Adjuvant treatments for resectable hepatocellular carcinoma

Hepatocellular carcinoma often recurs even after curative resection. Although some encouraging data showing improvements in recurrence-free times have been reported with the use of intraarterial 131I-lipiodol infusion, retinoids, interferon, or immunotherapy after hepatectomy, there is no consensus regarding standard adjuvant therapy for resectable hepatocellular carcinoma. A novel target agent, sorafenib, which has recently become a standard of care for advanced disease, may also be promising in an adjuvant setting to prevent early recurrence after curative surgery. In future trials, it will be important to identify appropriate target populations for each type of adjuvant approach; that is, an agent with definitive antitumor activity for high-risk patients, and one that shows chemoprevention for low-risk patients.     

Noncardiac chest pain

Opinion statement Noncardiac chest pain (NCCP) is a common condition with significant morbidity and economic implications. Psychological factors, gastroesophageal reflux disease (GERD), alteration in pain perception, and esophageal dysmotility play an important role in the pathogenesis of the disorder. Proton pump inhibitor (PPI) therapy is the most effective medical intervention for the treatment of GERD-related NCCP, as well as the most costeffective diagnostic strategy for this condition. Pain modulators such as tricyclic antidepressants, trazodone, and selective serotonin reuptake inhibitors infer a visceral analgesic effect and consequently are the treatment of choice for patients with non-GERD-related NCCP. Furthermore, cognitive behavioral therapy has also been shown to be useful in the management of subset of patients with non-GERD-related NCCP. Newer therapeutic modalities and interventions such as lower esophageal sphincter injection of botulinum toxin in NCCP patients with spastic esophageal motility disorders, theophylline, and 5-HT4 receptor agonists may supplement or replace current treatment for non-GERD-related NCCP. Future compounds may include new visceral analgesics or medications that interfere with the development of peripheral or central sensitization.     

Expiratory-Synchronized Sleep in a Quadriplegic Patient Using Inspiratory Neck Muscles To Breathe

In a patient with C3 quadriplegia causing complete diaphragm paralysis who developed inspiratory neck muscles (INM) hypertrophy to sustain ventilation, spontaneous breathing deeply altered sleep architecture, relegating sleep to the expiratory phase of the ventilatory cycle. A polysomnographic recording performed during mechanical ventilation (without INM activity), showed that sleep was abnormal but unaffected by the respiratory cycle. During spontaneous breathing, the polygraphic recordings showed expiratory microsleep episodes, with inspiratory arousals synchronous to bursts of INM activity. This case report illustrates the powerful adaptability of the respiratory and sleep control systems to maintain each vital function.     

Evaluation of the humoral immune response and cross reactivity against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> of mice immunized with liposomes containing glycolipids of <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

Mycobacterium smegmati s (Ms) is a nonpathogenic mycobacteria of rapid growth, which shares many characteristics with Mycobacterium tuberculosis (MTB), the major causative agent of tuberculosis. MTB has several cell wall glycolipids in common with Ms, which play an important role in the pathogenesis of tuberculosis and the induction of a protective immune response against MTB infection in some animal models. In this study, the humoral immune response and cross reactivity against MTB, of liposomes containing a mixture of cell wall glycolipids of Ms and commercial lipids was evaluated, in order to study its possible use as a component of a vaccine candidate against tuberculosis. Liposomes containing total lipids extracted from Ms, distearoyl phosphatidyl choline and cholesterol were prepared by the dehydration-rehydration technique. Balb/c mice were immunized with the liposomes obtained and the antibody response and cross reactivity against MTB were tested by ELISA. Total lipids extract from Ms showed the presence of several polar glycolipids in common with MTB, such as phosphatidylinositol mannosides. Liposomes that contained glycolipids of Ms were capable of inducing a specific IgG antibody response that allowed the recognition of surface antigens of MTB. The results of this study demonstrated the presence of immunogenic glycolipids in Ms, which could be included to enhance the protective effects of subunit vaccine formulations against tuberculosis.     

