Impact of a rectal and bladder preparation protocol on prostate cancer outcome in patients treated with external beam radiotherapy.

PURPOSE AND OBJECTIVE: To test the hypothesis that a rectal and bladder preparation protocol is associated with an increase in prostate cancer specific survival (PCSS), clinical disease free survival (CDFS) and biochemical disease free survival (BDFS). PATIENTS AND METHODS: From 1999 to 2012, 1080 prostate cancer (PCa) patients were treated with three-dimensional conformal radiotherapy (3DCRT). Of these patients, 761 were treated with an empty rectum and comfortably full bladder (RBP) preparation protocol, while for 319 patients no rectal/bladder preparation (NRBP) protocol was adopted. RESULTS: Compared with NRBP patients, patients with RBP had significantly higher BDFS (64% vs 48% at 10 years, respectively), CDFS (81% vs 70.5% at 10 years, respectively) and PCSS (95% vs 88% at 10 years, respectively) (log-rank test p < 0.001). Multivariate analysis (MVA) indicated for all treated patients and intermediate high-risk patients that the Gleason score (GS) and the rectal and bladder preparation were the most important prognostic factors for PCSS, CDFS and BDFS. With regard to high- and very high-risk patients, GS, RBP, prostate cancer staging and RT dose were predictors of PCSS, CDFS and BDFS in univariate analysis (UVA). CONCLUSION: We found strong evidence that rectal and bladder preparation significantly decreases biochemical and clinical failures and the probability of death from PCa in patients treated without daily image-guided prostate localization, presumably since patients with RBP are able to maintain a reproducibly empty rectum and comfortably full bladder across the whole treatment compared with NRPB patients.

Is there still a role for computed tomography and bone scintigraphy in prostate cancer staging? An analysis from the EUREKA-1 database.

PURPOSE: According to the current guidelines, computed tomography (CT) and bone scintigraphy (BS) are optional in intermediate-risk and recommended in high-risk prostate cancer (PCa). We wonder whether it is time for these examinations to be dismissed, evaluating their staging accuracy in a large cohort of radical prostatectomy (RP) patients. METHODS: To evaluate the ability of CT to predict lymph node involvement (LNI), we included 1091 patients treated with RP and pelvic lymph node dissection, previously staged with abdomino-pelvic CT. As for bone metastases, we included 1145 PCa patients deemed fit for surgery, previously staged with Tc-99m methylene diphosphonate planar BS. RESULTS: CT scan showed a sensitivity and specificity in predicting LNI of 8.8 and 98 %; subgroup analysis disclosed a significant association only for the high-risk subgroup of 334 patients (P 0.009) with a sensitivity of 11.8 % and positive predictive value (PPV) of 44.4 %. However, logistic multivariate regression analysis including preoperative risk factors excluded any additional predictive ability of CT even in the high-risk group (P 0.40). These data are confirmed by ROC curve analysis, showing a low AUC of 54 % for CT, compared with 69 % for Partin tables and 80 % for Briganti nomogram. BS showed some positivity in 74 cases, only four of whom progressed, while 49 patients with negative BS progressed during their follow-up, six of them immediately after surgery. CONCLUSIONS: According to our opinion, the role of CT and BS should be restricted to selected high-risk patients, while clinical predictive nomograms should be adopted for the surgical planning.

Technical considerations in transforaminal endoscopic spine surgery at the thoracolumbar junction: report of 3 cases.

OBJECTIVE In this study the authors describe the technical considerations and feasibility of transforaminal discectomy and foraminoplasty for the treatment of lumbar radiculopathy in patients who have herniated discs at the thoracolumbar junction. METHODS After institutional review board approval, charts from 3 consecutive patients with lumbar radiculopathy and T12-L1 herniated discs who underwent endoscopic procedures between 2006 and 2014 were reviewed. RESULTS Consecutive cases (n = 1316) were reviewed to determine the incidence and success of surgery performed at the T12-L1 level. Only 3 patients (0.23%) treated with endoscopic surgery for their herniated discs had T12-L1 herniated discs; the rest were lumbar or lumbosacral herniations. For patients with T12-L1 disc herniations, the average preoperative visual analog scale score was 8.3 (indicated in the questionnaire as describing severe and constant pain). The average 1-year postoperative visual analog scale score was 1.7 (indicated in the questionnaire as mild and intermittent pain). CONCLUSIONS Transforaminal endoscopic discectomy and foraminotomy can be used as a safe yet minimally invasive technique for the treatment of lumbar radiculopathy in the setting of a thoracolumbar disc herniation.

