Patients In Good Clinical Condition Research Articles

Practical guidelines for the management of adverse events of the T cell engager bispecific tebentafusp

Tebentafusp is a new T cell receptor bispecific fusion protein and the first approved treatment option for human leucocyte antigen-A*02:01 (HLA-A*02:01) metastatic uveal melanoma, with a proven benefit in overall survival versus the investigator’s choice. As a first-in-class therapeutic option, this Immune mobilising monoclonal T cell receptor Against Cancer (ImmTAC) is associated with a new adverse event (AE) profile. Based on clinical experience, a national expert group discussed recommendations for tebentafusp treatment, focusing on AE management. Further topics included prerequisites for initiating tebentafusp treatment, appropriate treatment setting, and patient selection criteria. To provide guidance for treating physicians, the resulting recommendations are summarised including a model standard operating procedure for AE management. Patients in good clinical condition and with a low tumour burden are good candidates for tebentafusp treatment, particularly if treated as early as possible after the diagnosis of metastatic disease. The safety profile of tebentafusp is manageable and includes two major pathologies: cytokine release syndrome (CRS) and skin-related events. Postdose monitoring should thus focus on pyrexia and hypotension as the first symptoms of cytokine release. To minimise the risk of hypotension associated with CRS, patients should receive intravenous fluids before starting treatment. The monitoring of liver values is crucial, as patients may experience an increase in transaminases, which can even manifest as tumour lysis syndrome.

Adherence to antidiabetic drug therapy and reduction of fatal events in elderly frail patients

BackgroundTo evaluate the protective effect of oral antidiabetic drugs in a large cohort of elderly patients with type 2 diabetes differing for age, clinical status, and life expectancy, including patients with multiple comorbidities and short survival.MethodsA nested case–control study was carried out by including the cohort of 188,983 patients from Lombardy (Italy), aged ≥ 65 years, who received ≥ 3 consecutive prescriptions of antidiabetic agents (mostly metformin and other older conventional agents) during 2012. Cases were the 49,201 patients who died for any cause during follow-up (up to 2018). A control was randomly selected for each case. Adherence to drug therapy was measured by considering the proportion of days of the follow-up covered by the drug prescriptions. Conditional logistic regression was used to model the risk of outcome associated with adherence to antidiabetic drugs. The analysis was stratified according to four categories of the clinical status (good, intermediate, poor, and very poor) differing for life expectancy.ResultsThere was a steep increase in comorbidities and a marked reduction of the 6-year survival from the very good to the very poor (or frail) clinical category. Progressive increase in adherence to treatment was associated with a progressive decrease in the risk of all-cause mortality in all clinical categories and at all ages (65–74, 75–84 and ≥ 85 years) except for the frail patient subgroup aged ≥ 85 years. The mortality reduction from lowest to highest adherence level showed a tendency to be lower in frail patients compared to the other categories. Similar although less consistent results were obtained for cardiovascular mortality.ConclusionsIn elderly diabetic patients, increased adherence to antidiabetic drugs is associated with a reduction in the risk of mortality regardless of the patients’ clinical status and age, with the exception of very old patients (age ≥ 85 years) in the very poor or frail clinical category. However, in the frail patient category the benefit of treatment appears to be less than in patients in good clinical conditions.

