Rutin and Hesperidin Revoke the Hepatotoxicity Induced by Paclitaxel in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities.

Paclitaxel, one of the most effective chemotherapeutic drugs, is used to treat various cancers but it is exceedingly toxic when used long-term and can harm the liver. This study aimed to see if rutin, hesperidin, and their combination could protect male Wistar rats against paclitaxel (Taxol)-induced hepatotoxicity. Adult male Wistar rats were subdivided into 5 groups (each of six rats). The normal group was orally given the equivalent volume of vehicles for 6 weeks. The paclitaxel-administered control group received intraperitoneal injection of paclitaxel at a dose of 2 mg/Kg body weight twice a week for 6 weeks. Treated paclitaxel-administered groups were given paclitaxel similar to the paclitaxel-administered control group together with oral supplementation of rutin, hesperidin, and their combination at a dose of 10 mg/Kg body weight every other day for 6 weeks. The treatment of paclitaxel-administered rats with rutin and hesperidin significantly reduced paclitaxel-induced increases in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transferase activities as well as total bilirubin level and liver lipid peroxidation. However, the levels of serum albumin, liver glutathione content, and the activities of liver superoxide dismutase and glutathione peroxidase increased. Furthermore, paclitaxel-induced harmful hepatic histological changes (central vein and portal area blood vessel congestion, fatty changes, and moderate necrotic changes with focal nuclear pyknosis, focal mononuclear infiltration, and Kupffer cell proliferation) were remarkably enhanced by rutin and hesperidin treatments. Moreover, the elevated hepatic proapoptotic mediator (caspase-3) and pro-inflammatory cytokine (tumor necrosis factor-α) expressions were decreased by the three treatments in paclitaxel-administered rats. The cotreatment with rutin and hesperidin was the most effective in restoring the majority of liver function and histological integrity. Therefore, rutin, hesperidin, and their combination may exert hepatic protective effects in paclitaxel-administered rats by improving antioxidant defenses and inhibiting inflammation and apoptosis.

Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

Adverse health and environmental outcomes of sewage treatment plant on surrounding groundwater with emphasis on some mitigation recommendations.

Water quality deterioration hinders economic and social development in developing countries that are facing freshwater security and shortages. Based on the collection of 29 water samples, this study focused on the relationship between sewage treatment plant and groundwater system surrounding it using multidisciplinary approach that combines the characterization of groundwater system and its connection with surrounding canal and drains, using chemical and isotopic characterization revealing that there is a direct relation between the surface water system and surrounding groundwater system. About 58% of the groundwater samples and all surface water samples in the investigated area are threatened by high concentrations of trace elements. The multivariate statistical analysis elucidates that anthropogenic effect and fertilizers sewage contamination are the main causes of groundwater pollution. Nearly, 31% and 11.5% of groundwater samples were posing oral chronic non-carcinogenic health risk and dermal chronic risk for adult, respectively, while all surface water samples were posing oral chronic non-carcinogenic health risk, with no dermal hazard. The uncharged species of Fe and Al are expected to be more mobile in groundwater because they would not be attracted to the surface charge of minerals. Inorganic ligands (HCO3-, SO42-, Cl-, and NO3-) act as nucleation centers that were linked with those trace elements creating new species with higher solubility degree in water that are transported away randomly for long distances in the water path.

Effects of pre-treatment with inulin on the kidney in lipopolysaccharide-induced endotoxemia in rats.

This study was aimed to evaluate the effects of inulin used as prebiotic on the kidney in lipopolysaccharide (LPS)-induced endotoxemia model. Wistar Albino rats were divided into four groups: Control group, LPS (endotoxemia) group, Inulin + LPS group in which LPS (1.5 mg/kg, E. coli, Serotype 0111: B4) was treated after inulin (500 mg/kg) given by gavage for 21 days and Inulin group. The animals were sacrificed 24 h after the last LPS injection. Kidney samples were taken for biochemical and immunohistochemical analyses. Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and myeloperoxidase (MPO) values were determined. In addition, kidney sections were stained for inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and interleukine-6 (IL-6) expression, and leukocyte infiltration. LPS caused oxidative stress and inflammation. Inulin administration could prevent oxidative stress and lipid peroxidation. Moreover, inulin decreased iNOS, TNF-α and IL-6 expression. However, it did not change the distribution of leukocytes in kidney tissues. These results suggest to promising benefits of inulin as prebiotic in reducing the effects of endotoxemia. Further studies should be conducted to evaluate the capacity of prebiotics in endotoxemia.

Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 3): an open-label, randomised phase III trial.

BACKGROUND: Treatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries. PATIENTS AND METHODS: In this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation. RESULTS: A total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (<1% versus 5%) and leukopenia (0% versus 5%). CONCLUSIONS: Consistent with the phase III LUX-Head & Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01856478.

Electrochemical hydroxyapatite-cobalt ferrite nanocomposite coatings as well hyperthermia treatment of cancer.

The fabrication of hydroxyapatite-Co-ferrite nanocomposite coatings was performed on stainless steel by chronoamperometry technique. HA-CoFe2O4 nanocomposite films were characterized using X-ray diffraction, scanning electron microscopy, and vibrating sample magnetometer (VSM). The results reveal that CoFe2O4 nanoparticles dispersed within the HA matrix have flake and strip shapes. The magnetic property of the nanocomposite was increased by increasing the concentration of CoFe2O4 and a good saturation magnetization value was found to be 20.6emu/g with 50% CoFe2O4. By comparing with pure CoFe2O4, the composite still retain moderate magnetization as well as its biocompatible characters. The specific absorption rate (SAR) values were altered according to the change in CoFe2O4 concentration and the maximum SAR value was 125W/g. The incorporation of CoFe2O4 nanoparticles with HA coating was increased the corrosion resistance of HA in simulated body fluid (SBF). The results indicated that HA-CoFe2O4 nanocomposite coating could be a promising surface treatment technique for stainless steel medical implants as well hyperthermia treatment of cancer.

The teratogenic effects of imatinib mesylate on rat fetuses.

Imatinib mesylate, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukemia and gastrointestinal stromal tumors. The aim of the present study is to investigate the effects of imatinib mesylate on the pregnant rats and their fetuses. Pregnant rats were divided into three groups; the first group served as a control group. The second and third groups were orally administered imatinib at doses of 36 mg/kg body weight or 54 mg/kg b.wt. on gestation days (SDs) 6 through 13 or SDs 13 through 19, respectively. All animals were sacrificed on the 20th day of gestation. Treatment with imatinib caused a reduction of maternal body weight gain, uterine and placental weights, increased rate of abortion and fetal resorptions. High dose of imatinib caused fetal congenital deformities represented in harelip, contraction of the fore limbs, and paralysis of the hind limbs, exencephaly, encephalocoele and distended abdominal wall, besides occurrence of wavy ribs and absence of other ribs in addition to skeletal growth retardation and lack of ossification of the most skeletal elements. The present work concluded that imatinib is teratogenic when given orally to pregnant rats at 54 mg/kg b.wt. and causes direct maternal or developmental toxicity.

Heterosubtypic immunity against human influenza A viruses, including recently emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function.

Induction of heterosubtypic immunity to influenza viral antigens is of paramount importance to the prevention of epidemics and potential pandemics. The 1997 incidence of avian influenza infections in humans in Hong Kong heightened the need for pandemic preparedness and a search for vaccines and vaccine delivery systems that can confer broad protection. In this report, we demonstrate that the delivery of H1N1 subtype influenza viral antigens as immunostimulating complexes (ISCOM) induces broad cross-protection in mice against challenge with various influenza virus subtypes, including the avian H9 and the H5 strains that were recently responsible for deaths in humans. The ISCOM delivery system induced high and long-lived serum antiviral antibodies and class I-restricted cytotoxic T-lymphocytes (CTL). Studies with perforin, IFN-gamma, and mu-chain gene knock-out mice demonstrated that the heterosubtypic protection required cross-reactive, functional cytotoxic T cells and nonhemagglutination inhibiting serum antibodies. Interferon-gamma, a major player in viral clearance by nonlytic mechanisms, did not appear to play a role in heterosubtypic immunity. Nonformulated H1N1 influenza antigens failed to induce significant CTL or long-lasting antibody responses or to protect mice against challenge with heterosubtypic viruses. Furthermore, while influenza virus infection induced a dominant nucleoprotein (NP)-specific CTL response in H2 mice, the ISCOM delivery system induced a dominant hemagglutinin-specific CTL response. Moreover, non-neutralizing but cross-reactive antibodies played a role in reducing viral titers by macrophages. These results suggest that exogenous delivery of influenza antigens as ISCOM can influence their antigen processing and presentation, their ability to induce/recall CTL specificities, and their capacity to mediate broad cross-protection against influenza virus variants.

