Intercomparison of treatment concepts for MR image assisted brachytherapy of cervical carcinoma based on GYN GEC-ESTRO recommendations.

PURPOSE: To perform a multicentre intercomparison study of treatment concepts for MRI assisted brachytherapy of cervix cancer based on recommendations of the Gynaecological GEC-ESTRO Working Group. METHODS: Each participating centre (IGR Paris, University Hospital Leuven, Medical University of Vienna) contributed data of one patient with comparable clinical features. GTV, High Risk CTV (HR CTV), Intermediate Risk CTV (IR CTV) and organ walls of bladder, rectum and sigmoid colon were delineated at the time of each brachytherapy fraction on axial MR images with the applicator in place. Dose-volume histograms were calculated to evaluate doses to tumour, target volumes and organs at risk. Dose values were biologically normalised to equivalent doses in 2 Gy fractions (EQD(2), equivalent to 50 cGy/h low dose rate) applying the linear-quadratic model. RESULTS: Total doses to point A from external beam therapy plus brachytherapy ranged from 85 to 91 Gy and were close to the dose covering 90% of HR CTV (D90=85-87 Gy). D90 of IR CTV was within 69-73 Gy. Doses to organs at risk were comparable. CONCLUSIONS: This study indicates the feasibility of the GEC-ESTRO recommendations. Despite different treatment concepts, biologically normalised total doses to tumour, target volumes and organs at risk were comparable.     

Options for salvage after failed initial treatment of anterior vocal commissure squamous carcinoma

Persistence or recurrent cancer in the anterior commissure (AC) after primary radiotherapy may remain localized to its pretreatment anatomical site. If so, endoscopic CO₂ laser excision, in experienced hands, may achieve complete tumor excision and result in cure for many patients. Occasionally, second and third recurrences may be similarly salvaged by further endoscopic surgery. The use of the vertical hemilaryngectomy is an alternative treatment for similar localized lesions, with a higher first time surgical tumor eradication rate, but with a more protracted hospitalization and a less satisfactory voice and swallowing outcome. In both types of such surgical salvage, CT scanning must demonstrate no evidence of cartilage invasion or destruction. When there is evidence of minimal thyroid cartilage invasion, then the supracricoid partial laryngectomy is an alternative conservation option, and is likely to result in a cure, with the retention of a voicing larynx without a stoma. When the tumor has increased in size from the original pretreatment dimension and/or site, then imaging must be used to identify possible cartilage invasion, in which case the likelihood of tumor eradication by endoscopic or external vertical partial laryngectomy is highly unlikely. The indications for the routine use of total laryngectomy for the treatment of recurrent or persistent cancer involving the AC must be reviewed; there is current evidence that cure can be achieved by a less radical procedure. However, total laryngectomy may remain the only treatment option for advanced or aggressive first time recurrence, or in patients who develop subsequent recurrence following previous less aggressive surgery (endoscopic or external).     

Risk of cancer among relatives of patients with glioma.

We report a population-based, retrospective study of 396 Icelandic people diagnosed with glioma in the years 1940-1995. The purpose of this study was to test whether astrocytomas, other glial tumors, other central nervous system tumors, or other cancers aggregate in families identified through glioma probands who were of Icelandic origin. Pedigrees of the 396 cases were traced by the Genetical Committee of the University of Iceland and linked to the Icelandic Cancer Registry. A total of 25,546 relatives, including 2,080 individuals with cancer were identified within these pedigrees. There was no statistically significant increase of glioma in relatives of glioma patients, nor was there any statistically significant increase in risk for other central nervous system tumors. There was no overall increase in incidence of all cancer combined, nor of specific common cancers (lung, prostate, breast, stomach, and colorectal) and uncommon cancers (melanoma and pancreas) in the relatives of glioma patients. Our results do not support the hypothesis of a familial aggregation of glioma indicative of a glioma susceptibility gene.     

Maturation of ovine uterine smooth muscle during development and the effects of parity

OBJECTIVES: To characterize changes in myometrial contractile proteins and myosin heavy chain (MHC) isoforms during ovine fetal and neonatal development and after pregnancy. We hypothesized that ovine myometrium demonstrates progressive cellular differentiation and maturation which begins in utero and extends into the postnatal period, and that pregnancy causes further cellular alterations. METHODS: Myometrium was obtained from female fetal (72- to 140-days of gestation, n = 19; term = approximately 145 days), postnatal (1 day to 3 months, n = 25), and parous noncycling nonpregnant (n = 9) sheep to measure total and soluble proteins, actin, MHC, and MHC isoforms. Contractile proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and expression of 200-kD MHC isoforms were determined with Western immunoblots. RESULTS: The contents of total and soluble proteins and actin and total myosin gradually increase (P <.003) during ovine development. Although the contribution of smooth-muscle 204-kD MHC increased (P <.001) from 23 +/- 8% of total MHC at <100 days of gestation to 75 +/- 2% 3 to 4 months postnatally, the 200-kD species fell proportionately. Before birth, MHC-B, a fetal isoform, is the predominant 200-kD protein; postnatally, it is replaced by SM2, demonstrating a switch from a synthetic to a mature contractile smooth-muscle phenotype. Pregnancy is associated with further increases in actin contents and redistribution of the contents of the 204-kD and SM2 MHC isoforms. CONCLUSIONS: Although the fetal and postnatal uterus has no known functional demand, ovine myometrial differentiation and maturation begin in the midtrimester and continue throughout the postnatal period. Thus, changes in smooth-muscle phenotype occur prenatally, as evidenced by a switch from MHC-B to SM2, which may signal completion of organ development and preparation for adult function. Pregnancy results in further modifications in myometrial proteins.     

