CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Individualised Estimation of Quality-adjusted Survival Benefit and Cost-effectiveness of Proton Beam Therapy in Intermediate-stage Hodgkin Lymphoma.

AIMS: Radiotherapy for Hodgkin lymphoma leads to the irradiation of organs at risk (OAR), which may confer excess risks of late effects. Comparative dosimetry studies show that proton beam therapy (PBT) may reduce OAR irradiation compared with photon radiotherapy, but PBT is more expensive and treatment capacity is limited. The purpose of this study is to inform the appropriateness of PBT for intermediate-stage Hodgkin lymphoma (ISHL). MATERIALS AND METHODS: A microsimulation model simulating the course of ISHL, background mortality and late effects was used to estimate comparative quality-adjusted life years (QALYs) lived and healthcare costs after consolidative pencil beam scanning PBT or volumetric modulated arc therapy (VMAT), both in deep-inspiration breath-hold. Outcomes were compared for 606 illustrative patients covering a spectrum of clinical presentations, varying by two age strata (20 and 40 years), both sexes, three smoking statuses (never, former and current) and 61 pairs of OAR radiation doses from a comparative planning study. Both undiscounted and discounted outcomes at 3.5% yearly discount were estimated. The maximum excess cost of PBT that might be considered cost-effective by the UK's National Institute for Health and Care Excellence was calculated. RESULTS: OAR doses, smoking status and discount rate had large impacts on QALYs gained with PBT. Current smokers benefited the most, averaging 0.605 undiscounted QALYs (range -0.341 to 2.171) and 0.146 discounted QALYs (range -0.067 to 0.686), whereas never smokers benefited the least, averaging 0.074 undiscounted QALYs (range -0.196 to 0.491) and 0.017 discounted QALYs (range -0.030 to 0.086). For the gain in discounted QALYs to be considered cost-effective, PBT would have to cost at most £4812 more than VMAT for current smokers and £645 more for never smokers. This is below preliminary National Health Service cost estimates of PBT over photon radiotherapy. CONCLUSION: In a UK setting, PBT for ISHL may not be considered cost-effective. However, the degree of unquantifiable uncertainty is substantial.

Platelet-Rich Plasma and Platelet-Rich Fibrin as a Regenerative Tool.

Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are used as a valuable adjunct in the treatment of maxillofacial rehabilitation. PRP used along with growth hormone helps in bone healing and tissue regeneration in the areas affected by bone and soft tissue-related defects. It aids not only in faster and better healing of the surgically debrided area but also in regeneration of the bone at a faster rate. This review comprises the applications of PRP and PRF and their uses in various procedures.

Deep vein thrombosis and euvolemic hyponatremia in a hypothyroid patient.

Hypothyroidism is a procoagulant state; hypothyroid females have greater risk of DVT than hypothyroid males. We present a case of primary hypothyroidism who presented with euvolemic hyponatremia and DVT that required thyroxine replacement and correction of hyponatremia. This highlights that hypothyroidism can present as euvolemic hyponatremia and deep vein thrombosis.

Correlation of cyclin D1 transcript levels, transcript type and protein expression with proliferation and histology among mantle cell lymphoma.

BACKGROUND: Cyclin D1 expression is central to mantle cell lymphoma (MCL) biology. The cyclin D1 gene produces two forms of mRNA: long (D1L) and short (D1S) versions. AIMS: To study the relationship between histology, cyclin D1 mRNA (transcript) levels, cyclin D1 transcript type, cyclin D1 protein expression by immunohistochemistry (IHC), and proliferation (Ki-67%). METHODS: 17 MCLs were initially studied for: levels of expression of cyclin D1 transcripts and for cyclin D1 transcript type by reverse-transcriptase PCR; intensity and percentage cyclin D1 protein expression by IHC; and Ki-67% by IHC. The relationship between cyclin D1 protein expression and proliferation was further validated on an independent set of 23 MCLs. RESULTS: MCLs expressed variable levels of cyclin D1 at both transcript and protein levels. Furthermore, D1L and D1S were the predominant transcripts in 69% and 31% of cases, respectively. While only 9% of cases with dominance of D1L had blastoid histology, 60% of the cases with dominance of the D1S had blastoid features. Furthermore, the levels of D1L showed direct correlation with cyclin D1 protein expression and Ki-67%. Among these cases, and in the independent set of MCLs (n = 40), the level of cyclin D1 protein expression directly correlated with Ki-67%. CONCLUSIONS: MCLs express variable levels of cyclin D1 transcripts and protein, and have variable proliferation (Ki-67%). Cases with dominance of D1S transcripts are more likely to be of blastoid morphology. There is correlation between D1L transcripts levels, cyclin D1 protein expression and Ki-67%.

Experience with neurocysticercosis in the UK: correct diagnosis and neurosurgical management of the small enhancing brain lesion.

Neurocysticercosis is a major cause of epilepsy and other neurological morbidity in endemic areas of the world but is exceptionally rare in the West. We have recently had experience of eight patients with this condition, seven presenting with epilepsy and single or multiple small, enhancing parenchymal lesions and one with hydrocephalus caused by a midbrain lesion. One lesion was stereotactically excised after it persisted, but in five other cases spontaneous cyst resolution was observed during expectant management with anticonvulsants. Two patients with multiple lesions were referred to us for further management but were free of active infection. Recent studies show that neurocysticercosis may often be diagnosed based upon the clinical, epidemiological and radiological features. Spontaneous cyst resolution is to be expected in this condition and suspected patients should be carefully observed and surgery avoided. We believe that this disease presents more commonly than has been appreciated in the UK and propose a protocol for management.

