The Size of Endotracheal Tube and Sore Throat after Surgery: A Systematic Review and Meta-Analysis

 Blogger's Note: for those who have had the 'pleasure' (ahem) of having an NG tube (eg. bowel obstruction) size does matter not only for comfort but having an impact on the ability to complete the procedure; if patients have had difficulties with the ng tube ask about size; seems rather odd that we would have to ask but it's a 'been there, done that....nurses are you paying attention?

Open access

Background

Recent studies showed that sore throat following endotracheal intubation was a common problem following surgery. The objective of this systematic review and meta-analysis of published randomized controlled trials (RCTs) or cohort studies was to estimate whether the size of endotracheal tube (ETT) affects the incidence of postoperative sore throat (POST) after general anesthesia.

Methods

The following databases were searched electronically: PubMed (updated to Dec 2012), EMBASE (updated to 15 Dec 2012), Google scholar, World Health Organization International Clinical Trials Registry Platform (Jul 2011), Chinese BioMedical Literature Database (1978 to Jul 2011), and China National Knowledge Infrastructure (1994 to Jul 2011). Studies comparing the size of endotracheal tube for elective surgery were included.

Results

Three trials with a total of 509 female patients were included in the current analysis. The size of ETT used were 6.0 mm and 7.0 mm. Pooled studies from these trials showed that the smaller size of ETT (6.0 mm) significantly decreased the incidence of POST in post-anesthesia care unit (PACU) (RR = 0.56, 95% CI 0.42–0.75, P<0.01) and at 24 h after surgery (RR = 0.69, 95% CI 0.48–0.99, P<0.05). A smaller size of ETT (6.0 mm) was associated with a lower incidence of PH in PACU (RR = 0.69, 95% CI 0.55–0.87, P<0.01), but did not affect the incidence of PH at 24 h after surgery (RR = 0.73, 95% CI 0.46–1.15, P>0.05).

Conclusion

Our meta-analysis suggests that patients under general anesthesia with a smaller size of ETT (6.0 mm) were associated with a lower incidence of POST in female patients. More studies with adequate numbers of patients were warranted to evaluate other size of ETT on the incidence of PH and POST after general surgery among different populations.


 

Interventions for promoting habitual exercise in people living with and beyond cancer | Cochrane Summaries

Cochrane - plain language summary plus abstract

Authors' conclusions: 

Interventions to promote exercise in cancer survivors who report better levels of adherence share some common behaviour change techniques. These involve setting programme goals, prompting practise and self-monitoring and encouraging participants to attempt to generalise behaviours learned in supervised exercise environments to other, non-supervised contexts. However, expecting most sedentary survivors to achieve current guideline recommendations of at least 150 minutes per week of aerobic exercise is likely to be unrealistic. As with all well-designed exercise programmes in any context, prescriptions should be designed around individual capabilities, and frequency, duration and intensity or sets, repetitions, intensity or resistance training should be generated on this basis.

- See more at: http://summaries.cochrane.org/CD010192/title-interventions-for-promoting-habitual-exercise-in-people-living-with-and-beyond-cancer#sthash.VIxGmevz.dpuf

ideline recommendations of at least 150 minutes per week of aerobic exercise is likely to be unrealistic. As with all well-designed exercise programmes in any context, prescriptions should be designed around individual capabilities, and frequency, duration and intensity or sets, repetitions, intensity or resistance training should be genera - See more at: http://summaries.cochrane.org/CD010192/title-interventions-for-promoting-habitual-exercise-in-people-living-with-and-beyond-cancer#sthash.VIxGmevz.dpuf

Title: Interventions for promoting habitual exercise in people living with and beyond cancer New

Bourke L, Homer KE, Thaha MA, Steed L, Rosario DJ, Robb KA, Saxton JM, Taylor SJC

Published Online: 

September 24, 2013

Question: What are the most effective ways to improve and sustain exercise behaviour in cancer survivors, that is, people living with and beyond cancer?
Background: Being regularly active for people living with and beyond cancer can have a wide range of beneficial effects. These range from improving quality of life to improving physical function. It might also reduce the risk of cancer recurrence and of dying from cancer. We know that most people living with and beyond cancer are not regularly physically active. So, we need to understand how to get those individuals who are not currently exercising to begin to be active and how to help them maintain this change in behaviour.
Study characteristics: We included only studies that compared an exercise intervention with a usual care comparison. Only studies including sedentary people over the age of 18 with the same cancer diagnosis were eligible. Participants must have been put in a group at random. We searched for evidence from research databases up to August 2012.
Key results: This review included 14 trials involving 648 participants. Evidence suggests that we have a poor understanding of how to encourage people living with and beyond cancer to meet current exercise recommendations. Furthermore, how trial investigators report what their exercise programme involved and how much of it the participants actually did is not good. However, we did find some evidence that setting exercise goals, prompting people to exercise, getting people to monitor their own behaviour and getting people to think about how to do exercise outside of a supervised environment could be helpful. In addition, we found some evidence suggesting that study participants are better able to tolerate the exertion of undertaking exercise for up to six months.
Quality of the evidence: The main problems that we found regarding the quality of studies in this review included not knowing how study investigators conducted randomisation for the trials, and whether investigators who were doing trial assessments knew to which group the person they were assessing had been randomly assigned.

