A 2-center review of histopathology of variants of upper urinary tract urothelial carcinoma and their impact on clinical outcomes.

INTRODUCTION: Similar to bladder cancer, about one third of upper tract urothelial carcinoma (UTUC) present variant histology (VH). We aim to evaluate the incidence, clinical characteristics and the impact on outcomes of VH in UTUC. METHODS: We consecutively enrolled 77 patients treated between 2009 and 2022 by radical surgery for UTUC from a secondary and a tertiary referral center. A pathology review of all specimens was performed by 1 independent uropathologist for each center. We compared pure UTUC and UTUC with VH and the accuracy of endoscopic biopsy. Descriptive and comparative analysis was performed to assess the association with clinical characteristics and the Kaplan-Meier estimator to compare outcomes. RESULTS: Median follow-up after surgery was 51 months. VH was present in 21/77 (28%) patients and 4/21 (19%) patients had multiple variants. The most frequent VH was squamous 12/21 (57%), followed by glandular 7/21 (33%) and micropapillary 3/21 variants (14%). Neuroendocrine carcinoma was present in 2 patients. Nested variant was found in 1 patient. Muscle invasive tumor (≥pT2) was present in 30/56 (54%) patients with pure UTUC and in 18/21 (86%) patients with VH (P < 0.05). Presence of carcinoma in situ was seen in 24/56 (43%) patients with pure UTUC and in 16/21 (76%) with VH (P < 0.05). Cumulative 8/56 (14%) with pure UTUC had a nonintravesical recurrence (6 patients with local and 2 distant recurrence) compared to 8/21 (38%) (3 local, 3 nodal, 2 distant) in the subgroup with VH (P < 0.05). Opposite effect was noted for bladder recurrence: 60% for pure UTUC vs. 29% for tumors with VH (P < 0.05). Review of preoperative endoscopic biopsy did not show the presence of VH in any patients. Differences in outcomes did not reach significance: 3yr-OS 63% vs. 42% (P 0.28) and 3yr-CSS 77% vs. 50% (P 0.7). CONCLUSION: Almost a third of UTUC present VH. Presence of VH is related to more aggressive tumor characteristics and associated with unfavorable outcomes. Due to a higher rate of extravesical recurrences in UTUC with VH, Follow-up controls should include cross sectional imaging and cystoscopy.

Biology of BCG response in non-muscle invasive bladder cancer - 2021 IBCN Updates Part III.

Bacillus Calmette-Guerin (BCG) remains the only FDA-approved first-line therapy in patients with high-risk non-muscle invasive bladder cancer. Recurrences, even after adequate BCG therapy, are common and the efficacy of second-line therapies remains modest. Therefore, early identification of patients likely to recur and treatment after recurrence remain critical unmet needs in the clinical care of bladder cancer patients. To address these deficits, a better understanding of the mechanisms of resistance to BCG-therapy is needed. The virtual update of the International Bladder Cancer Network (IBCN) on the biology of response to BCG focused on potential mechanisms and markers of resistance to intravesical BCG therapy. The insights from this meeting will be highlighted and put into context of previously reported mechanisms of resistance to BCG in this review.

First-line surgery in prolactinomas: lessons from a long-term follow-up study in a tertiary referral center.

