Low-grade serous ovarian cancer: State of the science.

In January 2019, a group of basic, translational, and clinical investigators and patient advocates assembled in Miami, Florida, to discuss the current state of the science of low-grade serous carcinoma of the ovary or peritoneum-a rare ovarian cancer subtype that may arise de novo or following a diagnosis of serous borderline tumor. The purpose of the conference was to review current knowledge, discuss ongoing research by established researchers, and frame critical questions or issues for future directions. Following presentations and discussions, the primary objective was to initiate future collaborations, uniform database platforms, laboratory studies, and clinical trials to better understand this disease and to advance clinical care outside the boundaries of single academic institutions. This review summarizes the state of the science in five principal categories: epidemiology and patient outcomes, pathology, translational research, patient care and clinical trials, and patients' perspective.

Methylnaltrexone for opioid-induced constipation in advanced illness.

BACKGROUND: Constipation is a distressing side effect of opioid treatment. As a quaternary amine, methylnaltrexone, a mu-opioid-receptor antagonist, has restricted ability to cross the blood-brain barrier. We investigated the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness. METHODS: A total of 133 patients who had received opioids for 2 or more weeks and who had received stable doses of opioids and laxatives for 3 or more days without relief of opioid-induced constipation were randomly assigned to receive subcutaneous methylnaltrexone (at a dose of 0.15 mg per kilogram of body weight) or placebo every other day for 2 weeks. Coprimary outcomes were laxation (defecation) within 4 hours after the first dose of the study drug and laxation within 4 hours after two or more of the first four doses. Patients who completed this phase were eligible to enter a 3-month, open-label extension trial. RESULTS: In the methylnaltrexone group, 48% of patients had laxation within 4 hours after the first study dose, as compared with 15% in the placebo group, and 52% had laxation without the use of a rescue laxative within 4 hours after two or more of the first four doses, as compared with 8% in the placebo group (P<0.001 for both comparisons). The response rate remained consistent throughout the extension trial. The median time to laxation was significantly shorter in the methylnaltrexone group than in the placebo group. Evidence of withdrawal mediated by central nervous system opioid receptors or changes in pain scores was not observed. Abdominal pain and flatulence were the most common adverse events. CONCLUSIONS: Subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation. Treatment did not appear to affect central analgesia or precipitate opioid withdrawal. (Clinical Trials.gov number, NCT00402038 [ClinicalTrials.gov].).

Safe Use of Subcutaneous Diphenhydramine in the Inpatient Hospice Unit.

BACKGROUND: Diphenhydramine (DPH) is most commonly used via oral, topical, intramuscular (IM) and intravenous (IV) routes for the palliation of pruritus, treatment of extrapyramidal symptoms, management of parkinsonism and for allergic reactions. However, many hospice patients are unable to take oral medications and/or do not have IV access. Moreover, topical administration has a relatively slow rate of absorption. For this reason, in the hospice setting it is not uncommon for diphenhydramine to be administered via the subcutaneous (SC) route secondary to its ease of access, low infection rates and its low levels of discomfort. In contrast, outside the hospice setting, subcutaneous DPH has not been widely used, primarily because of a handful of case reports published in the 1990's that report skin necrosis following subcutaneous administration of DPH for local anesthesia. Since these early case reports, however, there has been very little in the way of research to examine this further. The aim of this study is to provide objective data concerning the safe use of subcutaneous diphenhydramine, as part of our efforts to improve upon safe practices in our organization. METHODS: This is a retrospective review of records from 6 of our inpatient hospice units obtained from our pharmacy database for patients who received at least one subcutaneous injection of diphenhydramine between 2012-2015. Selected patients were then subsequently screened for post-administration skin necrosis, as recorded in our quality assurance database during the same time period. RESULTS: A total of 648 diphenhydramine subcutaneous injections were administered in109 individual patients. None of the patients were reported to have an adverse cutaneous reaction. CONCLUSIONS: This retrospective review demonstrates that subcutaneous diphenhydramine injection is a safe alternative to oral and other parenteral routes, and may be particularly valuable in terminally ill patients, who are often unable to swallow and are without IV access.

Methylnaltrexone for opioid-induced constipation in patients with advanced illness: a 3-month open-label treatment extension study.

Methylnaltrexone is a methylated form of the mu-opioid antagonist naltrexone that blocks peripheral effects of opioids without affecting centrally mediated analgesia. The authors conducted a 3-month open-label extension trial of methylnaltrexone in patients with advanced illness and opioid-induced constipation (OIC). Following completion of a 2-week double-blind (DB) trial, 82 patients with OIC who did not respond to laxatives received subcutaneous (SC) methylnaltrexone as needed for up to 3 months. Patients received 0.15 mg/kg as a first dose, adjusted to 0.3 mg/kg or 0.075 mg/kg as needed (maximum of one dose per 24 hours). Mean laxation response (rescue-free bowel movement within 4 hours) rates (DB phase, months 1, 2, 3 open-label phase) were 45.3%, 45.5%, 57.7%, and 57.3%, respectively, for patients treated with DB methylnaltrexone and 10.8%, 48.3%, 47.6%, and 52.1%, respectively, for patients treated with DB placebo. Median time to laxation among responders was 45 minutes (range 0-4 hours) for all doses. Approximately 50% of patients reported improvement in constipation distress. Patient and investigator global clinical impression of change scores also improved. There were minimal changes in pain scores and opioid withdrawal symptoms. Adverse events included abdominal pain and nausea, mostly mild or moderate in severity. SC methylnaltrexone administered PRN (as needed) for up to 3 months continued to rapidly induce laxation in advanced illness patients with OIC.

Palliative care and pain: new strategies for managing opioid bowel dysfunction.

Opioid analgesics are a cornerstone of pain therapy in the hospice and palliative care population. However, opioid-induced bowel dysfunction (OBD) is a commonly associated condition that frequently compromises the usefulness of these agents. Although its most common and debilitating symptom is constipation, the impact of OBD extends beyond constipation to encompass a myriad of gastrointestinal (GI) signs and symptoms, ranging from decreased gastric emptying and reflux to abdominal pain, cramping, bloating, nausea, and vomiting. Even after aggressive therapies to improve bowel function have been implemented, many patients continue to experience symptoms of OBD. To avoid these unwanted effects, some even choose to decrease or discontinue therapy with opioid analgesics, and experience inadequate pain control. The net result of OBD is a seriously negative impact on quality of life (QOL). For these reasons, it is important that palliative care practitioners have an adequate understanding of normal GI function and the underlying mechanisms responsible for OBD, the burden of OBD in the context of appropriate and effective pain management, and the benefits provided by effective pharmacotherapy. Several real-world cases are discussed to illustrate the application of optimal symptom management and the use of strategies that minimize the effects of OBD and improve patient QOL.