Congenital anomalies and genetic disorders in neonates and infants: a single-center observational cohort study.

Neonates with genetic disorders or congenital anomalies (CA) contribute considerably to morbidity and mortality in neonatal intensive care units (NICUs). The objective of this study is to study the prevalence of genetic disorders in an academic level IV NICU. We retrospective collected and analyzed both clinical and genetic data of all 1444 infants admitted to the NICU of the Radboudumc (October 2013 to October 2015). Data were collected until infants reached at least 2 years of age. A total of 13% (194/1444) of the patients were genetically tested, and 32% (461/1444) had a CA. A total of 37% (72/194) had a laboratory-confirmed genetic diagnosis. In 53%, the diagnosis was made post-neonatally (median age = 209 days) using assays including exome sequencing. Exactly 63% (291/461) of the patients with CA, however, never received genetic testing, despite being clinically similar those who did.Conclusions: Genetic disorders were suspected in 13% of the cohort, but only confirmed in 5%. Most received their genetic diagnosis in the post-neonatal period. Extrapolation of the diagnostic yield suggests that up to 6% of our cohort may have remained genetically undiagnosed. Our data show the need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management. What is Known: • Genetic disorders are suspected in many neonates but only genetically confirmed in a minority. • The presence of a genetic disorder can be easily missed and will often lead to a diagnostic odyssey requiring extensive evaluations, both clinically and genetically. What is New: • Different aspects of the clinical features and uptake of genetic test in a NICU cohort. • The need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management.

Systematic CT evaluation of reduction and hardware positioning of surgically treated calcaneal fractures: a reliability analysis.

INTRODUCTION: Up to date, there is a lack of reliable protocols that systematically evaluate the quality of reduction and hardware positioning of surgically treated calcaneal fractures. Based on international consensus, we previously introduced a 23-item scoring protocol evaluating the reduction and hardware positioning in these fractures based on postoperative computed tomography. The current study is a reliability analysis of the described scoring protocol. METHODS: Three raters independently and systematically evaluated anonymized postoperative CT scans of 102 surgically treated calcaneal fractures. A selection of 25 patients was scored twice by all individual raters to calculate intra-rater reliability. The scoring protocol consisted of 23 items addressing quality of reduction and hardware positioning. Each of these four-option questions was answered as: 'optimal', 'suboptimal (but not needing revision)', 'not acceptable (needing revision)' or 'not judgeable'. We used intraclass correlation coefficients (ICC's) to calculate inter- and intra-rater reliability. RESULTS: Inter-rater reliability of the overall 23-item protocol was good (ICC 0.66, 95% CI 0.64-0.69). Individual items that scored an inter-rater ICC ≥0.60 included evaluation of the calcaneocuboid joint, the posterior talocalcaneal joint, the anterior talocalcaneal joint, the position of the plate and sustentaculum screws and screws protruding the tuber and medial wall. The intra-rater reliability for the overall protocol was good for all three individual raters with ICC's between 0.60 and 0.70. CONCLUSION: Our scoring protocol for the radiological evaluation of operatively treated calcaneal fractures is reliable in terms of inter- and intra-rater reliability.

"Turn laterally to the left!". The need for uniform C-arm communication terminology during orthopaedic trauma surgery.

To avoid disturbed teamwork, unnecessary radiation exposure, and procedural delays, we designed and tested a uniform communication language for use in fluoroscopy-assisted surgical procedures. Input of surgeons and radiographers was used to create a set of commands. The potential benefit of this terminology was explored in an experimental setting. There was a tremendous diversity in the currently used terminology. Use of the newly designed terminology showed a reduction of procedural time and amount of images needed. Our first standardized Dutch language terminology can reduce total fluoroscopy time, number of images acquired, and potentially radiation exposure. For Dutch speaking colleagues, the developed terminology is freely available for use in their OR.

Retrospective study in 1020 cases on the rate of surgical site infections after lacrimal surgery without prophylactic systemic antibiotics.