Primary thyroid lymphoma: a retrospective analysis of prognostic factors and treatment outcome for localized intermediate and high grade lymphoma.

Non-Hodgkin's lymphoma presenting in the thyroid gland is uncommon. A review of the King Faisal Specialist Hospital and Research Centre (KFSH & RC) experience was performed to assess treatment outcome and prognostic factors in this rare extranodal presentation of localized lymphoma. Sixty patients treated at KFSH & RC between 1975 and 1995 were identified, and their records were reviewed retrospectively. Eight patients who had stage III or IV disease, low grade, or did not complete their prescribed treatment were excluded from the study. There were 38 female and 14 male patients with a median age of 59.5 years at the time of diagnosis (range: 10-87 years). Thirty-five of the 52 patients underwent diagnostic partial or total thyroidectomy at other institutions based on a preoperative assumption of thyroid carcinoma. All 52 patients had non-Hodgkin's lymphoma of intermediate (94%) or high (6%) grade. Detailed staging was carried out in all patients; 16 patients (31%) had disease confined to the thyroid gland (stage IE), whereas 36 (69%) had associated disease in cervical lymph nodes and/or the mediastinum (stage IIE) disease. All patients were treated with curative intent. A total of 18 patients (35%) were treated with a single-modality treatment--radiotherapy alone in 2, chemotherapy alone in 13, and surgery alone in the remaining 3 patients. The majority of patients (34/52; 65%) were treated with a combined-modality approach. The overall relapse-free survival (RFS) and overall survival (OS) at 5 years were 72% and 88%, respectively. There were no significant differences in outcome between those treated with single-modality and those with combined-modality therapy. A univariate analysis showed that the presence of mediastinal lymph node involvement was the most important prognostic factor affecting both RFS and OS. Patients with Hashimoto thyroiditis and without "B" symptoms were found to have a significantly higher RFS without influence on the OS. However, patients who had a good performance status (PS) of 0, 1, and 2 were found to have a significantly higher overall survival in comparison to those with poor performance status. Age, sex, stage, histology, lactic acid dehydrogenase level, tumor bulk, and the treatment modality were not found to correlate with RFS or OS. Mediastinal involvement and PS were found to be the most important independent prognostic factors influencing RFS and OS.

The correlation of Epstein-Barr virus expression and lymphocyte subsets with the clinical presentation of nodular sclerosing Hodgkin disease.

BACKGROUND: The pathogenesis of nodular sclerosing Hodgkin disease (HD) has been correlated with Epstein-Barr virus (EBV). The phenotype of lymphocytes in HD and its relations to clinical presentation and to EBV expression have not been characterized fully. Grade II HD is a more aggressive form of the disease. The authors studied cases of HD by flow cytometry (FCM) in an attempt to analyze the phenotype of lymphocytes in the involved lymph nodes and to characterize the phenotype of these lymphocytes in relation to EBV expression, tumor grade, and clinical presentation. MATERIALS AND METHODS The authors prospectively studied lymph nodes from 48 patients with the diagnosis of HD by FCM for T (CD3, CD4, and CD8) and B (CD19) lymphocytes. Ratios of helper to suppressor (CD4 to CD8) and ratios of T to B (CD3 to CD19) lymphocytes were calculated. In situ hybridization for EBV also was performed. The tumors were graded. Clinical data related to age and stage of the disease were retrospectively analyzed. RESULTS: There were 30 male and 18 female patients with an age range of 7 to 77 years (median, 17 yrs). EBV expression was seen in 24 (50%) cases. Eleven (23%) cases were classified as Grade II disease. All Grade II cases showed EBV expression, whereas only 13 (39%) cases of Grade I disease were positive (P = 0.03). EBV-positive cases had a median CD4 to CD8 ratio of 1.62, whereas EBV-negative cases had a ratio of 3.86 (P = 0.01). Grade I cases had a median CD4 to CD8 ratio of 4.58, whereas Grade II cases had a ratio of 1.62 (P = 0.007). EBV-positive cases had a median T-lymphocyte to B-lymphocyte ratio of 2.72, whereas EBV-negative cases had a ratio of 3.17 (P = 0.77). Grade I cases had a median T-lymphocyte to B-lymphocyte ratio of 3.51, whereas Grade II cases had a ratio of 1.71 (P = 0.001). A higher percentage of children was seen in the EBV-positive cases than in the negative ones (58% vs. 29%). Cases with low (< 1.5) CD4 to CD8 ratios showed more incidence of high-stage disease (Stages III and IV) than patients with higher ratios (81% vs. 51%). High-stage disease also was seen more frequently in patients with low (< 3) T- to B-lymphocyte ratios (71% vs. 50%). CONCLUSION: The authors found that the local immune response in HD may vary from one case to another. The findings also suggest that EBV may play a role in the pathogenesis of the disease in relation to T- and B-lymphocyte response. A more profound immune suppression and decrease in overall T and helper lymphocytes may be seen in aggressive EBV-positive variants of the disease. These changes may impact the initial presentation of the disease and perhaps its overall biologic behavior.

