Canadian consensus: oligoprogressive, pseudoprogressive, and oligometastatic non-small-cell lung cancer.

Background: Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (nsclc) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment. Methods: An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions. Results: Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified. Conclusions: In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged.

Procarbazine, lomustine and vincristine toxicity in low-grade gliomas.

BACKGROUND: Procarbazine, lomustine, and vincristine (pcv) significantly improve survival outcomes in lgg (low-grade gliomas). Administration of pcv to lgg patients increased tremendously over the past years as it went from 2 patients per year between 2005 and 2012 to 23 patients in 2015 only in our centre. However, serious hematological and non-hematological adverse events may occur. The purpose of this study was to evaluate the toxicity of pcv and its clinical relevance in our practice. METHODS: We retrospectively reviewed the charts of 57 patients with lgg who received pcv at the Centre hospitalier de l'Université de Montréal between 1 January 2005 and 27 July 2016. RESULTS: Procarbazine, lomustine, and vincristine were associated with severe hematological toxicity as clinically significant grade 3 anemia, neutropenia, and thrombocytopenia occurred in 7%, 10%, and 28% of patients, respectively. Other frequent adverse events such as the increase of liver enzymes, cutaneous rash, neurotoxicity, and vomiting occurred in 65%, 26%, 60%, and 40% of patients, respectively. Patients with prophylactic trimethoprim/sulfamethoxazole had more grade 3 hematological toxicity with pcv, especially anemia (p = 0.040) and thrombocytopenia (p = 0.003) but we found no increase in pcv toxicity in patients on concurrent anticonvulsants. Patients with grade 3 neutropenia had a significantly lower survival (median survival 44.0 months vs. 114.0 months, p = 0.001). Patients who were given pcv at diagnosis had more grade 3 anemia than those who received it at subsequent lines of treatment (p = 0.042). CONCLUSION: Procarbazine, lomustine, and vincristine increase survival in lgg but were also associated with major hematologic, hepatic, neurologic, and cutaneous toxicity. Anti-Pneumocystis jiroveci pneumonia (pjp) prophylaxis, but not anticonvulsants, enhances hematologic toxicity.

[Treatment of brain AVMS (TOBAS): A randomized controlled trial and registry]. / Le traitement des MAVS cérébrales (TOBAS) : une étude randomisée controlée avec registre.

OBJECTIVE: The management of unruptured and ruptured brain arteriovenous malformations (AVMs) remains controversial. The Treatment of Brain AVM Study (TOBAS) was designed to assess curative treatments in the management of AVMs. The purpose of our study is to provide a care trial context to brain AVM patients. METHODS: TOBAS is a pragmatic, prospective study including 2 randomized controlled trials and a registry. All AVM patients can be recruited. The preferred management modality will be predetermined prior to randomization by the team based on clinical judgment. Patients eligible for both conservative and interventional management will be randomly allocated conservative or curative treatment. Randomization will be stratified by a treatment modality (surgery, radiosurgery or embolization) and minimized according to a history of previous rupture and Spetzler-Martin grade. A second randomization will allocate eligible patients to embolization/no embolization prior to surgery or radiosurgery. The primary outcome of the study is death (any cause) or disabling stroke (mRS>2) at 10 years. All patients managed according to clinical judgment alone will be included in the registry. The study is registered under: wwwTrials.gov, ID: NCT02098252. EXPECTED RESULTS: A minimum recruitment of 540 patients is required to show that treatment can reduce the primary outcome by 10 % (from 25 to 15 %); 440 patients will be needed to show a 10 % increase in angiographic occlusion for a good clinical outcome with pre-embolization. CONCLUSION: The trial is designed to offer optimal and verifiable care to patients with brain AVMs in spite of the uncertainty. We are currently seeking the participation of multiple centers.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

The cancer patient's use and appreciation of the internet and other modern means of communication.