- See more at: http://summaries.cochrane.org/CD010192/title-interventions-for-promoting-habitual-exercise-in-people-living-with-and-beyond-cancer#sthash.VIxGmevz.dpuf

Title: Interventions for promoting habitual exercise in people living with and beyond cancer New

Bourke L, Homer KE, Thaha MA, Steed L, Rosario DJ, Robb KA, Saxton JM, Taylor SJC

Published Online: 

September 24, 2013

Question: What are the most effective ways to improve and sustain exercise behaviour in cancer survivors, that is, people living with and beyond cancer?
Background: Being regularly active for people living with and beyond cancer can have a wide range of beneficial effects. These range from improving quality of life to improving physical function. It might also reduce the risk of cancer recurrence and of dying from cancer. We know that most people living with and beyond cancer are not regularly physically active. So, we need to understand how to get those individuals who are not currently exercising to begin to be active and how to help them maintain this change in behaviour.
Study characteristics: We included only studies that compared an exercise intervention with a usual care comparison. Only studies including sedentary people over the age of 18 with the same cancer diagnosis were eligible. Participants must have been put in a group at random. We searched for evidence from research databases up to August 2012.
Key results: This review included 14 trials involving 648 participants. Evidence suggests that we have a poor understanding of how to encourage people living with and beyond cancer to meet current exercise recommendations. Furthermore, how trial investigators report what their exercise programme involved and how much of it the participants actually did is not good. However, we did find some evidence that setting exercise goals, prompting people to exercise, getting people to monitor their own behaviour and getting people to think about how to do exercise outside of a supervised environment could be helpful. In addition, we found some evidence suggesting that study participants are better able to tolerate the exertion of undertaking exercise for up to six months.
Quality of the evidence: The main problems that we found regarding the quality of studies in this review included not knowing how study investigators conducted randomisation for the trials, and whether investigators who were doing trial assessments knew to which group the person they were assessing had been randomly assigned.

- See more at: http://summaries.cochrane.org/CD010192/title-interventions-for-promoting-habitual-exercise-in-people-living-with-and-beyond-cancer#sthash.VIxGmevz.dpuf

The Cancer Genome Atlas Changes the Oncology Landscape _ commentaries

medscape

"The first analysis of the TGCA data was conducted by Giovanni Ciriello, PhD, and colleagues from the Memorial Sloan-Kettering Cancer Center in New York City. That team used genomic and epigenomic features to stratify 3299 tumors from 12 cancer types: bladder urothelial carcinoma, breast invasive carcinoma, colon and rectum adenocarcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, kidney renal clear-cell carcinoma, acute myeloid leukemia, lung adenocarcinoma, lung squamous cell carcinoma, ovarian serous cystadenocarcinoma, and uterine corpus endometrioid carcinoma.....

"The second analysis from the TGCA dataset was led by Rameen Beroukhim, MD, PhD, from Harvard Medical School, the Broad Institute of MIT, and the Dana-Farber Cancer Institute in Boston. That team characterized somatic copy-number alterations, such as deletions or amplifications (SCNAs), in 4934 cancers and genomic epigenetic features in 3299 tumors. They found whole-genome doubling in 37% of cancers, which was associated with higher rates of all other types of SCNAs......


 

Can Anonymous Posters on Medical Forums be Reidentified? Journal of Medical Internet Research

abstract

Background:  
Participants in medical forums often reveal personal health information about themselves in their online postings. To feel comfortable revealing sensitive personal health information, some participants may hide their identity by posting anonymously. They can do this by using fake identities, nicknames, or pseudonyms that cannot readily be traced back to them. However, individual writing styles have unique features and it may be possible to determine the true identity of an anonymous user through author attribution analysis. Although there has been previous work on the authorship attribution problem, there has been a dearth of research on automated authorship attribution on medical forums. The focus of the paper is to demonstrate that character-based author attribution works better than word-based methods in medical forums.

Objective: The goal was to build a system that accurately attributes authorship of messages posted on medical forums. The Authorship Attributor system uses text analysis techniques to crawl medical forums and automatically correlate messages written by the same authors. Authorship Attributor processes unstructured texts regardless of the document type, context, and content.

Methods: The messages were labeled by nicknames of the forum participants. We evaluated the system’s performance through its accuracy on 6000 messages gathered from 2 medical forums on an in vitro fertilization (IVF) support website.

Results: Given 2 lists of candidate authors (30 and 50 candidates, respectively), we obtained an F score accuracy in detecting authors of 75% to 80% on messages containing 100 to 150 words on average, and 97.9% on longer messages containing at least 300 words.

Conclusions: Authorship can be successfully detected in short free-form messages posted on medical forums. This raises a concern about the meaningfulness of anonymous posting on such medical forums. Authorship attribution tools can be used to warn consumers wishing to post anonymously about the likelihood of their identity being determined.

(J Med Internet Res 2013;15(10):e215)
doi:10.2196/jmir.2514

 

Journal of Clinical Epidemiology - Index (systematic reviews/commentaries)

index of articles (not open access)

see section " Considering Complexity in Systematic Reviews of Intervention" Commentaries
 

Complex interventions–how should systematic reviews of their impact differ from reviews of simple or complicated interventions?

open access

Hospitals should not make patients the hand-washing police

Blogger's Note/Opinion: one of the WHO Patient Safety mandates is the issue of handwashing which was adopted by many countries/institutions (patient safety campaigns); in efforts to include the patients' voices (and focus of efforts) there have been many errors albeit with good intentions; another example would be the act of 'apology' which has taken on a 'life' of its own outside of healthcare

media

Outcomes in Ovarian Cancer among Hispanic Women Living in the United States: A Population-Based Analysis

Open access

".....Despite these limitations, the current study provides the most extensive comparison of ovarian cancer patterns between Hispanic and non-Hispanic women in the United States. The observation that Hispanic women are diagnosed with ovarian cancer at an earlier age than non-Hispanic groups underscores the need for additional studies to explore this trend......." 

The population impact of familial cancer, a major cause of cancer

abstract

The population attributable fraction (PAF) defines the proportion of a disease that would be prevented if the exposure to a particular risk factor was avoided. Familial risk is a known risk factor for many cancers, but an unbiased estimation of the PAF for familial risk requires a large study population to include rare cancers.

PAFs and their corresponding standardized incidence ratios (SIRs) were calculated for familial relative risk among first-degree relatives (FDRs) and second-degree relatives (SDRs) diagnosed with the same (concordant) invasive or in situ cancers. Calculations were based on the Swedish Family-Cancer Database considering 8 148 737 individuals. To assess environmental effects, PAFs were also calculated for concordant cancers among spouses.

