CT-derived textural analysis parameters discriminate high-attenuation renal cysts from solid renal neoplasms.

AIM: To assess the utility of textural features on computed tomography (CT) to differentiate high-attenuation cysts from solid renal neoplasms among indeterminate renal lesions detected incidentally on CT. MATERIALS AND METHODS: Patients were included if they had an indeterminate renal lesion on CT that was subsequently characterised on ultrasound or magnetic resonance imaging (MRI). Up to three lesions per patient were included if they had a size ≥10 mm and density of 20-70 HU on unenhanced CT or any single phase of contrast-enhanced CT. Cases were categorised as benign or most likely benign cysts (Bosniak II and IIF) versus indeterminate (Bosniak III), mixed solid and cystic (Bosniak IV), or solid renal lesions. A random forest model was generated using 95 textural parameters and four clinical parameters for each lesion. RESULTS: Two hundred and thirty-four patients were included who had a total of 278 lesions. Of these, 193 (69%) were benign or most likely benign cysts and 85 (31%) were indeterminate, mixed cystic and solid, or solid renal lesions. The random forest model had an area under the curve of 0.71 (95% confidence interval [CI]: 0.65, 0.78), with a sensitivity and specificity of 81.2% and 38.9%, respectively. CONCLUSION: A multivariate model including textural and clinical parameters had moderate overall performance for discriminating benign or likely benign cysts from indeterminate, mixed solid and cystic, or solid renal lesions. This study serves as a proof of concept and may reduce the need for further follow-up by characterising a significant portion of indeterminate lesions on CT as benign.

Molecular imaging for cancer immunotherapy.

Immunotherapy has changed the treatment landscape for many cancers; however, not all patients treated have a favorable response and others can develop immune-related adverse events. A method to predict the treatment response to immunotherapeutic agents could allow for improved selection of patients more likely to benefit from treatment while sparing those who would suffer serious complications. While this has been an active area of research and has resulted in significant insights, current proposed mechanisms do not fully explain responses to therapy. One problem is that our understanding relies mostly on tumor biopsy samples that do not account for the complex spatiotemporal heterogeneity of cancers and their microenvironment. Radiolabeled probes targeting immune biomarkers and imaged using positron emission tomography with computed tomography could provide in vivo, real-time and non-invasive imaging of these biomarkers. Here we review the current field of functional nuclear imaging agents in immuno-oncology including antibodies and small molecule tracers to image PD-1, PD-L1, CTLA-4, T-cell markers and other targets being studied for potential therapies.

Gender differences in how physicians access and process information.

There is an absence of information on how physicians make surgical decisions, and on the effect of gender on the processing of information. A novel web based decision-matrix software was designed to trace experimentally the process of decision making in medical situations. The scenarios included a crisis and non-crisis simulation for endometrial cancer surgery. Gynecologic oncologists, fellows, and residents (42 male and 42 female) in Canada participated in this experiment. Overall, male physicians used more heuristics, whereas female physicians were more comprehensive in accessing clinical information (p < 0.03), utilized alternative-based acquisition processes in the non-crisis scenario (p = 0.01), were less likely to consider procedure-related costs (p = 0.04), and overall allocated more time to evaluate the information (p < 0.01). Further experiments leading to a better understanding of the cognitive processes involved in medical decision making could influence education and training and impact on patient outcome.

Re-irradiation with radiosurgery for recurrent glioblastoma multiforme.