As computers and smartphones continue to transform the doctor-patient relationship, it is essential that healthcare professionals understand how their patients wish to interact with these devices. The results from a satisfaction questionnaire of 225 Oncology patients treated in 2011 in Quebec, Canada provide insight into the manner in which patients have been and wish to communicate with their healthcare teams. The survey also addressed whether or not patients searched the Internet for supplementary information regarding their condition. Generally, patients were neutral regarding adopting greater usage of modern means of communication. The majority of patients did not want to be contacted via e-mail or SMS, nor did the patients want to make appointments or fill out surveys online. Forty four percent of patients used the Internet to learn more about their condition. Concerning the patients who were not provided with links to medically relevant websites, 44% wished their doctors had supplied them with such links. Though there was much overlap between the 44% of patients who went on the Internet to learn more about their condition and the 44% of the patients who wished their physicians provided them with such links, 14% of all the patients wished their medical teams had provided them with links, but did not independently search for medically relevant information about their condition. Using chi-square testing education level was found to be the best predictor of which patients searched the web for supplementary information about their conditions (p = 0.003). Contrary to findings in other studies, a comparable proportion of patients in each age-group used the Internet to research their condition. Given the wealth of web-resources available to cancer patients, it would be beneficial for both healthcare teams and their patients if physicians consistently offered a list of trustworthy websites to their patients.

The Canadian Association of Radiation Oncology scope of practice guidelines for lung, liver and spine stereotactic body radiotherapy.

AIMS: The Canadian Association of Radiation Oncology-Stereotactic Body Radiotherapy (CARO-SBRT) Task Force was established in 2010. The aim was to define the scope of practice guidelines for the profession to ensure safe practice specific for the most common sites of lung, liver and spine SBRT. MATERIALS AND METHODS: A group of Canadian SBRT experts were charged by our national radiation oncology organisation (CARO) to define the basic principles and technologies for SBRT practice, to propose the minimum technological requirements for safe practice with a focus on simulation and image guidance and to outline procedural considerations for radiation oncology departments to consider when establishing an SBRT programme. RESULTS: We recognised that SBRT should be considered as a specific programme within a radiation department, and we provide a definition of SBRT according to a Canadian consensus. We outlined the basic requirements for safe simulation as they pertain to spine, lung and liver tumours, and the fundamentals of image guidance. The roles of the radiation oncologist, medical physicist and dosimetrist have been detailed such that we strongly recommend the development of SBRT-specific teams. Quality assurance is a key programmatic aspect for safe SBRT practice, and we outline the basic principles of appropriate quality assurance specific to SBRT. CONCLUSION: This CARO scope of practice guideline for SBRT is specific to liver, lung and spine tumours. The task force recommendations are designed to assist departments in establishing safe and robust SBRT programmes.

What is the optimal management of dysphagia in metastatic esophageal cancer?

BACKGROUND: The palliation of dysphagia in metastatic esophageal cancer remains a challenge, and the optimal approach for this difficult clinical scenario is not clear. We therefore sought to define and determine the efficacy of various treatment options used at our institution for this condition. METHODS: We reviewed a prospective database for all patients managed in an esophageal cancer referral centre over a 5-year period. All patients receiving palliation of malignant dysphagia were reviewed for demographics, palliative treatment modalities, complications, and dysphagia scores (0 = none to 4 = complete). The Wilcoxon signed rank test was used to determine significance (p < 0.05). RESULTS: During 2004-2009, 63 patients with inoperable esophageal cancer were treated for palliation of dysphagia. The primary treatment was radiotherapy in 79% (brachytherapy in 18 of 50; external-beam in 10 of 50; both types in 22 of 50), and stenting in 21%. Mean wait time from diagnosis to treatment was 22 days in the stent group and 54 days in the radiotherapy group (p = 0.003). Mean duration of treatment was 1 day in the stent group and 40 days in the radiotherapy group (p = 0.001). In patients treated initially by stenting, dysphagia improved within 2 weeks of treatment in 85% of patients (dysphagia score of 0 or 1). However, 20% of patients presented with recurrence of dysphagia at 10 weeks of treatment. In the radiotherapy group, the onset of palliation was slower, with only 50% of patients palliated at 2 weeks (dysphagia score of 0 or 1). However, long-term palliation was more satisfactory, with 90% of patients remaining palliated after 10 weeks of treatment. CONCLUSIONS: In inoperable esophageal cancer at our centre, radiation treatment provided durable long-term relief, but came at a high price of a long wait time for initiation of treatment and a long lag time between initiation of treatment and relief of symptoms. On the other hand, endoluminal stenting provided more rapid and effective early relief from symptoms, but was affected by recurrence of dysphagia in the long-term. It is now time for a prospective randomized trial to assess the safety and efficacy of combined-modality treatment with both endoluminal stenting and radiation therapy compared with either treatment alone.

