Quality of life in 583 head and neck cancer survivors assessed with the FACE-Q head and neck cancer module.

OBJECTIVES: Long-term health-related quality of life (HRQOL) is frequently affected in head and neck cancer (HNC) survivors. Due to the shortage of studies investigating long-term patient-reported outcomes, we investigated long-term HRQOL using the novel FACE-Q HNC Module. METHODS: A retrospective cross-sectional single-center study was performed, including all patients who underwent curative treatment for HNC between 2006 and 2013. All eligible patients (n = 863) were invited to participate of whom 540 completed the questionnaires. Additionally, a prospective longitudinal cohort of 43 HNC patients treated between 2020 and 2022 was included who preoperatively filled in the FACE-Q, and at three, six, and 12 months postoperatively. HRQOL domain scores were analyzed to visualize group characteristics by tumor site and type of surgical resection. RESULTS: Both surgical and non-surgical HNC treatments predominantly affected long-term functional HRQOL domains (eating, salivation, speech, and swallowing), eating distress, and speaking distress, with distinct profiles depending on tumor site and type of treatment. In contrast, few long-term intergroup differences between HNC patients were observed for appearance, smiling, drooling distress, and smiling distress. Longitudinal data showed significant deterioration across all functional HRQOL domains in the short-term following treatment. Patients predominantly reported long-lasting negative treatment effects at 12 months follow-up for functional domains, whereas psychological domains showed near-complete recovery at group level. CONCLUSIONS: At long-term, various function-related and psychosocial HRQOL domains still are affected in head and neck cancer survivors. The results may serve to better inform patients with regard to specific treatments and highlight HRQOL domains which may potentially be optimized.

Long-term patient-reported outcomes after reconstructive surgery for head and neck cancer: A systematic review.

Current literature on reconstruction after head and neck cancer (HNC) focusses on short-term patient-reported outcomes (PROs), while there is a need for knowledge on long-term consequences. Embase, Medline, Web of Science, and Cochrane were searched for studies on health-related quality of life (HRQoL) after HNC reconstruction, using validated PROMs in at least 50 patients, and a follow-up of more than 1 year. Thirty studies were included, comprising 2358 patients with a follow-up between one and 10 years. The most used questionnaire was the UW-QoL v4. Reconstructive surgery was generally followed by diminished oral function, worsened by radiotherapy. Patients experienced anxiety and fear of cancer recurrence. However, there was a progressive decrease in pain over time with some flaps having more favorable HRQoL outcomes. Age and bony tumor involvement were not related to postoperative HRQoL. These results may lead to better patient counseling and expectation management of HNC patients.

Quality of Life and Complications after Nipple- versus Skin-Sparing Mastectomy followed by Immediate Breast Reconstruction: A Systematic Review and Meta-Analysis.

BACKGROUND: Nipple-sparing mastectomy (NSM) has emerged as an alternative procedure for skin-sparing mastectomy (SSM), followed by immediate breast reconstruction. Because oncologic safety appears similar, patient-reported outcomes (PROs) and complication risks may guide decision-making in individual patients. Therefore, the aim of this systematic review was to compare PROs and complication rates after NSM and SSM. METHODS: A systematic literature review evaluating NSM versus SSM was performed using the Embase, MEDLINE, and Cochrane databases. Methodologic quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. Primary outcomes were PROs and complications. Studies that evaluated BREAST-Q scores were used to perform meta-analyses on five BREAST-Q domains. RESULTS: Thirteen comparative studies including 3895 patients were selected from 1202 articles found. Meta-analyses of the BREAST-Q domains showed a significant mean difference of 7.64 in the Sexual Well-being domain ( P = 0.01) and 4.71 in the Psychosocial Well-being domain ( P = 0.03), both in favor of NSM. Using the specifically designed questionnaires, no differences in overall satisfaction scores were found. There were no differences in overall complication rates between the two groups. CONCLUSIONS: Patient satisfaction scores were high after both NSM and SSM; however, NSM led to a higher sexual and psychosocial well-being. No differences in complication rates were found. In combination with other factors, such as oncologic treatments, complication risk profile, and fear of cancer recurrence, the decision for NSM or SSM has to be made on an individual basis and only if NSM is considered to be oncologically safe.