S-17-3: ANTIDIABETIC DRUG THERAPY AND SURVIVAL IN ELDERLY FRAIL PATIENTS. REAL-LIFE EVIDENCE FROM ITALY

Objective: Aim of the study was to evaluate the protective effect of antidiabetic drugs in a large cohort of unselected elderly diabetic patients differing for their clinical status and life expectancy. The evaluation focused, in particular, on a group of patients with a very low survival rate because frail patients are usually excluded from intervention trials, limiting evidence on treatment effectiveness. The protective effect of drug therapy, quantified by the reduction in all-cause mortality with increased adherence to antidiabetic agent therapy, was studied by stratifying patients according to their life expectancy. Design and method: The Lombardy (Italy) residents, aged > 65 years, who received > 2 consecutive prescriptions of antidiabetic agents during 2012 were identified and the date of the third prescription was defined as the index date. A case-control study was nested into the cohort of antidiabetic drug users. Death from any cause was the outcome of interest, and cases were cohort members who died during follow-up (up to 2018). For each case, a control was selected and matched for age, gender, and clinical profile. Conditional logistic regression was used to model the risk of outcome associated with four categories of adherence to antidiabetic drugs. Adherence to drug therapy was measured by considering the proportion of days of the follow-up covered by the drugs. The analysis was stratified according to four categories of the clinical profile (good, intermediate, poor, and very poor) differing for life expectancies, as evaluated by a multisource comorbidity score able to accurately predict the risk of death. Results: Among the 276,336 patients in treatment with antidiabetic agents during 2012, 188,983 met the inclusion criteria and generated 49,219 deaths during follow-up, 49,201 of whom were matched to a control. The 6-year survival decreased from 85% to 52% from the group of patients with good to the group of patients with a very poor clinical status. Adherence to treatment was associated with a progressive decrease in the risk of mortality in all categories of clinical status. The reduction from lowest to highest adherence level was 36% (95% CI, 25–46%), 50% (44–56%), 38% (33–42%) and 26% (17–34%) from good to very poor clinical status (Figure). Conclusions: In a real-life context, adherence to antidiabetic drugs is associated with a reduction in the risk of mortality regardless of the clinical status of the patients. However, in more frail patients, the benefit of treatment is less than in patients in good clinical condition.

The optimal management of ruptured basilar artery dissecting aneurysms: a case series and scoping review.

The natural history of ruptured basilar artery dissecting aneurysms (BADAs) remains unclear compared to that of ruptured vertebral artery dissecting aneurysms (VADAs). In this study, we investigated the natural history and optimal management of ruptured BADAs. We identified 17 patients with ruptured BADA among 4586 patients with aneurysmal subarachnoid hemorrhage (SAH) treated in seven participating hospitals. A scoping literature review was undertaken to investigate prognostic factors. Six patients among the profiled patients (35.3%) died, all with poor SAH grades (World Federation of Neurological Societies Grade IV and V). Rebleeding after admission was observed in three patients (17.6%) with poor SAH grades. Aggressive treatment and conservative management were initiated in seven and ten patients, respectively. Patients with good SAH grades had significantly higher favorable treatment outcomes than those with poor grades (83.3% vs. 9.1%, P = 0.005). Moreover, based on a scoping review of 158 cases with ruptured BADA, including the patients from our series, approximately 90% of patients with good SAH grades had favorable outcomes. A good SAH grade and no rebleeding after admission were favorable prognostic factors (P < 0.0001 and P = 0.002, respectively). The rebleeding rates were 20.2%, 13.3%, and 6.3% for dilated, pearl and string, and stenotic lesions, respectively. We concluded that the natural history of isolated ruptured BADAs may be better than that of VADAs. Although definitive treatment, if possible, is undoubtedly important, conservative management with careful radiological follow-up for morphological changes might be a viable option for patients in good clinical condition and with non-dilated lesions.

Dynamics of the Third Wave of COVID-19 from the Perspective of the Emergency Department in a Large Regional Hospital-Single Center Observational Study.

Background: The outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic has caused many significant social and economic changes. The consecutive waves of the epidemic in various countries have had dissimilar courses depending on the methods used to combat it. The aim of this study was to determine the dynamics of the third wave of COVID-19 from the perspective of emergency departments (ED). Methods: This was a retrospective review of medical records from ED. The authors have identified the most frequent symptoms. Prognostic factors have been chosen—prognostic scales, length of stay (LOS)—and a number of resources required have been calculated. Results: As the time passed, there were fewer patients and they presented mild symptoms. A statistically significant difference was observed in the median of blood oxygenation measurement (p = 0.00009), CRP level (p = 0.0016), and admission rate. Patients admitted to the hospital required more resources at ED. LOS was shorter in patients discharged home (p < 0.0001). Conclusions: The blood oxygen saturation (SPO2) and CPR levels can be helpful in decision-making regarding medical treatment. The fast-track for patients in good clinical condition may shorten the duration of stay in ED, and reduce the number of required resources.

Indications and results of osteosynthesis for proximal humerus fragility fractures in elderly patients.

