Hypercalcemia with methotrexate pneumonitis: A rare, important and intriguing adverse event.

Methotrexate leading to hypercalcaemia is a rarely reported adverse event. We present three elderly patients with inflammatory arthritis who developed hypercalcemia probably due to methotrexate-induced granulomatous pneumonitis. All patients presented with worsening non-productive cough with dyspnea, nausea, loss of appetite, and confusion. Their clinical and radiologic features were consistent with methotrexate-induced pneumonitis. On evaluation, all patients concurrently had hypercalcemia with normal 25OH D3, and low PTH with markedly elevated levels of 1,25OH D3 seen in two patients. In all three patients, hypercalcemia and pneumonia responded to hydration, corticosteroids, and methotrexate withdrawal. There was no relapse of symptoms on long term follow-up. In these three patients with inflammatory arthritis, methotrexate-induced pneumonitis led to symptomatic hypercalcemia. Unless hypercalcemia is looked for and treated in this setting, the morbidity can be high.

Assessment of Patient Satisfaction Among Cancer Patients Undergoing Radiotherapy.

The patient-provider relationship is a key driver of patient satisfaction as it relates to overall healthcare experience. We surveyed patients undergoing radiation therapy to determine what they consider to be the most valued qualities in their interactions with the healthcare team. An ethics-approved 35-item patient satisfaction survey was developed in-house to gain insights on patients' perception of their relationship with the healthcare team throughout their cancer journey. There were 199 completed survey, median age 68 years, 54% women and 45% men. Almost all (95%) "agreed" or "strongly agreed" that their physicians had been sensitive and compassionate. Over 90% felt that they received adequate explanations about their treatment, and had their questions answered. The vast majority (93%) felt included in the decision-making process. Patients reported the 5 most highly rated qualities among their healthcare providers (HCPs) as knowledge, kindness, honesty, good communication, and a cheerful attitude. Overall satisfaction was high but areas for improvement were identified including being offered future appointments for further discussion, more information about clinical trials, other treatments, and community resources. Patients noted their HCPs tended to focus on the physical and emotional needs of patients, but spiritual and cultural needs were rarely addressed. Patients receiving radiotherapy reported high rates of satisfaction across many aspects of their care. These findings also reinforce the different aspects of holistic care that can be improved, and serve as a reminder to clinicians that patients perceive their role as more than just that of a medical expert.

Current practice in total-body irradiation: results of a Canada-wide survey.

BACKGROUND: Total-body irradiation (tbi) is used to condition patients before bone marrow transplant. A variety of tbi treatment strategies have been described and implemented, but no consensus on best practice has been reached. We report on the results of a survey created to assess the current state of tbi delivery in Canada. RESULTS: A 19-question survey was distributed to 49 radiation oncology programs in Canada. Responses were received from 20 centres, including 12 centres that perform tbi. A variety of tbi dose prescriptions was reported, although 12 Gy in 6 fractions was used in 11 of the 12 centres performing tbi. Half of the centres also reported using a dose prescription unique to their facility. Most centres use an extended-distance parallel-opposed-pair technique, with the patient standing or lying on a stretcher against a wall. Others translate the patient under the beam, sweep the beam over the patient, or use a more complicated multi-field technique. All but 1 centre indicated that they attenuate the lung dose; only 3 centres indicated attenuating the dose for other organs at risk. The survey also highlighted the considerable resources used for tbi, including extra staff, prolonged planning and treatment times, and use of locally developed hardware or software. CONCLUSIONS: At transplant centres, tbi is commonly used, but there is no commonly accepted approach to planning and treatment delivery. The important discrepancies in practice between centres in Canada creates an opportunity to prompt more discussion and collaboration between centres, improving consistency and uniformity of practice.

Spinal bone marrow necrosis with vertebral compression fracture: differentiation of BMN from AVN.

Bone marrow necrosis (BMN) is a rare malignancy-associated hematologic disorder characterized by necrosis of myeloid and stromal marrow elements with preservation of cortical bone. Overlap between the imaging appearances of BMN and avascular necrosis (AVN) raises the potential for diagnostic confusion. We report a case of BMN presenting with a traumatic multi-level vertebral body collapse, and finding that may potentially confound distinction between the two entities. We discuss important pathophysiologic, clinical, and radiologic differences between BMN and AVN with emphasis on features important in the differential diagnosis.

Pain assessment during conscious sedation for cervical cancer high-dose-rate brachytherapy.