Tumor lysis syndrome following hemi-body irradiation for metastatic breast cancer.

Tumor lysis syndrome (TLS) is a rare serious acute complication of cancer therapy, reported mainly following chemotherapy in patients with large tumor load and chemosensitive disease. These are mainly patients with non-Hodgkin's lymphoma, leukemia and rarely in solid tumors. It is less frequently described after radiotherapy for lymphoid and hematological malignancies. TLS following radiotherapy for solid tumors is a very rare complication. In this report/review we describe a seventy-three-year-old male patient with progressive metastatic carcinoma of the breast to the lungs, liver and bone. He was referred for radiotherapy because of generalized bony pains. The patient was planned for sequential hemi-body irradiation starting with the more symptomatic upper half body. After premedication, he was given 8.5 Gy to the mid point at the maximum chest separation with anterior lung attenuator limiting uncorrected lung dose to 6.15 Gy. A further 3.5 Gy electron boost to the fungating breast tumor was given to the 100%. Forty-eight hours after irradiation he developed hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia and renal failure. These clinical and biochemical changes are typical of tumor lysis syndrome (TLS). Despite hydration, and treating the hyperuricemia, the patient developed coma and died eight days after irradiation. The prophylaxis and management of TLS and in high-risk patients are described to avoid this frequently fatal complication.

High complete pathological response in locally advanced breast cancer using paclitaxel and cisplatin.

BACKGROUND: In an earlier study, we have demonstrated a high response rate in metastatic breast cancer using paclitaxel (P) and cisplatin (C). A phase II study using the same regimen (PC) has been conducted in locally advanced breast cancer (LABC). METHODS: A total of 72 consecutive patients with non-inflammatory LABC (T2 > or = 4 cm, T3 or T4, N0-N2, M0). Patients were scheduled to receive 3-4 cycles of the neoadjuvant PC (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2 on day 1) every 21 days. Patients were then subjected to surgery and subsequently received 6 cycles of FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) or 4 cycles of AC (doxorubicin 60 mg/m2, and cyclophosphamide 600 mg/m2). Patients then received radiation therapy, and those with hormone receptor positive tumors were given adjuvant tamoxifen intended for 5 years. RESULTS: The median age was 39 years (range, 24-78). Clinically, 7%, 58%, and 35% of patients had T2 > or = 4 cm, T3, and T4, respectively. Disease stage at diagnosis was IIB (33%), IIIA (27%), and IIIB (40%). Complete and partial clinical response to PC was demonstrated in 13 (18%), and 52 (72%) patients, respectively. Of those patients with evaluable pathologic response (68 patients), complete pathologic response (pCR) was achieved in 15 (22%) patients. At a median follow-up of 22 (+/- 3.5) months, 58 (81%) were alive with no recurrence, nine (12%) were alive with evidence of disease, and five (7%) were dead. None of the patients achieving pCR has developed any relapse. The median overall survival has not been reached for all 72 patients with a projected 3-year survival (+/- SE) of 90% (+/- 4%). The median progression-free survival (PFS) was 42.1 (+/- 4.8) months with a projected PFS of 74% +/- 7% at 3-years (for 68 patients). CONCLUSIONS: PC regimen in LABC produced a high pCR. The contribution of the other added modalities to survival could not be assessed.

