Radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma

About 20% of the patients with advanced hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are eventually delisted as a result of local tumor progression. Herein, we report our experience with conformal radiotherapy (CRT) as a novel bridge to LT. From July 2006 to August 2008, CRT was delivered in five or six fractions to patients with HCC listed for LT in whom either prior local therapies had failed or those not suitable for standard local therapies because of poor liver function or anatomic issues. Radiotherapy (RT) volumes and doses were individualized to spare the uninvolved liver with the goal of stabilizing the most aggressive HCC(s) in an attempt to reduce the chance of delisting as a result of tumor progression. Ten patients with tumor diameters ranging from 25 to 108 mm were treated. Eight out of 10 tumors were beyond Milan criteria. The median age was 55 (range 36–64). Seventy percent of the patients were male subjects. The median medical MELD score was 11 (range 9–17). The median irradiated HCC volume was 79 cc (range 15–798 cc). The median RT delivered dose was 33 Gy (range 8.5–54 Gy), in one to six fractions. The median dose to the uninvolved liver was 13.3 Gy (range 1.8–16.5). Nine patients completed their CRT as planned and one patient was transplanted after the first fraction. The treatment was well tolerated: Grade 1 nausea was reported in three patients, the platelet count decreased from 154 to 98 in one patient, and there were no other complications. No treated tumors progressed during or after the treatment. Two tumors remained stable; the rest had 10–50% regression, which was sustained on follow‐up imaging. The median follow up was 14 months (range 3–20). Local tumor control was achieved in all treated tumors.Two patients were delisted as a result of cancer progression outside the treated field (one in the context of systemic metastases; yet another with progression of other untreated HCC in the liver). Three patients are still waiting for transplantation. Five patients underwent LT with no complications attributable to the CRT. Explant pathology, available for five patients, showed tumor necrosis and fibrosis with sparing of the untreated parenchyma. All transplanted patients treated with CRT are cancer‐free. CRT is a safe and efficacious local bridging therapy for patients with advanced HCC who are on the waiting list for LT. Further studies are warranted to compare the effectiveness of CRT to other local treatment regimens for HCC.     

Prevalence of HLA-B27 in the general population and in patients with axial spondyloarthritis in Saudi Arabia

The prevalence of HLA-B27 in the general population and in axial spondyloarthritis (axSpA) patients in Saudi Arabia is unknown. The aim of this study was to evaluate the prevalence of HLA-B27 in these two populations and describe the delay in diagnosis of axSpA patients. The prevalence of HLA-B27 in the general population was evaluated using cord blood and healthy organ transplant donor databases. Data from patients with axSpA were collected retrospectively from five centers. Ankylosing spondylitis (AS) was diagnosed based on a positive X-ray, as evaluated by two independent readers. Patients with inflammatory bowel disease and psoriasis were excluded. A total of 134 axSpA patients were included, of whom 107 (79.9%) had AS, and most (67.2%) were males. HLA-B27 was positive in 60.4, 69, and 25.9% of patients with axSpA, AS, and non-radiographic axSpA (nr-axSpA), respectively. The median and interquartile range (IQR) ages at symptom onset and disease diagnosis were 26 (20–33) and 30 (25–38) years, respectively. The median delay to diagnosis was 3 (1–6) years. There was a negative correlation between the time of onset of symptoms and the delay in diagnosis (r = ?0.587). Male gender and HLA-B27 positivity were associated with a younger age at symptom onset/diagnosis (p < 0.05). HLA-B27 was positive in 82/3332 (2.5%) and 27/1164 (2.3%) individuals in the cord blood and healthy organ transplant donor databases, respectively. The prevalence of HLA-B27 is lower in the general Saudi population and in axSpA patients compared to Caucasians, thus, limiting its utility as a diagnostic criterion.     