Local tumor control remains a significant challenge in patients with glioblastoma multiforme (GBM). Despite aggressive radiation therapy approaches, most recurrences are within the high-dose field, limiting the ability to safely re-irradiate recurrence using conventional techniques. Fractionated stereotactic radiosurgery (fSRS) is a technique whose properties make it useful for re-irradiation. We retrospectively reviewed the charts of 14 patients with recurrent GBM treated with salvage radiosurgery. Seven patients were male and seven were female with a median age of 58 (range: 39-76). All patients had prior cranial radiation therapy to a median dose of 60 Gy (58-69). There were 18 lesions treated with a median tumor volume of 6.97 cm3 (0.54-50.0 cm3). fSRS was delivered in 1-3 fractions to a median dose of 24 Gy (18-30 Gy). Median follow-up for the cohort was 8 months (3-22 months). On follow-up MRI, 8 of 18 lesions had a radiographic response. The median time-to-progression following primary irradiation was 8 months (1-28 months) while the median time-to-progression (TTP) following fSRS was 5 months (1-16 months). Median local control following re-irradiation was 5 months and actuarial local control was 21% at 1-year. Overall survival following primary irradiation was 79% at 12 months and 46% at 2 years. Overall survival following re-irradiation was 79% at 6 months and 30% at 1 year. No significant treatment-related toxicity was seen in follow-up. These results indicate that re-irradiation for recurrent GBM using fSRS is well-tolerated and can offer a benefit in terms of progression-free survival (PFS).

Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha.

Hypoxia contributes to the progression of a variety of cancers by activating adaptive transcriptional programs that promote cell survival, motility and tumor angiogenesis. Although the importance of hypoxia and subsequent hypoxia-inducible factor-1alpha (HIF-1alpha) activation in tumor angiogenesis is well known, their role in the regulation of glioma-derived stem cells is unclear. In this study, we show that hypoxia (1% oxygen) promotes the self-renewal capacity of CD133-positive human glioma-derived cancer stem cells (CSCs). Propagation of the glioma-derived CSCs in a hypoxic environment also led to the expansion of cells bearing CXCR4 (CD184), CD44(low) and A2B5 surface markers. The enhanced self-renewal activity of the CD133-positive CSCs in hypoxia was preceded by upregulation of HIF-1alpha. Knockdown of HIF-1alpha abrogated the hypoxia-mediated CD133-positive CSC expansion. Inhibition of the phosphatidylinositol 3-kinase(PI3K)-Akt or ERK1/2 pathway reduced the hypoxia-driven CD133 expansion, suggesting that these signaling cascades may modulate the hypoxic response. Finally, CSCs propagated at hypoxia robustly retained the undifferentiated phenotype, whereas CSCs cultured at normoxia did not. These results suggest that response to hypoxia by CSCs involves the activation of HIF-1alpha to enhance the self-renewal activity of CD133-positive cells and to inhibit the induction of CSC differentiation. This study illustrates the importance of the tumor microenvironment in determining cellular behavior.

[Attachment process between an infant and his/her mother: the first year]. / Développement du processus d'attachement entre un bébé et sa mère.

Attachment theory is focused upon the development of the attachment process organized jointly by the child and the environmental factors which contribute to the development of the feeling of security. The authors focus on the mother-baby relationships and describe the normative process of attachment relationships during the first year of life. The ethologic perspective of this development is also summarized. The steps of the developing attachment relationship are described. The description of motherhood is focused on the bonding process, which is a more immediate and biologically based process and on caregiving which is a symmetrical motivational system as complex as the attachment one. The main factors known as having an impact on the two processes are described.

Management of single brain metastasis: a practice guideline.

