Therapeutic Decisions In Patients Research Articles

Effectiveness of [124I]-PET/CT and [18F]-FDG-PET/CT for Localizing Recurrence in Patients with Differentiated Thyroid Carcinoma

Although the prognosis of patients with differentiated thyroid carcinoma (DTC) is generally encouraging, a diagnostic dilemma is posed when an increasing level of serum thyroglobulin (Tg) is noted, without detection of a recurrent tumor using conventional imaging tools such as the iodine-131 whole-body scanning (the [131I] scan) or neck ultrasonography (US). The objective of the present study was to evaluate the diagnostic value of [124I]-PET/CT and [18F]-FDG-PET/CT in terms of accurate detection of both iodine- and non-iodine-avid recurrence, compared with that of conventional imaging such as the [131I] scan or neck ultrasonography (US). Between July 2009 and June 2010, we prospectively studied 19 DTC patients with elevated thyroglobulin levels but who do not show pathological lesions when conventional imaging modalities are used. All involved patients had undergone total thyroidectomy and radioiodine (RI) treatment, and who had been followed-up for a mean of 13 months (range, 6-21 months) after the last RI session. Combined [18F]-FDG-PET/CT and [124I]-PET/CT data were evaluated for detecting recurrent DTC lesions in study patients and compared with those of other radiological and/or cytological investigations. Nine of 19 patients (47.4%) showed pathological [18F]-FDG (5/19, 26.3%) or [124I]-PET (4/19, 21.1%) uptake, and were classed as true-positives. Among such patients, disease management was modified in six (66.7%) and disease was restaged in seven (77.8%). In particular, the use of the described imaging combination optimized planning of surgical resection to deal with locoregional recurrence in 21.1% (4/19) of patients, who were shown to be disease-free during follow-up after surgery. Our results indicate that combination of [18F]-FDG-PET/CT and [124I]-PET/CT affords a valuable diagnostic method that can be used to make therapeutic decisions in patients with DTC who are tumor-free on conventional imaging studies but who have high Tg levels.

Management Strategies for Elderly Patients with Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of lymphoma and most commonly presents in the sixth decade. Given the dramatic rise of the incidence of lymphoma since the late 1990s in patients who present over the age of 65, and the expected increase in the prevalence of DLBCL with the aging population, defining appropriately tailored modern therapy for elderly DLBCL patients is an increasingly important clinical concern. Moreover, age has been one of the most important adverse prognostic features, with numerous studies associating older age with inferior outcomes. Although it has been well established that B-cell diversity decreases with age, and that the loss of diversity can be associated with clonal expansion of B-cells, it remains unknown how this or other factors contribute to the pathogenesis and poor prognosis in elderly patients with DLBCL. Furthermore, elderly patients often have more comorbid illnesses, worse performance status, less hematologic reserve, and altered pharmacokinetics related to decreased metabolism and clearance of drugs. We examine the impact of these factors on therapeutic decision-making in patients with DLBCL and explore treatment alternatives for elderly individuals. Future research is needed not only to address treatment strategies but also to define the biologic heterogeneity between younger and older patients with DLBCL, so that more rational therapeutic approaches can be investigated.

Management Strategies for Elderly Patients with Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of lymphoma and most commonly presents in the sixth decade. Given the dramatic rise of the incidence of lymphoma since the late 1990s in patients who present over the age of 65, and the expected increase in the prevalence of DLBCL with the ageing population, defining appropriately tailored modern therapy for elderly DLBCL patients is an increasingly important clinical concern. Moreover, age has been one of the most important adverse prognostic features, with numerous studies associating older age with inferior outcomes. Although it has been well established that B-cell diversity decreases with age, and that the loss of diversity can be associated with clonal expansion of B-cells, it remains unknown how this or other factors contribute to the pathogenesis and poor prognosis in elderly patients with DLBCL. Furthermore, elderly patients often have more co-morbid illnesses, worse performance status, less haematologic reserve and altered pharmacokinetics related to decreased metabolism and clearance of drugs. We examine the impact of these factors on therapeutic decision-making in patients with DLBCL and explore treatment alternatives for elderly individuals. Future research is needed not only to address treatment strategies but also to define the biologic heterogeneity between younger and older patients with DLBCL, so that more rational therapeutic approaches can be investigated.

