Dynamics of High Risk Clinical Target Volume reduction during Brachytherapy and impact on its coverage in patients with inoperable cervical cancer.

Cervical cancer is the third most common cancer in women worldwide. Standard of care for patients with node positive or locally advanced tumors >4 cm is definitive radiotherapy and concurrent chemotherapy. Brachytherapy is an integral part of definitive radiotherapy for cervical cancer. The aim of the study was to show a dynamics of High Risk Clinical Target Volume (HR-CTV) reduction during Brachytherapy (BT) as a part of definitive treatment (External Beam Radiotherapy /EBRT/ +/- Chemotherapy /ChT/) depending on the initial Gross Tumor Volume (GTV) and its impact on HR-CTV coverage in patients with inoperable cervical cancer. We analyzed the dosimetric data for BT of 54 patients who have had Three Dimensional Planning of BT (3D BT). The Gross Tumor Volume, HR-CTV and organs at risk (OARs) were contoured on the magnetic resonance imaging (MRI), subsequently on the co-registered MRI images with computed tomography (CT). Point A and ICRU 38 rectal and bladder points were defined on reconstructed CT images. Patients were categorized on the basis of whether the 100% isodose line of the point-A prescription dose encompassed the HR-CTV (1st group) or not (2nd group). The 30cc volume has been determined as a cut-off value, which represented the most acceptable value of intermediate size of volumes. The initial mean value of GTV was 42cc. After completion of EBRT/ChT, the mean GTV was 3.24cc what was 91% reduction rate in relation to the initial value. We followed the dynamics of HR-CTV reduction during BT and have noted its minimal reduction from 24.3cc (mean value) at the time of the first fraction to the 24.1cc before fourth fraction. The mean V100 was 98% and increased with decreasing of the volume size (p=0.0063, Fisher's exact test). D90 (mean value was 96.3 Gy10) has been correlated with V100 and also, it increased with decreasing of the volume size (p=0.0003). The mean D0.1cc and D2cc of rectum doses were 80 Gy3 and 65.6 Gy3, respectively. The mean ICRU rectal dose for all patients was 67.2 Gy3. The mean D0.1cc (99.5 Gy3), D2cc (79.5 Gy3) and ICRU (75.2 Gy3) of bladder doses were acceptable. Dynamics of HR-CTV reduction during BT was minimal, although, significant reduction of the GTV was achieved after EBRT/ChT. This study revealed that the dose prescription of 7 Gy × 4 fractions to point A was not sufficient indicator for dose coverage of the HR-CTV. However, dosimetric parameters as V100 and D90 were strong indicators for coverage of HR-CTV which was inversely related to the volume of the target and the extension of tumor. However, dosimetric parameters for rectum and bladder (D0.1cc, D2cc and ICRU) did not show dependence on the target volumes.

Tumour metabolic activity measured by fluorodeoxyglucose positron emission tomography for radiotherapy planning as a prognostic factor for locally advanced non-small cell lung cancer.

OBJECTIVES: To analyse whether the maximum standardized uptake value of the positron emission tomography/computed tomography for radiotherapy planning was useful as a prognostic factor for tumour response and survival of patients with locally advanced non-small cell lung cancer. BACKGROUND: Increased 18F-fluoro-2-deoxyglucose uptake by lung cancer cells, measured as the maximum standardized uptake value, has been reported to predict the biologic aggressiveness of both early and advanced non-small cell lung cancer. METHODS: A prospective study was performed in 61 consecutive patients with unresectable stage IA-IIIB of non-small cell lung cancer. The mean age was 65 years. Seventy five percent of patients in the entire group received an induction chemotherapy. The mean dose of radiotherapy was 61Gy. All patients underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography for radiotherapy planning. RESULTS: Thirty six percent of the patients experienced a complete response and 20 % had a partial tumour response. Forty four percent of the patients suffered from a progressive disease. The maximum standardized uptake value of the primary tumour more than 11.4 was correlated with a worse tumour response (p = 0.0001) and a shorter survival of our patients (p = 0.0109). CONCLUSION: We found a correlation between the maximum standardized uptake value and the patient prognosis and lung cancer aggressiveness (Tab. 3, Fig. 5, Ref. 18).

Multiple metachronous malignant fibrous histiocytomas of the upper limbs -  a case report.