CONTEXT: Although consensus guidelines recommend dopamine agonists (DAs) as the first-line approach in prolactinomas, some patients may opt instead for upfront surgery, with the goal of minimizing the need for continuation of DAs over the long term. While this approach can be recommended in selected patients with a microprolactinoma, the indication for upfront surgery in macroprolactinomas remains controversial, with limited long-term data in large cohorts. We aimed at elucidating whether first-line surgery is equally safe and effective for patients with micro- or macroprolactinomas not extending beyond the median carotid line (i.e., Knosp grade ≤ 1). METHODOLOGY: Retrospective study of patients with prolactinomas Knosp grade ≤ 1 treated with upfront surgery. The primary endpoint was patients' dependence on DAs at last follow-up. The secondary endpoint was postoperative complications. Independent risk factors for long-term dependence on DAs were analyzed. RESULTS: A microadenoma was noted in 45 patients (52%) and a macroadenoma in 41 (48%), with 17 (20%) harboring a Knosp grade 1 prolactinoma. Median follow-up was 80 months. First-line surgery resulted in long-term remission in 31 patients (72%) with a microprolactinoma and in 18 patients (45%) with a macroprolactinoma (p = 0.02). DA therapy was ultimately required in 11 patients (24%) with microadenomas vs. 20 (49%) with macroadenomas (p = 0.03). As for the latter, DA was required in 13 patients (76%) with Knosp grade 1 macroadenomas vs. 7 patients (29%) with Knosp grade 0 macroadenomas (p = 0.004). There was no mortality, and morbidity was minimal. Knosp grade 1 prolactinomas (OR 7.3, 95% CI 1.4-37.7, p = 0.02) but not adenoma size (i.e., macroprolactinomas) were an independent predictor of long-term dependence on DAs. CONCLUSIONS: First-line surgery in patients with microprolactinomas or macroprolactinomas Knosp grade 0 resulted in a good chance of non-dependency on DA therapy. However, in patients with prolactinomas Knosp grade 1, first-line surgery cannot be recommended, as adjuvant DA therapy after surgery is required in the majority of them over the long term.

[Molecular tumor board-urothelial cancer]. / Molekulares Tumorboard ­ Urothelkarzinom.

BACKGROUND: Molecular tumor boards (MTB) are becoming more common. There are several molecular alterations in urothelial cancer a molecular tumor board can potentially rely on. OBJECTIVES: The aim is to specify molecular alterations and their correlations with different clinical endpoints and to highlight potential questions addressed to a MTB for urothelial cancer. MATERIALS AND METHODS: Descriptive review of the literature based on PubMed. RESULTS: The landscape of molecular alterations in urothelial cancer is heterogeneous. Thus, recent biomarker research has been focusing on biomarker panels and classifiers instead of single biomarkers. Recently, molecular subtypes of urothelial cancer have been identified and correlated with different clinical endpoints. Furthermore, circulating tumor cells and tumor DNA are under investigation as potential biomarkers. In addition to treatment response and prognosis, molecular markers are also needed to improve clinical staging prior to radical cystectomy or for proper patient selection for neoadjuvant chemotherapy. Erdafitinib is the first targeted therapy (fibroblast growth factor receptor [FGFR] alteration) in urothelial cancer that was recently approved (in the USA). CONCLUSIONS: Due to the lack of external validation, none of the identified biomarkers is currently established in clinical routine. In addition, there is no single driver mutation in urothelial cancer that facilitates the development of biomarkers and targeted therapies.

Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer.

Several (pre-) clinical trials are currently investigating the benefit of HER2-targeted therapy in urothelial bladder cancer (UBC). Patients with HER2 amplified UBC could potentially profit from these therapies. However, little is known about histomorphology, HER2 protein expression patterns and occurrence of alterations in the HER2 gene in their tumors. Among 150 metastasizing primary UBC, 13 HER2 amplified tumors were identified. Their histopathological features were compared with 13 matched, non-amplified UBC. HER2 protein expression was determined by immunohistochemistry. The 26 tumors were screened for mutations in exons 19 and 20 of the HER2 gene. UBC with HER2 amplification presented with a broad variety of histological variants (median 2 vs. 1), frequently featured micropapillary tumor components (77 % vs. 8 %) and demonstrated a high amount of tumor associated inflammation. Immunohistochemically, 10 of 13 (77 %) HER2 amplified tumors were strongly HER2 protein positive. Three tumors (23 %) were scored as HER2 negative. One of the HER2 amplified tumors harbored a D769N mutation in exon 19 of the HER2 gene; all other tested tumors were wild type. In conclusion, HER2 amplified UBC feature specific morphological characteristics. They frequently express the HER2 protein diffusely and are, therefore, promising candidates for HER2 targeted therapies. The detection of mutations at the HER2 locus might add new aspects to molecular testing of UBC.

The SRA protein UHRF1 promotes epigenetic crosstalks and is involved in prostate cancer progression.