Leadership and organizational ethics: the three dimensional African perspectives

This paper addresses the past, present and future aspects of African leadership and organizational ethics that have, are and will be key for any organization to sustain its systems and structures. Organizational ethics revolves around written and/or unwritten guidelines, ethical values, principles, rules and standards, that are drawn from the harmonious coexistence with the biosphere and it is how these elements are applied that dictates the style of leadership and the ethical thinking of the leaders. Africa has a wide range of complexities which are compounded by, inter alia, tribal divisiveness, selfish leadership, wealth inequality, and massive unemployment. Africans tend to draw their leadership and ethical practices and reflections from the events in the environment with which they have interacted for many years. However, in order to fully address and understand the African perspective in leadership and organizational ethics, a broad comprehension of the African diverse and complex landscape is needed through unravelling of the three dimensional existence of the people. African ethics, developed over time, unifies organizations and leadership since it is part of life and is practised, sub-consciously or unconsciously, by the people as they transform from one practice to the other, and during intergenerational transitions. Globalization, liberalization, technological changes and advancement, and market changes are rapidly transforming the environment in which organizations operate. In such a situation, an effective and true leader cannot be rigid but should be flexible, with the ability to use different leadership styles whenever the situation calls for it. Only those leaders with a three-dimensional perspective live inspiring lives, live with a cause and adopt organizational ethics and leadership styles that will stand the test of time. Despite Africa being the cradle of humankind, leadership and organizational ethics is still in its infancy and wanting, even with the new generation of young leaders. The future outlook of African organizational ethics and leadership is to be found in the intersection of changes in technology, life style, demographics and geopolitics with new trends emerging in global polity and economy.     

Clarifying values: an updated review

Background

Consensus guidelines have recommended that decision aids include a process for helping patients clarify their values. We sought to examine the theoretical and empirical evidence related to the use of values clarification methods in patient decision aids.

Methods

Building on the International Patient Decision Aid Standards (IPDAS) Collaboration’s 2005 review of values clarification methods in decision aids, we convened a multi-disciplinary expert group to examine key definitions, decision-making process theories, and empirical evidence about the effects of values clarification methods in decision aids. To summarize the current state of theory and evidence about the role of values clarification methods in decision aids, we undertook a process of evidence review and summary.

Results

Values clarification methods (VCMs) are best defined as methods to help patients think about the desirability of options or attributes of options within a specific decision context, in order to identify which option he/she prefers. Several decision making process theories were identified that can inform the design of values clarification methods, but no single “best” practice for how such methods should be constructed was determined. Our evidence review found that existing VCMs were used for a variety of different decisions, rarely referenced underlying theory for their design, but generally were well described in regard to their development process. Listing the pros and cons of a decision was the most common method used. The 13 trials that compared decision support with or without VCMs reached mixed results: some found that VCMs improved some decision-making processes, while others found no effect.

Conclusions

Values clarification methods may improve decision-making processes and potentially more distal outcomes. However, the small number of evaluations of VCMs and, where evaluations exist, the heterogeneity in outcome measures makes it difficult to determine their overall effectiveness or the specific characteristics that increase effectiveness.

     

Making decisions in a complex information environment: evidential preference and information we trust

Background

Informed decision making requires that those individuals making health and health-care decisions understand the advantages and disadvantages associated with particular health options. Research and theory suggest factors that contribute to the decision-making process: data on the likelihood of risks and benefits, level of certainty about outcomes, familiarity with the health issue, characteristics of information sources and presentation, and patient values and beliefs. As the health information environment increases in complexity, it becomes important to understand how interactions among information sources, family, and friends may affect the processing of health information and choices and their alignment with available evidence.

Analysis

This paper discusses the potential interactions among social networks, information sources and evidential preferences for health information as they influence health decisions. The role of family and friends who increasingly search for health information for others and the potential for information filtering influenced by second- or third-party attitudes and preferences is explored. Evidential preferences suggestive of the potential value of social math (creatively presented statistics) strategies for presenting data, the information-processing factors that may make personal experiences, anecdotes and testimonials that are often shared within social networks and may exert powerful influences on health decisions are examined in this article.

Conclusions

The paper concludes with recommendations for revised health-communication practices, health professional training to improve patient understanding in the clinical encounter, and directions for future research. Simple, direct, and socially relevant communications that avoid conflicts with the values and beliefs of the individual, as well as those of the family and social network, are recommended.

     

Correlation of molecular biomarker concentrations between synovial fluid and saliva of the patients with temporomandibular disorders

Objectives

The synovial membrane and fluid are involved in the pathogenesis of temporomandibular joint (TMJ) disorders. This study aims to assess the relationship between matrix metalloproteinase-2 (MMP-2), chemerin and prostaglandin (PGE₂) levels in the synovial fluid (SF) and saliva of patients with TMJ disorder regarding their role in inflammation and the value of being a candidate for predictive biomarkers in the disease. Also, it is aimed to find out whether chemerin’s main function triggers the formation inflammatory cytokine markers in the associated area.