BACKGROUND/AIMS: Data regarding the effectiveness of prophylactic systemic antibiotics (PSA) in lacrimal surgery is scarce. Therefore, we determined the postoperative surgical site infection (SSI) rate in lacrimal surgery without PSA. METHODS: We retrospectively analysed files of patients who underwent external (extDCR) or endoscopic endonasal dacryocystorhinostomy (endoDCR). We excluded patients with incomplete data (n = 68), acute a priori infection with the need for antibiotics (n = 15) and PSA post-operatively for other reasons (n = 28). Indications for surgery were canalicular stenosis (n = 51, 18.6% endoDCR vs n = 131, 19.5% extDCR), nasolacrimal duct obstruction (n = 118, 43.2% endoDCR vs n = 480, 64.3% extDCR) and mucocele/chronic dacryocystitis (n = 52, 19.0% endoDCR vs n = 187, 25.0% extDCR). RESULTS: In this study, 1020 DCR surgeries were performed in 899 patients. Postoperative SSI was diagnosed in eight patients (0.8%); exclusively after extDCR (1.1% of all extDCR). No SSIs were found in endoDCR cases. The prevalence between SSI in extDCR versus endoDCR did not prove significant (n = 8/747 0.8% vs n = 0/273 0%, p = 0.13). All patients diagnosed with SSI were successfully treated with systemic oral antibiotics. CONCLUSION: The prevalence of SSI after DCR is low and was effectively treated with oral antibiotics. In our study, SSI occurred rarely after extDCR and was not observed after endoDCR. We conclude that lacrimal surgery is safe without the routine administration of PSA.

Radiation optic neuropathy and retinopathy in patients with presumed benign intraorbital tumours treated with fractionated stereotactic radiotherapy.

PURPOSE: To assess the long-term effects of fractionated stereotactic radiotherapy (fSRT) for the treatment of (presumed) benign intraorbital tumours on visual acuity, visual fields, globe and eyelid position, and complications including radiation retinopathy and deviations of retinal nerve fibre layer (RNFL) on OCT. METHODS: Multi-centre retrospective follow-up study of a consecutive series of 25 patients treated in the Rotterdam Orbital Center (collaboration between Erasmus Medical Center and Rotterdam Eye Hospital) between 2002 and 2018. Data on the dose of fSRT, visual acuity, Humphrey field analyser (HFA) perimetry, globe and eyelid position were obtained from the medical records. RESULTS: In this retrospective consecutive series of 25 patients with a median follow-up of 104 months (range 48-215 months), 80.0% of the patients had presumed optic nerve sheath meningioma and 20.0 % presumed cavernous haemangioma with signs suggestive of recent growth. In most patients, a better visual acuity and RNFL thickness were observed after stereotactic radiotherapy. Improvement of the visual field defects was observed after treatment, with a mean deviation of -14.98 dB (12.9 SD) before treatment versus -4.56 dB (10.8 SD) after treatment, respectively. Significant, but small changes in exophthalmometry values were observed with a mean of 14.92 mm (7.9 SD) versus 13.79 mm (7.3 SD) after treatment, respectively. Only 3 patients (15.0%) developed radiation retinopathy after stereotactic radiotherapy. All patients with radiation retinopathy had presumed optic nerve sheath meningioma. CONCLUSIONS: Based on our results, fSRT is an effective treatment modality for this subset of orbital tumours with few complications and good long-term visual and cosmetic outcomes. FSRT is non-invasive and safer than surgery for lesions in the posterior orbit or around the optic nerve.

Adult orbital xanthogranuloma: long-term follow-up of treated cases.

BACKGROUND: Adult orbital xanthogranulomatous disease (AOXGD) is a group of rare disorders. Four subtypes are identified: adult-onset xanthogranuloma (AOX), adult-onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX), and Erdheim-Chester disease (ECD). Therapy options vary and little is known about the long-term effect of the treatment. In this study, we will describe the clinical behaviour, effect of treatment, and long-term outcome in a consecutive series of patients with AOXGD. METHODS: This is a descriptive, retrospective study with a long follow-up term of 21 patients with histologically proven AOXGD, treated between 1989 and 2021 in the Rotterdam Eye Hospital and Erasmus MC University Medical Center. RESULTS: Twenty-one patients with histologically proven AOXGD were included. The follow-up ranged from 2-260 months (median of 67 months). Six of the nine patients with AOX were treated with surgery alone, with recurrence in two. Three received systemic therapy, with recurrence in one. All four patients with AAPOX received systemic treatment, the disease recurred in two. Two patients with NBX were treated with surgery alone, with recurrence in one. Four required additional therapy with recurrence in two. Both patients with ECD required systemic therapy. CONCLUSIONS: Recognition of AOXGD is important, in particular, because of the potential severe systemic locations in the different subtypes. Surgical excision might be a sufficient therapy for patients with AOX. Patients with AAPOX, NBX, and ECD warrant systemic therapy. Currently, there is no conclusive evidence for a superior treatment strategy, but further studies are necessary to investigate treatment options.