Epigenetic silencing of tumour suppressor genes is an important mechanism involved in cell transformation and tumour progression. The Set and RING-finger-associated domain-containing protein UHRF1 might be an important link between different epigenetic pathways. Here, we report that UHRF1 is frequently overexpressed in human prostate tumours and has an important role in prostate cancer pathogenesis and progression. Analysis of human prostate cancer samples by microarrays and immunohistochemistry showed increased expression of UHRF1 in about half of the cases. Moreover, UHRF1 expression was associated with reduced overall survival after prostatectomy in patients with organ-confined prostate tumours (P < 0.0001). UHRF1 expression was negatively correlated with several tumour suppressor genes and positively with the histone methyltransferase (HMT) EZH2 both in prostate tumours and cell lines. UHRF1 knockdown reduced proliferation, clonogenic capability and anchorage-independent growth of prostate cancer cells. Depletion of UHRF1 resulted in reactivation of several tumour suppressor genes. Gene reactivation upon UHRF1 depletion was associated with changes in histone H3K9 methylation, acetylation and DNA methylation, and impaired binding of the H3K9 HMT Suv39H1 to the promoter of silenced genes. Co-immunoprecipitation experiments showed direct interaction between UHRF1 and Suv39H1. Our data support the notion that UHRF1, along with Suv39H1 and DNA methyltransferases, contributes to epigenetic gene silencing in prostate tumours. This could represent a parallel and convergent pathway to the H3K27 methylation catalyzed by EZH2 to synergistically promote inactivation of tumour suppressor genes. Deregulated expression of UHRF1 is involved in the prostate cancer pathogenesis and might represent a useful marker to distinguish indolent cancer from those at high risk of lethal progression.

Lhermitte-Duclos disease with atypical vascularization--case report and review of the literature.

OBJECTIVE: A case of Lhermitte-Duclos disease (LDD, dysplastic gangliocytoma) with atypical vascularization is reported. LDD is a rare cerebellar mass lesion which may be associated with Cowden's syndrome and the PTEN germline mutation. CASE MATERIAL: A 61-year-old male presented 15 years before with a transient episode of unspecific gait disturbance. Initial magnetic resonance (MR) imaging revealed a right-sided, diffuse, nonenhancing cerebellar mass lesion. No definitive diagnosis was made at that time, and the symptoms resolved spontaneously. 15 years later, the patient presented with acute onset of vomiting associated with headache and ataxic gait. MR imaging showed a progression of the lesion with occlusive hydrocephalus. The lesion depicted a striated pattern characteristic for LDD with T1-hypointense and T2-hyperintense bands, nonenhancing with contrast. After resection of the mass lesion, the cerebellar and hydrocephalic symptoms improved rapidly. The pathological examination confirmed the diagnosis of dysplastic gangliocytoma (WHO Grade I) with enlarged granular and molecular cell layers, reactive gliosis and dysplastic blood vessels. No other clinical features associated with Cowden's syndrome were present. CONCLUSIONS: This case illustrates that LDD with atypical vascularization is a slow-growing posterior fossa mass lesion which may remain asymptomatic for many years. Timing of surgical treatment and extent of resection in patients with LDD is controversial. The typical features on standard T1-/T2-weighted MR imaging allow a diagnosis without surgery in most cases. The authors believe that the decision to treat in these cases should be based on clinical deterioration.

Contribution of the apparent diffusion coefficient in perilesional edema for the assessment of brain tumors.

OBJECTIVES: Diffusion-weighted MRI is sensitive to molecular motion and has been applied to the diagnosis of stroke. Our intention was to investigate its usefulness in patients with brain tumor and, in particular, in the perilesional edema. METHODS: We performed MRI of the brain, including diffusion-weighted imaging and mapping of the apparent diffusion coefficient (ADC), in 16 patients with brain tumors (glioblastomas, low-grade gliomas and metastases). ADC values were determined by the use of regions of interest positioned in areas of high signal intensities as seen on T2-weighted images and ADC maps. Measurements were taken in the tumor itself, in the area of perilesional edema and in the healthy contralateral brain. RESULTS: ADC mapping showed higher values of peritumoral edema in patients with glioblastoma (1.75 x 10(-3)mm(2)/s) and metastatic lesions (1.61 x 10(-3)mm(2)/s) compared with those who had low-grade glioma (1.40 x10(-3)mm(2)/s). The higher ADC values in the peritumoral zone were associated with lower ADC values in the tumor itself. CONCLUSIONS: The higher ADC values in the more malignant tumors probably reflect vasogenic edema, thereby allowing their differentiation from other lesions.