Could machine learning improve the prediction of pelvic nodal status of prostate cancer patients? Preliminary results of a pilot study.

We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48-86%, 35-91%, and 17-79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.

Machine learning approach for the development of a crucial tool in suicide prevention: The Suicide Crisis Inventory-2 (SCI-2) Short Form.

The Suicide Crisis Syndrome (SCS) describes a suicidal mental state marked by entrapment, affective disturbance, loss of cognitive control, hyperarousal, and social withdrawal that has predictive capacity for near-term suicidal behavior. The Suicide Crisis Inventory-2 (SCI-2), a reliable clinical tool that assesses SCS, lacks a short form for use in clinical settings which we sought to address with statistical analysis. To address this need, a community sample of 10,357 participants responded to an anonymous survey after which predictive performance for suicidal ideation (SI) and SI with preparatory behavior (SI-P) was measured using logistic regression, random forest, and gradient boosting algorithms. Four-fold cross-validation was used to split the dataset in 1,000 iterations. We compared rankings to the SCI-Short Form to inform the short form of the SCI-2. Logistic regression performed best in every analysis. The SI results were used to build the SCI-2-Short Form (SCI-2-SF) utilizing the two top ranking items from each SCS criterion. SHAP analysis of the SCI-2 resulted in meaningful rankings of its items. The SCI-2-SF, derived from these rankings, will be tested for predictive validity and utility in future studies.

Impact of the Abbreviated Suicide Crisis Syndrome Checklist on Clinical Decision Making in the Emergency Department.

Objective: The suicide crisis syndrome (SCS), an acute negative affect state predictive of near-term suicidal behavior, is currently under review for inclusion as a suicide-specific diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM). While the predictive validity of the SCS for near-term suicidal behavior is well documented, its real-world clinical utility has yet to be evaluated. As such, this study evaluated how implementation of a novel assessment tool, the Abbreviated SCS Checklist (A-SCS-C), into the electronic medical records (EMRs) influenced disposition decisions in the emergency departments (EDs) of a large urban health system.Methods: Logistic regression analyses evaluated the impact of SCS diagnosis on 212 admission/discharge decisions after accounting for chief complaints of suicidal ideation (SI), suicidal behavior (SB), and psychosis/agitation.Results: The A-SCS-C was concordant with 86.9% of all non-psychotic disposition decisions. In multivariable analysis, the A-SCS-C had an adjusted odds ratio (AOR) of 65.9 (95% confidence interval: 18.79-231.07) for inpatient admission, whereas neither suicidal ideation nor behavior was a significant predictor. The effect size remained very high in 3 sensitivity analyses, the first using information from a different section of the EMR, the second in patients younger than 18 years, and the third in males and females separately (AORs > 30).Conclusions: SCS diagnosis, when implemented in ED EMRs alongside SI and SB, was strongly predictive of clinician decision making with regard to admission/discharge, particularly in non-psychotic patients, while SI and SB were noncontributory. Overall, our results show that the SCS, as a diagnostic entity, demonstrates robust clinical utility and may reduce the limitations of relying on self-reported SI as a primary basis of suicide risk assessment.

Pretreatment patient-specific IMRT quality assurance: a correlation study between gamma index and patient clinical dose volume histogram.