Squamous cell carcinoma of the oral tongue: an analysis of prognostic factors.

AIM: To identify the prognostic significance of different factors in patients with squamous cell carcinoma of the tongue. PATIENTS AND METHODS: Seventy-seven patients with carcinoma of the tongue were treated radically at the King Faisal Specialist Hospital and Research Centre between 1980 and 1989. Twenty patients (26%) were treated by resection alone, 11 (14%) with radiotherapy alone, and 46 (60%) with combined resection and radiotherapy. RESULTS: Forty-seven patients (61%) had T(1-2), 28 (36%) T(3-4), and two T(x) tumours. The regional nodes were clear in 53 (69%) and contained metastases in 24 patients (31%). Thirty patients (39%) developed recurrences, which were local in 9, regional in 14, locoregional in 5, and locoregional with metastatic disease in 2. The five and 10-year overall actuarial survival for all patients were 65% and 53%, respectively, and the corresponding relapse-free survival 56% and 50%. Univariate and multivariate analyses were done of seven variables - age (<40 compared with >/=40 years), sex, chewing tobacco use, smoking, TNM stage, surgical margins (clear or invaded), and treatment (resection, radiotherapy, or the combination). On univariate analysis chewing tobacco (P=0.04), smoking (P=0.01), invaded resection margins (P=0.04), involved regional lymph nodes (P=0.009), T4 tumours, and patients treated with radiotherapy alone (P=0.001) were associated with poor overall survival. Factors associated with shorter relapse-free survival were age >40 (P=0.03), chewing tobacco (P=0.04), invaded resection margins (P=0.01), and smoking (P=0.01). On multivariate analysis, invaded resection margins and smoking (P=0.04)(P=0.02) were associated with shorter overall survival and relapse-free survival (P=0.03 and (P=0.01), while chewing tobacco independently influenced relapse-free survival only (P=0.03). CONCLUSION: Invaded resection margins and smoking were the only independent prognostic factors that affected both overall and relapse-free survival. Those who chewed tobacco were at high risk of locoregional failure.

F-18 FDG uptake in breast infection and inflammation.

PURPOSE: Whole-body fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) scanning has been useful in the management of breast cancer. However, F-18 FDG uptake sometimes has been associated with benign breast disease. Four cases are reported of F-18 FDG breast uptake caused by infectious or inflammatory mastitis that mimics malignant disease. METHODS AND RESULTS: Two women had F-18 FDG whole-body scans for the evaluation of a large breast mass after inconclusive results of ultrasonography. In both cases, intense focal F-18 FDG breast uptake was noted that mimicked breast cancer. Histologic examination showed, in one patient, chronic granulomatous infiltration that likely represented tuberculous mastitis, because she showed a good clinical response to empirical anti-tuberculous treatment. The second patient had lactational changes associated with acute inflammation, and the culture grew Staphylococcus aureus. The breast mass completely disappeared 3 weeks after a course of antibiotic treatment. The other two patients had staging F-18 FDG PET scans 1 and 12 months after lumpectomy for breast carcinoma to detect residual, recurrent, or metastatic disease. Both scans showed a ring-like uptake in the involved breast, with superimposed intense focal uptake suggesting tumor necrosis centrally and malignant foci peripherally. In both cases, histologic examination revealed hemorrhagic inflammation secondary to postsurgical hematomas and no evidence of malignancy. CONCLUSION: Acute or chronic infectious mastitis and postsurgical hemorrhagic inflammatory mastitis should be considered in patients who have a breast mass, especially those with a history of tenderness or surgery.

25. Positron Emission Tomography in Hodgkin's Disease. Correlation with Computed Tomography and Gallium 67 Citrate Imaging.