Almost all cancers showed a significant familial risk. The highest PAFs were found for the common cancers of the prostate (13.94%), breast (7.46%) and colorectum (6.78%) among the FDRs. In the FDRs, the overall PAF for any concordant cancer was 4.20%, but in the SDRs, it was only 0.34%. The overall PAFs for in situ cancers were 0.86% and 0.56% for the FDRs and SDRs, respectively. The overall independent familial PAF was 5.96% for the invasive and in situ cancers in the FDRs and SDRs. The cancers between spouses yielded an overall PAF of 0.14%. For esophageal cancer, the risk among spouses was higher than the familial risk.

Our study shows that the overall familial PAF of 5.96%, although underestimated for sex-specific cancers, ranks as the third most common population burden after tobacco smoking and unhealthy diet.

 

The Evidence for Pharmacologic Treatment of Neuropathic Cancer Pain: Beneficial and Adverse Effects

abstract

Review Article

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Context

The prevalence of neuropathic pain in patients with cancer pain has been estimated to be around 40%. Neuropathic pain may be caused by tumor invasion and is considered as mixed nociceptive-neuropathic pain, or caused by an anticancer treatment and considered as purely neuropathic pain. The use of adjuvant analgesics in patients with cancer is usually extrapolated from their efficacy in nononcological neuropathic pain syndromes. (eg. diabetic neuropathy)

Objectives

In this systematic review, we sought to evaluate the evidence for the beneficial and adverse effects of pharmacologic treatment of neuropathic cancer pain.

Methods

A systematic review of the literature in PubMed and Embase was performed. Primary outcome measures were absolute risk benefit (ARB), defined as the number of patients with a defined degree of pain relief divided by the total number of patients in the treatment group, and absolute risk harm (ARH), defined as the fraction of patients who dropped out as a result of adverse effects.

Results

We identified 30 articles that fulfilled our inclusion criteria. Overall, ARB of antidepressants, anticonvulsants, other adjuvant analgesics, or opioids greatly outweighed ARH. There were no significant differences in ARB or ARH between the four groups of medication or between patients with mixed vs. purely neuropathic pain. Because of the low methodological quality of the studies, we could not draw conclusions about the true treatment effect size of the four groups of medications.

Conclusion

Once a diagnosis of neuropathic pain has been established in patients with cancer, antidepressants, anticonvulsants, or other adjuvant analgesics should be considered in addition to or instead of opioids.

 

Efficacy of Rapid-Onset Oral Fentanyl Formulations vs. Oral Morphine for Cancer-Related Breakthrough Pain: A Meta-Analysis of Comparative Trials

abstract

Context

Breakthrough cancer pain (BTcP) is widely recognized as a clinically significant complication of chronic cancer pain. With most BTcP episodes peaking in intensity within a few minutes and lasting for approximately 30 minutes, speed of onset is crucial for effective pain management. Although the last decade has seen the development of a number of rapid-onset fentanyl preparations, BTcP is still typically managed by supplemental or rescue doses of the patient's around-the-clock medication, such as oral morphine. Importantly, although the fentanyl preparations, such as fentanyl buccal tablet (FBT), sublingual fentanyl citrate orally disintegrating tablet (ODT), and oral transmucosal fentanyl citrate lozenge (OTFC), have all been proven to be efficacious in clinical studies, oral morphine has never been specifically tested in BTcP, other than as a comparator in studies of OTFC and fentanyl pectin nasal spray.

Objectives

To determine the relative contributions to pain relief from oral morphine and the fentanyl preparations using placebo as a common comparator.

Methods

Relevant studies were identified by review of the literature and used in a mixed-treatment meta-analysis to indirectly compare fentanyl preparations, morphine, and placebo for the treatment of BTcP.

Results

Analysis incorporating the five relevant studies identified revealed that although the fentanyl preparations provide superior pain relief vs. placebo in the first 30 minutes after dosing (FBT provided an 83% probability of superior pain relief, ODT 66%, and OTFC 73% vs. placebo), oral morphine performed little better than placebo (56% probability).

Conclusion

This mixed-treatment analysis suggests that FBT, ODT, and OTFC might provide more efficacious treatment options than oral morphine for BTcP.

 

Functional Impairments as Symptoms in the Symptom Cluster Analysis of Patients Newly Diagnosed With Advanced Cancer

abstract

Purchase $35.95

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Context

Symptoms and subsequent functional impairment have been associated with the biological processes of disease, including the interaction between disease and treatment in a measurement model of symptoms. However, hitherto cluster analysis has primarily focused on symptoms.

Objectives

This study among patients within 100 days of diagnosis with advanced cancer explored whether self-reported physical symptoms and functional impairments formed clusters at the time of diagnosis.

Methods

We applied cluster analysis to self-reported symptoms and activities of daily living of 111 patients newly diagnosed with advanced gastrointestinal (GI), gynecological, head and neck, and lung cancers. Based on content expert evaluations, the best techniques and variables were identified, yielding the best solution.

Results

The best cluster solution used a K-means algorithm and cosine similarity and yielded five clusters of physical as well as emotional symptoms and functional impairments. Cancer site formed the predominant organizing principle of composition for each cluster. The top five symptoms and functional impairments in each cluster were Cluster 1 (GI): outlook, insomnia, appearance, concentration, and eating/feeding; Cluster 2 (GI): appetite, bowel, insomnia, eating/feeding, and appearance; Cluster 3 (gynecological): nausea, insomnia, eating/feeding, concentration, and pain; Cluster 4 (head and neck): dressing, eating/feeding, bathing, toileting, and walking; and Cluster 5 (lung): cough, walking, eating/feeding, breathing, and insomnia.

Conclusion

Functional impairments in patients newly diagnosed with late-stage cancers behave as symptoms during the diagnostic phase. Health care providers need to expand their assessments to include both symptoms and functional impairments. Early recognition of functional changes may accelerate diagnosis at an earlier cancer stage.

 

Transdermal fentanyl for cancer pain - Cochrane Collaboration Summaries

Cochrane Summaries

Authors' conclusions: 

The randomised trial literature for effectiveness of transdermal fentanyl is limited, but it is an important medicine. Most studies recruited fewer than 100 participants and did not provide data appropriate for meta-analysis. Only a few reported how many patients had good pain relief but, where data were reported, a majority had no worse than mild pain within a reasonably short time period. The evidence pointed to a useful and significant reduction in complaints about constipation for transdermal fentanyl compared with oral morphine.