Treatment of hereditary angioedema with nanofiltered C1-esterase inhibitor concentrate (Cetor®): multi-center phase II and III studies to assess pharmacokinetics, clinical efficacy and safety.

From 1997, plasma-derived C1-inhibitor concentrate (Cetor®) has been available to HAE and AAE patients. Recently, a virus reducing 15 nm nanofiltration step has been introduced in the production process. A randomized, double-blind controlled cross-over study was performed to compare the pharmacokinetics (PK) of nanofiltered (C1-INH-NF) with conventional C1-inhibitor (C1-INH). Efficacy and safety were investigated in an open-label, on-demand and a prophylactic study. No differences in pharmacokinetic parameters between C1-INH and C1-INH-NF were found (13 non-symptomatic HAE patients). Both C1-inhibitor products equally increased plasma C4 levels. In the on-demand study, 14 acute angioedema attacks in 8 patients were analyzed. In the prophylactic study, 1 AAE and 5 HAE patients experienced in total 31 attacks during 748 observation days. In total 180,000 units of C1-INH-NF were administered. No product-related adverse events occurred, and no anti-C1-antibodies were induced. Nanofiltration in the production process of C1-inhibitor did not affect the pharmacokinetics, efficacy, and safety.

A spin triplet supercurrent through the half-metallic ferromagnet CrO2.

In general, conventional superconductivity should not occur in a ferromagnet, though it has been seen in iron under pressure. Moreover, theory predicts that the current is always carried by pairs of electrons in a spin singlet state, so conventional superconductivity decays very rapidly when in contact with a ferromagnet, which normally prohibits the existence of singlet pairs. It has been predicted that this rapid spatial decay would not occur if spin triplet superconductivity could be induced in the ferromagnet. Here we report a Josephson supercurrent through the strong ferromagnet CrO2, from which we infer that it is a spin triplet supercurrent. Our experimental set-up is different from those envisaged in the earlier predictions, but we conclude that the underlying physical explanation for our result is a conversion from spin singlet pairs to spin triplets at the interface. The supercurrent can be switched with the direction of the magnetization, analogous to spin valve transistors, and therefore could enable magnetization-controlled Josephson junctions.

IL-10 promotor haplotypes associated with susceptibility to and severity of bacterial corneal ulcers.

Interleukin-10 plays an important role in modulating inflammation and antimicrobial defences. In animal models for bacterial corneal ulcers, high IL-10 levels were associated with a better clinical outcome. We investigated whether IL-10 promotor haplotypes, known to determine IL-10 expression in vitro, are associated with susceptibility to and/or clinical outcome of bacterial corneal ulcers in patients. IL-10 promotor polymorphisms C-819T, G-1082A, A-2763C, and A-2849G for 83 patients with bacterial corneal ulcers and 115 healthy controls were determined by restriction fragment length PCR analysis. For 63 patients and all healthy controls the most frequently occurring IL-10 promotor haplotypes were inferred from these data using the program SNPHAP. A significant underrepresentation of the A-2849A genotype was observed in patients as compared to healthy controls. Both the -2763A allele and the IL-10.1 promotor haplotype were associated with a poor clinical outcome, whereas a favourable clinical outcome was seen in patients carrying the IL-10.2 promotor haplotype. Together, IL-10 promotor haplotypes associated with low IL-10 levels seem to protect against the onset of bacterial corneal ulcers. Once a corneal ulcer has developed, patients carrying IL-10 haplotypes associated with a high IL-10 expression may have a favourable outcome.

Odor recognition memory is not independently impaired in Parkinson's disease.

The results of previous studies in small groups of Parkinson's disease (PD) patients are inconclusive with regard to the presence of an odor recognition memory impairment in PD. The aim of the present study was to investigate odor recognition memory in PD in a larger group of patients. Odor recognition memory and detection thresholds were assessed using components of the "Sniffin' Sticks" test battery in 55 non-demented PD patients (Hoehn and Yahr stages I-III) and 50 control subjects of comparable age and sex. PD patients performed slightly but significantly worse than control subjects on the odor recognition memory task. After correction for odor detection scores, however, the difference in odor recognition memory performance between PD patients and controls was no longer statistically significant. These data indicate that odor recognition memory is not independently impaired in PD patients.

Cutaneous allergy testing in patients suspected of an allergic reaction to eye medication.