Proximal humerus fractures (PHF) are common injuries in the elderly population. Conservative treatment is indicated for undisplaced and stable fractures, which account for almost 80% of the cases. More complex fracture patterns might need surgery, with a wide variety of indication criteria and surgical techniques described in the literature. Surgical treatment should be reserved for patients in good clinical conditions, autonomous in daily living activities and able to adhere to postoperative rehabilitation protocols. In the elderly population with severe osteoporosis, cognitive impairment and clinical comorbidities, the risk of surgical failures is high. In these patients, the choice between surgical and conservative treatment, as well as for the type of procedure, is even more difficult, with no general consensus in the literature. Final indication is usually conditioned by surgeon’s experience and preference. Two independent reviewers (B.H and G.G) independently extracted studies on proximal humeral fractures. All selected studies were screened independently (B.H and G.G) based on title and abstract. Then the full text of any article that either judged potentially eligible was acquired and reviewed again. Any disagreement was resolved by discussing the full text manuscripts. Aim of the present paper is to review the literature about indications and results of osteosynthesis for proximal humerus fragility fractures in the elderly population.

Functional outcome 1 year after aneurysmal subarachnoid hemorrhage due to ruptured intracranial aneurysm in elderly patients

BackgroundPopulation aging raises questions about extending treatment indications in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). We therefore assessed functional status 1 year after treatment. MethodsThis study involved 310 patients, aged over 70 years, with ruptured brain aneurysm, enrolled between 2008 and 2014 in a prospective multicentre trial (FASHE study: NCT00692744) but considered unsuitable for randomisation and therefore analysed in the observational arms of the study: endovascular occlusion (EV), microsurgical exclusion (MS) and conservative treatment. The aims were to assess independence, cognition, autonomy and quality of life (QOL) at 1 year post-treatment, using questionnaires (MMSE, ADLI, IADL, EORTC-QLQ-C30) filled in by independent nurses after discharge. ResultsThe 310 patients received the following treatments: 208 underwent EV (67.1%), 54 MS (17.4%) and 48 were conservatively managed (15.5%). At 1 year, independence rates for patients admitted with good clinical status (WFNS I-III) were, according to the aneurysm exclusion procedure (EV, MS or conservative), 58.9%, 50% and 12.1% respectively. MMSE score was pathological in 26 of the 112 EV patients (23.2%), 10 of the 25 MS patients (40%) and 4 of the 9 patients treated conservatively (44%), without any statistically significant difference [Pearson's Chi2 test, F ratio=4.29; P=0.11]. Regarding QoL, overall score was similar between the EV and MS cohorts, but significantly lower with conservative treatment. ConclusionElderly patients in good clinical condition with aSAH should be treated regardless of associated comorbidities. Curative treatment (EV or MS) reduced mortality without increasing dependence, in comparison with conservative treatment.

Major gastrointestinal hemorrhage during anticoagulant therapy in patients with atrial fibrillation: when should treatment be resumed?

In patients with atrial fibrillation (AF) under oral anticoagulant therapy (OAT), over half of the hemorrhagic complications occur in the gastrointestinal (GI) tract, with an incidence of 1-4% per year. This complication mainly involves older patients, often very compromised from the clinical point of view; mortality rates are not negligible, varying between 4% and 15%. The purpose of the present review was to evaluate the utility of resuming OAT after a major GI hemorrhage in patients with AF. Four observational studies were found in the literature that specifically investigated this issue; three of them had a retrospective design. In these studies almost exclusively warfarin was utilized. OAT was discontinued in all patients at the beginning of GI hemorrhage; in about half of the patients anticoagulation was then restarted and in the other half it was definitively stopped. The results of these studies suggest a beneficial effect of OAT resumption, since it reduced the incidence of thromboembolic events and mortality with a not marked increase in hemorrhagic recurrences. However, these results should be interpreted with caution since, very likely, OAT was resumed in patients in good clinical condition - as suggested by the very low mortality rate during hemorrhagic recurrences (0.7%) - and not in those with very severe hemorrhage and/or very compromised from the clinical point of view. Because of this type of patient selection, we do not know the real hemorrhagic risk in patients resuming OAT after GI hemorrhage. This is a strong limitation in the decision making; in order to acquire this knowledge, randomized studies should be carried out. The evaluation whether or not to restart OAT should be made in the clinical context by a team including the gastroenterologist (or the physician taking care of the GI pathology) and the cardiologist. At present, clinical variables such as site and/or cause of GI bleeding, severity of the anemia and the degree of prolongation of the international normalized ratio, do not appear useful for decision making. The available data suggest that OAT should be resumed in "robust" elderly patients, if the source of bleeding has been identified and corrected, whereas in frail patients and/or with multiple comorbidities, the doubt often remains. The available literature does not offer clear data on the optimal duration of OAT discontinuation after an episode of major GI bleeding. The evaluation should be made in the clinical context; however, therapy discontinuation between 1 week and 1 month appears to be adequate in most cases. On the basis of indirect comparisons, which show many limitations, the most appropriate anticoagulants after GI hemorrhage appear to be warfarin, apixaban and low-dose edoxaban.