- See more at: http://summaries.cochrane.org/CD010270/transdermal-fentanyl-for-cancer-pain#sthash.17t1ozfL.dpuf

 

Non-cancer life stressors contribute to impaired quality of life in ovarian cancer patients

abstract

Purchase $39.95

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Highlights

•

Number and severity of life stressors were unrelated to participants' QOL before surgery.

•

Greater number of life stressors at one-year post surgery was related to poorer concurrent quality of life.

•

Greater number of life stressors prior to surgery predicted poorer overall QOL at one year.

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Objectives

Diagnosis and treatment for a life threatening illness such as cancer are known to be psychologically impactful. However, little is known about the influence that non-cancer life stressors have on the quality of life (QOL) of ovarian cancer patients. The goal of the present study was to examine associations between non-cancer life stressors and QOL in 123 women with invasive epithelial ovarian cancer who were followed prospectively and longitudinally for one year.

Methods

Mixed models for repeated measures were used to examine the relationship between life stressors and QOL pre-surgery and one year later, while adjusting for age, cancer stage, depressive symptoms, anxiety, and chemotherapy status (at one year). Prospective associations between QOL pre-surgery and one-year QOL were also examined.

Results

Number and severity of life stressors were unrelated to QOL of participants before surgery. At one year, however, participants experiencing a greater number of life stressors reported poorer concurrent physical well-being (PWB) (p = 0.015), functional well-being (FWB) (p < 0.0001), social well-being (SWB) (p = 0.0003), and total QOL (p < 0.0001). Similar effects were found for life event severity. Finally, experiencing a greater number of life stressors pre-surgery predicted poorer overall QOL one year post-diagnosis (p < 0.0001).

Conclusions

Non-cancer life stressors can substantially impact long-term QOL of ovarian cancer patients, adjusting for medical variables such as chemotherapy and cancer stage, thus highlighting the importance of evaluating the stress burden of patients in ongoing cancer care.

 

Clinical Risk Factors of PEGylated Liposomal Doxorubicin Induced Palmar Plantar Erythrodysesthesia in Recurrent Ovarian Cancer Patients

Blogger's Note: there is no indication in this abstract if underweight/low BMI was assess/to be assessed; it would 'seem' that the focus is normal+ body weight; given the issue of malnutrition in cancer patients it is an important concern

abstract

Purchase $39.95

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Highlights

•

Nearly 25% of recurrent ovarian cancer patients treated with PEGylated liposomal doxorubicin developed palmar plantar erythrodysesthesia (PPE).

•

Body mass index may be associated with PPE.

•

PPE occurred early in treatment and was not associated with time to progression.

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Introduction

Studies have shown that body composition, age, gender, changes in monocyte count and repeated dosing alter pharmacokinetic properties of PEGylated liposomal doxorubicin (PLD). However, limited information exists regarding the clinical risk factors of ovarian cancer patients who develop palmar plantar erythrodysesthesia (PPE) while receiving PLD for cancer recurrence.

Methods

We conducted a retrospective cohort analysis of consecutive patients with recurrent ovarian and primary peritoneal cancer who were treated with PLD from 2005–2009. Clinical and pathologic data were abstracted from electronic medical records. Statistical analyses were performed using univariate and bivariate analyses, logistic regression, and log rank-tests.

Results

Twenty-three percent (31/133) of patients developed PPE. Age, body mass index (BMI), race, stage, and histology did not significantly differ between PPE and non-PPE patients. There was a possible trend for decreasing PPE with increasing body mass index (BMI) (24.5% of normal weight, 27.5% of overweight; 23.8% of obese class I; 13.3% of obese class II; and 0% of obese class III), though not statistically significant. The number of chemotherapy regimens prior to PLD, and the mean cycles of PLD received did not differ between patients with and without PPE. 77.4% of PPE cases occurred within the first 3 infusion cycles. PPE was not associated with time to progression.

Conclusion

Nearly one-quarter of ovarian cancer patients receiving PLD will develop PPE. Further investigation of factors such as BMI associated with PPE may aid in patient selection for PLD, and future development of other nanoparticle and liposomal agents.

 

Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients

abstract

BACKGROUND:

Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well as large genomic rearrangements. However, a large number of mutations, including missense, silent, and intronic variants, are classified as variants of unknown clinical significance.

METHODS:

Intronic MLH1, MSH2, or MSH6 variants were investigated using in silico prediction tools and mini-gene assay to asses the effect on splicing.

RESULTS:

We describe in silico and in vitro characterization of nine intronic MLH1, MSH2, or MSH6 mutations identified in Danish colorectal cancer patients, of which four mutations are novel. The analysis revealed aberrant splicing of five mutations (MLH1 c.588 + 5G > A, MLH1 c.677 + 3A > T, MLH1 c.1732-2A > T, MSH2 c.1276 + 1G > T, and MSH2 c.1662-2A > C), while four mutations had no effect on splicing compared to wild type (MLH1 c.117-34A > T, MLH1 c.1039-8 T > A, MSH2 c.2459-18delT, and MSH6 c.3439-16C > T).

CONCLUSIONS:

In conclusion, we classify five MLH1/MSH2 mutations as pathogenic, whereas four MLH1/MSH2/MSH6 mutations are classified as neutral. This study supports the notion that in silico prediction tools and mini-gene assays are important for the classification of intronic variants, and thereby crucial for the genetic counseling of patients and their family members.