BACKGROUND: This observational study set out to evaluate the effectiveness of conscious sedation anesthesia for pain control during high-dose-rate (hdr) brachytherapy using a ring-and-tandem applicator system for patients with cervical cancer. METHODS: At the time of initiation of the hdr cervical cancer brachytherapy program at our institution, patients received a detailed symptom assessment during the procedures. Brachytherapy was carried out using a Smit sleeve, together with a ring-and-tandem applicator. Midazolam and an opioid-hydromorphone, morphine, or fentanyl-were the main agents used to achieve conscious sedation. RESULTS: From January 2009 to October 2010, 20 patients (median age: 45 years) underwent 57 procedures. All patients received chemoradiation with curative intent. The median duration of the procedures was 1.4 hours, and no significant cardiovascular events were noted. The total dose of intravenous midazolam used ranged from 0.5 mg to 8.5 mg (median: 2.5 mg). The total dose of intravenous morphine equivalent used ranged from 2.5 mg to 60 mg (median: 8 mg). The mean and median pain scores during the procedures were 1.4 and 1.1 respectively. Brief moments of moderate to severe incidental pain were noted at the time of certain events during the procedure-specifically during insertion of the ring-and-tandem applicator. The maximal pain score during the entire procedure ranged from 0 to 10 (median: 4.7). The period of recovery from conscious sedation was relatively brief (median discharge time: 1 hour). CONCLUSIONS: We were able to demonstrate that patients undergoing hdr brachytherapy for cervical cancer can achieve good pain control with conscious sedation.

Giant cell arteritis in Mumbai.

OBJECTIVE: To study the clinical profile of patients with giant cell arteritis in Mumbai. METHODS: From our database, patients with a diagnosis of giant cell arteritis (GCA) over a fifteen year period (January 1990 to December 2005) were included. Clinical manifestations, temporal artery biopsy, treatment, and follow-up data of these patients were analyzed. RESULTS: Twenty one patients with GCA were identified. However, data were available only for 16 patients. The median age was 66.5 years (58-78 yrs) with male to female ratio of 1:1. The mean time from symptom onset to diagnosis was 5.18 months (0.5-24 months). Clinical manifestations included new onset headache (15), fever (9), weight loss (9), jaw claudication (9), polymyalgia rheumatica (5), visual disturbances (3), scalp nodule (1), temporal artery tenderness (11), tortuosity (9), and scalp tenderness (6). ESR was elevated in 15 patients with a median of 106.5 mm at 1 hr (25-135 mm/hr). Temporal artery biopsy was done in 11 patients and confirmed the diagnosis in 10 patients. Color doppler study of the temporal arteries (9 patients) revealed halo sign (indicating arterial wall edema) in 6 patients. Biopsy as per site by color doppler study was performed in 6 of these patients and was positive in 5. All patients had a good initial response to steroids, however, on follow up, 3 patients required addition of methotrexate. At a median follow up (n = 14) of 6 months (range 6-156), steroids were successfully stopped in 7 patients at 1 to 3 years interval. The disease relapsed in 1 patient. Of the remaining 7 patients, 2 were steroid dependent and 5 patients were doing well on low dose prednisolone. CONCLUSION: GCA, though uncommon in India, should be suspected in all elderly patients with a new onset headache, fever, jaw claudication, or high ESR. Color doppler sonography is a useful noninvasive method for the diagnosis of GCA and also helps to identify the site to biopsy. Most respond to steroid therapy while some need addition of steroid sparing agents.

The importance of humour in oncology: a survey of patients undergoing radiotherapy.

Background: Humour has long been considered an important coping tool for patients with cancer, but published quantitative data about its significance are limited. The purpose of our study was to survey patients with cancer undergoing radiotherapy regarding their opinions about the use of humour in their care. Methods: An anonymous 35-item questionnaire evaluating the patient experience, including the value of humour, was developed by an interdisciplinary team of health care providers (hcps) working within the Radiation Medicine program. This anonymous, voluntary, paper-based survey for self-completion required approximately 10 minutes to finish and was administered during the fall of 2018 and the spring of 2019. Results: For the 199 patients who completed the survey [108 women, 89 men (2 respondents did not specify)], median age was 68 years. That group represents approximately 30%-35% of the patients on treatment during the study period. Almost all respondents (86%) indicated that, during their visits to the cancer centre, it was "somewhat important" or "very important" for health care providers (hcps) to use appropriate humour, and 61% of respondents indicated using humour "frequently" or "always" when dealing with their individual cancers. Most respondents (79%) said that humour decreased anxiety, and 86% indicated that laughing was considered "somewhat important" or "very important." Approximately 4% of respondents even listed "sense of humour" as being the most important quality that they looked for in their interactions with their hcps. Conclusions: Cancer patients undergoing radiotherapy clearly view humour as being important for coping and dealing with their disease, and oncology hcps should routinely consider incorporating the use of appropriate humour into the care that they provide.