Role of multidimensional assessment of frailty in predicting outcomes in older patients with glioblastoma treated with adjuvant concurrent chemo-radiation.

Our aim was to evaluate the impact of comorbidities, clinical and biological factors on outcomes in elderly GBM patients treated with surgery followed by concurrent radiation (RT) and Temozolomide (TMZ). Our sample includes 34 elderly patients with GBM who treated from January 2013 to December 2017. We collected data regarding age, extension of surgery, use of current medications, KPS, presenting symptoms, Prognostic Nutritional Index (PNI), Charlson Co-morbidity Index (CCI) and Frailty Index (FI). All of these parameters, measured before the start of RT-TMZ, were linked to clinical outcomes. With a median follow-up of 9.7 months, the median overall survival (OS) was 12.1 months and 1-year OS was 50%. In univariable analysis high KPS and total surgery were significantly associated with better OS. Also PNI, CCI and FI were a significant predictors of OS. At multivariate analysis KPS, type of surgery and FI remained a significant predictors of OS and, based on these parameters, we generated a prognostic score that, dividing patients into three risk categories, has proven to be a survival predictor, with an increase of the risk of death by 2.2 times for each increment of the score (HR 2.2, p = .0004). The appropriate management of elderly cancer patients with GBM is an important concern in oncology. Our data suggest that in elderly patients in good clinical conditions and with a low FI score, extensive surgery, when feasible without adding neurological impairment, followed by adjuvant RT-TMZ, should be considered.

Causes of poor outcome in patients admitted with good-grade subarachnoid haemorrhage

Surgical risk in patients with unruptured aneurysms is well known. The relative impact of surgery and natural history of subarachnoid haemorrhage (SAH) on patients in good clinical condition (World Federation of Neurological Surgeons [WFNS] grades 1 and 2) is less well quantified. The aim of this study was to determine causes of poor outcome in patients admitted in good grade SAH. A retrospective study of prospectively collected data among WFNS-1 and -2 patients: demographics, SAH and aneurysm-related data, surgical complications and outcome as assesed by the Glasgow Outcome Scale (GOS). Causes of poor outcome (GOS 1-3) were determined. During a 7-year period (2009-15), 56 patients with SAH WFNS-1 (39 patients) or WFNS-2 (17 patients) were treated surgically (21 men, 35 women; mean age, 52.4years). According to the Fisher scale, 19 patients were grade 1 or 2; 37 patients were grade 3 or 4. Most aneurysms were located at anterior communicating (26) or middle cerebral (15) artery. Altogether, 11 patients (19.6%) achieved GOS 1-3. This was attributed to SAH-related complications in six patients (rebleeding, vasospasm), surgery in four patients (postoperative ischaemia in two, haematoma and ventriculitis in one patient each), grand-mal seizure with aspiration in one patient. Age over 60years (p = 0.017) and presence of hydrocephalus (p < 0.001) were statistically significant predictors of poor GOS; other variables (e.g. sex, Fisher grade, aneurysm size or location, use of temporary clips, intraoperative rupture, vasospasm) were not significant. Patients admitted in good-grade SAH achieve favourable outcome following surgical aneurysm repair in the majority of cases. Negative factors include age over 60years and presence of hydrocephalus. Aneurysm surgery following good-grade SAH still carries a small but significant risk similar to that shown in large multi-institutional trials.

Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology).

The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblastoma is unclear. We performed a large multicenter retrospective study to analyze prognostic factors and clinical outcome in these patients. Inclusion criteria were age ≥65 years, newly histologically confirmed glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237 patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total resection was performed in 174 cases. MGMT was analyzed in 151 persons and was methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %. Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy. Progression-free survival and overall survival (OS) were 11.3 and 17.3 months, respectively. Overall survival was 19.4 vs 13.8 months for patients treated with RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2 versus 13.6 months for methylated and unmethylated MGMT (p < 0.001). On multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG PS 0-1 were independent predictors of longer survival. Twenty-five patients (10 %) had grade 3-4 haematological toxicity during the concomitant treatment. We showed that, in elderly patients in good clinical condition treated with concomitant treatment, standard-course irradiation might be more effective than short-course irradiation. Methylated MGMT remains the most important prognostic factor.