 

Googling a Patient

 Blogger's Note: obviously there is more to this than outlined in the abstract

abstract

"The twenty-six-year-old patient requested a prophylactic bilateral mastectomy with reconstruction because of an extensive family history of cancer. She reported that she had developed melanoma at twenty-five; that her mother, sister, aunts, and a cousin all had breast cancer; that a cousin had ovarian cancer at nineteen; and that a brother was treated for esophageal cancer at fifteen. The treating team was skeptical about this history, and they could find no documentation of the patient's reported melanoma. The surgeon wrote the patient's primary care physician, explaining that he had seen the patient and planned to proceed with the bilateral mastectomy and reconstruction. The primary care physician responded that he was unable to substantiate several of the patient's claims; some of his colleagues believed the family history to be fabricated. Trying to make sense of the discrepancies, the genetic counselor called a counselor colleague who had met with this patient. The colleague suggested that the in-house genetic counselor "google" the patient. The search revealed two Facebook pages linked to the patient. In one, apparently a personal profile, the patient stated that in addition to battling stage four melanoma, she had recently been diagnosed with breast cancer. She provided a link to a site where she solicited donations to attend a summit for young cancer patients. The other Facebook page featured numerous pictures of her with a bald head, as though she has been through chemotherapy. The genetic counselor showed the Facebook pages to the surgeon, who then decided not to operate. Should health care professionals "google" their patients?"
 

Getting to Know Ovarian Cancer Ascites: Opportunities for Targeted Therapy-Based Translational Research | Frontiers in Women's Cancer

open access (technical)

"Origin of Ascites

Under normal physiological conditions, capillary membranes of the peritoneal cavity continuously produce free fluid to keep the serosal surfaces of the peritoneal lining lubricated so that there is an easy passage of solutes between the peritoneum and the adjacent organs. Two thirds of this peritoneal fluid is reabsorbed into the lymphatic channels of the diaphragm and is propelled into the right subclavian vein by the negative intrathoracic pressure (16). In cases of disseminated intra-abdominal cancer, further increased production of peritoneal fluid is induced by the tumors due to the increased leakiness of tumor microvasculature and obstruction of the lymphatic vessels (17, 18). As a result, fluid accumulation in the peritoneal cavity exceeds fluid reabsorption, resulting in the build-up of ascites. It has been suggested that the flow of ascites currents within the peritoneal cavity dictate the routes of dissemination of ovarian cancer (11, 19). The physiological factors that drive this process are gravity, diaphragmatic pressure, organ mobility, and recesses formed by key anatomical structures (20). The three most common intra-abdominal sites of ovarian cancer metastasis are the greater omentum, right subphrenic region, and pouch of Douglas, areas which have easy access to ascites (21). Detached ovarian tumor cells either singly or in the form of multicellular spheroids primarily colonize to these distant sites under the influence of ascites flow; however, little is known about the impact of ascites flow on the heterogeneity of metastatic ovarian tumors that colonize to distant sites (20)......

Conclusion

The accessibility of ascites undeniably provides a rich source of tumor samples to monitor the course of chemotherapy treatment in patients. In addition, it also provides an opportunity for the identification of prognostic and treatment-monitor markers, as well as options for molecular profiling of both the cellular and soluble components. The cellular and molecular profile of individual ascites is a subject of inter-patient variations which will differ not only with the treatment protocol but also how each patient responds to a particular therapy. Hence, to provide a molecular characterization which would fit into a defined pattern to design appropriate targeted therapies would be challenging. Hence, long-term, longitudinal studies within the same patient cohorts, starting with chemonaive status and periodic evaluations of molecular and cellular characterization of the ascites components as the disease progresses would be useful to develop an individualized predictive profile which will be crucial for designing targeted therapies. The interrogation of soluble and cellular variations in ascites during the treatment regimen in patients may guide clinical decision making for patient management (134). This may form a basis for informed and effective personalized treatment approaches. Hence, with the advances in our understanding of the pathophysiology of ascites and the development of new methods which can delineate the cross talk between the different cellular components it is anticipated that more effective and targeted strategies for the management of ascites and ovarian cancer patients will be available in near future.

 

| Listening in on difficult conversations: an observational, multi-center investigation of real-time conversations in medical oncology

open access

Background

The quality of communication in medical care has been shown to influence health outcomes. Cancer patients, a highly diverse population, communicate with their clinical care team in diverse ways over the course of their care trajectory. Whether that communication happens and how effective it is may relate to a variety of factors including the type of cancer and the patient's position on the cancer care continuum. Yet, many of the routine needs of cancer patients after initial cancer treatment are often not addressed adequately. Our goal is to identify areas of strength and areas for improvement in cancer communication by investigating real-time cancer consultations in a cross section of patient-clinician interactions at diverse study sites.

Methods

In this paper we describe the rationale and approach for an ongoing observational study involving three institutions that will utilize quantitative and qualitative methods and employ a short-term longitudinal, prospective follow-up component to investigate decision-making, key topics, and clinician-patient-companion communication dynamics in clinical oncology.

Discussion

Through a comprehensive, real-time approach, we hope to provide the fundamental groundwork from which to promote improved patient-centered communication in cancer care. 

Background
“You have cancer.” Approximately 1.6 million people in the United States heard these
frightening words in 2012 in the context of a new cancer diagnosis [1]. In delivering a
diagnosis, making decisions about life-altering treatment, and ultimately helping patients
navigate through diagnosis, treatment, survivorship, and/or end-of-life care, oncology
clinicians carry a deep responsibility to offer information and support in a manner that will be
most helpful to their patients – a task which must be individualized for each interaction.
Clinicians serve as technical experts, while patients hold expert knowledge about their own
feelings, life circumstances and preferences; both play a crucial role informing in treatment
decisions. Family and friends can also play an important contributing role in the process of
diagnostic and treatment decision-making and in offering support in the midst of and after
treatment. Clinicians can help facilitate this multi-faceted conversation through patientcentered,
empathic interactions – arguably in a manner consistent with a shared-decision
making model [2]..........

Table 1 Study aims
Aim 1. To richly characterize the dynamics and quality of patient-clinician-companion interactions in
routine cancer care consultations by documenting the frequency, duration, and content of
conversations about key issues that are important to patients in their care.
1a. To describe the frequency, duration and content of routine cancer consultations surrounding key
challenging topics in the clinical dialogue.
1b. To examine in-depth the fundamental psycho-social dynamics of deliberations that occur between patients and clinicians during routine cancer care consultations.
1c. To assess the comprehensiveness of these discussions pertaining to key elements of informed decisionmaking.
1d. To assess the degree of content concordance between topics raised in the recorded conversations and what is documented in the medical record for each of the key topics.

Aim 2. To identify key characteristics of cancer consultation participants and dialogue that influence
subsequent clinical actions and short term outcomes.......