The effect of early fusion of the spheno-occipital synchondrosis on midface hypoplasia and obstructive sleep apnea in patients with Crouzon syndrome.

INTRODUCTION: The investigators hypothesized that patients with Crouzon syndrome and premature fusion of the spheno-occipital synchondrosis (SOS) more often have, or have more severe midface hypoplasia and obstructive sleep apnea (OSA). METHODS: A prospective cohort study was performed among patients with Crouzon syndrome to analyze SOS closure, midface hypoplasia represented by the sella-nasion angle (SNA) and OSA. RESULTS: Forty patients were included in whom the OSA-prevalence was 65%. Kaplan Meier analyses suggest a trend towards earlier closure of synchondrosis in patients with OSA (p = 0.066). The mean SNA was 74.7°. There was a positive effect of age on the SNA (p = 0.020). There was no difference in SNA for patients with an open SOS as compared to patients with a closed SOS after correction for age. CONCLUSIONS: The longitudinal data are suggestive of a trend towards earlier fusion of the SOS in patients with Crouzon syndrome and OSA as compared to patients with Crouzon syndrome without OSA. Although the SNA increases with age, our results suggest that this increase in independent closure of the SOS.

First Vault Expansion in Apert and Crouzon-Pfeiffer Syndromes: Front or Back?

BACKGROUND: Children with Apert and Crouzon-Pfeiffer syndromes are at risk of intracranial hypertension. Until 2005, when the authors switched to occipital expansion, their institution's preferred treatment was fronto-orbital advancement. However, it was still unclear whether (1) occipitofrontal head circumference (i.e., intracranial volume) was greater after occipital expansion than after fronto-orbital advancement; (2) the incidences of tonsillar herniation and papilledema were lower; and (3) visual acuity was better during follow-up. In these patients, the authors therefore compared fronto-orbital advancement with occipital expansion as the first surgical procedure. METHODS: Measurements included repeated occipitofrontal head circumference as a measure for intracranial volume; neuroimaging to evaluate tonsillar herniation; funduscopy to identify papilledema; and visual acuity testing. RESULTS: The authors included 37 patients (Apert syndrome, n = 18; Crouzon-Pfeiffer syndrome, n = 19). Eighteen underwent fronto-orbital advancement and 19 underwent occipital expansion (age at surgery, 1.0 versus 1.5 years; p = 0.13). Follow-up time in both groups was 5.7 years. The increase in occipitofrontal head circumference (+1.09 SD) was greater after occipital expansion than after fronto-orbital advancement (+0.32 SD) (p = 0.03). After occipital expansion, fewer patients with Crouzon-Pfeiffer syndrome had tonsillar herniation (occipital, three of 11; fronto-orbital advancement, seven of eight; p = 0.02); for both syndromes together, fewer patients had papilledema (occipital, four of 19; fronto-orbital advancement, 11 of 18; p = 0.02). Visual acuity was similar after fronto-orbital advancement and occipital expansion (0.09 versus 0.13 logarithm of the minimum angle of resolution) (p = 0.28). CONCLUSIONS: The authors' preference for occipital expansion as the initial craniofacial procedure in Apert and Crouzon-Pfeiffer syndromes is supported by the greater increase it produces in intracranial volume (as evidenced by the occipitofrontal head circumference), which reduces the incidences of tonsillar herniation and papilledema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The formation of the foramen magnum and its role in developing ventriculomegaly and Chiari I malformation in children with craniosynostosis syndromes.