One Stage Radical Removal of Intravenous Leiomyomatosis Extending to the Right Atrium via the Bilateral Gonadal Veins

Background Intravenous leiomyomatosis is a benign and rare smooth muscle cell tumor. Extension to the right heart is exceptional. Among the reported cases, the tumor is usually known to enter through the lumen of the iliac vein and grows into the inferior vena cava; involvement of bilateral gonadal veins is rarely reported. Complete tumor resection is the key to therapy. Case presentation A 25 year old female Chinese patient suffering from abdominal distention for 1 month, who was diagnosed with intravenous leiomyomatosis extending to the heart, from pre-operative imaging studies, is presented. A one stage procedure with complete excision of the tumor was performed. Histopathological findings confirmed the diagnosis of intravenous leiomyomatosis. The patient's post-operative recovery was uneventful, without recurrence and re-stenosis at 1 year follow up. Conclusion Intravenous leiomyomatosis may grow within veins along various routes. This case demonstrated intravenous leiomyomatosis with tumor extension through bilateral gonadal veins extending to the heart. It is believed that one stage radical resection can be a practical and effective alternative for the patients in good clinical condition. Long-term follow up is recommended because of the possibility of recurrence and metastases.

P17.53 * THE COMBINATION OF CARMUSTINE WAFERS AND FOTEMUSTINE IN RECURRENT GLIOBLASTOMA PATIENTS: OUR EXPERIENCE

BACKGROUND: In the last years, few advances have been made improving progression-free survival and overall survival in patients with glioblastoma multiforme. There is no standard treatment for recurrent disease. We analyzed the feasibility of a multimodal strategy with second surgery plus carmustine wafers in the surgical cavity followed by intravenous fotemustine administration. METHODS: Retrospectively, we analyzed patients with recurrent glioblastoma treated with this multimodal strategy: carmustine wafers positioned during second surgery and subsequently, fotemustine drug as second-line treatment performed between 14 and 21 days after the second surgery. Intravenous fotemustine was administrated at 100mg/m2 every week for 3 consecutive weeks followed by a 5-week rest period; subsequently, an infusion every 3 weeks until progression disease or unacceptable toxicity or until a maximum of 12 cycles. During fotemustine therapy tumor response was evaluated by clinician assessment and by brain magnetic resonance imaging according to Macdonald criteria every two months or when clinically indicated. RESULTS: Twenty-four patients were analyzed. The median age was 53.6 years; all patients had KPS between 90 and 100, 19 patients (79%) performed a gross total resection >98% and 5 (21%) a gross total resection >90%. Seventeen patients were available for MGMT gene analysis and 10 (59%) patients had methylated MGMT gene promoter. The median time from first and second surgery was 17 months. The median progression-free survival from second surgery was 6 months (95% CI 3.9-8.05) and the median OS was 14 months (95% CI 11.1 - 16.8 months). No significant association was found between the resection rate (GTR >98% vs GTR >90%) and PFS (p = 0.4) and OS (p = 0.9). All patients were evaluable for toxicity which was predominantly haematological: 5 patients (21%) experienced grade 3-4 thrombocytopenia and 3 patients (12%) grade 3-4 leukopenia . Among non-haematological toxicity: 5 patients (21%) had grade 1-2 asthenia, 2 patients (8%) had grade 1-2 nausea/vomiting and 2 patients (8%) reported hypertransaminasemia. CONCLUSION: This multimodal strategy may be feasible in patients with recurrent glioblastoma; in particular, for patients in good clinical conditions

Benefit of tumor resection for recurrent glioblastoma

In the treatment of glioblastoma (GBM) the impact of radical tumor resection as first line therapy is beyond controversy. The significance of a second resection in case of tumor-recurrence remains unclear and is an issue of debate. Since GBMs always recur, it is important to determine whether or not patients will benefit from repeat surgery. We performed a retrospective analysis of our prospectively collected database and evaluated all re-resected patients with primary GBM who underwent second surgery during a 3years period. All patients underwent early postoperative magnetic resonance imaging. We determined survival after re-resection with regard to possible prognostic factors using Kaplan-Meier estimates and Cox regression analyses. Forty patients were included in this study. Median age was 58years and median KPS score was 80. Average tumor volume was 5.5cm(3). A radiologically confirmed complete resection was achieved in 29 patients (72.5%). Median follow-up was 18.8months, and median survival after re-resection was 13.5months. Only complete removal of contrast enhancing tumor was significantly correlated with survival after re-resection according to multivariate analysis. There was a statistical trend for KPS score influencing survival. In contrast, time between first diagnosis and tumor-recurrence, tumor volume at recurrence, MGMT status and MSM score were not significantly correlated with survival after second surgery. In the event of tumor recurrence, patients in good clinical condition with recurrent GBM amenable to complete resection should thus not be withheld second surgery as a treatment option.

