The impact of cerebral metastases growth pattern on neurosurgical treatment

The surgical resection of cerebral metastases is one key element in a multimodal therapy of brain oligometastatic patients. Standard surgery alone is often not sufficient to achieve local control. Various reasons have been discussed including microscopic and macroscopic tumor rests after surgery and different growth patterns of cerebral metastases: In this review, we assessed the surgical standard technique and then analyzed the growth pattern of cerebral metastases and discussed its oncologic impact and new strategies in the surgical management of cerebral metastases. A major percentage of cerebral metastases are not sharply delimitated but show an irregular tumor-brain interface or even an infiltrative growth pattern. Different patterns of adjacent brain invasions have been described and may correlate with the prognosis of patients with cerebral metastasis. Even metastases of the same histological subtype and the same origin show a heterogeneous brain invasion pattern. Future therapeutic strategies might have to take this heterogeneity into account. An infiltrative growth pattern of cerebral metastases might be one reason for their extraordinary high local recurrence rate and might have an influence on the individual overall survival. An intraoperative detection of residual tumor and development of more radical surgical techniques is therefore an important neurooncological challenge and might result in better tumor control. Supramarginal resection of cerebral metastases is a promising approach.     

Predictors for a further local in-brain progression after re-craniotomy of locally recurrent cerebral metastases

Treatment of recurrent cerebral metastases is an emerging challenge due to the high local failure rate after surgery or radiosurgery and the improved prognosis of patients with malignancies. A total of 36 patients with 37 metastases who underwent surgery for a local in-brain progression of a cerebral metastasis after previous metastasectomy were retrospectively analyzed. Degree of surgical resection on an early postoperative MRI within 72 h after surgery was correlated with the local in-brain progression rate and overall survival. Complete surgical resection of locally recurrent cerebral metastases as confirmed by early postoperative MRI could only be achieved in 37.8%. Detection of residual tumor tissue on an early MRI following recurrent metastasis surgery correlated with further local in-brain progression when defining a significance level of p?=?0.05 but not after ?idák or Bonferroni significance level correction for multiple testing: However, definite local tumor control could finally be achieved in 91.9% after adjuvant therapy. Overall survival after recurrent metastasectomy was significantly higher as predicted by diagnosis-specific graded prognostic assessment (12.9?±?2.3 vs. 8.4?±?0.7 months; p?<?0.0001). However, our series involved a limited number of heterogeneous patients. A larger, prospective, and controlled study is required. Considering the adequate local tumor control achieved in the vast majority of patients, surgery of recurrent metastases may represent one option in a multi-modal treatment approach of patients suffering from locally recurrent cerebral metastases.     

5-ALA fluorescence behavior of cerebral infectious and inflammatory disease

Neurosurgical Review -     

Nuclear translocation of β‐catenin and decreased expression of epithelial cadherin in human papillomavirus‐positive tonsillar cancer: an early event in human papillomavirus‐related tumour progression?

Stenner M, Yosef B, Huebbers C U, Preuss S F, Dienes H‐P, Speel E‐J M, Odenthal M & Klussmann J P (2011) Histopathology 58 , 1117–1126 Nuclear translocation of β‐catenin and decreased expression of epithelial cadherin in human papillomavirus‐positive tonsillar cancer: an early event in human papillomavirus‐related tumour progression? Aims: High‐risk human papillomaviruses (HPVs) constitute an important risk factor for tonsillar cancer. This study describes changes in cell adhesion molecules during metastasis of HPV‐related and HPV‐unrelated tonsillar carcinomas. Methods and results: We examined 48 primary tonsillar carcinoma samples (25 HPV‐16 DNA‐positive, 23 HPV‐16 DNA‐negative) and their respective lymph node metastases for their HPV status and for the expression of p16, epithelial cadherin (E‐cadherin), β‐catenin, and vimentin. A positive HPV‐specific polymerase chain reaction finding correlated significantly with p16 overexpression in both primary tumours and their metastases (P < 0.0001 for both). In HPV‐unrelated carcinomas, the expression of E‐cadherin was significantly lower in metastases than in primary tumours (P < 0.001). In contrast, the expression of nuclear β‐catenin was significantly higher in metastases than in primary tumours (P = 0.016). In HPV‐related carcinomas, nuclear localization of β‐catenin expression was already apparent in primary tumours (P = 0.030). The expression of vimentin significantly correlated with the grading of the primary tumour (P = 0.021). Conclusions: Our data indicate that the down‐regulation of E‐cadherin and the up‐regulation of nuclear β‐catenin expression might be crucial steps during tumour progression of tonsillar carcinomas, being already present in primary tumours in HPV‐driven carcinomas, but becoming apparent in HPV‐unrelated tumours later in the process of metastasis.     

Hepatic granulomas: histological and molecular pathological approach to differential diagnosis–a study of 442 cases

Background/Aims: The incidence of hepatic granulomas is reported in 2–15% of liver biopsies. This study was carried out to evaluate the incidence and aetiology of hepatic granulomas in a German Institute of Pathology with specialization in liver diseases. Methods: A retrospective case review was performed on 12 161 liver biopsies of the Institute of Pathology (University of Cologne) between 1996 and 2004. Aetiology was determined according to histomorphological changes, clinicopathological data and liver tissue polymerase chain reaction (PCR) for detection of diverse putative pathogens in the liver tissue. Results: Four hundred and forty‐two liver biopsies revealed granulomatous lesions (3.63%). Two hundred and fifteen cases (1.77% of all biopsies and 48.64% of granulomatous lesions) were diagnosed as primary biliary cirrhosis. In 37 cases (0.3% of all biopsies and 8.37% of granulomatous lesions), the diagnosis of sarcoidosis was established. A positive PCR result for an infectious pathogen was obtained in 15 samples (3.39%) [Bartonella henselae (n=2), Listeria (n=3), Mycobacterium tuberculosis (n=3), Yersinia pseudotuberculosis (n=1), cytomegalovirus (n=2), Epstein–Barr virus (n=4)]. In six cases, a putative diagnosis was established according to the report of clinical conditions. In 11 cases (2.48%), drugs were the putative causative agent. In 158 cases (36%) a definite diagnosis could not be established. Conclusions: Hepatic granulomas have a broad range of underlying aetiologies. With a combined histological, clinical, serological, and molecular approach, we were able to clarify the cause in 64% of the cases. Owing to the diverse prognosis and therapeutic implications, a detailed interdisciplinary workup of all liver biopsies with granulomatous lesions is mandatory.     

Brugada-like electrocardiographic pattern induced by an episode of anemia

The mechanisms responsible for the undulating pattern of ST-segment elevations in the Brugada syndrome are still a matter of discussion. This report describes a young man with a Brugada-like electrocardiographic pattern. The specific ST-segment elevations were unmasked during an episode of anemia due to a duodenal ulcer.     

Is it a glioblastoma? In dubio pro 5-ALA!

Background  

Differential diagnosis of unclear contrast-enhancing cerebral lesions includes cerebral metastases as well as malignant glioma. In the majority of cases, a definite preoperative diagnosis by neuroradiological assessment alone cannot be made. Since the introduction of 5-ALA-induced fluorescence-guided resection in the treatment of glioblastoma (GBM), the preoperative putative diagnosis of metastasis vs. GBM triggers a specific preoperative preparation of the patients. We analyzed the patient population with known cancer outside the central nervous system who underwent surgery for an assumed cerebral metastasis and for whom the intraoperative diagnosis was corrected to a malignant glioma.