PURPOSE: Our aim was to determine the usefulness of allergy testing in patients with possible allergic reactions to an eye medication. METHODS: This retrospective study analyzed the usefulness of allergy testing in 90 patients who on the basis of their complaints were under suspicion of having an allergic response to eye medication. RESULTS: Among the 90 patients suspected of an allergic reaction to eye medication, the most common complaint was itching, while hyperemic conjunctivae were the most common symptom. Skin testing revealed an allergy to eye medication in 32 (36%) of the patients tested, which seemed to be the causal factor of the complaints in 22 cases (24%). The most frequent medication-associated allergies were directed against tobramycin, neomycin sulfate and thimerosal. Clinically relevant non-drug-related allergies occurred in 26 cases and were directed against nickel sulfate, Myroxylon pereirae and fragrance mix. Twenty-three patients were atopic and had positive skin prick tests against inhalation allergens such as house dust mites or dogs. CONCLUSION: Allergy testing was helpful to obtain a diagnosis of a clinically relevant allergy in 48 of the 90 patients who were referred under suspicion of having a contact allergy to eye medication.

Conjunctival Leiomyosarcoma, a Rare Neoplasm Always Originating at the Limbus? Report of a New Case and Review of 11 Published Cases.

PURPOSE OF THE STUDY: To describe the differential diagnosis and management of a rare conjunctival malignancy. PROCEDURES: A 79-year-old man presented with a conjunctival mass at the limbus. Excisional biopsy revealed a malignant mesenchymal tumor with myogenic differentiation. Six months later, three suspect lesions developed at the border of the previous excision. Pathological diagnosis pointed to a leiomyosarcoma. Adjuvant radiotherapy with strontium-90 brachytherapy was applied. After 3 years, there was neither recurrence nor distant metastases. A literature review revealed 11 cases of conjunctival leiomyosarcoma. RESULTS: All 12 cases seemed to originate at the limbal conjunctiva. Scleral invasion was found only in one patient with multiple previous resections. Corneal invasion was reported in two patients. Four patients had a globe-sparing resection. In two of them, margins were not tumor free and additional brachytherapy gave a tumor-free follow-up of 1 and 3 years. Four cases underwent an exenteration. CONCLUSION AND MESSAGE: Primary conjunctival leiomyosarcoma is a rare tumor with a favorable prognosis due to early detection and consequently limited size. Diagnosis involves histopathological investigation including immunohistochemistry. If possible, complete resection has the best prognosis. Adjunctive radiotherapy can be effective when the margins are not free and should be considered.

The correlation between intra-operative 2D- and 3D fluoroscopy with postoperative CT-scans in the treatment of calcaneal fractures.

OBJECTIVES: The aim of this study was to determine the correlation of the intra-operative fluoroscopic 2D- and 3D-images compared with a postoperative CT-scan, in terms of quality of reduction and fixation of calcaneal fractures. METHODS: Patients requiring open reduction and internal fixation (ORIF) of a calcaneal fracture were recruited as part of the EF3X-trial. During surgery, intra-operative images of fluoroscopic 2D- and 3D-imaging were obtained to assess the quality of the reduction and implant position. All patients received a postoperative CT-scan within one week. The operating surgeon evaluated intra-operatively both 2D- and 3D-images according to a 23-item scoring protocol on a 3-point Likert scale. A scoring panel, consisting of three clinical experts, evaluated all images in a blinded and independent fashion. Intraclass correlation coefficients (ICC) with their 95% confidence intervals (CI) were calculated using a two-way-random model with absolute agreement. RESULTS: A total of 102 calcaneal fractures were included. Agreement of 3D-imaging for the quality of reduction was better than 2D-imaging, although still fair, but for fixation moderate to good. Agreement between the 2D-images and the CT-scans was poor to fair. Intra-operative 2D-imaging received the highest ratings for image quality and interpretability, followed by CT-scanning. CONCLUSION: Implant position can be evaluated satisfactory with the aid of intra-operative 3D imaging. Although intra-operative 3D imaging had a better agreement with postoperative CT-scanning than 2D-imaging, there is a need to improve image quality and suppress scattering from implants to improve the additional value of intra-operative 3D imaging in calcaneal fracture reduction and fixation.

Posterior malleolar fracture morphology determines outcome in rotational type ankle fractures.

