Full Issue: Volume 13, Issue 1 - Winter 2018

Full Issue: Volume 13, Issue 1 - Winter 201

Intensity modulated radiation therapy and arc therapy: validation and evolution as applied to tumours of the head and neck, abdominal and pelvic regions

Intensiteitsgemoduleerde radiotherapie (IMRT) laat een betere controle over de dosisdistributie (DD) toe dan meer conventionele bestralingstechnieken. Zo is het met IMRT mogelijk om concave DDs te bereiken en om de risico-organen conformeel uit te sparen. IMRT werd in het UZG klinisch toegepast voor een hele waaier van tumorlocalisaties. De toepassing van IMRT voor de bestraling van hoofd- en halstumoren (HHT) vormt het onderwerp van het eerste deel van deze thesis. De planningsstrategie voor herbestralingen en bestraling van HHT, uitgaande van de keel en de mondholte wordt beschreven, evenals de eerste klinische resultaten hiervan. IMRT voor tumoren van de neus(bij)holten leidt tot minstens even goede lokale controle (LC) en overleving als conventionele bestralingstechnieken, en dit zonder stralingsgeïnduceerde blindheid. IMRT leidt dus tot een gunstiger toxiciteitprofiel maar heeft nog geen bewijs kunnen leveren van een gunstig effect op LC of overleving. De meeste hervallen van HHT worden gezien in het gebied dat tot een hoge dosis bestraald werd, wat erop wijst dat deze “hoge dosis” niet volstaat om alle clonogene tumorcellen uit te schakelen. We startten een studie op, om de mogelijkheid van dosisescalatie op geleide van biologische beeldvorming uit te testen. Naast de toepassing en klinische validatie van IMRT bestond het werk in het kader van deze thesis ook uit de ontwikkeling en het klinisch opstarten van intensiteitgemoduleerde arc therapie (IMAT). IMAT is een rotationele vorm van IMRT (d.w.z. de gantry draait rond tijdens de bestraling), waarbij de modulatie van de intensiteit bereikt wordt door overlappende arcs. IMAT heeft enkele duidelijke voordelen ten opzichte van IMRT in bepaalde situaties. Als het doelvolume concaaf rond een risico-orgaan ligt met een grote diameter, biedt IMAT eigenlijk een oneindig aantal bundelrichtingen aan. Een planningsstrategie voor IMAT werd ontwikkeld, en type-oplossingen voor totaal abdominale bestraling en rectumbestraling werden onderzocht en klinisch toegepast