PURPOSE: The aim of this work is to investigate the predictive power of a common conventional intensity modulated radiation therapy (IMRT) quality assurance (QA) performance metric, the gamma passing rate (%GP), through the analysis of the sensitivity and of the correlation between %GP and different dose discrepancies between planned dose-volume histogram (DVH) and perturbed DVH. The perturbed DVH is calculated by using a dedicated software, 3DVH (Sun Nuclear Corporation, Melbourne, FL), which is able to modify the dose distribution calculated by the treatment planning system (TPS) according to the dose discrepancies detected with planar measurements in order to predict the delivered 3D dose distribution in the patient. METHODS: Twenty-seven high-risk prostate cancer (PP) patients and 15 head and neck (HN) cancer patients, treated with IMRT technique, were analyzed. Pretreatment verifications were performed for all patients' plans by acquiring planar dose distributions of each treatment field with 2D-diode array. Measured dose distributions were compared to the calculated ones using the gamma index (GI) method applying both global (Van Dyk) and local normalization, and %GP were generated for each pair of planar doses using the following acceptance criteria: 1%∕1, 2%∕2, and 3%∕3 mm. Planar dose distributions acquired during pretreatment verifications, together with patient's DICOM RT plan, RT structure set, and RT dose files from TPS were loaded into the 3DVH software. Percentage dose differences (%DE) between DVHs, obtained by TPS and by 3DVH, were calculated; statistical correlation between %DE and %GP was studied by using Pearson's correlation coefficient (r). This analysis was performed, for each patient, on planning target volumes and on some typical organs at risk of the prostatic and head and neck anatomical district. The sensitivity was calculated to correctly identify the pretreatment plans with high dose errors and to quantify the incidence of false negatives, on varying the gamma index method. RESULTS: Analysis of %DE vs %GP showed that there were only weak correlations (Pearson's r-values < 0.8). The results also showed numerous instances of false negatives (cases where high IMRT QA passing rates did not imply good agreement in anatomy dose metrics) and the reverse, mainly for the 3%∕3 mm global gamma passing rate. CONCLUSIONS: The lack of correlation between conventional IMRT QA performance metrics gamma passing rates and dose errors in DVHs values and the low sensitivity of 3%∕3 mm global gamma method show that the most common published acceptance criteria have disputable predictive power for per-patient IMRT QA.

Quality indicators for hyperthermia treatment: Italian survey analysis.

AIM: Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field. MATERIAL AND METHODS: At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches. RESULTS: Three structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed. CONCLUSION: The survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.

Quantitative analysis of cerebrospinal fluid dynamics at phase contrast cine-MRI: predictivity of neurosurgical "Shunt" responsiveness in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: Aqueductal stroke volume (ACSV) measured by phase-contrast cine (PCC)-MRI has been proposed with controversy as a tool for the selection of patients with normal pressure hydrocephalus (NPH) as candidates for shunt-surgery. The aim of this study was to assess if PCC-MRI scan measurements of ACSV could select properly these patients. METHODS: We retrospectively reviewed charts and MRI of 38 shunted patients (72.16±6.16 years). ACSV measurements were performed 7-30 days before shunt and at the first and sixth months after surgery. Normally distributed variables were compared in the two groups (improved/unimproved) by t-test for baseline values and with repeated measures analysis of variance. RESULTS: Twenty-six patients (68,4%) improved after VPS (mean time of symptom onset was 8.15±7.19 months). Mean preoperative ACSV value was 271.85±143.03, which decreased by 21.6% (mean 213±125.14) at the first month and 40.3% sixth months after VPS (mean 162.15±91.5). Twelve patients (31.6%) did not improve (mean time of symptom onset was 29±5.62 months). Mean preoperative ACSV value was 79.83±31.24, decreased to 8.7% (mean 72.83±28.66) at first month after VPS. 21.2% (mean 62.83±31.12) after six months. We found statistical difference between preoperative ACSV of improved and unimproved patients (P<0.01), onset time of symptoms (P<0.01) and the changes in ACSV after one and six months in both groups (P<0.001). CONCLUSIONS: ACSV is useful to stratify patients with NPH after surgery (improved /not improved) suggesting to proceed with serial ACSV measurements before deciding treatment.

Radio hyperthermia for re-treatment of superficial tumours.

PURPOSE: Relapse remains an unsolved problem for previously radio-treated patients. Our purpose is to evaluate the role of radio-hyperthermia (RT-HT) in the retreatment of superficial recurrences. MATERIALS AND METHODS: From 1998 to 2007, 51 patients affected by four histological types (breast recurrences (group A), melanoma recurrences (group B), head and neck recurrences (group C), and others (group D)) of 76 superficial lesions, were enrolled at Mauriziano Hospital at the Research Institute of Cancer Care Candiolo (IRCC) in Turin. All patients had previously undergone RT except 6 patients of group B. The total mean retreatment dose was 31.8 Gy (20-60 Gy), while the mean of HT sessions was 5 (1 to 8), temperature ranged from 38.5 degrees C (T min) to 44 degrees C (T max). RESULTS: Acute cutaneous toxicity was 77.6% G1, 22.4% G2, none for G3. Forty-five days later we observed: for group A 65.9% complete response (CR), 29.5% partial response (PR), 4.5% non-response (NR); for group B 33.3% CR, 25% PR and 41.7% NR; for group C 40% CR, 13.3% PR, 46.7% NR, for group D 60% CR and 40% NR. 18 months later group A presented 72.7% local control (LC), 20.5% stable disease (SD) and 6.8% non-control (NC), group B 50% LC, 16,7% SD and 33.3% NC, group C 33.3% LC, 40% SD and 26.7% NC, group D 40% LC and 60% NC. Early response, size of lesions < or =3 cm, T max > or =42 degrees C and RT doses > or =40 Gy were predictive outcome factors. CONCLUSIONS: We confirmed that radio-hyperthermia is useful in re-irradiation with a very high patient compliance.