Montreal Cognitive Assessment Arabic version: Reliability and validity prevalence of mild cognitive impairment among elderly attending geriatric clubs in Cairo

Aim:   Mild cognitive impairment (MCI) is a clinical label which includes elderly subjects with memory impairment and with no significant daily functional disability. MCI is an important target for Alzheimer's dementia prevention studies. Data on the prevalence and incidence of MCI varies greatly according to cultural difference. The first aim of this study was to assess the reliability and validity of Montreal Cognitive Assessment (MoCA) Arabic version in MCI detection. The second was to determine the prevalence of MCI among apparently healthy elderly people attending geriatric clubs in Cairo.
Methods:   In stage I reliability & validity of MoCA Arabic version were assessed in reference to Cambridge Cognitive Examination (CAMCOG). In stage II prevalence of MCI was estimated using Arabic MoCA among apparently healthy elderly attending geriatric clubs. These geriatric clubs were randomly selected from different regions in Cairo governorate.
Results:   Test–retest reliability data of the Arabic MoCA were collected approximately 35.0 ± 17.6 days apart. The mean change in Arabic MoCA scores from the first to second evaluation was 0.9 ± 2.5 points, and correlation between the two evaluations was high (correlation coefficient = 0.92, P  < 0.001). The internal consistency of the Arabic MoCA was good, yielding a Cronbach's α on the standardized items of 0.83. In diagnosing mild cognitive impairment, the Arabic MoCA showed 92.3% sensitivity and 85.7% specificity. The prevalence of MCI among elderly subjects attending geriatric clubs in Cairo is 34.2% and 44.3% of healthy men and women, respectively.
Conclusion:   Older age, female sex and less education are the independent risk factors for MCI among apparently healthy elderly subjects attending geriatric clubs in Cairo.     

The impact of stimulus attributes on engagement of nursing home residents with dementia

We examined the influence of stimulus attributes on the engagement of 69 nursing home residents with dementia. Specifically, we looked at work-related stimuli versus manipulative block stimuli, and whether the color, size, and material of a stimulus affect the duration and quality of engagement. Engagement was assessed using the Observational Measurement of Engagement (OME). Results revealed a clear preference for the work-related rather than manipulative block stimuli. In addition, the study participants showed a significant preference for small rather than large blocks, regardless of color or material. The effect of material and color was not statistically significant. These findings may assist nursing home caregivers who wish to provide appropriate stimuli for engaging nursing home residents with dementia.     

Natural anti-inflammatory products and leukotriene inhibitors as complementary therapy for bronchial asthma

ObjectiveTo assess the efficacy of a combination of Boswellia serrata, licorice root (Glycyrrhiza glabra) and Tumeric root (Curcuma longa) as natural leukotriene inhibitor, antiinflammatory and antioxidant products respectively in controlling bronchial asthma.Subjects and methodsThe study comprised 63 patients with bronchial asthma that are further subdivided into two groups .Group 1 receiving oral capsule (combined herb) in a soft-gelatin capsule 3 times daily for 4 weeks and group 2 receiving placebo.Plasma leukotriene C₄ (LTC₄)_, nitric oxide (NO) and malondialdehyde (MDA) levels were measured and pulmonary function was also assessed in all patients enrolled in the study.ResultsThere was a statistically significant decrease in the plasma levels of LTC₄, (MDA), and NO in target therapy group when compared with placebo group.ConclusionThe used extract contained Boswellia serrata, Curcuma longa and Glycyrrhiza has a pronounced effect in the management of bronchial asthma.     

Pretreatment clinical variables associated with the response to intravitreal bevacizumab (Avastin) injection in patients with persistent diabetic macular edema

Background

The purpose of the study is to determine whether the pre-treatment clinical systemic variables and optical coherence tomography (OCT) findings are associated with the subsequent response to the intravitreal bevacizumab (IVB) in eyes with persistent diabetic macular edema (DME).

Design

Prospective, interventional non-comparative case series study.

Methods

38 Patients (45 eyes) with refractory diabetic macular edema; 16 females, 22 males with a mean aged 57.5 year. All patients had persistent DME not responded to other forms of treatments. Complete eye examination; best corrected visual acuity (BCVA) (represented as LOGMAR for adequate statistical analysis), slit-lamp exam, intraocular pressure measurement, stereoscopic biomicroscopy of the macula, and morphologic patterns of diabetic macular edema demonstrated by OCT.All patients had intravitreal injection of 0.05 mL = 1.25 mg bevacizumab (Avastin; Genentech, Inc., San Francisco, CA), and were followed up for 3 months. The pre and post-injection follow-up data were analyzed by Student-t test and Mann–Whitney test for two main outcome measures; visual acuity (LOGMAR) and central foveal thickness (CFT) changes over a period of three months, and the data included demographic factors, type, duration and the control of diabetes mellitus (HbA1C%), grade of diabetic retinopathy, renal function (serum creatinine level), serum cholesterol, blood pressure control and previous treatment by focal laser and/or intravitreal triamcinolone injection.