INTRODUCTION: Rotational type ankle fractures with a concomitant fracture of the posterior malleolus are associated with a poorer clinical outcome as compared to ankle fractures without. However, clinical implications of posterior malleolar (PM) fracture morphology and pattern have yet to be established. Many studies on this subject report on fragment size, rather than fracture morphology based on computed tomography (CT). The overall purpose of the current study was to elucidate the correlation of PM fracture morphology and functional outcome, assessed with CT imaging and not with -unreliable- plain radiographs. METHODS: Between January 2010 and May 2014, 194 patients with an operatively (ORIF) treated ankle fracture, were prospectively included in the randomized clinical EF3X-trial at our Level-I trauma center. The current study retrospectively included 73 patients with rotational type ankle fractures and concomitant fractures of the posterior malleolus. According to the CT-based Haraguchi fracture morphology, all patients were divided into three groups: 20 Type I (large posterolateral-oblique), 21 Type II (transverse medial-extension) and 32 Type III (small-shell fragment). At 12 weeks, 1 year and 2 years postoperatively the Foot and Ankle Outcome Scores (FAOS) and SF-36 scores were obtained, with the FAOS domain scores at two years postoperative as primary study outcome. Statistical analysis included a multivariate regression and secondary a mixed model analysis. RESULTS: Haraguchi Type II PM ankle fractures demonstrated significantly poorer outcome scores at two years follow-up compared to Haraguchi Types I and III. Mean FAOS domain scores at two years follow-up showed to be significantly worse in Haraguchi Type II as compared to Type III, respectively: Symptoms 48.2 versus 61.7 (p = 0.03), Pain 58.5 versus 84.4 (p < 0.01), Activities of Daily Living (ADL) 64.1 versus 90.5 (p < 0.01). CONCLUSION: Posterior malleolar ankle fractures with medial extension of the fracture line (i.e. Haraguchi Type II) are associated with significantly poorer functional outcomes. The current dogma to fix PM fractures that involve at least 25-33% of the tibial plafond may be challenged, as posterior malleolar fracture pattern and morphology - rather than fragment size - seem to determine outcome.

Merkel cell carcinoma of the eyelid review of the literature and report of patients with Merkel cell carcinoma showing spontaneous regression.

PURPOSE: To evaluate the clinical and histopathologic characteristics of Merkel cell carcinoma (MCC) of the eyelid. DESIGN: Retrospective case series and literature review. PARTICIPANTS: Three consecutive patients with MCC of the eyelid who were referred to the Ocular Oncology Unit of Leiden University Medical Center, Netherlands. METHODS: Clinical records and histopathologic material of patients with eyelid MCC were reviewed. The clinical presentation and treatment were evaluated. MAIN OUTCOME MEASURES: Clinical and histopathologic description of eyelid MCC, with histologic proof of spontaneous regression of the tumor. RESULTS: Three patients with MCC of the eyelid were included. Diagnosis was made by pathologic investigation and immunohistochemistry (S100, cytokeratin 20, epithelial membrane antigen, chromogranin). Two of the patients showed histologically proven complete spontaneous regression after nonradical excision of the tumor. After local excision, none of the MCCs demonstrated local recurrence, without regional or distant metastases. Mean clinical follow-up was 50 months. CONCLUSIONS: Nonocular MCC is known to recur in 66% of patients and to be lethal in almost 33%. Merkel cell carcinoma of the eyelid is a rare malignancy that can not be recognized clinically. Clinical differential diagnosis must be made with a chalazion, and histopathologic differential diagnosis must be made with small cell carcinomas. Close follow-up of these patients is advised because of the potential high recurrence rate and lymphatic spread. The immunologic phenomenon of spontaneous regression points out the importance of the immune system in this disease.

Angiosarcoma of the eyelid and periorbital region. Experience in Leiden with iridium192 brachytherapy and low-dose doxorubicin chemotherapy.

AIM: To report on the use of iridium(192) brachytherapy and doxorubicin chemotherapy as adjuvant therapy in 6 patients with angiosarcoma of the eyelid and periorbital region. MATERIAL AND METHODS: Tumor localization and diameter, signs of inflammation, histology and treatment are discussed in this retrospective study of 6 patients (age 46-87 yrs.) presenting with primary angiosarcoma in the eyelid. RESULTS: Six patients (4 elderly) with angiosarcoma localized in one or more eyelids, the face or multilocular were seen between 1987 and 2000. In one patient, a small nodular tumor did not recur within 4 years after radical excision. In another patient, the tumor was treated with surgery and iridium(192) wire brachytherapy and did not recur in 17 years of follow-up. In four patients with large diffuse tumors that were treated with doxorubicin, partial regression was achieved. The follow-up was >3 years (median 5 years). CONCLUSION: If radical surgery for angiosarcoma of the eyelid and periorbital region is not possible, adjuvant iridium(192) wire brachytherapy may prove beneficial. For widespread, diffusely growing tumors, and in elderly patients, low-dose (slowly, 20 mg i.v.) doxorubicin can be used weekly as adjuvant therapy, resulting in partial regression and longer survival rates than previously published by other authors.