Impact of 64-slice coronary CT on the management of patients presenting with acute chest pain: results of a prospective two-centre study

Our two-centre prospective study evaluates the usefulness of 64-slice coronary computed tomography (CCT) to rule out significant coronary artery stenosis in patients admitted in emergency departments (ED) for acute coronary syndromes (ACS) with low-to-intermediate risk score. Patients (175) admitted for acute chest pain (ACP), unmodified electrocardiogram and first troponin measurement within normal ranges were included. A second troponin measurement and a 64-slice CCT within 24 h were performed. Major adverse cardiac events (MACE) were recorded during follow-up (6 months ± 2). 64-slice CCT was either normal or showed non-significant coronary stenosis in the majority of patients (78%). 64-slice CCT depicted significant stenosis (>50% diameter) in 22% of patient whereas initial clinical and biological evaluation was reassuring. For negative CCTs, elevated troponin at second measurement did not modify the strategy or treatment of patients. No MACEs were noted during follow up. In 12% of patients CCT identified unsuspected non-coronary abnormalities. Our study confirms 64-slice CCT utility to rule out significant coronary artery stenosis in 8/10 patients admitted in ED with ACP or ACS with low-to-intermediate risk score. Early discharge with a negative 64-slice CCT is associated with very low risk of cardiac events at 6 months. • 64-slice coronary computed tomography (CCT) offers a critical role in acute chest pain. • 64-slice CCT allows differentiation between significant and non-significant coronary artery stenosis. • Normal 64-slice CCT allows rapid discharge of patients with ACP. • 64-slice CCT helps make appropriate therapeutic decision in patients with ACP.

Evaluación económica de la elastografía de transición (FibroScan®) en el diagnóstico de fibrosis hepática en pacientes con hepatitis C coinfectados con VIH

The assessment of liver fibrosis is crucial for taking therapeutic decisions in patients infected with HIV/AIDS coinfected with HCV, because it allows the prognosis of the disease and the prioritization of hepatitis C treatment in these patients. A discrete events model simulation (DEMS) and a Markov model have been developed to represent the evolution of liver fibrosis to cirrhosis in patients coinfected with HIV/HVC. The model evaluated two alternatives for the diagnosis and monitoring of these patients, transient elastography performed annually and liver biopsy performed every seven years. The models have been developed under Health Care System perspective and only considered direct medical costs (disease treatment and health state costs). One-way sensitivity analyses were carried out to assess the impact of parameters with higher uncertainty. A discount rate of 3% was applied. Base case analysis shows that the diagnosis and monitoring of patients with transient elastography is a dominant strategy compared with to liver biopsy, resulting in greater life expectancy at lower cost. The sensitivity analysis performed confirmed the robustness of these results. Transient elastography has proved to be a dominant strategy compared to liver biopsy in the diagnosis and monitoring of liver fibrosis in patients coinfected with HIV/HCV in Spain.

Methylation of the APAF-1 and DAPK-1 promoter region correlates with progression of renal cell carcinoma in North Indian population

Aberrant promoter hypermethylation of cancer associated genes occur frequently during carcinogenesis and may serve as a cancer biomarker. The aim of this study was to investigate the occurrence and relevance of promoter methylation of the tumor suppressor DAPK-1, APAF-1 () and SPARC in relation to different pathological stages and histological grades of tumor progression that might act as possible independent prognostic factor in the susceptibility towards renal cell carcinoma (RCC) in North Indian population. Three tumor suppressor gene promoters namely APAF-1, DAPK-1 and SPARC were assessed by methylation-specific PCR (MS-PCR) in 196 primarily resected renal cell tumors paired with the corresponding normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters, pathological stage and Fuhrman nuclear grade of RCC. Significant differences in methylation frequency among the four subtypes of renal tumors were found for APAF-1 (p < 0.001), DAPK-1 (p < 0.001) and SPARC (p = 0.182), when compared with the corresponding normal tissue. Male subjects showed stronger association of methylation frequency of all the three genes with RCC than the female subjects. Additionally, higher frequency of APAF-1, DAPK-1 and SPARC promoter methylation were directly correlated with higher tumor stage (p (trend) < 0.001). Higher frequency of promoter methylation of APAF-1 and SPARC were also associated with higher nuclear grade (p < 0.001 and p = 0.036, respectively). This gene panel might contribute to a more optimal diagnostic coverage and information, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

