Is there any role for physical therapy in chronic GvHD?

Chronic GvHD is the leading cause of non-relapse mortality in recipients of hematopoietic cell transplantation. Although the benefit of physical therapy (PT) has been reported in some GvHD studies, a literature gap is identified in demonstrating the exact role of different types of PT interventions and their impact on GvHD outcomes. An electronic search was undertaken using 13 peer-reviewed databases from 1994 to 2016. JADAD scoring method was used to score the quality of articles. PT interventions utilized for non-GvHD aspects of transplantation were excluded. Out of the 4775 articles on the electronic search, 297 articles were reviewed out of which 3 fulfilled the selection criteria. Moderately high evidence for effectiveness of supervised PT intervention was found, whereas moderate evidence for a self-administered exercise program was established. No safety concerns with PT were observed in any of the studies, however none of the studies were conducted to directly evaluate safety and effectiveness specifically in GvHD patients. PT is a safe but understudied therapy for GvHD. Limited evidence on the effectiveness of most PT interventions is available through randomized control trials. Well-designed trials are urgently needed for musculoskeletal GvHD especially with focused PT interventions.

Methadone analgesia in cancer pain patients on chronic methadone maintenance therapy.

Methadone is currently best known for its use as the maintenance drug in opioid addiction. The main concern when using methadone for the treatment of pain is its long and unpredictable half-life, which is associated with the risk of delayed toxicity. This may result in side effects such as sedation and respiratory depression if careful titration and close observation of individual patient responses are not performed. For this reason, methadone is often viewed as a second line opioid, after other opioids with a more predictable dose-response have been tried. We report six patients with long-term exposure to methadone as a treatment for heroin dependency, who were also treated with methadone for cancer pain. The first five patients were at least partially refractory to the analgesic effects of opioids other than methadone. All six patients achieved analgesia without sedation or respiratory depression from aggressive upward methadone titration. Methadone analgesia can be considered early in the course of treatment of patients with chronic exposure to methadone who develop new or worsening pain requiring opioid therapy.

Thyroid hormone changes in chronic spinal cord injury.

Spinal cord injury (SCI) impacts metabolic function and deranges various hormonal axes. Previous studies characterizing thyroid hormones in SCI reported depressed triiodothyronine (T3) and thyroxin (T4), primarily in acute tetraplegics. These studies cited an 11-13 percent incidence of low T3 syndrome (LT3S) in SCI patients, with an increased incidence in tetraplegics (20-36 percent). The purpose of this study was to evaluate thyroid function and determine the incidence and clinical relevance of LT3S in the chronic SCI population. Thyroid function tests were performed on 30 chronic SCI patients (14 tetraplegics and 16 paraplegics) and 30 age- and gender-matched controls. Mean T3 and T4 levels were significantly depressed in SCI patients relative to controls, while T3 resin uptake (T3RU) values were significantly elevated. LT3S only occurred in the SCI population with an incidence of 23.3 percent. SCI patients with LT3S did not differ significantly from those without in the level or completeness of injury, age or the interval since injury. They did, however, have co-existent pathology: decubiti, urinary tract infections, etc. When SCI patients with normal T3 were compared with controls, they still had depressed mean T3 levels. We conclude that LT3S occurs frequently in the chronic SCI population and suggest that depressed serum T3 levels may predispose SCI patients to sick euthyroidism in the face of minor pathologic insult.

The detection and treatment of cancer-related functional problems in an outpatient setting.

GOALS OF WORK: Cancer causes functional problems that are often neither detected nor treated in the outpatient setting. Patient-physician communication regarding functional issues may contribute. This study was conducted to quantify the degree of concordance between patient-identified functional problems and their documentation in the oncology-generated medical record. MATERIALS AND METHODS: We administered a 27-item questionnaire addressing cancer-related symptoms, signs, and functional problems to a consecutive sample of 244 patients undergoing outpatient cancer treatment. Oncology clinician-generated notation in the electronic medical record (EMR) was systematically reviewed for documentation of the instrument items. EMR review began the day of instrument completion and extended retrospectively for 6 months. MAIN RESULTS: Eighty-three percent (202) completed the survey with at least one cancer-related symptom, sign, or functional problem identified by 71.8%, 33.2% and 65.8% of patients, respectively. Difficulty with ambulation (23.9%) and balance (19.4%) were the most frequent functional problems. Clinician notes referred to 49% of patients' symptoms, but only 37% of their signs and 6% of their functional problems. Pain, weight loss, and nausea (ORs > 4.9, p < 0.004) were most likely to be documented while functional problems (OR 0.2, p < 0.0001) were the least likely to be noted. Two rehabilitation physician referrals were generated for pain and limb swelling, but no functional problems were formally addressed. CONCLUSION: Functional problems are prevalent among outpatients with cancer and are rarely documented by oncology clinicians. A more aggressive search for, and treatment of, these problems may be beneficial for outpatients with cancer.

Pain management in cancer rehabilitation.