 

The dilemma of post-ureteroscopy stenting

abstract

Do we actually need to place a ureteral stent after ureteroscopy (URS)? Despite strong evidence that they may be unnecessary, the placement of stents still seems to be a common occurrence with no consensus on the optimum indwell time or the method used for stent removal.

Proponents of post-URS stenting often quote the anecdote of the memorable patient who, having not been stented, developed pain and/or sepsis requiring an emergency return to theatre for stenting. Others suggest that a stent is akin to a comfort blanket allowing them, if not the patient, to sleep easier after the procedure. European Association of Urology (EAU) Guidelines¹ recommend that “stents be inserted in patients who are at increased risk of complications (e.g. residual fragments, bleeding, perforation, urinary tract infections or pregnancy) and in all doubtful cases, to avoid stressful emergencies.” Furthermore, most urologists would be inclined to place a stent after URS in a solitary kidney, in patients with renal impairment and to facilitate future access.

 

ICON6 ovarian cancer results may resurrect cediranib

 IMNG Oncology Report

Metastatic progression of breast cancer: insights from 50 years of autopsies The Journal of Pathology

abstract

There remain no clear guidelines for the optimal management of patients with metastatic breast cancer. To better understand its natural history, we undertook a detailed examination of 197 autopsies performed on women who died of breast cancer. We reviewed clinical, treatment, and pathology aspects of all cases and additionally, pathology features and biomarker expression (ER, PgR, HER2, EGFR, p53, Ki67, c-Kit, CK AE1/AE3) were assessed in detail for the primary tumour and matched metastases for 55 of the cases. Genomes of the primary tumour and multiple metastases were analyzed by array-based comparative genomic hybridization for six cases. 945 metastatic deposits were identified with a median of four per patient. The most common organs involved were lung/pleura (80%), bone (74%), liver (71%), and non-axillary lymph nodes (55%). Major findings included: i) patients with CNS metastases were more likely to have bone metastases (p<0·013); ii) younger age was associated with metastasis to the liver (≤49 years; p<0·001) and to gynaecological organs (≤49 years; p=0·001); iii) surgical excision of the primary tumour was associated with metastasis to the liver (p=0·002) and iv) ER and PgR showed down-regulation during progression in a non-random manner, particularly in lung/pleura (ER: p<0·001), liver, and bone metastases. Genomic analysis revealed DNA copy number variation between the primary tumour and metastases (e.g. amplification of 2q11.2–q12.1 and 10q22.2–q22.3) but little variation between metastases from the same patient.

In summary, the association of CNS and bone metastases, liver and gynaecological metastases in young women and the risk of liver metastases following surgery have important implications for management of patients with breast cancer. Clonal heterogeneity of the primary tumour is important in developing metastatic propensity and the change in tumour phenotype during progression/colonization highlights the importance of sampling metastatic disease for optimal treatment strategies.

 

Distinct molecular profiles in Lynch syndrome-associated and sporadic ovarian carcinomas

abstract

Ovarian carcinoma in Lynch syndrome (LS) is associated with unexpectedly high survival; yet, beyond DNA mismatch repair (MMR) defects, the developmental mechanisms are unknown. We used established (genetic) and new (epigenetic) classifiers of ovarian cancer to explore similarities and differences between LS-associated and sporadic diseases. To this end, all available ovarian carcinomas (n = 20) from MMR gene mutation carriers ascertained through a nation-wide registry and 87 sporadic ovarian carcinomas of the main histological types were molecularly profiled. LS-ovarian carcinomas were mostly of nonserous histology (12 endometrioid, seven clear cell and one serous), diagnosed at a mean age of 45.7 years, and associated with a 10-year survival of 87%. Among LS-ovarian carcinomas, 19/20 (95%) were MMR-deficient vs. 11/87 (13%) among sporadic cases (p < 0.0001). In a striking contrast to the sporadic cases, the expression of p53 was normal and KRAS/BRAF mutations absent in all LS-ovarian carcinomas. PIK3CA mutations, suggested to be a favorable prognostic factor, occurred with a frequency of 6/20 (30%), which was comparable to sporadic tumors of endometrioid or clear cell type. Tumor suppressor genes were more frequently methylated and LINE-1 hypomethylation less common in LS-ovarian carcinomas compared to their sporadic counterparts. The patterns of genetic and epigenetic alterations reflected the origin as LS vs. sporadic cases on one hand and the histological type on the other hand.

In conclusion, the significant molecular differences observed between LS-associated and sporadic ovarian carcinomas help explain the different behavior of these tumors and emphasize the need for tailored clinical management. 

Anti-PARP Study Called 'Flat-Out Successful'

medpage

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Note that this phase I study of the PARP-inhibitor BMN 673 demonstrated an acceptable safety profile and promising efficacy results among women with BRCA-associated breast and ovarian cancer.
• Be aware that a phase III, randomized trial of the agent is currently underway and will provide more definitive evidence as to the drugs benefit.

 

New insights into public perceptions of cancer

open access

"Survey participants were from six countries: the United States, France, Germany, Italy, Japan, and the United Kingdom. These countries were selected for their significant influence in shaping broader policy models in cancer care. The survey was carried out by GfK, one of the leading research companies with extensive experience of research of this nature." 

Editorial: Robotic surgery in oncology

open access

 

How do researchers conceive of spousal grief after cancer? A systematic review of models used by researchers to study spousal grief in the cancer context - Fasse - 2013 - Psycho-Oncology - Wiley Online Library

abstract

Background

Although spouses bereaved after cancer are considered vulnerable people, there have been few empirical studies to explore grief specifically in this context.

Methods

Using PsycINFO, Medline, and the PRISMA statement, we systematically searched the literature by intersecting ‘cancer’ and ‘grie*’, ‘cancer’ and ‘bereave*’, and ‘cancer’ and ‘mourn*’.