QUESTIONS: Should patients with confirmed single brain metastasis undergo surgical resection? Should patients with single brain metastasis undergoing surgical resection receive adjuvant whole-brain radiation therapy (wbrt)? What is the role of stereotactic radiosurgery (srs) in the management of patients with single brain metastasis? PERSPECTIVES: Approximately 15%-30% of patients with cancer will develop cerebral metastases over the course of their disease. Patients identified as having single brain metastasis generally undergo more aggressive treatment than do those with multiple metastases; however, in the province of Ontario, management of patients with single brain metastasis varies. Given that conflicting evidence has been reported, the Neuro-oncology Disease Site Group (dsg) of the Cancer Care Ontario Program in Evidence-based Care felt that a systematic review of the evidence and a practice guideline were warranted. OUTCOMES: Outcomes of interest were survival, local control of disease, quality of life, and adverse effects. METHODOLOGY: The medline, cancerlit, embase, and Cochrane Library databases and abstracts published in the proceedings of the annual meetings of the American Society of Clinical Oncology (1997-2005) and American Society for Therapeutic Radiology and Oncology (1998-2004) were systematically searched for relevant evidence. The review included fully published reports or abstracts of randomized controlled trials (rcts), nonrandomized prospective studies, and retrospective studies. The present systematic review and practice guideline has been reviewed and approved by the Neuro-oncology dsg, which comprises medical and radiation oncologists, surgeons, neurologists, a nurse, and a patient representative. External review by Ontario practitioners was obtained through an electronic survey. Final approval of the guideline report was obtained from the Report Approval Panel and the Neuro-oncology dsg. QUALITY OF EVIDENCE: The literature search found three rcts that compared surgical resection plus wbrt with wbrt alone. In addition, a Cochrane review, including a meta-analysis of published data from those three rcts, was obtained. One rct compared surgical resection plus wbrt with surgical resection alone. One rct compared wbrt plus srs with wbrt alone. Evidence comparing srs with surgical resection or examining srs with or without wbrt was limited to prospective case series and retrospective studies. BENEFITS: Two of three rcts reported a significant survival benefit for patients who underwent surgical resection as compared with those who received wbrt alone. Pooled results of the three rcts indicated no significant difference in survival or likelihood of dying from neurologic causes; however, significant heterogeneity was detected between the trials. The rct that compared surgical resection plus wbrt with surgical resection alone reported no significant difference in overall survival or length of functional independence; however, tumour recurrence at the site of the metastasis and anywhere in the brain was less frequent in patients who received wbrt as compared with patients in the observation group. In addition, patients who received wbrt were less likely to die from neurologic causes. Results of the rct that compared wbrt plus srs with wbrt alone indicated a significant improvement in median survival in patients who received srs. No quality evidence compares the efficacy of srs with surgical resection or examines the question of whether patients who receive srs should also receive wbrt. HARMS: Pooled results of the three rcts that examined surgical resection indicated no significant difference in adverse effects between groups. Postoperative complications included respiratory problems, intracerebral hemorrhage, and infection. One rct reported no significant difference in adverse effects between patients who received wbrt plus srs and those who received wbrt alone. TARGET POPULATION: The recommendations that follow apply to adults with confirmed cancer and a single brain metastasis. This practice guideline does not apply to patients with metastatic lymphoma, small-cell lung cancer, germ-cell tumour, leukemia, or sarcoma. RECOMMENDATIONS: Surgical excision should be considered for patients with good performance status, minimal or no evidence of extracranial disease, and a surgically accessible single brain metastasis amenable to complete excision. Because treatment in cases of single brain metastasis is considered palliative, invasive local treatments must be individualized. Patients with lesions requiring emergency decompression because of intracranial hypertension were excluded from the rcts, but should be considered candidates for surgery. To reduce the risk of tumour recurrence for patients who have undergone resection of a single brain metastasis, postoperative wbrt should be considered. The optimal dose and fractionation schedule for wbrt is 3000 cGy in 10 fractions or 2000 cGy in 5 fractions. As an alternative to surgical resection, wbrt followed by srs boost should be considered for patients with single brain metastasis. The evidence is insufficient to recommend srs alone as a single-modality therapy. QUALIFYING STATEMENTS: No high-quality data are available regarding the choice of surgery versus radiosurgery for single brain metastasis. In general, the size and location of the metastasis determine the optimal approach. The standard wbrt regimen for management of patients with single brain metastasis in the United States is 3000 cGy in 10 fractions, and this treatment is usually the standard arm in randomized studies of radiation in patients with brain metastases. Based solely on evidence, the understanding that no reason exists to choose 3000 cGy in 10 fractions over 2000 cGy in 5 fractions is correct; however, fraction size is believed to be important, and therefore 300 cGy daily (3000/10) is believed to be associated with fewer long-term neurocognitive effects than 400 cGy daily (2000/5) in the occasional long-term survivor. For that reason, many radiation oncologists in Ontario prefer 3000 cGy in 10 fractions. No data exist to either support or refute that preference; therefore, finding a resolution to this issue is not currently possible. The Neuro-oncology dsg will update the recommendations as new evidence becomes available.

Patellar resurfacing in total knee replacement: a ten-year randomised prospective trial.

