Longitudinal perioperative patient-reported outcomes in open compared with minimally invasive hysterectomy.

BACKGROUND: There are few prospective studies in the gynecologic surgical literature that compared patient-reported outcomes between open and minimally invasive hysterectomies within enhanced recovery after surgery pathways. OBJECTIVE: This study aimed to compare prospectively collected perioperative patient-reported symptom burden and interference measures in open compared with minimally invasive hysterectomy cohorts within enhanced recovery after surgery pathways. STUDY DESIGN: We compared patient-reported symptom burden and functional interference in 646 patients who underwent a hysterectomy (254 underwent open surgery and 392 underwent minimally invasive surgery) for benign and malignant indications under enhanced recovery after surgery protocols. Outcomes were prospectively measured using the validated MD Anderson Symptom Inventory, which was administered perioperatively up to 8 weeks after surgery. Cohorts were compared using Fisher exact and chi-squared tests, adjusted longitudinal generalized linear mixed modeling, and Kaplan Meier curves to model return to no or mild symptoms. RESULTS: The open cohort had significantly worse preoperative physical functional interference (P=.001). At the time of hospital discharge postoperatively, the open cohort reported significantly higher mean symptom severity scores and more moderate or severe scores for overall (P<.001) and abdominal pain (P<.001), fatigue (P=.001), lack of appetite (P<.001), bloating (P=.041), and constipation (P<.001) when compared with the minimally invasive cohort. The open cohort also had significantly higher interference in physical functioning (score 5.0 vs 2.7; P<.001) than the minimally invasive cohort at the time of discharge with no differences in affective interference between the 2 groups. In mixed modeling analysis of the first 7 postoperative days, both cohorts reported improved symptom burden and functional interference over time with generally slower recovery in the open cohort. From 1 to 8 postoperative weeks, the open cohort had worse mean scores for all evaluated symptoms and interference measures except for pain with urination, although scores indicated mild symptomatic burden and interference in both cohorts. The time to return to no or mild symptoms was significantly longer in the open cohort for overall pain (14 vs 4 days; P<.001), fatigue (8 vs 4 days; P<.001), disturbed sleep (2 vs 2 days; P<.001), and appetite (1.5 vs 1 days; P<.001) but was significantly longer in the minimally invasive cohort for abdominal pain (42 vs 28 days; P<.001) and bloating (42 vs 8 days; P<.001). The median time to return to no or mild functional interference was longer in the open than in the minimally invasive hysterectomy cohort for physical functioning (36 vs 32 days; P<.001) with no difference in compositive affective functioning (5 vs 5 days; P=.07) between the groups. CONCLUSION: Open hysterectomy was associated with increased symptom burden in the immediate postoperative period and longer time to return to no or mild symptom burden and interference with physical functioning. However, all patient-reported measures improved within days to weeks of both open and minimally invasive surgery and differences were not always clinically significant.

Acupuncture for reduction of symptom burden in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation: a randomized sham-controlled trial.

PURPOSE: Hematopoietic stem cell transplantation (HCT) is potentially curative for a number of hematologic malignancies, but is associated with high symptom burden. We conducted a randomized sham-controlled trial (RCT) to evaluate efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan followed by autologous HCT (AHCT) were randomized to receive either true or sham acupuncture once daily for 5 days starting the day after chemotherapy. Patients and clinical evaluators, but not acupuncturists, were blinded to group assignment. Symptom burden, the primary outcome was assessed with the MD Anderson Symptom Inventory (MDASI) at baseline, during transplantation, and at 15 and 30 days post transplantation. RESULTS: Among 60 participants, true acupuncture produced nonsignificant reductions in overall MDASI core symptom scores and symptom interference scores during transplantation (P = .4 and .3, respectively), at 15 days (P = .10 and .3), and at 30 days posttransplantation (P = .2 and .4) relative to sham. However, true acupuncture was significantly more efficacious in reducing nausea, lack of appetite, and drowsiness at 15 days (P = .042, .025, and .010, respectively). Patients receiving sham acupuncture were more likely to increase pain medication use posttransplantation (odds ratio 5.31, P = .017). CONCLUSIONS: Acupuncture was well tolerated with few attributable adverse events. True acupuncture may prevent escalation of symptoms including nausea, lack of appetite, and drowsiness experienced by patients undergoing AHCT, and reduce the use of pain medications. These findings need to be confirmed in a future definitive study. TRIAL REGISTRATION: NCT01811862.