Poster - Thur Eve - 73: Prediction of risks of cardiac mortality and secondary cancers after radiotherapy for Hodgkin's lymphoma, non-Hodgkin's lymphoma, and breast cancer.

PURPOSE: To predict the risks of late, radiation-induced effects for young patients with Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), or breast cancer (BC) if treated with intensity modulated proton therapy (IMPT) compared to 3D conformal photon radiotherapy (3D-CRT). Late effects considered were cardiac mortality and secondary cancer in the lungs and breasts (for female patients). METHODS: Patient data were acquired for twenty-six patients (ages 12-29) who were treated with 3D-CRT for HL, NHL, or BC in 2010. Original CT simulation images were used to re-plan the patients with IMPT using commercially-available treatment planning software. The contours of the organs at risk were reviewed by a single physician and modified for consistency. The dose-volume data of the 3D-CRT plans and the new IMPT plans were analyzed to model the risks of late effects. The relative seriality model was used to predict excess risk of cardiac mortality at fifteen years post-irradiation. A modified linear quadratic model was used to predict the Excess Absolute Risk (EAR) for induction of lung cancer and breast cancer at thirty years post-irradiation. RESULTS: For 3D-CRT and IMPT respectively, the mean excess risks of cardiac mortality were 0.9% and 0.5%. Mean EARs for lung cancer were 17.5 cases per 10,000 persons per year (PY) and 10.1 PY. Mean EARs for breast cancer were 8.2 PY and 2.8 PY. CONCLUSIONS: IMPT may significantly reduce the risks of radiation-induced cardiac mortality and secondary cancer in the lungs and breasts of young patients receiving radiotherapy for HL, NHL, or breast cancer.

Indication of electron neutrino appearance from an accelerator-produced off-axis muon neutrino beam.

The T2K experiment observes indications of ν(µ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Δm(23)(2)| = 2.4×10(-3) eV(2), sin(2)2θ(23) = 1 and sin(2)2θ(13) = 0, the expected number of such events is 1.5±0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2θ(13) < 0.28(0.34) for δ(CP) = 0 and a normal (inverted) hierarchy.

Inter- and intra-observer variation in soft-tissue sarcoma target definition.

PURPOSE: To evaluate inter- and intra-observer variability in gross tumor volume definition for adult limb/trunk soft tissue sarcomas. PATIENTS AND METHODS: Imaging studies of 15 patients previously treated with preoperative radiation were used in this study. Five physicians (radiation oncologists, orthopedic surgeons and a musculoskeletal radiologist) were asked to contour each of the 15 tumors on T1-weighted, gadolinium-enhanced magnetic resonance images. These contours were drawn twice by each physician. The volume and center of mass coordinates for each gross tumor volume were extracted and a Boolean analysis was performed to measure the degree of volume overlap. RESULTS: The median standard deviation in gross tumor volumes across observers was 6.1% of the average volume (range: 1.8%-24.9%). There was remarkably little variation in the 3D position of the gross tumor volume center of mass. For the 15 patients, the standard deviation of the 3D distance between centers of mass ranged from 0.06 mm to 1.7 mm (median 0.1mm). Boolean analysis demonstrated that 53% to 90% of the gross tumor volume was common to all observers (median overlap: 79%). The standard deviation in gross tumor volumes on repeat contouring was 4.8% (range: 0.1-14.4%) with a standard deviation change in the position of the center of mass of 0.4mm (range: 0mm-2.6mm) and a median overlap of 93% (range: 73%-98%). CONCLUSION: Although significant inter-observer differences were seen in gross tumor volume definition of adult soft-tissue sarcoma, the center of mass of these volumes was remarkably consistent. Variations in volume definition did not correlate with tumor size. Radiation oncologists should not hesitate to review their contours with a colleague (surgeon, radiologist or fellow radiation oncologist) to ensure that they are not outliers in sarcoma gross tumor volume definition. Protocols should take into account variations in volume definition when considering tighter clinical target volumes.

Initial McGill experience with fluorodeoxyglucose pet/ct staging of soft-tissue sarcoma.