MRI of Crohn’s disease: from imaging to pathology

Technological advances in the area of magnetic resonance imaging (MRI) raised expectations on the potential role of this imaging modality for evaluation of the gastrointestinal tract, especially on Crohn's disease (CD), based on the high spatial and tissue resolution as well as lack of ionizing radiation. Available evidence indicates that MRI has a high diagnostic accuracy for the detection of disease activity, location of the lesions, and also for determining the severity of the disease, which together are the main aspects for the therapeutic decision-making in patients with CD. MRI provides a high accuracy in detection of strictures, characterization of fistulizing lesions and extraluminal complications such us abscesses which are a key finding for considering medical and surgical options. Knowledge of the pathological substrate of inflammatory lesions in CD as well as extraenteric lesions may improve diagnostic image interpretation, and thus contribute to optimize patient care.

Serial intestinal endoscopic examinations of patients with persistent diarrhea after allo-SCT

Gastrointestinal (GI) GVHD after allo-SCT is diagnosed on the basis of symptoms and findings in endoscopic mucosal biopsy specimens. However, GI symptoms often persist despite treatment and whether a second endoscopy may be helpful in determining the most suitable therapy is not established. We identified 31 patients with persistent diarrhea who underwent more than one endoscopic study. All cases underwent serial microbiological stool analysis and CMV-detecting assays on serum and biopsies. Of the 31 initial GI biopsies, 20 (64.5%) were classified as GVHD, two (6.5%) as GVHD with CMV, four (13%) as non-CMV infection, and five (16%) as normal or unspecific. The second GI biopsies were diagnostic of GVHD in nine cases (29%), GVHD simultaneously with CMV infection in four (13%), regenerative changes post-GVHD in five (16%), CMV infection in four (13%), and normal or unspecific in nine (29%). In 22 of the 31 patients (71%), the histological findings of the second/third endoscopic biopsies differed from the findings of the first endoscopy and led to a therapy change in 77%. In conclusion, serial GI endoscopies are of reliable diagnostic value and can impact on therapeutic decision-making for patients with persistent diarrhea after allo-SCT.

Diagnostic efficacy of myeloperoxidase for the detection of acute coronary syndromes

Early diagnosis of acute coronary syndrome (ACS) is frequently a challenging task, while immediate risk stratification remains crucial for the prompt implementation of appropriate therapy in this setting. Employing markers that increase rapidly after the symptom onset may enhance triage and therapeutic decision-making in patients suspected for ACS. Myeloperoxidase (MPO) exerting proinflammatory and pro-oxidative properties is suggested as a reliable early marker for ACS associated with unfavourable clinical outcome. We assessed the diagnostic efficacy of plasma MPO alone or in combination with cardiac troponin I (cTnI) for detecting ACS in patients presenting with chest pain initiating within 6h before the hospital admission. A study group consisted of 253 patients diagnosed with ACS and 47 subjects having other heart disease or unspecified chest pain. Clinically healthy volunteers (n=124) served as controls. MPO concentration was measured in plasma (Abbott Diagnostics, USA), while serum was assayed for cTnI, creatine-kinase MB, lipids, glucose, creatinine, brain natriuretic peptide type B and C-reactive protein. Both MPO and cTnI values were significantly lower in non-ACS subjects than in patients with ACS. At 97·5th percentile as cut-off, the superiority of MPO over cTnI was observed in patients with unstable angina and non-ACS subjects. Considerably higher MPO concentrations were demonstrated in the troponin-negative ACS patients on admission who became troponin-positive after 6h. Combined evaluation of MPO and cTnI possessed remarkably higher sensitivity than assessment of cTnI alone in all patients with ACS. Myeloperoxidase substantially facilitates the early diagnosis of ACS.