The combination of carmustine wafers and fotemustine in recurrent glioblastoma patients: a monoinstitutional experience.

Background. To date, there is no standard treatment for recurrent glioblastoma. We analyzed the feasibility of second surgery plus carmustine wafers followed by intravenous fotemustine. Methods. Retrospectively, we analyzed patients with recurrent glioblastoma treated with this multimodal strategy. Results. Twenty-four patients were analyzed. The median age was 53.6; all patients had KPS between 90 and 100; 19 patients (79%) performed a gross total resection > 98% and 5 (21%) a gross total resection > 90%. The median progression-free survival from second surgery was 6 months (95% CI 3.9–8.05) and the median OS was 14 months (95% CI 11.1–16.8 months). Toxicity was predominantly haematological: 5 patients (21%) experienced grade 3-4 thrombocytopenia and 3 patients (12%) grade 3-4 leukopenia. Conclusion. This multimodal strategy may be feasible in patients with recurrent glioblastoma, in particular, for patients in good clinical conditions.

Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

These Clinical Practice Guidelines are endorsed by the Japanese Society of Medical Oncology (JSMO) incidence and epidemiology Multiple myeloma (MM) accounts for 1% of all cancers and ∼10% of all haematological malignancies. The incidence in Europe is 4.5–6.0/100 000/year with a median age at diagnosis of between 65 and 70 years; the mortality is 4.1/100 000/year. Almost all patients with MM evolve from an asymptomatic pre-malignant stage termed monoclonal gammopathy of undetermined significance (MGUS). MGUS progresses to MM at a rate of 1% per year. In some patients, an intermediate asymptomatic but more advanced pre-malignant stage termed smouldering (or indolent) multiple myeloma (SMM) can be recognised. SMM progresses to myeloma at a rate of 10% per year over the first 5 years following diagnosis, 3% per year over the following 5 years and 1.5% per year thereafter [1]. diagnosis Diagnosis of MM should be based on the following tests: [1] -Detection and evaluation of the monoclonal (M-) component by serum and/or urine protein electrophoresis (concentrate of 24 h urine collection); nephelometric quantification of IgG, IgA and IgM immunoglobulins; characterisation of the heavy and light chains by immunofixation; and serum-free light-chain (FLC) measurement; -Evaluation of bone marrow (BM) plasma cell infiltration: BM aspiration and/or biopsies are the standard options to evaluate the number and characteristics. Moreover, the BM sample should be used for cytogenetic/fluorescence in situ hybridization (FISH) studies and also has the potential for immunophenotypic and molecular investigations; -Evaluation of lytic bone lesions: a radiological skeletal bone survey, including spine, pelvis, skull, humeri and femurs is necessary. A magnetic resonance imaging (MRI) or computed tomography (CT) scan may be needed to evaluate symptomatic bony sites, even if the skeletal survey is negative and the patient has symptoms suggesting bone lesions. Moreover, MRI provides greater detail and is recommended whenever spinal cord compression is suspected. Fluorodeoxyglucose positron emission tomography is currently under evaluation but should not be systematically used; -Complete blood cell count, with differential serum creatinine and calcium level.