BACKGROUND: Soft-tissue sarcoma spreads predominantly to the lung. The frequency with which positron-emission tomography (pet) detects metastases not already obvious by chest computed tomography (ct) or clinical examination is currently unclear. METHODS: We retrospectively identified cases of soft-tissue sarcoma. Ewing sarcoma, rhabdomyosarcoma, and gastrointestinal stromal tumour were excluded, as were cases in which patients underwent imaging for follow-up, response assessment, or recurrence. Patients all had undergone diagnostic chest ct as part of their staging. Directed studies were requested to follow up on abnormal findings in the clinical history or physical examination. All charts and pre-treatment imaging were reviewed retrospectively. RESULTS: From 2004 to 2008, 75 patients met the criteria for the present review. Their median age was 51 years. In 21% of cases, the primary tumour had been removed (by excisional biopsy or unplanned excision) before staging. Of the previously unresected primary tumours, 97% were avid for fluorodeoxyglucose. Of all tumours, 81% were intermediate or high grade (Fédération Nationale des Centres de Lutte Contre le Cancer grades 2-3). The primary tumour was stage T2b in 69% of cases. The most common primary site was a lower extremity (55%). The most common pathologic diagnoses were leiomyosarcoma (21%), liposarcoma (19%), and synovial sarcoma (17%). At the end of staging, 17% of patients were considered to have metastatic disease. Imaging by pet was negative for distant disease in 64 of the 75 cases. In 7 of the 64 cases, metastatic disease was evident on chest ct (negative predictive value: 88%). Imaging by pet was positive in 8 cases, with 5 of those already known to have metastases, 2 having pathologically proven false positives, and 1 being a new finding of a pulmonary metastasis (positive predictive value: 75%). The pet imaging was indeterminate in 3 patients (none of whom subsequently developed metastatic disease). Two incidental benign parotid tumours were found. Overall, only 1 patient was upstaged as a result of pet imaging (1.3%). In addition, pet did not alter the management of patients already know to have M1 disease (no new organ sites identified). CONCLUSIONS: Although pet may be helpful in specific circumstances, routine use of fluorodeoxyglucose pet imaging for detection of metastatic disease as part of the initial staging of soft-tissue sarcoma added little to imaging by chest ct and was unlikely to alter management in our series.

Clinical significance of molecular biomarkers in glioblastoma.

AIM: To review the impact of molecular biomarkers on response to therapy and survival in patients with primary glioblastoma (GBM). MATERIALS & METHODS: Tissue specimens were analyzed for p53 mutations, EGFR amplification, loss of PTEN and p16, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Demographic and clinical data were gathered from medical records. RESULTS: Clinical and pathological data of 125 patients were collected and analysed. MGMT promoter methylation was associated with improved median overall survival (OS) (61 vs. 42 weeks, p = 0.01) and was an important prognosticator independent of age at diagnosis, extent of resection and post-operative ECOG performance status (HR 2.04, 95% CI 1.11-3.75). Among patients with MGMT promoter methylation, survival was significantly improved with chemoradiotherapy (CRT) over radiotherapy (RT) alone (71 vs. 14 weeks, p < 0.01). Furthermore, amongst those treated with temozolomide (TMZ) based CRT, the presence of EGFR amplification, maintenance of PTEN and wild-type p53 and p16 were each associated with trends towards improved survival. CONCLUSION: MGMT promoter methylation is a strong, independent prognostic factor for OS in GBM. EGFR amplification, maintenance of PTEN, wild-type p53 and p16 all appear to be associated with improved survival in patients treated with CRT. However, the prognostic value of these biomarkers could not be ascertained and larger prospective studies are warranted.

Fractionated stereotactic radiotherapy in the treatment of pituitary macroadenomas.

BACKGROUND: The use of fractionated stereotactic radiotherapy (FSRT) has evolved with technical advances in noninvasive immobilization, radiation delivery, and image guidance. The application of FSRT to pituitary tumours is aimed at reducing toxicity through improved dose conformality and reduced treatment margins. The aim of the present paper is to report our own experience and to review the published data on FSRT for pituitary macroadenomas. METHODS: Between September 2000 and October 2005, 13 patients with pituitary macroadenoma underwent FSRT at our institution. In 12 patients, radiotherapy treatment followed surgical resection (transsphenoidal resection in 8, frontal craniotomy in 3, and multiple transsphenoidal resections followed by craniotomy in 1). In 4 patients, the tumours were functional (2 adrenocorticotropic hormone-secreting, 1 prolactinoma, and 1 growth hormone-secreting); the tumours in the remaining patients were clinically non-secretory. Before radiation, 3 patients had panhypopituitarism, and 6 patients had visual field defects. All patients were treated with FSRT using non-coplanar micro-multileaf collimation portals. A median dose of 50.4 Gy (range: 45-60 Gy) was prescribed to the 76.9%-95.2% isodose surface and delivered in 1.8-Gy fractions. The median planning target volume (gross tumour plus 3 mm) was 33.5 cm3 (range: 3.2-75 cm3). RESULTS: After a median follow-up of 24 months (range: 6-60 months), local control was 100%. One patient achieved clinical complete response. Treatment was well tolerated acutely for all patients. Neither radiation-induced optic neuropathy nor any radiation-related endocrine dysfunction was observed in our patients. CONCLUSIONS: In accordance with published series, we found FSRT to be safe and effective in the management of large pituitary macroadenomas.