Visual fields and ocular conditions in accessory sinus affections

• The optic nerves, optic canals, sphenoid bone, chiasma and central artery of the retina vary greatly in their relations. The optic canals vary greatly in length in different subjects, and often slightly in the same subject. They are much longer than is usually supposed. The central artery of the retina arises from the ophthalmic much further back than is usually believed, and sometimes within the optic canal if that structure be long. The intra cranial portions of the optic nerves vary in length from 7 m.m. to 14.5 m.m., and the diameter from 3.5 m.m. to 6.5 m.m. in different subjects. The table of bone between the limbus sphenoidalis and the olivary eminence (i.e.,the roof of the sphenoid sinus) varies in antero -posterior length from 4.5. m.m. to 9 m.m. ,but is usually about 5 m.m. This is of importance because only when it is large can the optic chiasma rest upon it, explaining the infrequency of bi- temporal heinianopsia in sphenoidal sinusitis. The Pituitary fossa,in antero -posterior diameter, from 5.5. m. ?2. to 11.5 m.m. ,more usually the latter; when it is large the table of bone above -mentioned is small and vice versa. The optic chiasma may be so anterior as to occupy the usually accepted position in the optic sulcus of the sphenoid bone, but only very rarely, much more usually it lies over the pituitary fossa. • Some form of visual field contraction occurs in 90 per cent of all cases. The visual fields for green and red, particularly the former, are, with rare exceptions, much more contrac- ted than the field for white. Therefore, white and green are the best tests to employ. General - more or less concentric - contraction occurred in about 76 per cent of cases, and is the most frequently observed. Temporal contraction occurred 15 times, or 50 per cent, and 8 of those 15 were bitemporal contractions; but bi-temporal hemianopsia is extremely rare. Altitudinal contraction occurred in 8 cases. A small island of vision may remain long after the rest of the nerve has become blind from papilloedema. Central scotoma is said to be the field defect usually observed in sinus affections, it is uncommon only occurring twice in this series, because most of the cases are chronic, and the toxins only affect the nerve by filtration and therefore affect the peripheral fibres (producing peripheral contractions), as the macular fibres of the nerve, excepting near the globe, are central in position (within the nerve); whereas in acute cases central scotoma is observed as it is either produced by pressure or by the toxins being conveyed by the blood stream. Bi-temporal hemianopsia is the only characteristic field of vision of a particular sinus, and that sinus the sphenoidal: because it can only be produced by involvement of the chiasma. Bi-temporal contractions are most usually observed in sphenoidal sinusitis, because the nasal sides of the nerves are in contact with that sinus. The visual field contractions are of much the sane_ character in the acute and chronic cases, though differing greatly in onset. Visual field contractions in association with nasal suppuration point: strongly to the suppuration being of sinus origin, and therefore the fields are an aid to diagnosis. Visual field contractions do not occur apparently in mucoceles, because they are unassociated with toxins. The contractions observed are not due to reflex irritation of the nose. They may be caused by direct pressure either within the optic canal by swelling, or within the nerve sheath by hydrops vaginae nervi optici, causing pressure, or by optic neuritis. But in chronic cases most frequently by percolation of toxins from the sinus cavity through the wall into the orbit affecting the nerve directly. This is usually unassociated with ophthalmoscopic changes. The visual fields may be contracted by post -operative oedema, pressing upon the optic nerve. The visual fields may become rapidly contracted, and restored by treatment; but treatment in the chronic has often little or no effect, because either the nerve is permanently damaged, or that sufficient toxin passes through from the pus which is usually secreted for a long time after operation, to keep up the contraction; or that the nerves only slowly recover in these chronic cases. • Optic neuritis may be in the form of Retro-bulbar which is rare and only occurs in acute cases: or as a Fine Hazy Neuritis usually observed in chronic cases, and is not uncommon; or as Choked Disc (Papilloedema) which is rare, and generally associated with chronic cases; and as Gross Neuritis, which, when present, is usually in acute cases. The Hazy neuritis may be observed in any of the sinuses and is probably due to toxins causing hydrops vaginae nervi optici and pressure upon the nerve. Choked Disc can probably only occur in the posterior group of sinuses, and is due to oedema within the optic canal caused by the toxin; and gross neuritis by inflammatory changes within the nerve by toxins brought by the blood stream and lymphatics, and mostly observed in the posterior group of sinuses. The kind of neuritis and its intensity is some guide to the sinus involved and the variety of sinusitis, but not absolutely. The neuritic process may be very intense and very acute in onset, and under appropriate treatment recovery may by very rapid. Vision may be almost completely restored after weeks of absolute blindness, and after neuritis has been present for even years with suitable treatment of the sinus affected, blindness and intense neuritis do not necessarily mean a bad prognosis. Atrophy may supervene in some degree, either as post-neuritic, or presenting the appearance of a primary atrophy. • Hippus reaction of the pupils in sinus affections is not infrequently observed, and for which there is no cdequate explanation. • The Central Artery may become obstructed from pressure or inflammatory oedema of the vascular coats, and present the appearance of embolus. • Muscular paralysis and paresis is not commonly due to sinus affections as is generally supposed. Myositis may occur. • Acute and chronic, primary, and secondary glaucoma may be excited by sinusitis; the primary by venous stasis, and the secondary by inflammatory affections of the uveal tract. • Affections of the Uveal tract are very uncommon, because the ciliary arteries by which toxins enter the globe are so well protected by a thick mass of fat from the sinuses. • From the foregoing conclusions, it is clear that the nose must be examined in all obscure ocular conditions

Central nervous system. Sense organs

Навчальний посібник рекомендований для студентів вищих медичних навчальних закладів IV рівня акредитації, які вивчають анатомію людини англійською мовою

Malignant melanoma and other malignancies of the nasal cavity and the paranasal sinuses in Sweden