The emerging role of IG-IMRT for palliative radiotherapy: a single-institution experience.

Many modern radiotherapy centers now have image-guided intensity-modulated radiotherapy (IG-IMRT) tools available for clinical use, and the technique offers many options for patients requiring palliative radiotherapy. We describe a single-institution experience with IG-IMRT for short-course palliative radiotherapy, highlighting the unique situations in which the technique can be most effectively used.

Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma.

The iliac crest is the sampling site for minimal residual disease (MRD) monitoring in multiple myeloma (MM). However, the disease distribution is often heterogeneous, and imaging can be used to complement MRD detection at a single site. We have investigated patients in complete remission (CR) during first-line or salvage therapy for whom MRD flow cytometry and the two imaging modalities positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed at the onset of CR. Residual focal lesions (FLs), detectable in 24% of first-line patients, were associated with short progression-free survival (PFS), with DW-MRI detecting disease in more patients. In some patients, FLs were only PET positive, indicating that the two approaches are complementary. Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively. FLs were a rare event (12%) in first-line MRD-negative CR patients. In contrast, patients achieving an MRD-negative CR during salvage therapy frequently had FLs (50%). Multi-region sequencing and imaging in an MRD-negative patient showed persistence of spatially separated clones. In conclusion, we show that DW-MRI is a promising tool for monitoring residual disease that complements PET and should be combined with MRD.

Adult onset Still's disease: a study of 14 cases.

We studied the clinical profile, laboratory parameters, disease course, and outcomes of patients with adult onset Still's disease (AOSD). A retrospective analysis of adult patients with Still's disease diagnosed from 2000 to 2004 was carried out. Their clinical features and laboratory findings at presentation, disease course, and outcomes were analyzed. Data of 14 patients with Still's disease were analyzed. The age at disease onset ranged from 16 to 59 years with a mean of 29.85, the male to female ratio being 9:5. The mean duration of illness from onset of symptoms to presentation was 14.5 months (range). The most common clinical manifestations were fever (n = 14), articular symptoms (n = 14), rash (n = 8), weight loss (n = 12), and sore throat (n = 5). Elevated ESR was present in all patients with a mean of 98.3 mm at 1 h. Hepatic enzymes were elevated in seven patients at disease onset. The mean duration of follow up was 19.14 months (range). Three patients progressed to chronic arthropathy. Cyclosporine led to dramatic recovery in five patients. Macrophage activation syndrome (MAS) was present in two patients, one after sulfasalazine therapy. One patient with MAS died. Still's disease, although uncommon, has characteristic constellation of clinical and laboratory features and should be considered in the differential diagnosis of fever of unknown origin. Nonsteroidal anti-inflammatory drugs, steroids, and methotrexate may not be always effective, and cyclosporine is an effective drug in resistant cases. Sulfasalazine should be avoided in cases of AOSD.

Contemporary management of stage I testicular seminoma: a survey of Canadian radiation oncologists.

Recently published studies clearly indicate that there are now several acceptable options for managing stage i testicular seminoma patients after orchiectomy. We therefore decided to survey Canadian radiation oncologists to determine how they currently manage such patients and to compare the results with previous surveys. Our results demonstrate that adjuvant single-agent chemotherapy is being considered as an option by an increasing proportion of radiation oncologists (although it is not considered the preferred option), the routine use of radiotherapy is declining, and surveillance is becoming increasingly popular and is recommended most often.

The preferred treatment for stage I seminoma: a survey of Canadian radiation oncologists.

AIMS: To evaluate the preferences of radiation oncologists for managing stage I seminoma. MATERIALS AND METHODS: An electronic survey evaluating the management of stage I seminoma patients was sent to Canadian radiation oncologists to determine their treatment recommendations and preferences. RESULTS: The survey completion rate was 74% among eligible respondents (78/105). Most (56%) felt that surveillance was the preferred treatment for patients, whereas 31% thought that adjuvant radiotherapy was best, 1% chose adjuvant chemotherapy as being the preferred option and 12% were unsure. Most would choose the same treatment for themselves if they were diagnosed with stage I seminoma. A previously published survey found that most respondents considered radiotherapy as the best option. CONCLUSIONS: Most Canadian radiation oncologists now favour surveillance for most stage I seminoma patients.