Ureasil Organic-Inorganic Hybrid as a Potential Carrier for Combined Delivery of Anti-Inflammatory and Anticancer Drugs.

There continues to be a need to develop controlled-release systems loaded with multiple drugs with distinct pharmacological activities, such as anti-inflammatory and anticancer effects, which are able to provide the desired release of each drug, as a function of time. To this end, an elegant strategy was developed for the incorporation, in a one-step process, of the anti-inflammatory drug naproxen (NAP) and the anticancer drug 5-fluorouracil (5FU) into a ureasil organic-inorganic hybrid matrix. A ureasil-poly(oxyalkylene) (UPEO) matrix was prepared using a sol-gel route to obtain a versatile dual-drug delivery system. Small-angle X-ray scattering (SAXS) measurements and Fourier transform infrared spectroscopy (FTIR) demonstrated that the UPEO network is preserved upon loading with the two drugs NAP and 5FU. There was excellent agreement between the macroscopic swelling behavior (water uptake) and surface wettability (determined using contact angle measurements), with this behavior being closely correlated with the release profiles and playing an important role in the sustained delivery of both drugs from the hybrid matrix. The amounts of both drugs released simultaneously could be finely controlled by adjusting the pH of the aqueous medium, with the release presenting stimulus-responsive behavior. In an aqueous PBS medium, the dual-UPEO-release system presented excellent potential as a vehicle for the release of the water-soluble 5FU and water-insoluble NAP drugs, at identical rates, using a single carrier. This novel and adjustable dual-drug delivery UPEO system is a promising hybrid material carrier with the ability to simultaneously incorporate a wide range of therapeutic agents for the treatment of various diseases, including cancers.

Effects of fluconazole in the prophylaxis of oropharyngeal candidiasis in patients undergoing radiotherapy for head and neck tumour: results from a double-blind placebo-controlled trial.

Fluconazole is recommended in the prophylaxis of oropharyngeal candidiasis (OPC) in patients undergoing radiotherapy for head-neck tumours; however, the actual effectiveness of fluconazole in this setting remains unclear. Adult patients with cervico-cephalic carcinoma submitted to radical or adjuvant radiotherapy were randomized to 100 mg fluconazole (n = 138) or matched placebo (n = 132) oral suspension once daily from the sixth session of radiotherapy up to the end of treatment. The final analysis of the investigation showed a higher rate of the OPC outbreak-free survival in the fluconazole compared with placebo (P = 0.008 in the log-rank test). The mean time (95% CI) to OPC outbreak was 56 (53-59) days in the fluconazole group and 47 (43-51) days with placebo. The mean duration of radiotherapy was 43.5 and 39.9 days, respectively in the two groups (P = 0.027). Adverse effects were reported in 70.3% of patients in the fluconazole group and in 67.4% with placebo. The results showed prophylaxis with fluconazole given in irradiated patients with head-neck tumours significantly reduces the rate and the time to development of OPC compared with placebo.

Growth laws in cancer: implications for radiotherapy.

Comparing the conventional Gompertz tumor growth law (GL) with the "Universal" law (UL), which has recently been proposed and applied to cancer, we have investigated the implications of the growth laws for various radiotherapy regimens. According to the GL, the surviving tumor cell fraction could be reduced ad libitum, independent of the initial tumor mass, simply by increasing the number of treatments. In contrast, if tumor growth dynamics follows the Universal scaling law, there is a lower limit of the surviving fraction that cannot be reduced further regardless of the total number of treatments. This finding can explain the so-called tumor size effect and re-emphasizes the importance of early diagnosis because it implies that radiotherapy may be successful provided that the tumor mass at treatment onset is rather small. Taken together with our previous work, the implications of these findings include revisiting standard radiotherapy regimens and treatment protocols overall.