IDH Mutations Can Be Detected In 28.7% of All Normal Karyotype AML and Have Unfavourable Impact on the NPM1+/FLT3-ITD- Genotype

AbstractAbstract 102 Introduction:Mutations in IDH1 and IHD2 have recently been shown to play an important role in AML. As they code for enzymes from the citric acid cycle mutations within these genes from the mechanistical point of view are a totally new kind of mutation associated with AML. In IDH1 one mutational hot spot (amino acid R132) and in IDH2 two hotspots (R140 and R172) have been reported. We aimed at further delineating the impact of IDH1 and IDH2 mutations in AML and analyzed the interaction with other mutations in normal karyotype (NK) AML. Methods:526 AML patients were selected according to normal karyotype and availability of mutational status for FLT3-ITD, NPM1 and MLL-PTD. Further mutation analyses were available in subgroups of the cohort (FLT3-TKD: n=318, CEBPA: n=369, RUNX1: n=174, NRAS: n=220). Female/male ratio was 283/243 and age ranged from 20.0–90.1 years (median, 66.9 years). 435 had de novo AML (82.6%), 71 AML following MDS (s-AML,13.5%) and 20 AML after previous treatment of other malignancies (t-AML, 3.8%). The respective base exchanges in R132, R140, and R172 were analysed by a melting curve assay with subsequent sequencing of the positive samples. Results:Overall, in 151 pts (28.7%) IDH mutations (IDHmut) were detected. In detail, 68 mutations (12.9% of all cases) were detected in IDH1 (R131C: n=35, R131L: n=17, R131H: n=7, R131G: n=6, R131S: n=3) and 83 mutations (15.8%) in IDH2 (R140Q: n=72, R140L: n=2, R140W: n=1, N141G: n=1, R174K: n=7). IDH1mut and IDH2mut were mutually exclusive in this cohort. IDH1mut were more frequent in females (18.2% vs 8.6 % in males, p=0.001), whereas there was no sex difference for IDH2. According to history IDH1 was equally distributed in de novo AML, s-AML and t-AML whereas IDH2 was more frequent in de novo compared to s- and t-AML (19.6% vs. 7.6 vs 11.8%, p=0.048). According to FAB the most prevalent subtype was FAB M1 with IDHmut in 23.2% compared to 9.8% in all other FAB (in detail: IDH1: 44.8% vs. 23.9%, IDH2: 27.0% vs. 15.1%; p<0.001, for both). IDH1 was underrepresented in M4 (4.9% vs. 15.0 % in all other subtypes, p=0.004), whereas the distribution of IHD2 was not different in M4 vs. all others. The immunophenotype (n= 297) of IDHmut cases tended to be more immature and featured a lower expression of monocytic markers. The analyzed 78 IDHmut cases, as compared to 219 IDHwt cases, showed a significantly higher expression of MPO and CD117 while CD116, CD11b, CD14, CD15, CD36. CD56, CD64, CD65 and CD7 were lower expressed. Age, WBC count, and platelet count were not different between IDH1, IDH2 and IDHwt cases. IDH mutations are not mutually exclusive of other mutations. However, the frequency of CEBPAmut in IDHmut compared to IDHwt was decreased (7.7% vs. 13.7, p=0.001) (IDH1: 0% vs 11.7%, p=0.022 and IDH2: 7.7% vs 13.4%, p=0.053). MLL-PTD was more frequent in IDHmut vs. IDHwt (44.7 vs. 5.8%, p=0.039), however, this is restricted to IDH1mut vs. IDH1wt (26.3 vs. 6.3%, p=0.018). RUNX1mut are distributed equally in IDH2mut and IDH2wt (20.0% vs 27.3%) but are underrepresented in IDH1mut compared to IDH1wt (2.2% vs. 28.7%, p=0.068). FLT3-ITDs are equally distributed between IDHmut and IDHwt, however, those IDH1mut with FLT3-ITD have lower FLT3-ITD/FLT3wt ratios compared to FLT3-ITD+ IDH1wt cases (mean: 0.16 vs. 0.72; p=0.005). All other mutations were distributed equally in IDHmut compared to IDHwt. For survival analysis only cases with de novo AML <65 years were included (n=164, IDHmut: n=37, n=, IDHwt: 127). In the total analysis there was no effect on overall survival or event free survival (EFS). However there was a trend for shorter EFS of the IDHmut vs. IDHwt (median: 439 days vs. not reached, p=0.080) in cases with NPM1+/FLT3-ITD- genotype. For IDH2 there was a significant adverse effect in the NPM1+/FLT3-ITD- group (median EFS: 397 vs. 679 days, p=0.045). Summary:IDH mutations belong to the most frequent mutations in NK AML and can occur together with all other known mutations. There is a high preponderance for the FAB M1 subtype and a more immature immunophenotype for both IDH mutations and a strong female preponderance for IDH1. In addition, an adverse prognostic impact of IDH mutations was shown for the NPM1+/FLT3-ITD- genotype. Further analyses should focus on the definition of the role and place of IDH mutations for therapeutic decisions in patients with AML. Disclosures:Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Alpermann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Takotsubo cardiomyopathy in acute coronary syndrome; clinical features and contribution of cardiac magnetic resonance during the acute and convalescent phase