How should we describe the benefits of palliative radiotherapy?

The value of radiotherapy for palliation is well known to oncologists but not necessarily to other physicians. Using terms such as symptom improvement ratio (sir) and number needed to treat (nnt) rather than traditional response rates might be more appropriate in describing the benefits of palliative radiotherapy to other health care professionals.

Awareness and use of the Rapid Palliative Radiotherapy Program by family physicians in Eastern Ontario: a survey.

The Ottawa Rapid Palliative Radiotherapy Program (RPRP) was established in 1999 with the goal of facilitating access by family physicians to radiotherapy services for patients with advanced symptomatic cancer. Two years later, an audit revealed that of the 148 patients treated by the program, only 19 had been referred by family physicians.We therefore assessed awareness of the RPRP and perceptions of the effectiveness of palliative radiotherapy on the part of family physicians by surveying a random sample of family physicians in Eastern Ontario.Response rate was 50%. Only 18% of family physicians were aware of the RPRP, although 56% had previously referred patients for palliative radiotherapy. Among responders, 80% regularly provided palliative care, and these physicians were much more likely to be aware of and to refer patients for palliative radiotherapy.Our survey confirms the key role that family physicians play in providing care to patients with advanced cancer. However, significant deficits in family physician awareness of palliative radiotherapy programs and in knowledge of the effectiveness of palliative radiotherapy should be addressed to improve patient care.

Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13.

We previously showed that introduction of a normal, neomycin-tagged human chromosome 11 reduces the metastatic capacity of MDA-MB-435 (435) human breast carcinoma cells by 70-90% without affecting tumorigenicity, suggesting the presence of one or more metastasis suppressor genes encoded on human chromosome 11. To identify the gene(s) responsible, differential display comparing chromosome 11-containing (neo11/ 435) and parental, metastatic cells was done. We describe the isolation and functional characterization of a full-length cDNA for one of the novel genes, designated breast-cancer metastasis suppressor 1 (BRMS1), which maps to human chromosome 11q13.1-q13.2. Stably transfected MDA-MB-435 and MDA-MB-231 breast carcinoma cells still form progressively growing, locally invasive tumors when injected into mammary fat pads but are significantly less metastatic to lungs and regional lymph nodes. These data provide compelling functional evidence that breast-cancer metastasis suppressor 1 is a novel mediator of metastasis suppression in human breast carcinoma.

Evaluating changes in stage I seminoma management: a single institution review.

PURPOSE: Historically adjuvant radiotherapy has been routinely recommended for stage I seminoma patients but surveillance has become an increasingly popular option over the last decade. We therefore decided to review the approach currently used by the radiation oncologists at our center. METHODS: A 14-item questionnaire evaluating physician opinions about treatment options for stage I seminoma patients was developed at the Ottawa Hospital Regional Cancer Centre (OHRCC). It was sent to all the radiation oncologists at OHRCC treating genitor-urinary (GU) malignancies for self-completion. RESULTS: All the GU radiation oncologists completed the survey for a response rate of 100% (7/7). Most (71%) have been treating GU malignancies for at least 5 years with the median being 9 years. At present, all consider surveillance and adjuvant radiotherapy as standard treatment options for stage I seminoma patients, and recommend these to patients. They give patients information about the treatment options but also give their personal recommendations as well. Most have been routinely discussing surveillance as an option since the late 1990's. Clinical data from the OHRCC confirms that there has been a significant increase in the proportion of stage I seminoma patients being managed by surveillance over the past 15 years. Currently almost half of patients are choosing surveillance. CONCLUSIONS: There appears to be a fairly uniform approach towards the management of stage I seminoma patients at the OHRCC. Radiation oncologists are now routinely offering both surveillance and adjuvant radiotherapy as reasonable option for these patients, and this is consistent with the recently published literature on this topic.

Analysis of mechanisms underlying BRMS1 suppression of metastasis.