Cytotoxic effect of sodium hypochlorite 0.5% (NaOCl) on ocular melanoma cells in vitro.

PURPOSE: Excision with or without adjuvant cryotherapy or brachytherapy is the treatment of choice in conjunctival melanoma. Adjuvant rinsing with alcohol or sodium hypochlorite peroperatively (Dakin's solution) is used in some centers to prevent seeding of melanoma cells. The purpose of this research is to compare the cytotoxicity of sodium hypochlorite (NaOCl) with other potential cytotoxic solutions in the treatment of conjunctival melanoma. METHODS: Three uveal melanoma cell lines (OCM8, Mel285, and Mel270) and one conjunctival melanoma cell line (CM2005.1) were tested in a proliferation test (CellTiter 96 AQueous One Solution Cell Proliferation Assay, Promega, Madison, WI). The 96-well plates were coated with melanoma cells and treated with sodium hypochlorite 0.5%, sodium bicarbonate (1.4% and 8.4%), ethanol 99%, or sodium chlorite during 3, 5, or 15 minutes. Each solution was tested in several dilutions. RESULTS: In all cell lines, no surviving cells were observed after treatment of 3 minutes with sodium hypochlorite. Ethanol 99% had a similar effect. A reduction of 70% of viable cells could be reached using sodium bicarbonate 1.4% or 8.4%. Water reduced the amount of viable cells by 40%. CONCLUSIONS: Sodium hypochlorite is cytotoxic for melanocytic cells in vitro. Its use may reduce local seeding of tumor cells and may decrease metastasis after extirpation of an extended ocular tumour. Further in vivo evaluation of sodium hypochlorite is required.

[Nonfunctioning pituitary macroadenomas: diagnosis, treatment and follow-up]. / Niet-functionerende macroadenomen van de hypofyse: diagnostiek, behandeling en follow-up.

*Nonfunctioning pituitary adenomas are benign tumours characterised by the absence of hormone overproduction. *Clinical symptoms are caused by the mass effects of the tumour. The main symptoms are pituitary insufficiency, visual field defects, vision impairment and headache. *Treatment is unnecessary for tumours less than 1 cm, and an expectative approach can be used for some patients with larger tumours but no visual field defects. *Transsphenoidal surgery is indicated for patients with visual field defects. *Because nonfunctioning adenomas can recur, lifelong follow-up after treatment is necessary. *Poor quality of life has been reported in treated patients with nonfunctioning pituitary adenomas, which may be due to the intrinsic imperfections of hormonal replacement therapy.

[Transsphenoidal resection of pituitary adenomas: long-term results from the Leiden University Medical Center]. / Transsfenoïdale resectie van hypofyseadenomen: langetermijnresultaten van het Leids Universitair Medisch Centrum.

OBJECTIVE: To evaluate the long-term outcome of transsphenoidal resection of pituitary adenomas at the Leiden University Medical Center (LUMC), The Netherlands. DESIGN: Retrospective, descriptive. METHOD: 416 consecutive patients undergoing surgery for pituitary adenoma at the LUMC between 1978 and 2004 were included; 174 patients with non-functioning macroadenomas (NFMA), 164 patients with acromegaly and 78 patients with Cushing's disease. RESULTS: Biochemical remission was achieved in 66% of patients with acromegaly, and 72% of patients with Cushing's disease; incidence of pituitary failure was low in these patients (5% and 18% respectively). In 82% of the patients with NFMA visual function improved whereas the percentage with any degree of pituitary failure increased from 85% (preoperatively) to 95% (postoperatively). During follow-up of 10-15 years, the recurrence rate for acromegaly and Cushing's disease was 9% and for NFMA it was 15%. CONCLUSION: Transsphenoidal resection is an effective treatment in most, but not all, patients with pituitary adenomas. The surgical results at the LUMC are comparable with those obtained in important international centres. All patients cured by surgery need lifelong follow-up, because of the real risk of recurrent disease.