Morbidity in 201 patients with small sized meningioma treated by microsurgery.

BACKGROUND: The management of patients with small, often asymptomatic meningiomas is controversial and includes observation, microsurgery (MS) and stereotactic radiosurgery (SRS). The purpose of this retrospective study was to analyze the morbidity and the extent of removal after MS for small (< or =3 cm) intracranial meningiomas and compare these results to those of SRS reported in the literature. METHODS: All patients with an intracranial meningioma with a maximum diameter up to 3 cm operated on in our institution over a 10 year period (1992-2002) were included in the study and retrospectively analyzed. Patients were grouped into asymptomatic and symptomatic and according to tumor location as: group I (cranial vault, parasagittal, lateral sphenoid), group II (falx, frontobasal, medial sphenoid, parasellar and tentorial), group III (cavernous sinus, petroclival, petrosal, CPA and foramen magnum). FINDINGS: There were a total of 201 patients, of whom 102 were asymptomatic and 99 were symptomatic. The overall risk of permanent neurological morbidity was 4.9% in asymptomatic and 23.2% in symptomatic patients. The combined risk in asymptomatic and symptomatic patients was 5.4% in group I, 11.5% in group II, and 39.9% in group III lesions. Radical removal was achieved in all patients in group I, in 93.7% of group II, and 80% of group III lesions. There was no disease related mortality. CONCLUSIONS: MS provides excellent efficacy and morbidity results in groups I and II meningiomas, especially in asymptomatic patients and might therefore be considered the first choice of treatment for these patients. The results of MS in group III were worse than those of SRS reported in the literature.

Technical and clinical success of infrarenal endovascular abdominal aortic aneurysm repair: A 10-year single-center experience.

OBJECTIVE: The aim of our retrospective study was to review our single-center experience with aortic abdominal aneurysm (AAA) repair retrospectively. MATERIAL AND METHODS: From 1995 to 2005, 70 consecutive patients affected by AAA were treated by endovascular stent-graft repair. Mean follow-up was 23.9 months. Follow-up investigations were performed at 6 and 12 months and yearly thereafter. Five different stent-graft designs were compared to each other. Primary technical success (PTS), assisted primary technical success (APTS), primary clinical success (PCS) and secondary clinical success (SCS) were evaluated. RESULTS: All over PTS was achieved in 94.3%, APTS in 97.1%, PCS in 61.4%, APCS in 64.3% and SCS in 70%. There were 3 type I endoleaks, 25 type II endoleaks, 4 type III endoleaks, 8 limb problems, 5 conversions to open surgery, 10 aneurysm sac expansions and 14 device migrations. Patients with newer generation devices showed better results than patients with first generation prosthesis. In addition results were better for grafts with suprarenal fixation (versus infrarenal fixation) and grafts with barbs and hooks (versus grafts without barbs and hooks). Patients with bad anatomic preconditions showed a higher complication rate. CONCLUSION: Contrary to first generation products, new stent-graft designs show acceptable technical and clinical results in endovascular AAA aneurysm repair. However, this therapy still should be reserved only for patients with significant comorbities and suitable anatomic conditions.

[Simultaneous defect of visual fields and loss of libido--a coincidence?]. / Gleichzeitiger Gesichtsfelddefekt und Libidoverlust - Zufall?