BACKGROUND: Soft-tissue sarcomas are rare tumors with the incidence of multiple metachronous or synchronous lesions in the extremities being even more uncommon. In effort to preserve the function of upper extremities, limb-salvage surgery became the treatment of choice for soft-tissue sarcomas. Subsequent adjuvant chemotherapy, as well as radiotherapy, is believed to decrease local recurrence rates, however, their effect on overall survival remains unclear. CASE: We report herein a case of symmetrical bilateral metachronous malignant fibrous histiocytomas of the shoulder. A 19-year-old patient presented with stiffness and pain in the right shoulder. The same symptoms developed 1.5 years later in the other shoulder. The culprit tumors are reported metachronous with regard to the succession in the onset of symptoms. Wide tumor resection was performed in both shoulders, and postoperative radiotherapy was then conducted. Chemotherapy was not indicated after the first surgery; whereas, in the second case it was the patient who refused the recommended adjuvant chemotherapy. CONCLUSION: The phenomenon of either metachronous or synchronous incidence of multiple soft tissue sarcomas is very rare and systematic reporting of every new case in the literature could contribute to further knowledge of tumors unique behavior.Key words: malignant fibrous histiocytoma - radiotherapy - upper extremity - neoplasms - multiple primary.

[Penile disassembly technique: a new approach in the surgical reconstruction of hypospadias]. / Technique de désassemblage du pénis: une nouvelle approche de la chirurgie reconstructrice de l'hypospade.

We report our experiences with penile disassembly technique in the treatment of severe hypospadias. During a period from November 1995 to December 1997 the technique was applied to 102 patients, aged from 9 months to 32 years. The principle of the technique involves separation of the penis into its component parts: glans cap with neurovascular bundle (dorsally) together with undivided or divided urethra and urethral plate (ventrally), and corpora cavernosa. After correction of the curvature and different techniques of urethroplasty the penile entities are joined into normal anatomical relationships. Our goal was also to achieve some degree of penile enlargement in small hypospadiac penises. The patients were followed from 4 to 29 months (mean 19.2 months). Straightening of the penis was achieved in all cases without recurrence of curvature. Complications were related to urethroplasty: 3 urethral stenoses, 2 fistulas and 2 diverticulum. Penile disassembly technique is very effective for most severe hypospadias. Possibility of penile augmentation is real with this technique.

[Radiotherapy of local recurrence of rectal carcinoma]. / Radioterapija lokalnih recidiva karcinoma rektuma.

In retrospective, non-randomized study were analyzed 45 patients with local recurrences of rectal carcinoma treated by combined external beam radiotherapy (EBRT) and "High dose rate (HDR) remote afterloading" brachytherapy in the period from January 1st, 1988 to May 1st, 1988. Depending on the localization of the local recurrent disease, 20 patients were with vaginal relapse, 13 with vaginal and presacral, 9 with perineal and 3 with presacral and rectal. Combined radiotherapy was applied as follows: 33 patients (73.3%) had EBRT with endovaginal brachytherapy, 3 (6.7%) EBRT plus intraluminal brachytherapy and 9 (20%) patients EBRT plus interstitial brachytherapy. Techniques with 3 and 4 field for EBRT were used and doses ranged 45-65 Gy with convenient fractionation were applied, combined with the doses ranged 15-35 Gy for brachytherapy. Radiotherapy was planned according to the computer tomography cross image on simulator with computer planning. Complete regression of the tumor was observed in 19 patients (42.2%), and partial in 23 patients (51.1%). Median follow-up period was 34 months (8-72). Acute radiation adverse effects were registered in 32 patients, and late sequels in 6 (13.3%). Overall 3-year survival rate was 54% and disease-free survival rate was 34% in the same period.

Nonoperative treatment of achalasia.

Twelve children with achalasia were treated by the technique of balloon dilatation in the years 1984-1991. Follow-up from 2 to 8 years (mean 3.5 years) showed complete relief of obstruction in 10 patients, while two required esophagomyotomy. Balloon dilatation is effective in the treatment of achalasia.

[Multiple endocrine neoplasia type IIa]. / Prikaz bolesnice multiplom endokrinom neoplazijom tipa dva-A

A gradual manifestation first of parathyroid and then od thyroid and adrenal endocrinopathy in 38-year old female patient, with the syndrome of Multiple Endocrine Neoplasia (MEN) type IIa--Sippl syndrome, is presented. The first diagnosis was hyperparathyroidism, which is unusual in this syndrome, as only a half of the patients affected with MEN IIa have hyperparathyroidism. The diagnosis of medullary thyroid carcinoma is operatively established. The syndrome is diagnosed after the manifestation of the clinical signs of pheochromocytoma. This syndrome is hereditary in autosomal and dominant way. Our patient is the first member in the risk family: the family medical history of our patient was negative. As this syndrome can appear in the age range from 2-67, we intend to make the screening of all the members of the patient's family.