Objectives. Takotsubo cardiomyopathy (TTC) is a diagnostic entity that is increasingly being recognized. Data from cardiac magnetic resonance (CMR) imaging and its impact on differential diagnosis are limited. Methods and results. After 26 months, coronary angiography revealed normal coronary arteries and left ventriculography and/or echocardiography left ventricular dysfunction with apical ballooning in 20 patients with acute coronary syndrome (ACS). Four patients were excluded from CMR and in three patients an alternative diagnosis was revealed. Thirteen patients (all female; 60 ± 8 years) with TTC underwent a multisequential CMR, in which all showed myocardial oedema with an elevated T2 ratio in the apical region (2.4 ± 0.4; p < 0.001 vs. healthy controls), and five patients an elevated global relative enhancement (gRE; 3.7 ± 1.4; p < 0.05 vs. healthy controls). No late gadolinium enhancement (LGE) was detected on CMR. Follow-up after 132 ± 33 days showed a normalized left ventricular ejection fraction, myocardial mass, T2 ratio, and gRE in all patients. Conclusions. TTC is a small but definite group among patients with ACS and normal coronary arteries. CMR allows differentiating TTC from other causes such as myocarditis and cardiomyopathies, as well as to identify the transient increase of myocardial mass and resolution of myocardial oedema as the systolic dysfunction improves. Therefore, CMR might add valuable information for the differential diagnoses and therapeutic decision-making in patients with suspected TTC.

Correlation between systemic lupus erythematosus disease activity index, C3, C4 and anti-dsDNA antibodies

Background: Therapeutic decisions in systemic lupus erythematosus (SLE) are based on the disease activity and nature of organ involvement. There are various clinical and laboratory methods to assess the lupus flares. Methods: Fifty one SLE patients with active disease (lupus flare) were studied. Systemic lupus erythematosus disease activity index (SLEDAI), C3, C4 and anti-double stranded DNA levels were estimated and repeated monthly till remission. After remission these tests were done three monthly. Values of serological parameters were then correlated with SLEDAI score. Result: Thirteen (25.4%) patients had predominantly renal involvement while 38 (74.6%) patients had non-renal affliction. Musculoskeletal and mucocutaneous symptoms were the commonest features of lupus flare (90%). It was observed that 12 out of 13 (92.3%) patients with active renal involvement had low C3 levels and 11 (84.6%) had low C4 levels. The anti-dsDNA levels were elevated in all patients with predominant renal flare. In non-renal flare anti-dsDNA titre was raised only in 35% cases. Low C3 and C4 levels were noticed in 43% and 53% of non-renal flares respectively. Significant positive correlation was noticed between SLEDAI score and anti-dsDNA levels (0.01 level two-tailed prediction) and a significant negative correlation was observed with SLEDAI and C3, C4 levels (0.01 and 0.05 levels, two-tailed prediction) in our patients. On subgroup analysis it was noticed that this correlation is stronger for renal lupus. Negative correlation of SLEDAI and complement levels was not observed in non-renal flares. Conclusion: Calculation of SLEDAI is a vital clinical tool for assessment of SLE patients. Serial estimation of anti-dsDNA titre, C3 and C4 levels help us diagnose lupus flare and make appropriate therapeutic decisions in patients with high SLEDAI score.