Results

The LOGMAR and central foveal thickness (CRT) improved in 30/45 eyes (67%) and 32/45 eyes (72%), respectively during a mean follow-up time of three months. The mean LOGMAR visual acuities were 0.64 (SD ± 0.34), 0.61 (SD ± 0.31) and 0.60 (SD ± 0.32) at pre-injection, at 1 month post-injection and at 3 months post-injection, respectively; but this mean increase in vision was statistically not significant (P value = 0.099). The mean foveal thicknesses were 444.95 μm (SD ± 127.36), 394.95 μm (SD ± 138.03) and 378.32 μm (SD ± 112.01) at pre-injection, 1 month post-injection and 3 months post-injection, respectively, this decrease in the foveal thickness was statistically significant (P value <0.001). The pre and post-injections values of the variables for diabetic duration, diabetic control (HbA1c) and OCT pattern of macular edema showed significant statistical correlations (P < 0.05) with LOGMAR only, however the values of the variables for serum creatinine and cholesterol show statistical correlation (P < 0.05) with both LOGMAR and CFT.

Conclusions

Chronicity and inadequate control of diabetes mellitus, nephropathy, hyperlipidemia and presence of vitreomacular attachment (VMA) are factors associated with poor vision progress after intravitreal bevacizumab injection.     

Phase 2 trial of preoperative irinotecan plus cisplatin and conformal radiotherapy,followed by surgery for esophageal cancer

BACKGROUND:

Esophagectomy for locally advanced esophageal cancer (LAEC) is associated with limited survival. Trimodality therapy yields a small survival advantage, with cisplatin and 5‐fluorouracil regimens most frequently studied. Newer regimens may impact these poor outcomes. This phase 2 trial assessed the feasibility and efficacy of induction chemoradiotherapy with cisplatin and irinotecan followed by esophagectomy.

METHODS:

Patients with LAEC of the thoracic esophagus or gastroesophageal junction underwent chemotherapy with preoperative irinotecan (65 mg/m²) plus cisplatin (30 mg/m²) on Weeks 1, 2, 4, 5, 7, and 8 with concurrent conformal radiotherapy (40 grays [Gy]/20 fractions during Weeks 4‐7) and external beam boost (10 Gy/5 fractions at Week 8). Esophagectomy was performed between Weeks 12 and 16. Pathologic response was the primary endpoint with follow‐up data on progression, survival, and toxicity as secondary endpoints.

RESULTS:

Fifty‐two patients were enrolled from November 2002 to October 2005. Nineteen patients had American Joint Committee on Cancer stage II, 22 had stage III, and 11 had stage IVA disease. Grade 3 to 4 toxicity (graded according to the National Cancer Institute Common Toxicity Criteria 2.0) during induction included neutropenia (36%), febrile neutropenia (8%), diarrhea (10%), and esophagitis (4%). Three patients withdrew from treatment due to toxicity. There was 1 treatment‐related death. Clinical responses included complete response in 2%, partial response in 30%, stable disease in 62%, and progressive disease in 6% of patients. Dysphagia improved/resolved in 72% of patients during induction. Forty‐three patients underwent esophagectomy and 7 (16%) achieved pathologic complete responses. Median and 3‐year overall survival for patients receiving trimodality therapy was 36 months and 51%, respectively.

CONCLUSIONS:

In LAEC, concurrent irinotecan/cisplatin and radiotherapy followed by esophagectomy is reported to be associated with dysphagia improvement in 72% of patients, a significant but manageable toxicity profile, and encouraging survival compared with historic controls. Cancer 2010. © 2010 American Cancer Society.     

Human herpesvirus‐6 encephalitis following chemotherapy induction for acute myelogenous leukemia

We report a case of human herpesvirus‐6 (HHV‐6) encephalitis in a neutropenic patient who had undergone chemotherapy induction for acute myelogenous leukemia while on broad‐spectrum antimicrobial therapy. The patient displayed symptoms of confusion, amnesia, and lethargy. Diagnosis was made via polymerase chain reaction analysis of cerebrospinal fluid. Electroencephalogram and magnetic resonance imaging of the brain were unremarkable. Following diagnosis, the patient was successfully treated with ganciclovir. HHV‐6 encephalitis should be considered in immunocompromised patients who become encephalopathic.