Resection versus biopsy of glioblastomas in eloquent brain areas

The aim of this study was to compare resection and biopsy of glioblastoma (GBM) in eloquent brain areas (EBA). This was a prospective evaluation of 38 patients with GBM in EBA. 22 were treated by surgical resection and 16 by biopsy. Preoperative KPS, neurological status and size of lesion on MRI were assessed. One week and three months postoperatively KPS, neurological status and Performance Status (PS) WHO were evaluated. Extent of resection (EOR) and overall survival (OS) were described. Overall mean age of the patients was 64.3 years, the mean lesion size in the resection group was 47.7 mm and in the biopsy group 51.0 mm. Worsening or development of permanent neurological deficits 3 months after surgery were significantly lower in the resection group (23%), than the biopsy group (94%). In the resection group the median pre and postoperative KPS three months after surgery was 80.0. In the biopsy group the median pre and postoperative KPS was 68.1 one week after the procedure. In the resection group, 3 months after surgery, the median PS was 1, in the biopsy group one week after surgery the median PS was 2. The difference was statistically insignificant. The mean OS after resection was 12.2 months, and after biopsy 3.5 months. The difference was highly statistically significant. The mean EOR was 90%. This is the first prospective study, to our knowledge, that compares the results of resection and biopsy of primary GBM in EBA. For patients in good clinical condition with tumors in or near EBA, recommended is as radical resection of GBM as possible.

Width of 3. Ventricle: Reference Values and Clinical Relevance in a Cohort of Patients with Relapsing Remitting Multiple Sclerosis

Objectives:To estimate the quantity of multiple sclerosis (MS) patients with brain atrophy as indicated by third ventricular enlargement using transcranial colourcoded ultrasound (TCCS).Methods:The width of the 3. ventricle was assessed by TCCS in 70 healthy controls (male 31, female 39, mean age 41 ± 15 years, age range 18 – 79 years), and in a cohort of 54 patients with relapsing remitting MS (male 16, female 38, mean age 40 ± 10 years, median EDSS 2 [1-3]). Results:In the controls, the width of the 3. ventricle increased with age (without any sex differences) from 3.0 ± 0.76 mm in the age group < 40 years to 4.0 ± 0.74 mm in the age group of 60 years or more (ANOVA p=0.0001). Derived from regression analysis, the upper limit of the 95% Confidence Interval for each year provided cutoff points according to which 14 of 54 patients (25%) exhibited an enlarged 3. ventricle. In a multivariate regression analysis, the width of the 3. ventricle over all MS patients was significantly related to EDSS (Spearman rho , r=0.446, p<0.005) and to MS duration (r=0.319, p<0.005). Conclusions:Even in MS patients in good clinical conditions the rate of patients with brain atrophy determined by TCCS is high.

External hemipelvectomy as treatment for solitary coxofemoral metastasis from endometrial carcinoma: Case report and review of the literature

The best treatment for bone metastasis from endometrial cancer as a presenting feature is unclear. We report the first case in the literature of coxofemoral metastases from endometrial cancer treated by surgical approach. Then, after a careful review of the literature, we discuss the best therapeutic option for this subset of patients. A 62-year-old woman with pain, erythema and swelling of the left leg and no history of postmenopausal bleeding underwent biopsy of the leg, which revealed a moderately differentiated endometrial carcinoma, infiltrating muscle and adipose tissues. There were no other sites of distal spread. A literature review was conducted by searching the items 'endometrial cancer' and 'bone metastasis' in MEDLINE and EnBase up to September 2010. The patient was treated with neoadjuvant chemotherapy, but she did not show a clinical response. By considering her prognosis and quality of life, we decided to perform for the first time a total abdominal hysterectomy with bilateral salpingo-oophorectomy in addition to an external hemipelvectomy with a limb amputation and partial ilium and pubic preservation. Thirty months after the procedure the patient is still alive. No other similar results are present in the literature. Patients in good clinical condition with a single bone metastasis of endometrial cancer should be treated aggressively with surgery, as survival can be extended with an acceptable quality of life.

New Roads Open Up for Implementing Immunotherapy in Mesothelioma

Treatment options for malignant mesothelioma are limited, and the results with conventional therapies have been rather disappointing to this date. Chemotherapy is the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival of only 2 months. Therefore, there is urgent need for a different approach to battle this malignancy. As chronic inflammation precedes mesothelioma, the immune system plays a key role in the initiation of this type of tumour. Also, many immunological cell types can be found within the tumour at different stages of the disease. However, mesothelioma cells can evade the surveillance capacity of the immune system. They build a protective tumour microenvironment to harness themselves against the immune system's attacks, in which they even abuse immune cells to act against the antitumour immune response. In our opinion, modulating the immune system simultaneously with the targeting of mesothelioma tumour cells might prove to be a superior treatment. However, this strategy is challenging since the tumour microenvironment possesses numerous forms of defence strategies. In this paper, we will discuss the interplay between immunological cells that can either inhibit or stimulate tumour growth and the challenges associated with immunotherapy. We will provide possible strategies and discuss opportunities to overcome these problems.