The Colicin E1 TolC-Binding Conformer: Pillar or Pore Function of TolC in Colicin Import?

The mechanism by which the drug export protein TolC is utilized for import of the cytotoxin colicin E1 across the outer membrane and periplasmic space is addressed. Studies of the initial binding of colicin E1 with TolC, occlusion of membrane-incorporated TolC ion channels, and the structure underlying the colicin-TolC complex were based on the interactions with TolC of individual colicin translocation domain (T-domain) peptides from a set of 19 that span different segments of the T-domain. These studies led to identification of a short 20-residue segment 101-120, a "TolC box", located near the center of the colicin T-domain, which is necessary for binding of colicin to TolC. Omission of this segment eliminated the ability of the T-domain to occlude TolC channels and to co-elute with TolC on a size-exclusion column. Far-ultraviolet circular dichroism spectral and thermal stability analysis of the structure of T-domain peptides implies (i) a helical hairpin conformation of the T-domain, (ii) the overlap of the TolC-binding site with a hinge of the helical hairpin, and (iii) a TolC-dependent stage of colicin import in which a central segment of the T-domain in a helical hairpin conformation binds to the TolC entry port following initial binding to the BtuB receptor. These studies provide the first structure-based information about the interaction of colicin E1 with the unique TolC protein. The model inferred for binding of the T-domain to TolC implies reservations about the traditional model for colicin import in which TolC functions to provide a channel for translocation of the colicin in an unfolded state across the bacterial outer membrane and a large part of the periplasmic space.

Patient-Reported Outcomes Accurately Measure the Value of an Enhanced Recovery Program in Liver Surgery.

BACKGROUND: Enhanced recovery (ER) pathways have become increasingly integrated into surgical practice. Studies that compare ER and traditional pathways often focus on outcomes confined to inpatient hospitalization and rarely assess a patient's functional recovery. The aim of this study was to compare functional outcomes for patients treated on an Enhanced Recovery in Liver Surgery (ERLS) pathway vs a traditional pathway. STUDY DESIGN: One hundred and eighteen hepatectomy patients rated symptom severity and life interference using the validated MD Anderson Symptom Inventory preoperatively and postoperatively at every outpatient visit until 31 days after surgery. The ERLS protocol included patient education, narcotic-sparing anesthesia and analgesia, diet advancement, restrictive fluid administration, early ambulation, and avoidance of drains and tubes. RESULTS: Seventy-five ERLS pathway patients were clinically comparable with 43 patients simultaneously treated on a traditional pathway. The ERLS patients reported lower immediate postoperative pain scores and experienced fewer complications and decreased length of stay. As measured by symptom burden on life interference, ERLS patients were more likely to return to baseline functional status in a shorter time interval. The only independent predictor of faster return to baseline interference levels was treatment on an ERLS pathway (p = 0.021; odds ratio = 2.62). In addition, ERLS pathway patients were more likely to return to intended oncologic therapy (95% vs 87%) at a shorter time interval compared to patients on the traditional pathway (44.7 vs 60.2 days). CONCLUSIONS: In oncologic liver surgery, enhanced recovery's primary mechanism of action is reduction in life interference by postoperative surgical symptoms, allowing patients to return sooner to normal function and adjuvant cancer therapies.

Incidence and predictive factors of pain flare after spine stereotactic body radiation therapy: secondary analysis of phase 1/2 trials.