[Congenital mesoblastic nephroma]. / Kongenitalni mezoblastni nefrom.

Four children with congenital mesoblastic nephroma were treated at the Children's University Hospital in Belgrade, between 1979 and 1990. In relation to the total number of children cured from renal tumours (44), diagnosis of congenital mesoblastic nephroma was confirmed in 9% of all cases with renal tumours. The age of all diagnosed patients was under one year. Three patients developed unilateral and one patient bilateral congenital mesoblastic nephroma. The authors also stress the importance of differential diagnosis between congenital mesoblastic nephroma and other renal tumours, since therapy and prognosis of these tumours are different. In a case of bilateral congenital mesoblastic nephroma that later relapsed with malignant alteration, it is questionable whether bilateral nephrectomy was the most appropriate treatment.

Epispadias surgery--Belgrade experience.

From 1987 to 1991, 46 patients underwent surgical treatment for epispadias. Of these, 14 had isolated epispadias and 22 had epispadias within the exstrophy/epispadias complex. The patients ranged in age from 6 months to 20 years. To correct the genital aspect of the anomaly the basic principles of Ransley's technique were used. In addition, the island flap technique was used for the most severe, so-called "cripple" form. In patients with exstrophy/epispadias complex, only elongation of the penis was performed during primary reconstruction, while the correction of epispadias, using the above techniques, was performed in the second-stage operation. Complications occurred in 6 patients.

Bladder exstrophy and anterior pelvic osteotomy.

Between August 1988 and December 1991, 36 children with bladder exstrophy underwent surgery for primary bladder reconstruction. Each child was either untreated or had already been treated unsuccessfully. The operative technique involved bilateral osteotomy of the superior ramus of the pubic bone. In infants the cartilaginous ischiopubic junction, acting as an articulation, allowed symphyseal approximation, while in older children this was achieved by fracture of the inferior ramus of the pubic bone. The bladder was either closed or, in most cases, the exstrophic bladder plate was inserted deep into the pelvis, allowing subsequent epithelialisation of the bladder and further formation and growth. Follow-up up for 3.5 years showed bladder capacities of 40 to 150 ml. Some patients underwent an additional augmentation enterocystoplasty. Primary bladder reconstruction remained uncompromised in 7 patients who developed moderate (and 1 complete) rediastasis of the pubic bones. All exstrophic bladders are reconstructible, particularly in older children.

[Surgery in recurrence of undescended testes]. / Hirurgija recidiva nesputenog testisa.

In the period from Jan. '80 to Dec. '87 at the Pediatric Surgical Clinic in Belgrade 119 patients were operated upon or 147 recurrencies of undescended testes; in 28 cases (23.52%) there were bilateral recurrences. 4 patients were twice unsuccessfully operated on at the same side. The authors analyse the causes of failures of orchiopexy; the proved mistakes were divided into four groups: a) Mistakes due to the undiscovering of the testis, b) unpreparation, or insufficiently preparated the testis from surrounding tissues, c) insufficiently shortening of the testis' way toward the scrotum, and d) mistakes being occasionally arised during the fixation of the testis into the scrotum. During the first unsuccessful operation 20 testes have atrophied, so that a reintervention consisted only in the exploration. In other cases the testis was placed into the scrotum regardless whether it was normal or hypotrophic. In two cases a Fowler-Stephens procedure was carried out, and in one case an autotransplantation of the testis was done. An improvement was found in 89 testes (60.57%), while 38 cases (25.85%) remained with the same characteristics, as they were in the course of our surgical interventions.

[Stenosis of the external urethral opening as one of the causes of recurrent urinary infections in girls--surgical treatment]. / Stenoza spoljasnjeg otvora uretre kao jedan od uzroka recidivantnih urinarnih infekcija u zenske dece--hirurska leenje.

105 middleaged girls (8.4 years) were operated upon at this Clinic because of distal meatal stenosis (DMS) as one of the causes of recurrent urinary infections and/or tenacious dysuria. Meatoplasty, one small surgical intervention, does treat about 78.1% infections of the urinary tract, as well as about 36.8% vesicoureteral reflux (VUR) of the I and II grade. The fibrous ring which is an anatomical alteration of DMS, is primarily obstructive lesion, which is appearing most frequently associated with urinary infection. In one quarter of cases in which a meatoplasty did not show a clinical improvement, one should think over the more radical surgery either at the urinary neck or at the vesico-ureteral junction. Spontaneous improvement or/and regression of VUR, in one third of cases following meatoplasty is an encouraging datum; but this intervention by itself is not a method for its treatment. A small number of complications, one stress incontinence only, demonstrate a reliability of this procedure in selected cases. Meatoplasty and dilatation of stenosed urethral meatus are alternative methods, which give similar results and their use mainly depends on the urologist's affinity to this method.

