The influence of host factors and immunogenetics on lymphocyte responses to Hepagene vaccination

We have shown that both demographic and immunogenetic factors are involved in the immune responses of Hepagene vaccinated individuals who were persistent nonresponders to 'S' containing hepatitis B vaccines. The HLA-DRB1 0701; DQB1 0202 genotype was found to be associated with a decline of anti-HBs antibodies (anti-HBs) and were frequent in those individuals who remained nonresponders following booster vaccination. Contrary to previously published 'S' vaccination data, Hepagene stimulated T-cell responses showed a lack of correlation with the humoral responses. Limiting dilution analysis demonstrated that the cellular immune response is associated with the kinetics of exposure to Hepagene rather than magnitude of the anti-HBs response. It remains that despite the inclusion of the pre-S proteins 74% nonresponder vaccinated individuals failed to produce > 100 IU/l of anti-HBs. However, these were persistent nonresponders and it was therefore encouraging that two doses of Hepagene did seroconvert (> 10 IU/L) 61% of this difficult group.     

Intraoperative radiation therapy for carcinoma of the gallbladder

The recognition of a high incidence of local failure following surgical management of adenocarcinoma of the gallbladder has led to the use of adjuvant radiation therapy. In order to deliver higher doses to the gallbladder bed, intraoperative radiation therapy (IORT) has been used both with and without external beam radiation.The experience to date is reviewed. Ten patients have been treated, all of whom had either gross residual or unresected disease. The median survival for the group was approximately 1 year. There were no long-term survivors. The IORT did not contribute to the overall morbidity.Because of the limited number of patients and the advanced nature of the disease, the role of IORT in the management of gallbladder carcinoma has yet to be determined. The utility of this modality will most likely reside in the treatment of minimal residual disease at the time of cholecystectomy rather than in the palliative treatment of unresectable tumors.

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Resumen El reconocimiento de la elevada tasa de falla local en el tratamiento del adenocarcinoma de la vesícula biliar, ha motivado el uso de radioterapia adyuvante. Con el objeto de administrar altas dosis de irradiación al lecho de la vesícula billiar, se ha utilizado la radioterapia intraoperatoria (RTIO) con y sin irradiación externa.Se revisa la experiencia hasta la fecha. Diez pacientes han sido tratados, todos con enfermedad macroscópica residual o no resecable. La sobrevida media para el grupo fue de aproximadamente un año; no hay sobrevivientes a largo plazo. La RTIO no contribuyó a la morbilidad global.Debido al limitado número de pacientes y a lo avanzado de la enfermedad, el rol de la RTIO está aun por determinar. La utilidad de esta modalidad muy posiblemente habrá de residir en el tratamiento de enfermedad residual miima en el momento de la colecistectomiá, más qu en el tratamiento paliativo de tumores no resecables.

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Résumé Reconnaître la fréquence importante des échecs locaux à la suite du traitement chirurgical de l'adénocarcinome de la vésicule a amené à ajouter la radiothérapie. Pour pouvoir donner des doses plus importantes au lit de la vésicule, l'irradiation peropératoire (IP) a été administrée à la fois avec et sans irradiation externe. L'expérience à ce jour a été passée en revue. Dix patients ont été traités qui avaient soit une grosse tumeur résiduelle soit un cancer non réséqué. La survie moyenne du groupe était d'un an à peu près. Il n'y a eu aucun survivant à long terme. L'IP n'a rien changé à la mortalité globale. Compte tenu du nombre limité des patients et de la nature avancée de la maladie, le rôle de l'IP dans le traitement du cancer de la vésicule reste à déterminer. La valeur de l'IP sera probablement de traiter la petite tumeur résiduelle au moment de la cholécystectomie plutôt que les tumeurs non résécables.

     

The longitudinal relationship of hemoglobin, fatigue and quality of life in anemic cancer patients: results from five randomized clinical trials.

BACKGROUND: Anemia is common in cancer and has been associated with fatigue and reduced health-related quality of life (HRQOL). We report the association between hemoglobin and fatigue and the impact of reducing fatigue on several domains of HRQOL. PATIENTS AND METHODS: These analyses were based on five randomized trials. Patients completed the Functional Assessment of Cancer Therapy (FACT) Anemia scales and numeric rating scales of Energy, Activity and Overall Health at baseline and after the 12-week treatment period. t-tests and linear regression models were used to evaluate associations. Analyses were stratified into three groups: solid tumor chemotherapy patients, lymphoproliferative malignancy chemotherapy patients and non-chemotherapy patients. RESULTS: Adjusted mean differences (95% CI) in FACT Fatigue change scores between hemoglobin responders (> or =2 g/dl increase) and non-responders were 3.0 (1.2, 4.7), 2.8 (0.6, 5.0) and 5.8 (2.2, 9.5) among the solid tumor, lymphoproliferative malignancy and non-chemotherapy groups, respectively. Significantly greater improvements (P <0.01) were observed in the FACT well-being scales for patients with meaningful improvement in fatigue (FACT Fatigue change score > or =3 points). After controlling for other factors, patients whose fatigue improved reported substantially greater improvements in energy, ability to perform usual activities and overall health (P <0.0001). CONCLUSIONS: Across five trials of cancer patients on and off chemotherapy, hemoglobin response was associated with meaningful improvements in fatigue, which, in turn, was associated with improved physical, functional, emotional and overall well-being.     

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.     