We present the case of a 60 year old male patient with incidentally detected visual abnormalities. Detailed personal history revealed a hypogonadism that had been present for several years. Further investigations established the diagnosis of an infiltrative macroadenoma. Medical treatment with cabergoline led to a rapid regression of ophthalmologic symptoms and, subsequently, of tumor size. In male subjects symptoms of hypogonadism are often reported only late in the course of the disease, thereby leading to a generally larger tumor size at the point of diagnosis. In contrast to other pituitary tumors that are mainly treated by surgery, medical treatment with dopamine agonists is the principal therapeutic option in prolactinomas.

Treatment outcomes and mortality of 94 patients with acromegaly.

BACKGROUND: Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003. METHOD: The cohort consisted of 94 patients who had been followed for 0.3-31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0 microg/l and a random GH value of <2.5 microg/l. FINDINGS: Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1 cm), 65% with meso-adenomas (> or = 1 cm to <2 cm) and 27% with macro-adenomas (> or = 2 cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin LAR) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2 cm. The standardized mortality ratio was 1.30 (95% CI 0.52-2.67) for patients in remission and 1.38 (95% CI 0.51-3.00) for patients with persistent acromegalic activity. CONCLUSIONS. Most patients with adenomas of <2 cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2 cm and more than 80% of patients with adenomas of > or = 2 cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.

The impact of tumour volume and surgery on the outcome of adults with supratentorial WHO grade II astrocytomas and oligoastrocytomas.

BACKGROUND: The study was performed to elucidate the impact of tumour volume and surgical resection on the long-term outcome of patients with supratentorial, diffuse, World Health Organization (WHO) grade II astrocytomas and oligo-astrocytomas. METHOD: After analysing 79 adult patients consecutively diagnosed between 1991 and 2000, we selected a group of 42 patients treated by surgery without adjuvant therapy. The tumour volume was defined as the whole region of T2-hyperintensity and measured interactively on pre- and postoperative and follow-up Magnetic Resonance Imaging (MRI) using a dedicated imaging software. Volumetric, clinical, and histological data were analysed for correlation with tumour progression (TP), malignant transformation (MT), drop in functional status (DKPS) and overall survival (OS). FINDINGS: Pre- and postoperative tumour volumes, and the involvement of more than one lobe were strongly associated with worse outcome. Preoperative tumour volume was the strongest predictor of OS (p<0.01) and the only predictor of MT (p<0.05). The absolute and relative volumes of tumour removed by surgery were not significantly associated with outcome. CONCLUSIONS. Initial tumour volume, measured as the volume of T2-hyperintensity on MRI, and tumour extension are the strongest predictors of outcome in patients with supratentorial diffuse astrocytic WHO Grade II tumours. The potential benefit of aggressive tumour resection needs to be investigated in a prospective controlled trial.

Additive effect of glial cell line-derived neurotrophic factor and neurotrophin-4/5 on rat fetal nigral explant cultures.

Transplantation of embryonic dopaminergic neurons is an experimental therapy for Parkinson's disease, but limited tissue availability and suboptimal survival of grafted dopaminergic neurons impede more widespread clinical application. Glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-4/5 (NT-4/5) exert neurotrophic effects on dopaminergic neurons via different receptor systems. In this study, we investigated possible additive or synergistic effects of combined GDNF and NT-4/5 treatment on rat embryonic (embryonic day 14) nigral explant cultures grown for 8 days. Contrary to cultures treated with GDNF alone, cultures exposed to NT-4/5 and GDNF+NT-4/5 were significantly larger than controls (1.6- and 2.0-fold, respectively) and contained significantly more protein (1.6-fold). Treatment with GDNF, NT-4/5 and GDNF+NT-4/5 significantly increased dopamine levels in the culture medium by 1.5-, 2.5- and 4.7-fold, respectively, compared to control levels, and the numbers of surviving tyrosine hydroxylase-immunoreactive neurons increased by 1.7-, 2.1-, and 3.4-fold, respectively. Tyrosine hydroxylase enzyme activity was moderately increased in all treatment groups compared to controls. Counts of nigral neurons containing the calcium-binding protein, calbindin-D28k, revealed a marked increase in these cells by combined GDNF and NT-4/5 treatment. Western blots for neuron-specific enolase suggested an enhanced neuronal content in cultures after combination treatment, whereas the expression of glial markers was unaffected. The release of lactate dehydrogenase into the culture medium was significantly reduced for GDNF+NT-4/5-treated cultures only. These results indicate that combined treatment with GDNF and NT4/5 may be beneficial for embryonic nigral donor tissue either prior to, or in conjunction with, intrastriatal transplantation in Parkinson's disease.