Combined static-dynamic MR urography for the simultaneous evaluation of morphology and function in urinary tract obstruction

Objective. A new approach, combined static-dynamic MR urography is evaluated to determine its potential utility for the functional-morphological diagnosis of paediatric urinary tract obstruction. In this initial investigation we sought to evaluate the procedure by imaging the urinary tract of piglets. Materials and methods. Twenty-nine healthy piglets were studied with MR urography (MRU), ^{99 m}Tc-MAG3 diuretic renal scintigraphy (DRS), ultrasound (US) and excretory urography (EU). The functional and morphological findings were compared. For MRU we combined a respiration-triggered 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA injection. Results. MRU depicted the complete urinary tract with superior image quality compared to EU. Calculation of time-intensity curves from the dynamic sequence permitted determination of single kidney function from parenchymal ROIs and urinary excretion using the whole kidney ROI. MRU and DRS showed significant agreement in the assessment of both single kidney function and urinary excretion. Disturbances of urinary drainage were generally caused by an overfilled bladder. Conclusions. Combined static-dynamic MRU is well suited for the depiction of the complete urinary tract and for the determination of individual kidney function and urinary excretion in the piglet. Received: 21 February 2000 Accepted: 14 March 2000     

Combined static-dynamic MR urography for the simultaneous evaluation of morphology and function in urinary tract obstruction

PURPOSE: To assess the diagnostic value of combined static-dynamic MR urography (MRU) for the functional-morphological evaluation of experimentally induced urinary tract obstruction in the piglet. MATERIALS AND METHODS: In 20 piglets unilateral ureteric stenosis was created operatively. Post-surgery repeated comparative examinations were obtained with MRU, diuretic renal scintigraphy (DRS), excretory urography (EU) and ultrasound (US). MRU was performed as a combination study with a static 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA with frusemide administration. RESULTS: MRU allowed complete depiction of the prestenotic urinary tract and of the stenosis in all cases. In 43 comparative studies MRU was superior to EU in 36, EU to MRU in 2. When single kidney function was calculated with both MRU and DRS, results were highly correlated (r = 0.92). When urinary excretion was compared, significant agreement was achieved with concordant findings in 86% and slightly discordant results in 12%. CONCLUSIONS: Static-dynamic MR urography permits excellent depiction of experimentally induced urinary tract obstruction in piglets and reliable assessment of individual renal function and urinary excretion. Two advantages of the method stand out--it does not require radiation and it permits functional-morphological correlation.     

Double-blind crossover study of sacral nerve stimulation for fecal incontinence

PURPOSE: Patients with fecal incontinence not amenable to simple repair may have to undergo major reconstructive surgery or resort to a stoma. Sacral nerve stimulation is an alternative approach that may diminish incontinence by altering sphincter and rectal motor function. This study is the first double-blind trial examining the effectiveness of this therapy. METHODS: Two patients with passive fecal incontinence who had been implanted for nine months with a permanent sacral nerve stimulator and electrode were studied using fecal incontinence diaries, anorectal physiological tests, and quality-of-life assessments (SF-36 health survey). The trial period consisted of two two-week periods, with the stimulator turned on for two weeks and off for two weeks. The main investigator and the patients were blinded to the status of the stimulator. RESULTS: There was a dramatic difference between the number and severity of episodes of incontinence when the stimulator was turned onvs. turned off (Patient 1, 20vs. 2 episodes; Patient 2, 4vs. 0 episodes; offvs. on). There was an increase in squeeze pressure (Patient 1, 70vs. 100 cm H₂O; Patient 2, 60vs. 90 cm H₂O; offvs. on), with moderate increases in resting pressure and rectal threshold and urge volumes. Quality-of-life measurements showed a marked improvement prestimulationvs. nine months after permanent stimulation. CONCLUSIONS: There is a marked, unequivocal improvement in symptoms of fecal incontinence with sacral nerve stimulation shown in this double-blind crossover trial. Sacral nerve stimulation improves the quality of life in selected patients with fecal incontinence.A grant and all the equipment used in this study were supplied by Medtronic INTERSTIM, Maastricht, the Netherlands.