New variant Creutzfeldt-Jakob disease.

Since the report of new variant Creutzfeldt-Jakob Disease (nvCJD) in humans last year, the search was on for direct evidence to link the condition to Bovine Spongiform Encephalopathy (BSE). The first case nvCJD was noted 10 years after the recognition of BSE in UK cattle. A direct link is now established. There are, however, some 'protective' mechanisms, the most important of which are the inefficiency of the gastric route of introducing the infected material, the species barrier and genetic 'predisposition'. None of these is full proof and time will tell whether feeding ruminants with their own species will turn out to be a major public health disaster?

Spontaneous intracranial hypotension: clinical and magnetic resonance imaging characteristics.

The syndrome of spontaneous intracranial hypotension (SIH) is an uncommon cause of postural headache. We describe three patients with classical low pressure headache associated with low CSF pressure, one of whom presented with sudden deafness and another with a unilateral VIth nerve palsy. Initial magnetic resonance imaging (MRI) scans revealed bilateral diffuse subdural fluid collections in all three cases. Follow up MRI scans performed on two patients at 6 months demonstrated partial resolution of the subdural collections but persistent striking meningeal enhancement despite clinical recovery. These findings differ from previous reported cases wherein clinical resolution of postural symptoms was preceded or closely followed by resolution of the MRI changes.

Spatial and temporal auditory processing deficits following right hemisphere infarction. A psychophysical study.

Higher auditory function in a patient was investigated following a right hemisphere infarction between the middle and posterior cerebral artery territories involving the insula. The patient complained of lack of musical appreciation and a battery of tests confirmed a dissociated receptive musical deficit in the presence of normal appreciation of environmental sounds and speech. The ability to detect continuous changes in sound frequency in the form of sinusoidal frequency modulation was preserved. There was, however, a deficit in the analysis of rapid temporal sequences of notes which could underlie his musical deficit. This case provides further evidence for the existence of amusia as a distinct form of auditory agnosia, but does not support the hypothesis that bilateral lesions are required to produce such a deficit. Unexpectedly, the patient was also found to have a deficit in the perception of apparent sound-source movement. We suggest that this deficit is analogous to the visual phenomenon of akinetopsia, and is in accord with PET work suggesting involvement of areas outside primary auditory cortex in sound movement perception. A possible common deficit in auditory temporal and spatial 'scene analysis' is discussed.

Evidence for a sound movement area in the human cerebral cortex.

Human listeners can localize sounds by the difference in both arrival time (phase) and loudness between the two ears. Movement of the sound source modulates these cues, and responses to moving sounds have been detected in animals in primary auditory cortex and in humans in other cortical areas. Here we show that detection of changes in the interaural phase or amplitude difference occurs through a mechanism distinct from that used to detect changes in one ear alone. Moreover, a patient with a right hemisphere stroke is unable to detect sound movement, regardless of whether it is defined by phase or by loudness cues. We propose that this deficit reflects damage to a distinct cortical area, outside the classical auditory areas, that is specialized for the detection of sound motion. The deficit is analagous to cerebral akinotopsia (motion blindness) in the visual system, and so the auditory system may, like the visual system, show localization of specialized functions to different cortical regions.

Deficiency of complex II of the mitochondrial respiratory chain in late-onset optic atrophy and ataxia.

Defects of the mitochondrial respiratory chain are increasingly being recognized as an important cause of neurological disease in humans. In many of these patients, the biochemical defect results from an abnormality of the mitochondrial genome. Respiratory chain defects involving complex II, which is entirely encoded by the nuclear genome, are comparatively rare. We report the clinical and biochemical findings in 2 elderly sisters who presented with late-onset neurodegenerative disease. In both patients, a partial deficiency of complex II (approximately 50% of control values) was shown to be present in mitochondria from muscle and platelets. The enzyme defect was not expressed in cultured skin fibroblasts or immortalized lymphocytes. There was an overexpression of the 70-kd flavoprotein subunit in muscle mitochondria from both patients, although we showed that this subunit is present in normal amounts in mitochondrial membranes. Our studies highlight the diversity of the clinical presentation of respiratory chain disease and that complex II deficiency should enter the differential diagnosis of certain patients with late-onset neurodegenerative disease.

Giant cell arteritis presenting as oculomotor nerve palsy with pupillary dilatation.

Acute complete oculomotor palsy with headache is a classical presentation of an extrinsic compression most commonly due to a posterior communicating artery aneurysm. We present a patient with such a presentation but with histologically proven giant cell arteritis. This possibility should be considered especially in the elderly to avoid complications and the need for angiography.

Progressive myoclonic ataxia without ragged red fibres: Unverricht-Lundborg disease vs Ramsay Hunt syndrome.

We describe eight patients from three families presenting with myoclonus, ataxia, infrequent seizures and minimal intellectual impairment. All were Arabs from different parts of the Arabian peninsula. The new consensus on terminology, genetic and clinical definition of Baltic myoclonus, Ramsay Hunt syndrome and Unverricht-Lundborg disease suggests that our group are best categorised under the term of progressive myoclonic ataxia of the Unverricht-Lundborg type. Moreover, this report reinforces the existence of this syndrome outside Scandinavia.