OBJECT: Craniosynostosis syndromes are characterized by prematurely fused skull sutures, however, less is known about skull base synchondroses. This study evaluates how foramen magnum (FM) size, and closure of its intra-occipital synchondroses (IOS) differ between patients with different craniosynostosis syndromes and control subjects; and whether this correlates to ventriculomegaly and/or Chiari malformation type I (CMI), intracranial disturbances often described in these patients. METHODS: Surface area and anterior-posterior (A-P) diameter were measured in 175 3D-CT scans of 113 craniosynostosis patients, and in 53 controls (0-10 years old). Scans were aligned in a 3D multiplane-platform. The frontal and occipital horn ratio was used as an indicator of ventricular volume, and the occurrence of CMI was recorded. Synchondroses were studied in scans with a slice thickness ≤1.25 mm. A generalized linear mixed model and a repeated measures ordinal logistic regression model were used to study differences. RESULTS: At birth, patients with craniosynostosis syndromes have a smaller FM than controls (p < 0.05). This is not related to the presence of CMI (p = 0.36). In Crouzon-Pfeiffer patients the anterior and posterior IOS fused prematurely (p < 0.01), and in Apert patients only the posterior IOS fused prematurely (p = 0.028). CONCLUSION: The FM is smaller in patients with craniosynostosis syndromes than in controls, and is already smaller at birth. In addition to the timing of IOS closure, other factors may influence FM size.

The occipitofrontal circumference: reliable prediction of the intracranial volume in children with syndromic and complex craniosynostosis.

OBJECT Patients with syndromic and complex craniosynostosis are characterized by the premature fusion of one or more cranial sutures. These patients are at risk for developing elevated intracranial pressure (ICP). There are several factors known to contribute to elevated ICP in these patients, including craniocerebral disproportion, hydrocephalus, venous hypertension, and obstructive sleep apnea. However, the causal mechanism is unknown, and patients develop elevated ICP even after skull surgery. In clinical practice, the occipitofrontal circumference (OFC) is used as an indirect measure for intracranial volume (ICV), to evaluate skull growth. However, it remains unknown whether OFC is a reliable predictor of ICV in patients with a severe skull deformity. Therefore, in this study the authors evaluated the relation between ICV and OFC. METHODS Eighty-four CT scans obtained in 69 patients with syndromic and complex craniosynostosis treated at the Erasmus University Medical Center-Sophia Children's Hospital were included. The ICV was calculated based on CT scans by using autosegmentation with an HU threshold < 150. The OFC was collected from electronic patient files. The CT scans and OFC measurements were matched based on a maximum amount of the time that was allowed between these examinations, which was dependent on age. A Pearson correlation coefficient was calculated to evaluate the correlations between OFC and ICV. The predictive value of OFC, age, and sex on ICV was then further evaluated using a univariate linear mixed model. The significant factors in the univariate analysis were subsequently entered in a multivariate mixed model. RESULTS The correlations found between OFC and ICV were r = 0.908 for the total group (p < 0.001), r = 0.981 for Apert (p < 0.001), r = 0.867 for Crouzon-Pfeiffer (p < 0.001), r = 0.989 for Muenke (p < 0.001), r = 0.858 for Saethre- Chotzen syndrome (p = 0.001), and r = 0.917 for complex craniosynostosis (p < 0.001). Age and OFC were significant predictors of ICV in the univariate linear mixed model (p < 0.001 for both factors). The OFC was the only predictor that remained significant in the multivariate analysis (p < 0.001). CONCLUSIONS The OFC is a significant predictor of ICV in patients with syndromic and complex craniosynostosis. Therefore, measuring the OFC during clinical practice is very useful in determining which patients are at risk for impaired skull growth.

The role of the posterior fossa in developing Chiari I malformation in children with craniosynostosis syndromes.