Materials and methods

Thirty-two samples of SF and saliva were obtained from patients with disc displacement without reduction with limited opening (DDWORwLO). Mann-Whitney-U test was used for the comparisons of the biomarker levels in SF and saliva. The correlation between chemerin and BMI (Body Mass Index) is analyzed by non-parametric Spearman’s rho correlation coefficient.

Results

For all of the three biomarkers, statistically significant differences were found between SF and saliva. An unexpectedly high level expression of chemerin was observed in SF. A statistically significant, positive correlation was observed between PGE₂ -MMP-2, and chemerin-PGE₂ in saliva, chemerin and MMP-2 in SF, respectively (p = 0.031, r = 0.382 / p = 0.039, r = 0.366 / p = 0.032, r = 0.379). A positive correlation was determined between saliva and SF levels of PGE₂ (p = 0.016, r = 0.421).

Conclusions

Chemerin, MMP-2, and PGE₂ can play a role as an inflammatory factor for the development of TMJ disorder.

Clinical relevance

The search for molecular markers in TMJ and the inhibition of the associated molecular signaling mechanism is important to reduce joint inflammation and cartilage degradation.

     

Radiotherapy for SMAD4-negative musculoskeletal lesions from pancreatic cancer

Background

Pancreatic cancer (PC) predominantly metastasizes to liver, lung, and peritoneum. Metastatic disease correlates with SMAD4 status. Musculoskeletal metastases (MSM) are rare in pancreatic cancer. The role of radiation therapy (RT) in patients with musculoskeletal metastases is not clear.

Methods

We present a case of a woman with musculoskeletal metastases of PC evolving 4 years after Whipple’s procedure and adjuvant therapy. She was treated with RT for 7 MSM. Radiation dose was 15–45 Gy, delivered in doses of 2.5–5 Gy per fraction. SMAD4 status was examined by immunohistochemistry. Furthermore we undertook a review of the literature to examine the value of RT in musculoskeletal metastasis of PC.

Results

In the presented patient we treated 7 MSM of SMAD4-mutant PC with RT. RT achieved local control in 4 of the 7 MSM. At the resection margin of one MSM recurrent tumor was observed after RT. The status of one MSM was unknown and one MSM showed local progression. Follow-up revealed progression of pain in 1 of the 7 MSM. Except of hyperpigmentation no side effects occurred. There was no dose–correlation effect on tumor control observed. A review of the literature showed that a musculoskeletotrophic phenotype of metastases is rare in PC. MSM of PC are rapidly increasing soft tissue masses causing pain and loss of anatomical function. RT as a treatment option for musculoskeletal metastasis is described in the current literature in only 2 cases. Radiotherapy aims to achieve local control, pain relief, and to maintain anatomical function.

Conclusion

Radiotherapy is an effective and well-tolerated approach for multiple musculoskeletal metastases of PC.

     

The incidence of radioepidermitis and the dose-response relationship in parotid gland cancer patients treated with 125I seed brachytherapy

Background

We studied the incidence and dose–response relationship of radioepidermitis in parotid gland carcinoma patients treated with [¹²⁵I] seed brachytherapy in the hopes of designing an optimized pre-implant treatment plan that would reduce the incidence and severity of radioepidermitis in patients receiving this therapy.

Patients and methods

Between January 2007 and May 2010, 100 parotid gland cancer patients were treated postoperatively with [¹²⁵I] seed brachytherapy. The matched peripheral dose (MPD) was 80–140 Gy, and [¹²⁵I] seed activity was 0.7–0.8 mCi. The mean dose delivered to the skin was calculated in the post-implant CT on day 0 following implantation. Grades of acute and late dermatitis were evaluated at 2, 6, 12, and 18 months post-implantation.

Results

Most patients experienced grade 0–2 acute and late skin side effects (86 and 97?%, respectively), though a small subset developed severe complications. Most grade 1–3 effects resolved within 6 months of implantation, though some grade 1–3 effects and all grade 4 effects remained unchanged throughout the 18-month follow-up period. Grade 3 and 4 effects were most prominent (75 and 25?%, respectively) with doses of 110–140 Gy; doses higher than 140 Gy produced only grade 4 effects.

Conclusion

[¹²⁵I] seed brachytherapy produced acceptable levels of acute and late radioepidermitis with a good clinical outcome. A mean dose under 100 Gy delivered to the skin was safe, though doses of 110–140 Gy should be given with caution and extra monitoring; doses greater than 140 Gy are dangerous and likely to produce grade 4–5 effects.