Concurrent radiotherapy does not affect adjuvant CMF delivery but is associated with increased toxicity in women with early breast cancer.

We evaluated whether concurrent radiotherapy (RT) affected delivery and toxicity of adjuvant intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in women with operable breast cancer. The medical charts of 321 consecutive breast cancer patients who received CMF either alone for 6 cycles, or for 4 cycles following of an anthracycline (A-CMF) were reviewed. One hundred forty-four women underwent radiotherapy concurrently with CMF. Optimal CMF delivery (success as opposite to failure) was defined as the combined achievement of an average relative dose intensity (aRDI) > or = 85% and an average percent of the total dose (aPTD) > or = 90% for the three drugs in the CMF regimen. Multivariate logistic regression analysis showed that concurrent-RT did not affect CMF delivery (OR for success 1.391 p=0.230). The sequential A-CMF regimen (OR for success 0.208, 95% C.I. 0.120-0.360, p<0.001) and age > or = 56 (OR for success 0.351, 95% C.I. 0.200-0.161, p<0.001) were independently associated with suboptimal CMF delivery. Moreover, concurrent RT was independently associated with increased leukopenia, thrombocytopenia, upper abdominal pain, mucositis and fatigue. Our retrospective analysis suggests that concurrent-RT has no impact on optimal CMF delivery, but it increases the burden of CMF-related toxicity.

NOD-SCID mice irradiation with medical accelerators: Dosimetric and radiobiological results.

PURPOSE: Preclinical studies normally requires dedicated instruments due to the small anatomical scales involved, but the possibility of using clinical devices for this purpose may be of economical, scientific and translational interest. In the present work the accurate description of treatment planning, dosimetric results, radiotoxicity and tumor response of the irradiation of NOD-SCID mice were presented. Two medical linear accelerators, TrueBeam STx and Tomotherapy Hi-ART, were compared. NOD-SCID mice irradiation with Tomotherapy is a novelty, as well as the comparison of different irradiation techniques, devices and dose fractionations. METHODS: Human derived glioblastoma multiforme neurospheres were injected in immunocompromised NOD-SCID mice to establish xenograft models. Mice were anaesthetized and placed in a plexiglas cage pieboth to perform CT scan for treatment planning purposes and for the irradiation. Three fractionation schedules were evaluated: 4Gy/1 fraction, 4Gy/2 fractions and 6Gy/3 fractions. Tomotherapy planning parameters, the presence of a bolus layer and the irradiation time were reported. After irradiation, mice were examined daily and sacrificed when they showed signs of suffering or when tumor volume reached the established endpoint. Outcomes regarding both radiotoxicity and tumor response were evaluated comparing irradiated mice as respect to their controls. RESULTS: Survival analysis showed that Tomotherapy irradiation with 6Gy/3 fractions with a bolus layer prolong mice survival (log-rank test, p<0.02). Tumor volume and mice survival were significantly different in irradiated xenografts as compared to their controls (t-test, p<0.03; log-rank, p<0.05). CONCLUSION: The radiobiological potential of Tomotherapy in inducing tumor growth stabilization is demonstrated.

Quality indicators in the intensity modulated/image-guided radiotherapy era.

PURPOSE: To propose new Quality Indicators (QIs) for the Intensity Modulated(IMRT)/Image-Guided(IGRT) Radiotherapy techniques. MATERIALS AND METHODS: Two structure, 10 process and 2 outcome QIs were elaborated. A working group including Radiation Oncologist, Medical Physicist and Radiation Technologists was made up. A preliminary set of indicators was selected on the basis of evidenced critical issues; the criteria to identify more relevant and specific QIs for IMRT/IGRT were defined; structure, process and outcome QIs were defined. The elaborated indicators were tested in four Italian Radiotherapy Centers. RESULTS: Fourteen indicators were proposed. Seven indicators were completely new while a new standard is proposed for four indicators based on Validation Centers (VC) data. No change was reported for 3 indicators. The indicators were applied in the four VC. The VC considered were able to respect all indicators except indicator 2 for one Center. DISCUSSION AND CONCLUSION: QIs may provide useful measures of workload and service performances.

Transforaminal endoscopic treatment of lumbar radiculopathy after instrumented lumbar spine fusion.