PURPOSE/OBJECTIVE(S): To perform a secondary analysis of institutional prospective spine stereotactic body radiation therapy (SBRT) trials to investigate posttreatment acute pain flare. METHODS AND MATERIALS: Medical records for enrolled patients were reviewed. Study protocol included baseline and follow-up surveys with pain assessment by Brief Pain Inventory and documentation of pain medications. Patients were considered evaluable for pain flare if clinical note or follow-up survey was completed within 2 weeks of SBRT. Pain flare was defined as a clinical note indicating increased pain at the treated site or survey showing a 2-point increase in worst pain score, a 25% increase in analgesic intake, or the initiation of steroids. Binary logistic regression was used to determine predictive factors for pain flare occurrence. RESULTS: Of the 210 enrolled patients, 195 (93%) were evaluable for pain flare, including 172 (88%) clinically, 135 (69%) by survey, and 112 (57%) by both methods. Of evaluable patients, 61 (31%) had undergone prior surgery, 57 (29%) had received prior radiation, and 34 (17%) took steroids during treatment, mostly for prior conditions. Pain flare was observed in 44 patients (23%). Median time to pain flare was 5 days (range, 0-20 days) after the start of treatment. On multivariate analysis, the only independent factor associated with pain flare was the number of treatment fractions (odds ratio = 0.66, P=.004). Age, sex, performance status, spine location, number of treated vertebrae, prior radiation, prior surgery, primary tumor histology, baseline pain score, and steroid use were not significant. CONCLUSIONS: Acute pain flare after spine SBRT is a relatively common event, for which patients should be counseled. Additional study is needed to determine whether prophylactic or symptomatic intervention is preferred.

A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy.

Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aß myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy.

Quantifying fatigue in (long-term) colorectal cancer survivors: a study from the population-based patient reported outcomes following initial treatment and long term evaluation of survivorship registry.

BACKGROUND: Few studies specifically focus on fatigue of (long-term) colorectal cancer (CRC) survivors or compare fatigue levels with a normative population. Association between surviving multiple primary cancers and fatigue is also explored. METHODS: Survivors diagnosed from 1998 to 2009 were identified from the Eindhoven Cancer Registry. In total, 3739 (79%) respondents and an age- and gender-matched normative population (n=338) completed questionnaires on fatigue and psychological distress. RESULTS: More survivors reported feeling fatigued than the normative population (39% versus 22%, p<0.0001). Short-term survivors (<5 years post-diagnosis) had the highest mean fatigue scores compared with long-term survivors (≥5 years post-diagnosis) or the normative population (21±7 versus 20±7 versus 18±5, p<0.0001, respectively). Having primary cancers prior to CRC was associated with more fatigue. Surgery+chemoradiation was independently associated with fatigue (odds ratio (OR): 1.63, 95% confidence interval (CI): 1.17-2.29, p=0.004) as were anxiety (OR: 1.16, 95% CI: 1.12-1.19, p<0.0001) and depressive symptoms (OR: 1.38, 95% CI: 1.33-1.43, p<0.0001). CONCLUSIONS: Fatigue is a significant problem, especially for short-term CRC survivors. The association between chemoradiation and fatigue suggests that patients could benefit from better information on treatment side-effects. When treating fatigue, clinical care should also focus on survivors' psychological needs, especially survivors of multiple primary cancers.

Subclinical peripheral neuropathy is a common finding in colorectal cancer patients prior to chemotherapy.

PURPOSE: Of the numerous complications associated with cancer and cancer treatment, peripheral neuropathy is a deleterious and persistent patient complaint commonly attributed to chemotherapy. The present study investigated the occurrence of subclinical peripheral neuropathy in patients with colorectal cancer before the initiation of chemotherapy. EXPERIMENTAL DESIGN: Fifty-two patients underwent extensive quantitative sensory testing (QST) before receiving chemotherapy. Changes in multiple functions of primary afferent fibers were assessed and compared with a group of healthy control subjects. Skin temperature, sensorimotor function, sharpness detection, and thermal detection were measured, as was touch detection, using both conventional (von Frey monofilaments) and novel (Bumps detection test) methodology. RESULTS: Patients had subclinical deficits, especially in sensorimotor function, detection of thermal stimuli, and touch detection that were present before the initiation of chemotherapy. The measured impairment in touch sensation was especially pronounced when using the Bumps detection test. CONCLUSIONS: The patients with colorectal cancer in this study exhibited deficits in sensory function before undergoing chemotherapy treatment, implicating the disease itself as a contributing factor in chemotherapy-induced peripheral neuropathy. The widespread nature of the observed deficits further indicated that cancer is affecting multiple primary afferent subtypes. Specific to the finding of impaired touch sensation, results from this study highlight the use of newly used methodology, the Bumps detection test, as a sensitive and useful tool in the early detection of peripheral neuropathy.