UNLABELLED: Significant pain is experienced by the majority of cancer patients during the course of their illness. Despite the widespread availability of effective therapy, undertreatment remains common. Opioid pharmacotherapy has emerged as the mainstay of cancer pain management. Coanalgesic administration, disease-modifying therapies, and interventional strategies may be used concurrently to augment pain relief. Adequate pain management is a requisite condition for successful rehabilitation of patients with neoplasms. OVERALL ARTICLE OBJECTIVE: To describe common cancer- and treatment-related pain syndromes and the analgesic approaches commonly utilized in the management of cancer pain.

Cardiopulmonary rehabilitation and cancer rehabilitation. 4. Oncologic rehabilitation.

UNLABELLED: This self-directed learning module highlights the treatment and rehabilitation of patients with cancer by means of a case study format. It is part of the chapter on cardiac, pulmonary, and cancer rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article reviews medical and rehabilitation issues in patients with various types of cancer. Cases were selected to cover problems seen in both younger and older patient populations. Identification of common sequelae of cancer and cancer treatments, associated rehabilitation challenges, and appropriate interventions are included. OVERALL ARTICLE OBJECTIVE: To summarize the medical and rehabilitation issues in patients with various types of cancer.

Growth factor receptors and the progression of breast cancer.

Interference with autocrine or paracrine loops offers a potential means of treatment of tumors which currently lack effective therapies. Hormonally responsive breast cancers generally respond to treatment with antiestrogens but a frequent occurrence is an outgrowth of populations of tumor cells that are no longer dependent on estrogen for growth. If the acquisition of the ability to constitutively express growth factors or growth factor receptors is associated with this form of tumor progression, identification of the growth factors and their receptors having the capability of reducing the dependence on estrogen for growth is an important first step in the design of strategies aimed at interfering with their function. Experimental systems employing transfection with eukaryotic expression vectors are described that are designed to test the hypothesis that overexpression of epidermal growth factor receptor or the related protein C-ERB-B2 may confer an increased growth rate under conditions of estrogen deprivation. The transfected cells are also being used to explore the molecular mechanisms underlying the regulation of epidermal growth factor receptor expression by estrogen.

Emergence of MCF-7 cells overexpressing a transfected epidermal growth factor receptor (EGFR) under estrogen-depleted conditions: evidence for a role of EGFR in breast cancer growth and progression.

Overexpression of epidermal growth factor receptor (EGFR) is correlated with loss of estrogen receptor and poor prognosis in breast cancer. To investigate this phenomenon, we transfected a cytomegalovirus expression vector directing the expression of EGFR into estrogen receptor-positive MCF-7 breast cancer cells and into a clone of MCF-7 cells previously transfected with transforming growth factor alpha. Cells arising from single clones or pooled polyclonal populations maintained in charcoal-stripped calf serum, a medium devoid of estrogen, overexpressed EGFR. Switching these cells to a medium containing fetal calf serum or charcoal-stripped calf serum plus 17 beta-estradiol resulted in the emergence of a population expressing low EGFR levels. Loss of expression was not a consequence of nonspecific repression of the cytomegalovirus promoter, because expression of the fibroblast growth factor (FGF)-4 complementary DNA in a similar vector was not lost in fetal calf serum. While loss of EGFR overexpression in fetal calf serum was seen at both the protein and mRNA levels, Southern blotting shows that this was not due to loss of the transfected gene. Subclones of a cell population with low EGFR expression were capable of increasing expression upon estrogen withdrawal, demonstrating that the changes in EGFR expression were reversible and suggesting a growth advantage conferred by EGFR overexpression under these restrictive growth conditions. Overexpression of EGFR did not result in loss of ER expression. These results suggest a role for overexpression of EGFR in the growth of estrogen receptor-positive breast cancer cells in the absence of estrogen.

Autocrine growth stimulation by secreted Kaposi fibroblast growth factor but not by endogenous basic fibroblast growth factor.

We studied the different potentials of a secreted and a nonsecreted member of the fibroblast growth factor (FGF) family to induce autocrine growth stimulation in human adrenal cortex carcinoma cells (SW-13). These epithelial cells express basic FGF (bFGF) cell surface receptors, and picomolar concentrations of bFGF suffice to induce anchorage-independent growth. The requirement for exogenously added bFGF contrasts with the intracellular storage of biologically active bFGF in SW-13 cells greater than 10,000-fold in excess of the concentration needed to stimulate anchorage independent growth. To study whether the expression of a secreted FGF would alter the growth phenotype of these cells, we transfected them with an expression vector coding for the Kaposi-fgf (K-fgf) oncogene. In contrast to controls, K-fgf-transfected cells secrete significant amounts of biologically active K-fgf protein into the growth media, show up to 50-fold increased colony formation in soft agar, and grow into rapidly progressing, highly vascularized tumors in athymic nude mice. A reversible inhibition of the autocrine growth stimulation in vitro is brought about by the polyanionic compound suramin. We conclude that FGF has to be released from SW-13 cells to function fully as a growth stimulator in vitro and in vivo.