Purpose: To compare the sensitivity of F18 - FDG Positron Emission Tomography (PET), Computed Tomography (CT) and Planar Gallium 67-Citrate (GS) in the diagnosis of Hodgkin's Disease.Materials and Methods: Thirty (30) adult patients with histopathologically confirmed diagnosis of Hodgkin's Disease between Oct 97 and June 98 at KFSH & RC had the three diagnostic imaging modalities for the initial work up; in twenty eight patients for newly diagnosed and in two patients for recurrent disease. Nodular sclerosis was the histological subtype in 25 patients, mixed cellularity in 3 and lymphocytic predominance in 2.Results: For the initial evaluation of the results, a positive site by any of the three diagnostic imaging modalities was considered actual location of the disease. The patient-site sensitivity of PET, CT and for GS were 93.33%, 80% and 53.3% respectively. False negative results were observed in 2 patients with PET, 7 with CT and 14 with GS. The Spleen was the commonest site for false negative result in GS (4 patients) axilla and bones in CT (2 patients each), the 2 patients with false negative results with PET were in the lung. The difference in sensitivity between PET and GS was statistically significant (P = 0.002), but was not significant between PET and CT (P = 0.18). Although CT showed better sensitivity and accuracy when compared with GS, that didn't reach statistical significance (P = 0.09).Conclusion: PET Scan has the highest sensitivity in the initial evaluation in this small group of patients with Hodgkin Disease, especially when compared with GS. Evaluations of the final sensitivity, specificity and accuracy of these imaging modalities will be presented.

Low-grade astrocytoma--a retrospective analysis of 102 patients.

One hundred and two patients (57 males, 45 females, median age 17 years) with histologically proven low-grade astrocytoma (grades I, II) treated between 1978 and 1994 were retrospectively analyzed at the King Faisal Specialist Hospital & Research Center. Microscopic investigation showed 50 patients (48%) with grade I tumors as opposed to 52 patients (52%) with grade II tumors. Fifteen patients (15%) had complete surgical excision, 55 (52%) had partial excision and 32 (31%) had biopsy only; 68 patients (66%) received external radiotherapy with a median dose of 54 Gy (range 45-68.5 Gy). With a median follow-up of 3.3 years, the 5 and 10 years, overall actuarial survival rates were 78% and 62%, respectively while the progression-free survival rates at 5 and 10 years were 69%, and 35%, respectively. Age and performance status were significant prognostic factors in terms of overall survival on univariate (p = 0.05 and 0.05, respectively) and multivariate analysis (p = 0.005 and 0.006, respectively).

Positron emission tomography in breast cancer: a clinicopathological correlation of results.

We conducted a retrospective study to evaluate the sensitivity, specificity and accuracy of positron emission tomography (PET) scans in 109 patients with primary recurrent or metastatic breast cancer. All patients had a PET scan, X-ray or CT scan of the chest, an ultrasound or CT scan of the liver and a bone scan. Mammography was available for 86 patients. Correlation between the PET scan result and histological findings were made. The sensitivity, specificity and accuracy of the PET scan were calculated for both the primary tumour (T) and lymph nodes (N). In patients with metastasis (M) the accuracy of the PET scan was compared with other imaging modalities. Histological results of the site in question were available in only 105 patients. Information for the primary tumour was available for 93 patients and for nodes in 74. The PET scan was accurate in 89.2% for (T), with 3.2% false positive and 7.6% false negative. For (N) the PET scan was accurate in 90.5% with 9.5% false negative. In the 86 patients who underwent both mammography and PET scanning, the PET scan was more accurate in 89.5% versus 72% (p = 0.0003). In the 19 patients with metastasis, the PET scan was in agreement with other imaging modalities in 100% of cases. PET scanning is the only non-invasive imaging procedure that will detect tumours in the breast, lymph nodes, lung, liver, bone and bone marrow with high sensitivity, specificity and accuracy. It is a valuable tool in the management of patients in all stages of breast cancer for diagnosis, staging and following treatment response.

Ewing's Sarcoma of the Head and Neck: A Retrospective Analysis of 24 Cases.

Introduction and purpose. Primary Ewing's sarcoma arising from the bones of the head and neck region is extremely rare representing only 1- 4% of all Ewing's sarcoma cases. Previous reports suggest a better prognosis for that particular anatomic site. The purpose of this study was to analyze the clinico-epidemiologic characteristics of that rare clinical presentation, as well as its patterns of failure and prognosis following treatment.Materials and methods. This study included a retrospective review of the medical records of patients with the diagnosis of Ewing's sarcoma of the head and neck region treated at King Faisal Specialist Hospital and Research Center between 1975 and 1996.Results. Out of a total number of 24 cases analyzed, there were 17 males and 7 females with a ratio of 2.4:1. The median age at diagnosis was 16.5 years. A painful swelling was the most common clinical presentation.The maxilla was the most common site of presentation (9/24 cases). There were 3/24 cases who presented with metastatic disease at diagnosis.The majority of patients (16/24 cases) had a tumor size >10 cm. Most patients were treated with systemic chemotherapy plus localized irradiation following an initial biopsy.With a mean follow up of 3.4 years, the 5-year actual overall survival (OS) for the whole group was 53%, while the 5-year actuarial disease-free survival (DFS) was 30%. These figures were higher than those repor ted from our institution for young patients (