Hypoglycemia Unawareness Is Associated With Reduced Adherence to Therapeutic Decisions in Patients With Type 1 Diabetes: Evidence from a Clinical Audit

We thank Graveling and Frier (1) for their comments, which underline the clinical difficulties in managing patients with impaired awareness of hypoglycemia (IAH). An audit of a U.K.-based structured education program for patients with type 1 diabetes, Dose Adjustment For Normal Eating (DAFNE), found that 48% of those who reported IAH at …

Hypoglycemia Unawareness Is Associated With Reduced Adherence to Therapeutic Decisions in Patients With Type 1 Diabetes: Evidence from a Clinical Audit

Smith et al. (1) have demonstrated that people with type 1 diabetes who have impaired awareness of hypoglycemia (IAH), diagnosed on clinical history alone, are less likely to adhere to therapeutic decisions. This finding is of clinical importance as the syndrome of IAH is often very difficult to manage, and the reluctance …

The presence of circulating tumor cells does not predict extravesical disease in bladder cancer patients prior to radical cystectomy

Objective Due to imprecise clinical staging, the finding of extravesical and node-positive disease at the time of radical cystectomy (RC) for patients with clinically localized bladder cancer is not uncommon. Circulating tumor cells (CTCs) have been shown to be present in the peripheral blood of patients with metastatic urothelial carcinoma. The object of this study was to evaluate the ability of CTCs to predict extravesical disease in bladder cancer patients prior to RC. Materials and methods Peripheral blood samples from 43 patients with bladder cancer were evaluated using the CellSearch (Veridex, LLC, Raritan, NJ) CTC assay prior to RC. The sensitivity, specificity, and positive predictive value (PPV) of CTC status in predicting extravesical disease was calculated. Receiver operating characteristic (ROC) curves were generated to quantify the ability of CTCs to predict extravesical and node-positive disease. Results CTCs were detected in 9 (21%) patients prior to RC. The sensitivity, specificity, and PPV of CTC status in predicting extravesical disease were 27%, 88% and 78%, respectively. The accuracy of CTC status in predicting extravesical (≥pT3 or node-positive) disease for the entire cohort was 0.576. In a model incorporating preoperative hydronephrosis, CTC status did not improve the predictive accuracy for extravesical disease (0.576 vs. 0.585, P = 0.915). Conclusion CTCs were detected in low numbers in a small percentage (21%) of patients prior to undergoing RC at our institution. CTC status was not a robust predictor of extravesical or node-positive disease in this cohort. CTC status is not likely to be a clinically useful parameter for directing therapeutic decisions in patients with ≤cT2 bladder cancer.

Influence of Narrow Band Imaging (NBI) Videobronchoscopy on the Assessment of Central Lung Cancer Extension and Therapeutic Decision

ABSTRACTObjectives: Determination of specificity and sensitivity of narrow band imaging (NBI) in the assessment of tumor extension in centrally located lung cancer, when compared to white light bronchoscopy (WLB) alone, and evaluation of possible influence of NBI on therapeutic decision in patients with lung cancer. Patients and methods: We evaluated 36 patients with suspected lung cancer. All patients underwent WLB followed by NBI bronchoscopy. We were using videobronchoscope BF-1T180 and EVIS LUCERA SPECTRUM processor unit. Results: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for NBI in the assessment of tumor extension were 97.8, 85, 93.7, and 94.4%, respectively; and for WLB 92.3, 60, 69.6, and 88.9%, respectively. In 14 patients, NBI revealed more extensive tumor than WLB (p =.0057). In eight patients, NBI showed significant influence on therapeutic decision (p =.001). Conclusion: NBI videobronchoscopy had better specificity and sensitivity in the assessment of tumor extension in centrally located lung cancer, and it might play a significant role in the therapeutic decision.

Brown-Sequard-type myelopathy due to cervical disc herniation associated with severe carotid stenosis prompting rapid combined corpectomy and carotid endarterectomy under deep anticoagulant therapy

Background context The risk of stroke because of carotid retraction during an anterior cervical spine surgery as well as the risk of bleeding complications after an anterior cervical corpectomy under deep anticoagulation and antiplatelet therapy is a surgical issue poorly addressed in the literature. Purpose To describe the feasibility and safety of a simultaneous carotid endarterectomy and anterior corpectomy and fusion under deep anticoagulation in a patient with a cervical spinal cord compression and a severe carotid artery stenosis. Study design Case report. Methods The authors describe the case of a 79-year-old man who had a 1-month history of progressive pain in the neck and left arm, associated with progressive weakness in the left arm and leg. He also presented a history of coronaropathy and bilateral severe carotid stenosis for which he was receiving a regimen of antiplatelet therapy. Results The cervical magnetic resonance imaging demonstrated a C4–C5 disc herniation migrating down to C5. His condition worsened rapidly during hospitalization prompting a rapid decompression. Given the necessity of a C5 corpectomy and the risk of stroke during anterior cervical spine surgery, it was therefore decided to undertake the surgical procedure under efficient anticoagulant and antiplatelet therapy. A combined endarterectomy and spinal decompression and fusion were then performed. The postoperative course was uneventful, and the patient recovered neurologically. Conclusions This case suggests that such a combined carotid endarterectomy and cervical corpectomy with fusion under anticoagulant and antiplatelet therapy is feasible. However, even if the unique clinical presentation of our patient led us to undertake such a surgical strategy, therapeutic decision in patients presenting with both severe carotid stenosis and cervical spinal cord compression should rely on a case-by-case analysis.