A series of 100 consecutive osteoarthritic patients was randomised to undergo total knee replacement using a Miller-Galante II prosthesis, with or without a cemented polyethylene patellar component. Knee function was evaluated using the American Knee Society score, Western Ontario and McMaster University Osteoarthritis index, specific patellofemoral-related questions and radiographic evaluation until the fourth post-operative year, then via questionnaire until ten years post-operatively. A ten-point difference in the American Knee Society score between the two groups was considered a significant change in knee performance, with alpha and beta levels of 0.05. The mean age of the patients in the resurfaced group was 71 years (53 to 88) and in the non-resurfaced group was 73 years (54 to 86). After ten years 22 patients had died, seven were suffering from dementia, three declined further participation and ten were lost to follow-up. Two patients in the non-resurfaced group subsequently had their patellae resurfaced. In the resurfaced group one patient had an arthroscopic lateral release. There was no significant difference between the two treatment groups: both had a similar deterioration of scores with time, and no further patellofemoral complications were observed in either group. We are unable to recommend routine patellar resurfacing in osteoarthritic patients undergoing total knee replacement on the basis of our findings.

Hemangioendothelioma of the spinal cord with intramedullary extension.

OBJECTIVE: Hemangioendotheliomas (HE) are vascular neoplasms that rarely involve the neuraxis. We report a rare case in the literature of intradural HE of the spinal cord with intramedullary extension. CLINICAL PRESENTATION AND INTERVENTIONS: A 41-year-old gentleman presented with low back pain, numbness and urinary retention. Imaging revealed a spinal tumor causing complete blockage at the level of T12. The tumor was resected and postoperative radiotherapy was delivered for residual disease. No disease was seen on MRI after 48 months of clinical and radiological follow-up. CONCLUSION: Complete excision of HE is the treatment of choice. Radiotherapy may play a role in the management of this lesion.

Anal melanoma in the era of sentinel lymph node mapping: a diagnostic and therapeutic challenge.

Melanoma of the anal canal is a rare malignancy that often has an atypical presentation. Locoregional metastases, which are often present at the initial presentation, may occur in both groin and pelvic lymph nodes, but the utility of lymph node dissection remains unknown. We explored the possibility of applying the technique of sentinel lymph node (SLN) mapping to anal melanoma. SLN mapping was performed in 2 patients with anal melanoma. Radioactive tracer and blue dye were injected around the lesions. The SLN was identified pre-operatively by lymphoscintigraphy, and at surgery with a hand-held gamma detector and by visualization of the dye. The SLN was identified in both patients, only in the groin in one and only in the presacral region in the other. One patient had a wide local excision of the anal lesion with house flap anoplasty, while the other had abdominoperineal resection with total mesorectal excision. There were no SLN metastases in either patient. The technique of SLN mapping and biopsy is easily adapted to surgery for malignant melanoma of the anus. SLN mapping and biopsy could aid in planning surgical strategy, but definitive conclusions may only be reached after more experience has been acquired.

Preoperative and postoperative levels of interleukin-6 in patients with acute appendicitis: comparison between open and laparoscopic appendectomy.

BACKGROUND: Cytokine interleukin-6 (IL-6) is an early marker of systemic inflammatory response and tissue damage. This study aimed to evaluate the levels of IL-6 after open and laparoscopic appendectomy to compare the degree of surgical stress associated with these procedures. METHODS: The levels of IL-6 were measured pre- and postoperatively in the plasma of 37 consecutive patients with a diagnosis of acute appendicitis. After preoperative randomization, 22 patients underwent open appendectomy, and 15 patients underwent laparoscopic appendectomy. RESULTS: The preoperative concentrations of IL-6 were 7.2 +/- 5.6 pg/ml in the open appendectomy group, as compared with 12.1 +/- 9.7 pg/ml in the laparoscopic appendectomy group (p < 0.05). The postoperative levels were 16.9 +/- 15.7 and 23.2 +/- 19.4 pg/ml, respectively. The mean postoperative to preoperative ratio of IL-6 was slightly higher for open (2.7 +/- 2.4) than for laparoscopic (2.3 +/- 1.6) appendectomy, but the difference did not reach statistical significance. CONCLUSION: The operative stress in open as compared with laparoscopic appendectomy is not reflected by circulating levels of IL-6.

