1 activation. STAT1, therefore, seems to represent a new molecular target of the protective treatment also against brain injury associated to a number of brain pathologies. Either understanding the molecular mechanism of anti-STAT1 action of these compounds or identification of other anti-STAT1 compounds are urged.

Balancing the shortcomings of microscope and endoscope: endoscope-assisted technique in microsurgical removal of recurrent epidermoid cysts in the posterior fossa.

BACKGROUND: We report about endoscope-assisted surgery of epidermoid cysts in the posterior fossa focusing on the application of neuro-endoscopy and the clinical outcome in cases of recurrent epidermoid cysts. MATERIAL AND METHODS: 25 consecutively operated patients with an epidermoid cyst in the posterior fossa were retrospectively analysed. Surgeries were performed both with an operating microscope (OPMI Pentero or NC 4, Zeiss Company, Oberkochen, Germany) and endoscopic equipment (4 mm rigid endoscopes with 30° and 70° optics; Karl Storz Company, Tuttlingen, Germany) under continuous intraoperative monitoring. Surgical reports and DVD-recordings were evaluated for identification of adhesion areas and surgical details. RESULTS: 7 (28%) of the 25 patients were recurrences of previously operated epidermoid cysts. Mean time to recurrence was 17 years (8-22 years). In 5 cases the endoscope was used as an adjunctive tool for inspection/endoscope-assisted removal of remnants. The effective time of use of the endoscope was limited to the end stage of the procedure, but was very effective. CONCLUSION: In a modern operative setting and with the necessary surgical experience recurrent epidermoid cysts may be removed with excellent clinical results. The combined use of microscope and endoscope offers relevant advantages in demanding anatomic situations.