Lymphocyte infiltration and prognosis in colorectal cancer

For the clinical management of colorectal cancer and selection of patients for adjuvant therapy, it is essential to assess the risk of disease recurrence and metachronous metastasis at the time of diagnosis. The tumour–node–metastasis (TNM) staging system, which refers to the local expansion of the tumour, involvement of lymph nodes, and the presence of metastases to distant organs, has been established as the best available means to make therapeutic decisions in patients with colorectal cancer.

Advances in the Pharmacological Treatment of Gastro-Oesophageal Cancer

Despite a sharp decline in the incidence of gastric cancer during the second half of the 20th century, this malignancy remains the second leading cause of cancer mortality in the world. The incidence and mortality rate of gastric cancer increase with age; at present, the median ages at diagnosis are 67 years for men and 72 years for women in the US. This article reviews and discusses current medical treatment options for both the general population and elderly gastric cancer patients. Management of localized gastric cancer has changed significantly over recent years. Adjuvant chemoradiation is not generally recommended outside the US. After decades of trials of adjuvant chemotherapy with inconclusive results, a significant survival benefit for perioperative combination chemotherapy - as compared with surgery alone - in patients with resectable or locally advanced gastro-oesophageal cancer was recently demonstrated in the UK MAGIC trial. A further large, randomized trial from Japan demonstrated a significant survival benefit for adjuvant chemotherapy with S-1 after D2 resection for gastric cancer. However, both trials are applicable only to the population in which the trials were conducted. Specific data on elderly patients are missing. For patients with metastatic disease, oral fluoropyrimidines, such as capecitabine, have been developed. In Asian patients, treatment with the oral fluoropyrimidine S-1 is safe and effective. Docetaxel, oxaliplatin and irinotecan have demonstrated activity against gastric cancer in appropriately designed, randomized, phase III trials and have increased the available treatment options significantly. In addition, according to preliminary data, trastuzumab in combination with chemotherapy has significantly improved activity when compared to chemotherapy alone in patients with human epidermal receptor (HER)-2-positive gastric and gastro-oesophageal cancers. Thus, therapeutic decisions in patients with advanced gastric cancer may be adapted to the molecular subtype and co-morbidities of the individual patient. Data from retrospective analyses suggest that oxaliplatin seems to be better tolerated than cisplatin in elderly patients.

Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk stratification

Chagas heart disease (CHD) results from infection with the protozoan parasite Trypanosoma cruzi and is the leading cause of infectious myocarditis worldwide. It poses a substantial public health burden due to high morbidity and mortality. CHD is also the most serious and frequent manifestation of chronic Chagas disease and appears in 20-40% of infected individuals between 10-30 years after the original acute infection. In recent decades, numerous clinical and experimental investigations have shown that a low-grade but incessant parasitism, along with an accompanying immunological response [either parasite-driven (most likely) or autoimmune-mediated], plays an important role in producing myocardial damage in CHD. At the same time, primary neuronal damage and microvascular dysfunction have been described as ancillary pathogenic mechanisms. Conduction system disturbances, atrial and ventricular arrhythmias, congestive heart failure, systemic and pulmonary thromboembolism and sudden cardiac death are the most common clinical manifestations of chronic Chagas cardiomyopathy. Management of CHD aims to relieve symptoms, identify markers of unfavourable prognosis and treat those individuals at increased risk of disease progression or death. This article reviews the pathophysiology of myocardial damage, discusses the value of current risk stratification models and proposes an algorithm to guide mortality risk assessment and therapeutic decision-making in patients with CHD.