Does adjuvant alpha-interferon improve outcome when combined with total skin irradiation for mycosis fungoides?

BACKGROUND: Patients with mycosis fungoides (MF) experience frequent disease recurrences following total skin electron irradiation (TSEI) and may benefit from adjuvant therapy. OBJECTIVES: To review the McGill experience with adjuvant alpha-interferon (IFN) in the treatment of MF. METHODS: From 1990 to 2000, 50 patients with MF were treated with TSEI: 31 with TSEI alone and 19 with TSEI + IFN. Median TSEI dose was 35 Gy. In the TSEI + IFN group, IFN was given subcutaneously at 3 x 10(6) units three times per week starting 2 weeks prior to start of TSEI, continued concurrently with the radiation and for an additional 12 months following TSEI. The TSEI alone group included 16 men and 15 women with a median age of 61 years (range 31-84). The TSEI + IFN group included 14 men and five women with a median age of 51 years (range 24-83). Clinical stage was IA, IB, IIA, IIB, III and IVA in 2, 9, 4, 8, 1 and 7 patients of the TSEI group and 0, 3, 3, 7, 4 and 2 patients of the TSEI + IFN group. RESULTS: Median follow up for living patients was 70 months. All patients responded to treatment. Complete response (CR) rate was 65% following TSEI and 58% following TSEI + IFN (P = 0.6). Median overall survival (OS) was 61 months following TSEI and 38 months following TSEI + IFN (P = 0.4). Acute grade II-III dermatitis was seen in all patients. Fever, chills or myalgia were seen in 32% of patients treated with TSEI + IFN. CONCLUSIONS: Concurrent IFN and TSEI is feasible, with acceptable toxicity. Even when controlling for disease stage, the addition of IFN did not appear to increase CR rate, disease-free survival or OS.

[Development and application of a clinical vignette to assess the quality of cancer care]. / Développement et application d'une vignette clinique pour apprécier la qualité des soins en oncologie.

BACKGROUND: In conjunction with a study focusing on the implementation and effect of an integrated care network for cancer patients in the Monteregie region in Quebec, the vignette research strategy was adopted to assess the quality of care provided by the interdisciplinary teams working with this clientele. This research strategy has only recently been used to assess professional practices. This article adopts a resolutely methodological angle in order to describe a rigorous, innovative, transferable experience from the standpoint of the elaboration of a vignette. METHODS: We adopted a six-step approach to elaborate the vignette. This vignette includes the description of collaboration with clinicians. The approach assured us of attaining high content validity from the standpoint of facets of its relevance, completeness and intelligibility to respondents. Our clinical vignette describes a sequence of events stemming from the care coordination of a 58-year-old man suffering from rectal cancer. Data were collected through group interviews with the interdisciplinary teams (n=5) under study. The professionals present were asked to describe their usual practices with respect to the events described in the vignette. We adopted two data analysis strategies: (i) a comparison of practices revealed through the interviews with anticipated responses in light of the guidelines of the "Programme québécois de lutte contre le cancer"; and (ii) an analysis according to facets of the quality of care. RESULTS: Team professional practices seem to evolve towards the care package valued by the "Programme québécois de lutte contre le cancer". Differences were also observed between the teams from the standpoint of the continuity of care. CONCLUSION: Our study shows that it is possible to develop a vignette that enables us to understand professional practices in an interdisciplinary context provided that a rigorous approach is adopted. This approach, which can be transferred to the study of similar phenomena, makes it possible to document the care offered and contribute to the renewal of professional practices.

Hypofractionated stereotactic radiotherapy for low grade glioma at McGill University: long-term follow-up.