Death-associated protein 3 (Dap-3) is overexpressed in invasive glioblastoma cells in vivo and in glioma cell lines with induced motility phenotype in vitro.

PURPOSE: To discover the genetic determinants of glioma invasion in vivo, we compared the mRNA expression profiles of glioblastoma cells residing at the tumor core versus those at the invasive rim of a human tumor resection. EXPERIMENTAL DESIGN: From a single glioblastoma specimen, 20,000 individual cells from each region (core and invasive rim) were collected by laser capture microdissection and analyzed by mRNA differential display. Differential expression of gene candidates was confirmed by laser capture microdissection and quantitative reverse transcription-PCR in additional glioblastoma multiforme specimens, and the role in migration was further evaluated in glioma cell lines in vitro. RESULTS: Reproducible overexpression the death-associated Protein 3 (Dap-3) mRNA (NM 004632, GenBank; also reported as human ionizing resistance conferring protein mRNA, HSU18321, GenBank) by invasive cells was identified. Although the full-length Dap-3 protein has been described as proapoptotic, the NH(2)-terminal fragment can act in a dominant negative way resulting in protection from programmed cell death. In glioma cell lines T98G and G112 with an induced motility phenotype, Dap-3 was up-regulated at the mRNA and protein level as assessed by quantitative reverse transcription-PCR, cDNA microarray, and Western blot analysis. These cells showed an increased resistance to undergo camptothecin-induced apoptosis, which was overcome by effective Dap-3-antisense treatment. Antisense treatment also decreased the migration ability of T98G cells. CONCLUSIONS: Dap-3 is up-regulated in invasive glioblastoma multiforme cells in vivo and in glioma cells with an induced motility phenotype in vitro. When migration is activated, Dap-3 is up-regulated and cells become resistant to apoptosis. These findings suggest that Dap-3 confers apoptosis-resistance when migration behavior is engaged.

Identification and validation of P311 as a glioblastoma invasion gene using laser capture microdissection.

The mRNA expression profiles from glioblastoma cells residing at the tumor core and invasive rim of a human tumor resection were compared. From a single tumor specimen, 20,000 single cells from each region were collected by laser capture microdissection. Differential expression of 50-60 cDNA bands was detected. One of the sequences overexpressed by the invasive cells showed 99% homology to the P311 gene, the protein product of which is reported to localize at focal adhesions. Relative overexpression of P311 by invading glioblastoma cells compared with tumor core was confirmed by quantitative reverse transcription-PCR of six glioblastoma specimens after laser capture microdissection collection of rim and core cells. In vitro studies using antisense oligodeoxynucleotides and integrin activation confirmed the role of P311 in supporting migration of malignant glioma cells. Immunochemistry studies confirmed the presence of the P311 protein in tumor cells, particularly at the invasive edge of human glioblastoma specimens.

Intratumoral arteriovenous shunting in malignant gliomas.

OBJECTIVE: Intratumoral arteriovenous shunting in glioblastomas has been suspected but neither proven nor quantified. METHODS: Using a previously described technique of selective intra-arterial intratumoral injection of 99mTc-labeled microparticles (macroaggregated albumin), we measured the amount of radioactivity, by cerebral and pulmonary scintigraphy, in seven patients with malignant gliomas (six with glioblastomas and one with an anaplastic oligodendroglioma). The pulmonary shunt index was calculated as a percentage from the pulmonary/pulmonary plus cerebral radioactivity ratio. RESULTS: The results revealed a mean pulmonary shunt index of 67% (range, 47-89%), indicating that most of the microparticles injected into the tumor via the arterial route bypassed the tumor and reached the lungs. The measured arteriovenous shunting was greater when the injection was performed in an artery exclusively perfusing the tumor. CONCLUSION: Important intratumoral arteriovenous shunting exists in glioblastomas. The potential consequences of this finding for intra-arterial treatment strategies are discussed.