Results

Gathering 76 studies (2000–2013) that met the inclusion criteria for bereavement in adulthood, bereavement of an adult loved one and evidence-based research, we found the following:

1. Spousal relationships are not systematically examined in the current dominant models of grief.
2. Theoretically derived determinants of spousal grief after cancer and empirically derived ones converge toward the necessity to include the caregiving experience as determining grief reactions.
3. A growing body of literature concerning prolonged grief disorders now provides integrative reflections regarding the characteristics of spousal loss, predictors, and associated therapeutic interventions in the cancer context.

Conclusions

Few empirical studies (20 of 76) target spousal bereavement specifically after cancer. The process of adaptation to loss is usually decontextualized, removing any consideration of the relationship to the deceased or the experience of caregiving and dying. Our findings suggest that this topic warrants more studies that use both prospective and mixed methodologies, as well as explore typical grief needs and experiences of bereaved spouses

 

Clinical features and outcomes of neck lymphatic metastasis in ovarian epithelial carcinoma

open access




Conclusions
A subgroup of EOC patients with NLNM (Neck lymph node metastasis) who presented limited pelvic cancer had much better overall survival than patients who had cancer spreading beyond the pelvic cavity or were diagnosed with NLNM at cancer recurrence.

Consent
This study was conducted with approval from the institutional review board from the
National Taiwan University College of Medicine (201101054RC). Written informed consent
was obtained from the patient for the publication of this report and any accompanying
images.

Comparison of serious adverse reactions between thalidomide and lenalidomide: analysis in the French Pharmacovigilance database

thalidomide and lenalidomide

$39.95 / €34.95 / £29.95 *

Thalidomide and lenalidomide are structural analogs and immunomodulatory drugs. Lenalidomide appears to have a different safety profile than thalidomide and could be less toxic, and as far as we know, we did not found any study comparing their safety profile. The objective of our study was to review and compare serious adverse drug reactions (SADRs) of thalidomide and lenalidomide spontaneously reported to the French Pharmacovigilance database. We extracted all medically confirmed spontaneous reports of SADR for lenalidomide-based regimens and thalidomide-based regimens from the French Pharmacovigilance database. A “serious” adverse drug reaction (ADR) was defined as an ADR that is fatal or life threatening, which causes hospitalization or prolongation of hospitalization, or permanent or significant disability. The study period was between marketing of 2 drugs and January 15, 2012. A total of 392 SADRs related to thalidomide-based regimens were identified in 244 patients and 377 SADRs related to lenalidomide-based regimens in 220 patients. In spite of their structural analogy, this study highlights interesting differences between lenalidomide and thalidomide’s safety profile: nervous system and vascular disorders are more frequent with thalidomide-based regimens while hematologic, skin, infectious disorders and secondary primary cancers are more frequent with lenalidomide-based regimens.

 

Central European BRCA2 mutation carriers: birth cohort status correlates with onset of breast cancer (+ ovarian cancer reference)

abstract

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Background

Mutations in brca1 and 2 genes lead to a significant increase in the lifetime risk of developing breast (BC) and ovarian cancer (OC).There are indications that birth cohort can influence the cancer risk in brca1 mutation carriers. Therefore, we investigated the risks for BC and OC associated with brca2 mutations in a cohort of female mutation carriers of a genetically heterogeneous Central European population.

Patients and Methods

This study included 246 women in whom a functional mutation in the brca2 gene had been identified at our institution. At the time of analysis, 153 women had developed cancer (142 BC, 9 OC, 2 BC and OC). Risks were estimated using the product limit method. The log rank test was used to compare different strata.

Results

After correction for risk-reducing surgeries, the cumulative risk of developing cancer to age 70 was found to be 88% for BC (95% CI 81–95%) and 31% for OC (95% CI 17–45%). Female brca2 mutation carriers born in 1958 or later were at a significantly higher risk of developing BC at a younger age (p < 0.001), while no such age cohort-dependent correlation was found for OC.

Conclusion

The age cohort-dependent early onset in BC in women born after 1958 strongly suggests the importance of exogenous factors such as lifestyle modification while this does not seem to be the case for OC. Female brca2 mutation carriers should be counseled about their age cohort-dependent breast cancer risk.

 

FDA Alert: Metoclopramide Injection And Ondansetron Injection by Hospira: Recall - Glass Strand Particulates Caused By Glass Supplier

FDA Alert

Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel (in mice)

open access

Palliative and hospice care in gynecologic cancer: A review

abstract

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Highlights

•

Palliative care incorporates symptom management and end of life care.

•

Palliative care is markedly underutilized in gynecologic cancer.

•

Early palliative care referral favorably impacts quality of life and cost of care.

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Despite the increasing availability of palliative care, oncology providers often misunderstand and underutilize these resources. The goals of palliative care are relief of suffering and provision of the best possible quality of life for both the patient and her family, regardless of where she is in the natural history of her disease. Lack of understanding and awareness of the services provided by palliative care physicians underlie barriers to referral. Oncologic providers spend a significant amount of time palliating the symptoms of cancer and its treatment; involvement of specialty palliative care providers can assist in managing the complex patient. Patients with gynecologic malignancies remain an ideal population for palliative care intervention. This review of the literature explores the current state of palliative care in the treatment of gynecologic cancers and its implications for the quality and cost of this treatment.

 

Pre-operative imaging with CA125 is a poor predictor for granulosa cell tumors

abstract

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Highlights

•

Granulosa cell tumors are almost exclusively complex and are most frequently greater than 10 cm.

•

There was a near equal distribution of granulosa cell tumors with a CA125 greater than or less than 35.

•

If complexity and a CA125 level > 35 are used to predict GCTs, we will frequently fail to predict them.

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Objective

To determine the radiographic characteristics of ovarian granulosa cell tumors (GCTs) and to evaluate the use of CA125 levels > 35 in combination with imaging as an algorithm for preoperative diagnosis.

Methods

A retrospective analysis of women from two academic medical centers who were diagnosed with ovarian GCT between January 1998 and August 2012 was conducted. Clinical data included tumor appearance on pre-operative imaging and CA125 levels. Ovarian cysts were defined as complex if imaging exhibited multicystic areas, hemorrhagic, solid, or cystic and solid components. A CA125 level > 35 was abnormal.