BACKGROUND: Transforaminal endoscopic discectomy and foraminotomy is a well-described minimally invasive technique for surgically treating lumbar radiculopathy caused by a herniated disc and foraminal narrowing. OBJECTIVE: To describe the technique and feasibility of transforaminal foraminoplasty for the treatment of lumbar radiculopathy in patients who have already undergone instrumented spinal fusion. STUDY DESIGN: Retrospective study. SETTING: Hospital and ambulatory surgery center METHODS: After Institutional Review Board approval, charts from 18 consecutive patients with lumbar radiculopathy and instrumented spinal fusions who underwent endoscopic procedures between 2008 and 2013 were reviewed. RESULTS: The average pain relief one year postoperatively was reported to be 67.0%, good results as defined by MacNab. The average preoperative VAS score was 9.14, indicated in our questionnaire as severe and constant pain. The average one year postoperative VAS score was 3.00, indicated in our questionnaire as mild and intermittent pain. LIMITATIONS: This is a retrospective study and only offers one year follow-up data for patients with instrumented fusions who have undergone endoscopic spine surgery. CONCLUSION: Transforaminal endoscopic discectomy and foraminotomy could be used as a safe, yet, minimally invasive and innovative technique for the treatment of lumbar radiculopathy in the setting of previous instrumented lumbar fusion. IRB approval: Meridian Health: IRB Study # 201206071J

Vestibular apparatus disorders after external radiation therapy for head and neck cancers.

External irradiation of different head and neck cancers may involve parts of the ear. The vestibular function of 25 patients in which the inner ear was comprised in the irradiated volume was investigated by electronystagmography (ENG). Doses administered to the vestibular system ranged between 2800 and 5120 cGy. Five patients suffered subjective vertigo or dizziness. Eleven patients (three out of five with vertigo) showed vestibular abnormalities to ENG (44% of the total). Altered responses to specific tests were as follow: six patients to the bithermal caloric stimulation, two to the pendular-sinusoidal test and the other three to both of them. Patients were evaluated 3 and 6 months after the ending of the radiation therapy course. At the first evaluation, abnormalities to caloric test were noted in three patients (12%) and to sinusoidal rotatory test in one patient (4%). At the second evaluation, rates of abnormal response increased to 36% and 20%, respectively. Vestibular disorders seemed to be scantly related to the total radiation dose. Data of literature are discussed in order to identify possible implications on treatment planning.

Fusarium endophthalmitis in an intravenous drug abuser.

PURPOSE: We studied a case in which a patient had unilateral retinal infiltrates and a retinal vasculopathy resembling frosted branch angiitis. He later admitted to injecting cocaine intravenously. METHODS: The patient underwent a pars plana vitrectomy and received intravitreal and intravenous amphotericin B. RESULTS: The vitreous fluid grew Fusarium dimerium. There was rapid response to the treatment and full recovery of vision. CONCLUSION: Fusarium species should be considered as a potential pathogen in intravenous drug abusers with endogenous endophthalmitis and in patients with unilateral frosted branch angiitis.

High prognostic impact of growth fraction parameters in advanced stage laryngeal squamous cell carcinoma.

One hundred and two cases of laryngeal squamous cell carcinoma, all treated in the same center with total or supraglottic laryngectomy, bilateral neck dissection and postoperative radiotherapy, were investigated with both Ki67 and MIB-1 monoclonal antibodies. The aim was to determine the prognostic impact of growth fraction markers in a homogeneous series of patients. All samples were stained with Ki67 monoclonal antibody on frozen sections, and with MIB-1 monoclonal antibody on paraffin sections, using the ABC immunoperoxidase method. The percentage of positive cells was compared in each case with the overall and disease-free survival, pathologic stage and histologic grading. The values obtained from Ki67 and MIB-1 counts were similar and highly correlated (r=0.90). Two groups of cases with low and high proliferation rate (59 and 43 respectively) were obtained by splitting up the whole series, on the basis of the median value; 84. 6% of the patients with high proliferation relapsed and/or died due to the tumor within two years from diagnosis whereas, at time of writing, 94% of the patients with low proliferation are alive and well (p<0.00001). No relation was found between growth fraction and histologic grading, pathologic stage (pT and pN) and site of the tumor. Only lymph node involvement was correlated with disease-free survival. Our results indicate that Ki67/MIB-1 index represents an independent variable to determine long-term prognosis in laryngeal squamous cell carcinomas. We recommend its use in diagnostic protocols, to distinguish high risk subsets of patients who might benefit from more aggressive treatments.