Introduction of normal, neomycin-tagged human chromosome 11 (neo11) reduces the metastatic capacity of MDA-MB-435 human breast carcinoma cells by 70-90% without affecting tumorigenicity. Differential display comparing MDA-MB-435 and neo11/435 led to the discovery of a human breast carcinoma metastasis suppressor gene, BRMS1, which maps to chromosome 11q13.1-q13.2. Stable transfectants of MDA-MB-435 and MDA-MB-231 breast carcinoma cells with BRMS1 cDNA still form progressively growing, locally invasive tumors when injected in mammary fat pads of athymic mice but exhibit significantly lower metastatic potential (50-90% inhibition) to lungs and regional lymph nodes. To begin elucidating the mechanism(s) of action, we measured the ability of BRMS1 to perturb individual steps of the metastatic cascade modeled in vitro. Consistent differences were not observed for adhesion to extracellular matrix components (laminin, fibronectin, type IV collagen, type I collagen, Matrigel); growth rates in vitro or in vivo; expression of matrix metalloproteinases, heparanase, or invasion. Likewise. BRMS1 expression did not up regulate expression of other metastasis suppressors, such as NM23, Kai1, KiSS1 or E-cadherin. Motility of BRMS1 transfectants was modestly inhibited (30-60%) compared to parental and vector-only transfectants. Ability to grow in soft agar was also decreased in MDA-MB-435 cells by 80-89%, but the decrease for MDA-MB-231 was less (13-15% reduction). Also, transfection and re-expression of BRMS1 restored the ability of human breast carcinoma cells to form functional homotypic gap junctions. Collectively, these data suggest that BRMS1 suppresses metastasis of human breast carcinoma by complex, atypical mechanisms.

A cost-outcome analysis of adjuvant postmastectomy locoregional radiotherapy in premenopausal node-positive breast cancer patients.

PURPOSE: To calculate cost-effectiveness and cost-utility ratios for adjuvant postmastectomy locoregional radiotherapy in premenopausal node-positive breast cancer patients and to place these ratios in the context of generally accepted medical expenditures. MATERIALS AND METHODS: A spreadsheet-based activity costing model using 1997 Canadian (cdn) capital, operating, and administrative costs has been used to identify, from the institutional perspective, the incremental cost of adding radiotherapy to surgery and chemotherapy for this group of patients. Outcome data were derived from two recently published clinical trials and were converted to discounted incremental life years and quality-adjusted life years gained. Recommended health economics principles were employed in the quantification of both costs and outcomes, and a sensitivity analysis was performed. Three referenced publications provide a context within which to evaluate the calculated cost-effectiveness and cost-utility ratios. RESULTS: The incremental cost of adjuvant radiotherapy for this group of patients is calculated to be approximately $7,000cdn in 1997 Canadian dollars and in the Canadian socialized health-care environment. Based on published work the discounted incremental outcome benefit is calculated to be 0.5 life years or 0.45 quality-adjusted life years at ten years. Thus, cost effectiveness and cost-utility ratios are estimated to be $14,000cdn and $15,600cdn, respectively. CONCLUSION: Within the context of generally accepted medical expenditures, adjuvant postmastectomy locoregional radiotherapy for premenopausal node-positive breast cancer patients would be regarded as a cost-effective treatment strategy.

Staging investigations in patients with breast cancer: the role of bone scans and liver imaging.

HYPOTHESIS: Metastatic workup for patients newly diagnosed as having breast cancer is variable, especially for early disease (T1-2 N0-1). Routine bone scans and liver imaging are often performed without any evidence to support their usefulness. DESIGN: A retrospective review of patients with breast cancer referred to our center during a 2-year period was performed to determine the value of staging investigations in detecting metastases. RESULTS: Of the total 250 patients referred to our center after initial diagnosis, 25 (10.0%) were diagnosed as having metastases, 23 of whom had either clinical symptoms or signs suggestive of metastatic disease or abnormalities on routine blood work or chest x-ray examinations. Only 2 patients with metastatic disease were diagnosed solely on bone scan results; none were diagnosed solely on liver imaging (either with an ultrasound or radionuclide isotope liver scan). Overall, 3% (5/161) of patients with pathologic T1-2 N0-1 disease had metastases diagnosed compared with 30% (18/61) of patients with pathologic stage T3-4 or N2 disease. CONCLUSIONS: Our results confirm the low yield of routine bone scans and liver imaging among patients with asymptomatic, pathologically confirmed, early stage (T1-2 N0-1) breast cancer. Therefore, we do not recommend these tests for such patients, although intensive investigations are appropriate for more advanced (stage T3-4 or N2) tumors.

Systemic lupus erythematosus in males.

Systemic Lupus Erythematosus is a disease commonly seen in women. A few male kindreds have however been described. In this study, twelve male patients of a series of 175 patients with SLE have been analysed. Arthritis was the most frequent manifestation observed. Renal involvement was seen in as many as 41.65% of patients.