Results

One hundred and fifteen women were diagnosed with GCTs, of whom 63 underwent pre-operative imaging. Median age at surgery was 46 years (12–87). Forty women had preoperative ultrasounds, 43 had CT scans and 20 underwent both modalities. GCTs were almost exclusively classified as complex cysts in 62 (98%) cases. The most common morphology was solid and cystic (n = 44 (70%)). Forty-four (70%) patients had tumors > 10 cm. Forty-two patients had a pre-operative CA125 performed. Eighteen (43%) patients had complex masses and CA125 > 35. Twenty-three (55%) had CA125 < 35 with a complex mass, and one (2%) had a unilocular cyst with a CA125 > 35.

Conclusions

In this study, there was a near equal distribution of patients with complex masses and CA125 levels > or < 35. If established strategies to predict malignancy are applied to GCTs, we will frequently fail to make the diagnosis pre-operatively. Additional research is necessary to generate an appropriate algorithm to guide pre-operative referral to a gynecologic oncologist.

 

Ovarian cancer patients with localized relapse: Clinical outcome and prognostic factors

no abstract

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The Gynecologic Oncology Group (GOG) Report — July 2013

no abstract

 

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Epithelial cell-adhesion molecule-directed trifunctional antibody immunotherapy for symptom management of advanced ovarian cancer

 Blogger's Note: note reference: "these patients traditionally exhibit reduced intravascular volume, making diuretic use an unattractive option.13"; note also the more detailed comments regarding the EpCam gene


open access

Abstract: 

Despite advances in cytotoxic chemotherapy and surgical cytoreduction, disease recurrence continues to be a troubling problem in patients with advanced-stage epithelial ovarian cancer (EOC). Malignant ascites affects approximately 10% of patients with recurrent EOC and is associated with troublesome symptoms, including abdominal pressure, distension, dyspnea, pelvic pain, and bowel/bladder dysfunction. To date, no effective therapy has been identified for the treatment of malignant ascites in patients with recurrent, advanced-stage ovarian cancer. Recently, immune modulation has gained attention as a novel approach to anti-cancer therapy. This review explores the role of epithelial cell-adhesion molecule (EpCAM)-directed immunotherapy, with a specific focus on the mechanism of action of the trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3). In addition, clinical trials exploring the use of catumaxomab in the treatment of malignant ascites in patients with ovarian cancer are reviewed.

"....Ultimately, as with all novel therapies, symptom relief and treatment goals must be weighed against patient discomfort and adverse events. Careful patient selection, and identification of risk factors, to help reduce significant side effects associated with treatment are required."



 

Embracing change: The key to revolutionizing SGO’s future. The 2013 Society of Gynecologic Oncology Presidential Address. Sunday, March 10, 2013. By Ronald D. Alvarez, MD. 2012–2013 SGO President

no abstract

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Second Opinion: Should It Be No Opinion?

medscape

The "Physician Trustee"

The key to finding an initial exemplary specialist whose first opinion can be trusted is to have that specialist identified by another knowledgeable physician who can represent the patient's interest. Such a "physician trustee" can be a primary care physician with whom the patient has a solid relationship. Alternatively, it can be a physician who is a friend, relative, or acquaintance of the patient. In either case, the physician trustee has to take the time and make an effort to identify specialists he knows in the field in which the patient needs care. The physician trustee must then make the additional effort to identify a first-rate specialist in the field and to explore the qualities, reputation, and results of the specialist by speaking to those who have worked with him directly and know him firsthand, which is not an easy task.......
 

blog: The real scandal: science denialism at Susan G. Komen for the Cure® : The Last Word On Nothing

The Last Word On Nothing

"Is breast cancer threatening your life? This Susan G. Komen for the Cure® ad leaves no doubt about who’s to blame —you are......

Ovarian Cancer: A Brief Historical Overview of Intraperitoneal Trials

abstract

"The standard platinum-based treatment of previously untreated advanced ovarian cancer continues to evolve because despite high response rates to such first-line treatment, a majority of patients will experience relapse. For many years, the optimal treatment for women with advanced ovarian cancer has been maximum cytoreductive surgery followed by intravenous (IV) platinum and taxane chemotherapy. Later, several randomized multicenter phase III clinical trials demonstrated that intraperitoneal (IP) chemotherapy was superior to standard IV chemotherapy when there was minimal residual disease after primary debulking surgery. The underlying rationale for use of IP therapy is based on the dose-effect relationship for platinum drugs in ovarian cancer. However, barriers to implementation of IP therapy in the routine clinical setting include concern for toxicity, tolerability of planned treatment, and catheter-related complications. In this article, we highlight the key trials and recent directions in IP therapy of ovarian cancer and briefly discuss another approach to the delivery of IP chemotherapy, known as hyperthermic intraperitoneal chemotherapy."

 

Ovarian Cancer in BRCA Mutation Carriers: Improved Outcome After Intraperitoneal (IP) Cisplatin

abstract

BACKGROUND:

Ovarian cancer arising in women with BRCA mutations is known to have a more favorable outcome and to be more responsive to platinum-based regimens than in those without a hereditary background. We analyze our previously published intraperitoneal (IP) studies in relation to BRCA mutation status and update their outcomes.

METHODS:

Among 62 patients with ovarian cancer enrolled in IP platinum doublet studies in clinical trials (with etoposide (n = 18), with floxuridine (n = 30), and with topotecan (n = 14)), a deleterious BRCA mutation was eventually identified in 10 patients. The outcomes in these BRCA mutation carriers are described and compared with survival of others in respective trials.

RESULTS:

Ten patients that were confirmed to have BRCA mutations-all with high-grade and stages IIC to IV disease-survived a median of 10 years (range: 4-18+) after receiving IP cisplatin-based regimens. Two continue with no evidence of disease since their IP treatment, while four others remain alive with recurrences after 8, 9, 10, and 11 years, respectively.

CONCLUSIONS:

This experience suggests that IP cisplatin leads to favorable long term outcomes in advanced ovarian cancer in women with defective homologous recombination (i.e., with deleterious BRCA mutations). Whether such cisplatin dose-intensification from IP relative to (intravenous) IV drug administration leads to superior results in these mutation carriers requires further study.