Evaluation of the new type of military bullet and rifling.

The 5.56-mm caliber SS 109 projectile was fired from 7.7'' and 12'' twist rifles, respectively, into soap blocks and porcine thighs at 50-metre range using a standardized experimental setup. For comparison, the effects of the 5.56-mm M 193 bullet fired from the 7.7'' twist barrel and M-16 assault rifle were tested. The volume of residual cavity in soap, the shape and sizes of live tissue wounds, and the mass of surgically debrided devitalized tissue were measured. The effects of the two projectiles at 7.7'' twist were found similar in soap; the SS 109 produced more tissue damage than the M 193 missile. Using the 12" twist rifle, a significant increase in wounding capacity of SS 109 projectile was found. In conclusion, nonsignificant differences in local effects between the two projectiles using the 7.7'' twist rifles were found, and markedly increased effects of the SS 109--12'' system were ascribed to decreased essential stability and its earlier tumbling in penetrating a target. The soap as a live tissue simulant has proven its reliability in testing small-caliber arms.

[Ureterocystoneostomy using the psoas hitch technic--outside variant]. / Ureterozystoneostomie nach der Psoas-Hitch-Technik--"Outside"-Variante.

This paper presents the "outside" variant of the standard psoas hitch procedure. Two basic principles of the procedure are: lateralisation and fixation of the bladder at the psoas muscle; the long and straight reimplantation of the ureter on the posterior, lateral or anterolateral bladder wall using the extravesical approach. The main indications were the extensive changes of the ureter in case of neurogenic bladder dysfunction and the reduced bladder capacity with the changes of the mucous membrane. The procedure was also applied in those cases where the standard procedure would have been indicated. The advantages and disadvantages of the procedure in relation to the standard psoas hitch procedure are discussed. During 1982 to 1985 this procedure was applied in 67 cases. The age ranged from 2 months to 14 years. With 9 patients the operation was performed bilaterally. The time interval between the operations was from 3 to 6 months. Tailoring of the ureter was undertaken in 3 cases. The complications were: One ureter stenosis that was solved by means of the same technique, and three parahiatal diverticula formations without clinical manifestations.

[Study of the mechanism of injuries due to high velocity projectiles]. / Eksperimentalni prilog proucavanju mehanizma povredivanja projektilima velike pocetne brzine.

In the experiments on pigs wounds on the muscle-connective tissues of the thighs were made at 50 meter range by projectiles of military Rifles M 48, M 70, M 16A FAL (the length of the wound canal from 214 to 228 mm), M 91/30 and Dragunov (the length of the wound canal from 160 to 164 mm). The mass of tissue excised at primary surgical debridement was taken as a criterium of the primary devitalization of tissue, the amount of the transferred energy was calculated as well as other parameters of the terminal ballistics. Shooting through the glycerine-soap blocks under the same conditions were parallelly performed. The examinations have shown that the degree of the primary mechanical injury depended on the amount of the transferred energy, which depended not only on the high initial velocity of the bullet but also on the disintegrated, deformed and fragmented bullet after passage through the tissue. The mass of the excised tissue can be a reliable criterium for evaluation of wound severity. There is a good correlation with the volume of the cavity in the soap blocks so that they can be used in experiments as simulant biological media.

A method for predicting effects of military rifles.

Comparative analysis of penetration of military bullets through soap blocks and an average 220 mm long trajectory through live muscle in pigs, at 50 m range, using Yugoslav M 48 cal. 7.9 mm and M 70 cal. 7.62 mm, Belgian FAL cal. 7.62 mm and American M 16 A 1 cal. 5.56 mm rifles were performed. The volume of residual cavity in soap (Z) and the mass of surgically excised dead tissue (G) were inter-related and a power curve G = a Zb was determined, yielding a coefficient of correlation 1.00. Another series of tests using two Soviet rifles - M 1891/30 cal 7.62 mm and Dragunov cal. 7.62 mm with average trajectory length in pigs 160 mm, was effected. Applying the same regression coefficients "a" and "b" from previous studies, a prediction of G from Z was found to be correct with less than 10% error, as compared to really excised tissue by a surgeon. In conclusion, a mathematical model derived from soap tests can be reliably applied for predicting injury made in vivo by standard military rifles.