Principles of the morbidity and mortality conference.

The goals of the morbidity and mortality conference are learning from mistakes, recognising problems, and being aware of the risks of one's own procedures. Data are continuously collected, complications are classified, and the results of surgery are analyzed. By analysing and discussing the results every three months, total case mortality, mortality of specific procedures, incidence of haematomas, infection rate and incidence of thromboses and emboli are known and a continuous quality control is possible.

Transdural cauda equina incarceration after microsurgical lumbar discectomy: case report.

OBJECTIVE AND IMPORTANCE: Complications usually occur when they are least expected. We present an unusual case of nerve entrapment after microsurgical discectomy. CLINICAL PRESENTATION: A patient undergoing uneventful first lumbar microsurgical discectomy developed severe back and leg pain and a progressive neurological deficit during the first postoperative night. Herniation of cauda equina nerve roots had occurred through an unnoticed minimal defect in the dura, which had not caused cerebrospinal fluid leakage. The roots were incarcerated and swollen, and they filled the space of the resected nucleus pulposus. It was presumed that elevation of intra-abdominal pressure and consequent increased intraspinal pressure during extubation led to the herniation of arachnoid and cauda equina roots. The nerve roots were then trapped and incarcerated in the manner of bowel loops in an abdominal wall hernia. INTERVENTION: During reoperation, the nerve roots were repositioned into the dural sac. The patient recovered without further complications and without long-term sequelae. CONCLUSION: All dural tears that occur during intraspinal surgery, even if they are small and the arachnoid is intact, should be closed with stitches or at a minimum with a patch of muscle or gelatin sponge with fibrin glue. Care should be taken to avoid increased intra-abdominal pressure during extubation. Excessive pain and progressive neurological dysfunction occurring shortly after microsurgical lumbar discectomy or any intraspinal procedure is indicative of possible hemorrhage with subsequent compression of nerve roots. The case reported here provides anecdotal evidence that this situation can also be caused by a herniation of cauda equina nerve roots through a small dural defect that was not evident during the initial operation.

Sellar reconstruction with resorbable vicryl patches, gelatin foam, and fibrin glue in transsphenoidal surgery: a 10-year experience with 376 patients.

OBJECT: Closure of the sella turcica after transsphenoidal surgery is mainly accomplished with autologous muscle fascia and fat or muscle; this requires a second surgical incision. The authors review the results of using resorbable vicryl patches, gelatin foam, and fibrin glue for sellar reconstruction. METHODS: A review was conducted of 376 consecutive patients who underwent surgery for pituitary adenomas, cysts, or subdiaphragmatic craniopharyngiomas in the sella turcica that the senior author (R.W.S.) had performed or directly supervised over the last 10 years. The sellar reconstruction was performed with a commercially available, synthetic absorbable patch composed of polyglactin 910/poly-p-dioxanone, gelatin foam, and fibrin glue. The patch is essentially resorbed in 2 to 3 months and replaced by fibrous collagen tissue. There were 117 small, 112 medium-sized, and 147 large lesions. The overall nonendocrine postoperative morbidity rate was 2.8%, and included visual deterioration, meningitis, secondary epistaxis, nasal septum complication, and cerebrospinal fluid (CSF) leakage. Two patients with macroadenomas needed reoperation for persistent CSF leakage, which comprised 0.5% of the whole series or 0.8% of the 259 patients with medium-sized or large lesions. There was no mortality and no morbidity related to the implanted material, and in particular no delayed empty sella syndrome. CONCLUSIONS: Closure of the sella turcica with a synthetic absorbable vicryl patch, gelatin foam, and fibrin glue after transsphenoidal surgery is safe and very effective in preventing postoperative CSF fistulas. The use of this technique obviates the need for a second surgical incision and shortens the operating time. Because of the progressive resorption of the substitute material, the interpretation of postoperative magnetic resonance studies was not significantly hindered.