Radiation therapy for retinoblastoma: a retrospective review of 120 patients.

PURPOSE: To characterize the patient population and treatment outcomes in patients with Retinoblastoma (RB) referred for External Beam Orbital Radiotherapy (EBORT) to King Faisal Specialist Hospital & Research Centre (KFSH&RC), Riyadh, Saudi Arabia from 1976 to 1993. METHODS AND MATERIALS: A retrospective study of 120 patients with RB affecting a total of 192 eyes. Patients were divided into three groups. Group A are 60 patients (64 eyes) treated with EBORT to the intact eye to preserve vision. Reese-Ellsworth (RE) Staging was: 1: 12%; 2: 10%; 3: 12%; 4: 23%; and 5: 43%. Twenty-eight patients (47%) also received Vincristine, Adriamycin, and Cyclophosphamide chemotherapy (C/T). Mean follow-up, per patient, was 48.5 months. Standard treatment until 1992 was 45 Gy in 12 fractions of 3.75 Gy, three times weekly over 18 days. Assuming the alpha/beta ratio for early effects and tumor control at 10, Tk = 21 days, Tpot = 5 days, then the Biological Equivalent Dose (BED) was 62 Gy10 for early effects, and 101 Gy3 for late effects. Group B are 28 patients (28 eyes) treated for curative intent with EBORT to the orbit for locally advanced disease, usually after enucleation (24 eyes). Nineteen patients (83%) also had C/T. Mean follow-up was 22.6 months. Group C are 37 patients with advanced disease treated with radiotherapy for palliation. Seventeen (46%) also received C/T. Mean follow-up was 11.7 months. RESULTS: Group A-following EBORT useful vision was retained in RE Stage 1 to 5: 7 of 7, 6 of 6, 4 of 8, 10 of 15, and 7 of 28 eyes, respectively. There was no significant difference between patients who received adjuvant chemotherapy and those who did not. Complications included cataract (27%), retinopathy (25%), vitreous hemorrhage (19%), and orbital deformities (11%). In Group B the local control rate was 71%. In Group C, 10 (27%) of the 37 patients were alive at last contact, and 27 (73%) were either terminal or dead of disease. None of Group A or B patients had positive CSF cytology, bone scan, or bone marrow examination. In Group C 19% had positive CSF cytology, and bone marrow, and 14% had a positive bone scan. CONCLUSIONS: 1) EBORT preserved useful vision in a significant proportion of patients even in eyes with advanced RE Stage RB, but longer follow-up is likely to reveal an even higher complication rate with this regime. 2) High dose per fraction probably contributed to the increased complications. 3) Chemotherapy did not demonstrate any effect on retaining vision in this study. 4) For disease that is confined to within the eye clinically and radiologically, invasive procedures for CSF cytology, bone marrow examination, and bone scan do not seem warranted. 5) The optimum technique, fractionation, and dosage for RB is still not well defined.

Chemical synthesis of Haemophilus influenzae glycopeptide conjugates.

A simple procedure for conjugating synthetic fragments of the capsular polysaccharide of Haemophilus influenzae type b, poly-3-beta-D-ribose-(1,1)-D-ribitol-5-phosphate (sPRP) to linear peptides is described. The procedure consists of (i) reacting the amino group of amino-heptyl sPRP with m-maleimidobenzoyl-N-hydroxysuccinimide (MBS) in phosphate buffer, pH 7.5; (ii) selectively coupling the MBS-modified sPRP to the sulfhydryl group of the cysteine residue of peptides containing functional T-helper cell epitope(s). The glycopeptide conjugates were purified by gel filtration chromatography, biochemically characterized, and elicited protective level of anti-PRP antibody responses in rabbits.