Small, well-defined, unresectable low-grade gliomas are attractive targets for stereotactic irradiation. Fractionated stereotactic irradiation of these targets has the theoretical benefit of increased normal tissue sparing beyond that provided by the physical characteristics of stereotactic radiosurgery. From July 1987 to November 1992, 21 patients were treated for low-grade glioma at our institution using a hypofractionated regimen of stereotactic radiotherapy. All patients had well-circumscribed, < 40 mm tumors. No patient had had prior radiotherapy. All lesions were histologically proven WHO grade I or II glial tumors. Lesions involved sensitive brain structures and were deemed unresectable. A typical dose of 42 Gy was delivered in 6 fractions over a two-week period using rigid immobilization and a linac-based dynamic stereotactic radiosurgical technique. Patients had a median age of 23 years (9-74) and were predominantly female (60%). Median tumor diameter was 20 mm. With a median follow-up for living patients of 13.3 years, the actuarial 5, 10, and 15-year overall survival rates are 76%, 71%, and 63%, respectively. Treatment was acutely well tolerated although three patients experienced late post-therapy complications. Our results and those of 241 patients treated in nine other institutional series are reviewed. Despite some examples of favorable short-term outcomes, all reported series are highly selected and thus likely biased. The data regarding the use of SRS is limited and, in our opinion, insufficient to claim a clear therapeutic advantage to SRS in the initial management of low-grade glioma. Our own results with hypofractionated stereotactic radiotherapy are similar to those expected with standard therapy.

[Prostate and seminal vesicle displacement following urethrography: a computed tomography-based study]. / Déplacements de la prostate et des vésicules séminales suite à l'uréthrographie: une étude par tomographie axiale.

PURPOSE: It has been suggested that urethrography used for localization of the prostate apex may cause a systematic cranial displacement of the organ. Our objective was to use CT-CT image registration to identify if a clinically relevant systematic shift occurs in the position of the prostate and seminal vesicles following retrograde urethrography. PATIENTS AND METHODS: Patients were scanned twice at the time of simulation. They were imaged supine, bladder empty. Scan resolution was 512x512 with 5 mm cuts. After the first CT sequence, with the patient still on the CT couch, an urethrogram was performed. The patients were then re-scanned. The image sets were registered through the use of external skin fiducials. A single author reviewed x, y and z-axis displacement. Z-axis motion of the prostate was also assessed by having three blinded radiation oncologists mark the cranial limit of the prostate on all 104 image sets. RESULTS: Fifty-two pairs of CT scans were analyzed for post-urethrogram organ displacement. The mean x axis displacement of the prostate was 0.016 mm (P=0.8), the mean y-axis displacement was 1.3 mm anterior (P<0.001). Mean z-axis displacement of the prostate, using the blinded assessments, was a 1.35 mm cranial shift (P<0.0001). Analogous shifts were identified for the seminal vesicles. CONCLUSION: Our results suggest a small cranial and anterior displacement of the prostate and seminal vesicles following retrograde urethrography.

Heterogeneity of human Ro ribonucleoproteins (RNPS): nuclear retention of Ro RNPS containing the human hY5 RNA in human and mouse cells.

Ro ribonucleoproteins (RNPs) are autoantigens that result from the association of a 60-kDa protein (Ro60) with a small RNA (hY1, hY3, hY4 or hY5 in humans, mY1 or mY3 in mice). Previous studies localized Ro RNPs to the cytoplasm. Because Ro RNPs containing hY5 RNA (Ro(hY5) RNPs) have unique biochemical and immunological properties, their intracellular localization was reassessed. Subcellular distribution of mouse and human Ro RNPs in intact and hY-RNA transfected cells was assessed by immunoprecipitation and Northern hybridization. Human Ro(hY1--4) RNPs as well as murine Ro(mY1, mY3) RNPs are exclusively cytoplasmic. Ro RNPs containing an intact hY5 RNA, but not those containing a mutated form of hY5 RNA, are found in the nuclear fractions of human and mouse cells. Ro(hY5) RNPs are stably associated with transcriptionally active La protein and are known to associate with RoBPI, a nuclear autoantigen. Our results demonstrate that Ro(hY5) RNPs are specifically present in the nucleus of cultured human and murine cells. The signal for nuclear localization of Ro(hY5) RNPs appears to reside within the hY5 sequence itself. In conclusion, we suggest that the unique localization and interactions of primate-specific Ro(hY5) RNPs reflect functions that are distinct from the predicted cytoplasmic function(s) of more conserved Ro RNPs.