Cancer genetics/epigenetics and the X chromosome: possible new links for malignant glioma pathogenesis and immune-based therapies.

Human high-grade gliomas (HGGs) are rapidly progressing heterogeneous brain tumors of unknown etiology and there are no effective treatment modalities available. The recent discovery of cancer-specific antigens has opened new doors for specific tumor-targeted treatments using passive and active immunotherapeutic strategies. In particular, SEREX (serological analysis of recombinant cDNA expression libraries) has aided in the discovery of numerous new tumor antigens. These specific tumor antigens are located on chromosome X and are expressed predominantly in the testes among normal organs, and hence termed Cancer/Testis Antigens (CTAs). We found that the vast majority of HGG patients overexpress a receptor for an immune regulatory cytokine, interleukin 13 (IL-13), which differs from the normal tissue physiological receptor. Interestingly, the HGG-associated receptor protein, IL-13R alpha, is expressed solely in the testes and its gene is localized to chromosome X, which mirror the expression pattern and genomic localization of CTAs. There is little evidence for frequent gross structural abnormalities on chromosome X in HGG. Although the mechanism that causes X chromosome-linked CTAs to be aberrantly expressed in tumors is not fully understood, evidence is beginning to point toward the DNA methylation dysregulation that occurs in tumor cells as being implicit in this process and perhaps in the oncogenic process as well. Therefore, further study of the phenomenon of CTAs may bring the dual benefit of better understanding tumorigenesis and providing new molecular tools for better management of HGGs. Also, we propose that the X chromosome may in fact be an important player in HGG oncogenesis.

A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis.

BACKGROUND: Cerebral metastasis is a common oncologic problem that occurs in 15-30% of cancer patients; approximately half such metastases are single. Previous retrospective studies and two randomized trials reported that the addition of surgical extirpation prior to radiation therapy increased survival, neurologic function, and quality of life compared with radiation alone in patients with a single brain metastasis. METHODS: A randomized controlled trial was conducted in which patients with a single brain metastasis were allocated to undergo radiation alone or surgery plus radiation. Radiation consisted of 3000 centigray to the whole brain in 10 fractions. RESULTS: Forty-three patients received radiation alone and 41 patients surgery plus radiation. All but two of the study patients died. No difference in survival was detected between the groups; the median survival for the radiation group was 6.3 months (95% confidence interval, 3-11.4) compared with 5.6 months for the surgery plus radiation group (95% confidence interval, 3.9-7.2) (P = 0.24). Most patients died within the first year (69.8% in the radiation arm vs. 87.8% in the surgery plus radiation arm). There were no significant differences in the 30-day mortality, morbidity, or causes of death. Extracranial metastases was an important predictor of mortality (relative risk, 2.3). The mean proportion of days that the Karnofsky performance status was > or = 70% did not differ between the 2 groups. CONCLUSIONS: This trial failed to demonstrate that the addition of surgery to radiation therapy improved outcome of patients with a single brain metastasis. Thus, the efficacy of surgery plus radiation compared with radiation alone needs to be addressed by further clinical trials and/or a meta-analysis.

Early patellofemoral revision following total knee arthroplasty.

A consecutive series of 289 Miller-Galante (Zimmer, Warsaw, IN) total knee arthroplasties were studied, with particular reference to the patellofemoral joint. Sixteen knees were initially excluded; the remaining 273 arthroplasties were followed for 14 to 44 months. Thirty patients (11%) had patellofemoral pain. Twenty patients (7.3%) had revision patellofemoral surgery. Fourteen patients had revision surgery for patellar maltracking, of which 10 had resolution of their symptoms, 2 were improved, 1 had no change, and 1 developed a prosthetic infection. Six patients who had no evidence of patellar maltracking had revision surgery with a cemented metal-backed patellar component. Only two of these patients had symptom improvement from their revision surgery. A higher than usual incidence of patellar maltracking (5%) is reported. The first-generation Miller-Galante femoral component may contribute to the relative instability of patellofemoral tracking. Those patients with patellar maltracking were greatly improved by revision surgery; the results of revision surgery for anterior knee pain without associated patellar maltracking were disappointing.