Ploidy profile of morphologically normal squamous epithelium adjacent to high grade cervical intraepithelial neoplasia

We have investigated the ploidy profile of morphologically normal mucosa adjacent to high grade CIN (   n = 16  ) and also from normal cervix ( n = 18). DNA ploidy was assessed using flow cytometry and image analysis. All cases were diploid by both modalities. Our results show that morphologically normal squamous mucosa has a stable ploidy profile even when it lies adjacent to high grade CIN. This finding supports the view that high grade CIN is a neoplastic expansion of transformed cells rather than the result of a field change effect.     

Transjugular craniotomy for the management of jugular foramen tumors with intracranial extension.

OBJECTIVES: To elucidate indications and outcomes with the transjugular craniotomy for resection of jugular foramen tumors with intracranial extension. The transjugular approach is a lateral craniotomy conducted through a partial petrosectomy traversing the jugular fossa combined with resection of the sigmoid sinus and jugular bulb, which often have been occluded by disease. STUDY DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: Twenty-eight patients with intracranial jugular foramen tumors who underwent a total of 30 surgical procedures. MAIN OUTCOME MEASURES: Pathologic findings, surgical approach, extent of tumor resection, rate of facial nerve mobilization and ear canal closure, facial and lower cranial nerve outcomes, and hearing preservation. RESULTS: Tumors included schwannoma (37%), meningioma (33%), glomus jugulare (23%), and chordoma (7%). The surgical approaches were tailored to maximize functional preservation, and included the transjugular (53%), translabyrinthine (17%), retrosigmoid (10%), and far lateral (7%) craniotomies. Translabyrinthine (3%) or transcondylarfar lateral (3%) approaches were occasionally used in combination with the trans-jugular approach. Most procedures were managed in a single stage (90%), but three patients with massive tumor in the neck required two stages. Microsurgical gross total and near-total tumor removal (37% each) were commonly achieved, although subtotal resections (27%) were occasionally performed. In only a minority of cases was facial nerve mobilization (7%) or ear canal closure (21%) required. If present preoperatively, Grade I facial nerve function was usually maintained (22 of 24 [92%]) and Hearing Class A or B could always be maintained (9 of 9 [100%]). As expected, new lower cranial nerve dysfunction was common (8 of 30 [27%]), although over half of the patients had complete lower nerve palsy preoperatively (16 of 30 [53%]). CONCLUSION: Most patients with jugular foramen tumors with intracranial extension can be managed with a single-stage transjugular craniotomy. Facial nerve mobilization or ear canal closure is usually not required, permitting conservation of facial function and hearing, when present preoperatively.     

Sustaining better diabetes care in remote indigenous Australian communities*

Problem: Inhabitants of Torres Strait Islands have the highest prevalence of diabetes in Australia and many preventable complications. In 1999, a one year randomised cluster trial showed improved diabetes care processes and reduced admissions to hospital when local indigenous health workers used registers, recall and reminder systems, and basic diabetes care plans, supported by a specialist outreach service. This study looked at whether those improvements were sustained two years after the end of the trial.

Design: Three year follow up clinical audit of 21 primary healthcare centres, and review of admissions to hospital in the previous 12 months.

Background and Setting: Remote indigenous communities in far north east Australia, population about 9600, including 921 people with diabetes.

Key Measures for Improvement: Number of people on registers, care processes (regular measures of weight, blood pressure, haemoglobin A1c, urinary protein concentration, and concentrations of serum lipids and creatinine), appropriate clinical interventions (drug treatment and vaccinations), and intermediate patient outcome measures (weight, blood pressure, and glycaemic control). Admissions to hospital.

Strategies for Change: Audit and feedback to clinicians and managers; provision of clinical guidelines and a clear management structure; workshops and training.

Effects of Change: The number of people on registers increased from 555 in 1999 to 921 in 2002. Most care processes and clinical interventions improved. The proportion of people with good glycaemic control (haemoglobin A1c 7%) increased from 18% to 25% in line with increased use of insulin (from 7% to 16%). The proportion of those with well controlled hypertension (< 140/90) increased from 40% to 64%. The proportion admitted to hospital with a diabetes related condition fell from 25% to 20%. Mean weight increased from 87 kg to 91 kg.

Lessons Learnt: In remote settings, appropriate management structures and clinical support for people with diabetes can lead to improvements in care processes, control of blood pressure, and preventable complications that result in admission to hospital. Control of weight and glycaemia are more difficult and requires more active community engagement. Priorities now include increasing the availability and affordability of good food, achieving weight loss, and increasing appropriate use of hypoglycaemic agents, including insulin.

     

What is the difference between squamous cell carcinoma and adenocarcinoma of the cervix? A matched case–control study

The objective of this study was to investigate the efficacy of treatment strategies in patients with adenocarcinoma (AC) of the cervix and compare it with those with squamous cell carcinoma (SCC) of the cervix. Women with FIGO (1994) stage IB1 AC, especially pathologic tumor size of 2-4 cm, treated with class III hysterectomy, were compared with those with SCC treated with comparable strategy in a case-controlled study. Eighty patients (20 cases, 60 controls) were analyzed. Lymphvascular space invasion (P = 0.01) and lymph node metastasis (P = 0.07) were more frequent in patients with SCC than in those with AC. However, there was no significant difference in depth of stromal invasion (P = 0.51) and invasion of the parametrium (P = 0.44) between two groups. And there was also no statistically significant difference in disease-free survival (P = 0.86) and overall survival (P = 0.89) between two groups. Primary radical surgery followed by adjuvant therapy, same as for SCC, would be acceptable for AC with pathologic tumor size of 2-4 cm. Although it was difficult to determine whether AC recurred more systemically, more effective treatment strategies than those currently available for AC should be considered to reduce the systemic recurrence.