Background: Malignancies emerging in the nasal cavity and the paranasal sinuses are rare and accounts for 5% of all head and neck malignancies and 0.1% of all malignancies in Sweden. The incidence of sinonasal malignancy (SNM), except sinonasal malignant melanoma (SNMM), has been reported to decrease since 1960 in Sweden. Despite similar improvement in the prognosis of other malignancies, treatment of SNM still yields a poor survival outcome. About 1–2% of all malignant melanomas originate from mucosal membranes in the genitourinary, digestive and the respiratory regions, whereas mucosal melanomas are most frequently located in the nasal cavity, followed by sites in paranasal sinuses in the head and neck region. The incidence of cutaneous malignant melanoma (CMM) continues to increase in many parts of the world, possibly due mainly to the effects of sun-related behaviour; however, the incidence of mucosal melanomas such as vulvar and ano-rectal melanoma display a more complicated pattern with a stable or decreasing incidence rate. We now know that the incidence of SNMM is increasing in Sweden, as we have documented one of the largest consecutively studied SNMM groups in the world. Nevertheless, the underlying mechanism remains unclear. The treatment options for these patients have remained the same over the years; mainly radical surgery followed by radiotherapy. Alternatively, recent molecular-targeted therapy has become available for sub-groups of patients with malignant melanomas. Such therapeutic advances stress the importance of investigating the aetiology and molecular characteristics of SNMM, which are not yet well. Aims: Given the rarity of SNM and SNMM, relevant knowledge is limited. Therefore, the overall aim of this thesis was to examine the clinical characteristics and features of SNMM and SNM and to determine the occurrence of molecular alterations. They include KIT, NRAS and BRAF mutation frequencies and mutation frequency of the TERT (Telomerase Reverse Transcriptase) promotor gene in SNMM. Results: In the first project, we identified 3221 patients from the Swedish National Cancer Registry diagnosed with primary malignancies arising from the nasal cavity, paranasal sinuses, or both, during the period 1960 through 2011. The anatomical site, gender and age, incidence and survival were scrutinized. We found that the incidence of sinonasal malignancies decreased except for SNMM and adenoid cystic cancer during the study period. More than 50% of these malignancies involved the nasal cavity. The five-year relative survival was highest for patients with adenoid cystic cancer followed by adenocarcinoma. Those with SNMM and undifferentiated carcinoma had the poorest prognosis. In the second project we identified 186 SNMM patients during the period 1960 through 2000 in Sweden from the National Swedish Cancer Registry (SCR). We investigated the incidence, gender, age, primary anatomical sites, geographic distribution, treatment and survival. In this population the incidence of SNMM increased during the study period. The incidence for females was higher than for males, and the incidence increased with age for both genders. We found that about 70% of the tumours were clinically described as amelanotic. Surgery was the most common primary treatment. The five-year disease- specific survival rates were poor for both genders, but females had a better survival than males. The survival rate improved for both genders during the study period, regardless of therapeutic strategy. We conclude that the incidence of SNMM in Sweden increased significantly from 1960 through 2000 but not as rapidly as that of CMM. In the third project, we analysed 56 primary SNMMs, the largest number, as far as we know, for mutations in KIT (exons 11, 13 and 17), NRAS (exons 1 and 2) and BRAF (exon 15) identified by using direct sequencing. Twelve of the 56 (21%) tumours contained mutations in these oncogenes, 2 tumours harboured KIT mutations, another 2 harboured BRAF mutation and 8 had NRAS mutations. We found a higher frequency of mutations in tumours originating from the paranasal sinuses compared to tumours from the nasal cavity (p=0.027). In the fourth project we analysed 49 SNMM tumours for TERT promotor gene mutations, since former investigators found only a few driver mutations for these patients, who were never previously examined for this mutation. Recent studies of CMM have shown a high frequency (>70%) of driver mutations in this gene. TERT promoter mutations occur at a moderate frequency in SNMM. We suggest that SNMM tumours should be included in molecular characterization, since these alterations probably will be therapeutic targets in the near future

An Observational study comparing the effect of Sphenopalatine Artery Block on bleeding in Endoscopic Sinus Surgery

This is a cross sectional observational study done in a tertiary care centre. 55 patients coming to the ENT department of Government Stanley Medical College from 2015 – 2016 were included in this study. Of these there were 28 males and 27 females. All the patients met the inclusion criteria decided upon at the beginning the study. Ethical committee clearance for the study was obtained and written informed consent for the study was taken from each patient. All patients had bilateral nasal sinus disease and endoscopic sinus surgery was performed on both sides. The procedure done on both sides were the same in each case. 20 minutes prior to surgery one side was chosen randomly and sphenopalatine artery block was administered via the greater palatine canal approach. A mixture of lignocaine (2%) and adrenaline (1:80000) was used for infiltration. The surgery was done in an alternating fashion where the surgeon would operate for 15 minutes on one side and then move onto the other side. The field was graded for bleeding at 30 minute intervals. Wormald Grading System was used. The results were tabulated and the Wilcoxon Signed Rank Test was done at each time interval to see if there was a statistically significant difference in the grades of on both sides at each time interval. It was found that for each time interval up to 120 minutes there was a significant decrease in the bleeding on the blocked side. However after 120 minutes the bleeding on both sides appeared to be same. In conclusion sphenopalatine artery block given prior to surgery will be effective in reducing bleeding in FESS for the first 2 hours after which the effect of the block wears away

Investigation of CSF outflow in mice by in vivo, dynamic magnetic resonance imaging

The anatomical routes for the clearance of cerebrospinal fluid (CSF) remain incompletely understood. However, recent evidence has given strong support for routes leading to lymphatic vessels. A current debate centers upon the routes through which CSF can access lymphatics, with evidence emerging for either direct routes to meningeal lymphatics or along cranial nerves to reach lymphatics outside the skull. Here, a method was established to infuse contrast agent into the ventricles using indwelling cannulae during imaging of mice at 2 and 12 months of age by magnetic resonance imaging. As expected, a substantial decline in overall CSF turnover was found with aging. Quantifications demonstrated that the bulk of the contrast agent flowed from the ventricles to the subarachnoid space in the basal cisterns. Comparatively little contrast agent signal was found at the dorsal aspect of the skull. The imaging dynamics from the 2 cohorts revealed that the contrast agent was cleared from the cranium through the cribriform plate to the nasopharyngeal lymphatics. On decalcified sections, we confirmed that fluorescently labeled ovalbumin drained through the cribriform plate and could be found within lymphatics surrounding the nasopharynx. In conclusion, routes leading to nasopharyngeal lymphatics appear to be a major efflux pathway for cranial CSF