OBJECTIVE: Patients with craniosynostosis syndromes are at risk of increased intracranial pressure (ICP) and Chiari I malformation (CMI), caused by a combination of restricted skull growth, venous hypertension, obstructive sleep apnea (OSA), and an overproduction or insufficient resorption of cerebrospinal fluid. This study evaluates whether craniosynostosis patients with CMI have an imbalance between cerebellar volume (CV) and posterior fossa volume (PFV), that is, an overcrowded posterior fossa. METHODS: Volumes were measured in 3D-SPGR T1-weighted MR scans of 28 'not-operated' craniosynostosis patients (mean age: 4.0 years; range: 0-14), 85 'operated' craniosynostosis patients (mean age: 8.0 years; range: 1-18), and 34 control subjects (mean age: 5.4 years; range: 0-15). Volumes and CV/PFV ratios were compared between the operated and not-operated craniosynostosis patients, between the individual craniosynostosis syndromes and controls, and between craniosynostosis patients with and without CMI. Data were logarithmically transformed and studied with analysis of covariance (ANCOVA). RESULTS: The CV, PFV, and CV/PFV ratios of not-operated craniosynostosis patients and operated craniosynostosis patients were similar to those of the control subjects. None of the individual syndromes was associated with a restricted PFV. However, craniosynostosis patients with CMI had a significantly higher CV/PFV ratio than the control group (0.77 vs. 0.75; p = 0.008). The range of CV/PFV ratios for craniosynostosis patients with CMI, however, did not exceed the normal range. CONCLUSION: Volumes and CV/PFV ratio cannot predict which craniosynostosis patients are more prone to developing CMI than others. Treatment should focus on the skull vault and other contributing factors to increased ICP, including OSA and venous hypertension.

Foramen magnum size and involvement of its intraoccipital synchondroses in Crouzon syndrome.

BACKGROUND: Cranial sutures and synchondroses tend to close prematurely in patients with Crouzon syndrome. This influences their skull vault and skull base development and may involve in common disturbances such as increased intracranial pressure and cerebellar tonsillar herniation. The authors' hypothesis was that Crouzon patients patients have a smaller foramen magnum than controls because of premature fusion of the intraoccipital synchondroses, putting them at risk for cerebellar tonsillar herniation. Therefore, foramen magnum size and time of intraoccipital synchondroses closure were evaluated and were related to the presence and degree of cerebellar tonsillar herniation. METHODS: The foramen magnum surface area and anteroposterior diameter were measured on three-dimensional computed tomographic scans of 27 Crouzon patients and 27 age-matched controls. Scans had a slice-thickness between 0.75 and 1.25 mm and were aligned in a three-dimensional reformatting platform. The t test was used to study size differences. Synchondroses were graded as described by Madeline and Elster and studied with ordinal logistic regression analysis. RESULTS: Crouzon patients had a smaller foramen magnum surface area (602 mm versus 767 mm, p < 0.001) and anteroposterior diameter (31 mm versus 35 mm, p < 0.001) compared with controls. Differences stayed constant over time. Intraoccipital synchondroses closed 3 to 9 months earlier in Crouzon patients than in controls (p < 0.05). CONCLUSIONS: Since intraoccipital synchondroses close earlier in Crouzon patients, from early life on their foramen magnum is smaller compared with controls. Within Crouzon patients, the presence of cerebellar tonsillar herniation could not be related to foramen magnum size. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Encoding of whisker input by cerebellar Purkinje cells.

The cerebellar cortex is crucial for sensorimotor integration. Sensorimotor inputs converge on cerebellar Purkinje cells via two afferent pathways: the climbing fibre pathway triggering complex spikes, and the mossy fibre­parallel fibre pathway, modulating the simple spike activities of Purkinje cells. We used, for the first time, the mouse whisker system as a model system to study the encoding of somatosensory input by Purkinje cells.We show that most Purkinje cells in ipsilateral crus 1 and crus 2 of awake mice respond to whisker stimulation with complex spike and/or simple spike responses. Single-whisker stimulation in anaesthetised mice revealed that the receptive fields of complex spike and simple spike responses were strikingly different. Complex spike responses, which proved to be sensitive to the amplitude, speed and direction of whisker movement, were evoked by only one or a few whiskers. Simple spike responses, which were not affected by the direction of movement, could be evoked by many individual whiskers. The receptive fields of Purkinje cells were largely intermingled, and we suggest that this facilitates the rapid integration of sensory inputs from different sources. Furthermore, we describe that individual Purkinje cells, at least under anaesthesia, may be bound in two functional ensembles based on the receptive fields and the synchrony of the complex spike and simple spike responses. The 'complex spike ensembles' were oriented in the sagittal plane, following the anatomical organization of the climbing fibres, while the 'simple spike ensembles' were oriented in the transversal plane, as are the beams of parallel fibres.