The M. D. Anderson symptom inventory-head and neck module, a patient-reported outcome instrument, accurately predicts the severity of radiation-induced mucositis.

PURPOSE: To compare the M. D. Anderson Symptom Inventory-Head and Neck (MDASI-HN) module, a symptom burden instrument, with the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) module, a quality-of-life instrument, for the assessment of mucositis in patients with head-and-neck cancer treated with radiotherapy and to identify the most distressing symptoms from the patient's perspective. METHODS AND MATERIALS: Consecutive patients with head-and-neck cancer (n = 134) completed the MDASI-HN and FACT-HN before radiotherapy (time 1) and after 6 weeks of radiotherapy or chemoradiotherapy (time 2). The mean global and subscale scores for each instrument were compared with the objective mucositis scores determined from the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. RESULTS: The global and subscale scores for each instrument showed highly significant changes from time 1 to time 2 and a significant correlation with the objective mucositis scores at time 2. Only the MDASI scores, however, were significant predictors of objective Common Terminology Criteria for Adverse Events mucositis scores on multivariate regression analysis (standardized regression coefficient, 0.355 for the global score and 0.310 for the head-and-neck cancer-specific score). Most of the moderate and severe symptoms associated with mucositis as identified on the MDASI-HN are not present on the FACT-HN. CONCLUSION: Both the MDASI-HN and FACT-HN modules can predict the mucositis scores. However, the MDASI-HN, a symptom burden instrument, was more closely associated with the severity of radiation-induced mucositis than the FACT-HN on multivariate regression analysis. This greater association was most likely related to the inclusion of a greater number of face-valid mucositis-related items in the MDASI-HN compared with the FACT-HN.

Russian Brief Pain Inventory: validation and application in cancer pain.

To validate the Russian version of the Brief Pain Inventory (BPI-R) and to examine predictors of inadequate pain management, 221 Russian patients with advanced-stage hematological malignancies or solid tumors completed the BPI-R and a Russian-language Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36-R). Factor analysis of the BPI-R found two underlying constructs, pain severity and pain interference, with Cronbach alphas of 0.93 and 0.95, respectively. Concurrent validity was established by comparing BPI-R items with SF-36-R scales. The BPI-R detected significant differences in pain severity and interference levels by Eastern Cooperative Oncology Group (ECOG) performance status, supporting known-group validity. Determination of the Pain Management Index revealed that 68% of the patients were inadequately treated by World Health Organization standards. Having advanced-stage disease and not receiving chemotherapy predicted inadequate pain management in a multivariate logistic regression model. The Russian version of the BPI is psychometrically sound in its reliability and validity.

Cancer-related symptom assessment in Russia: validation and utility of the Russian M. D. Anderson Symptom Inventory.

This multicenter cross-sectional study (n=226) validated the Russian-language M. D. Anderson Symptom Inventory (MDASI-R) in Russian cancer patients with hematological malignancies or solid tumors. The Russian-language Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36-R) also was used for validation. Factor analysis found three underlying constructs for symptom items--general, treatment-related, and affective symptoms--with Cronbach alphas of 0.86, 0.68, and 0.90, respectively. Convergent validity was established by comparing MDASI-R items with SF-36-R subscales. The MDASI-R detected significant differences in symptom severity and interference levels by performance status, supporting known-group validity. The most prevalent symptoms were fatigue, sleep disturbance, pain, sadness, and poor appetite; 53% of the sample reported one to four moderate-to-severe symptoms (>or=5 on 0-10 scale). Symptoms interfered most with work and general activity. Medical professionals underestimated the severity of pain, fatigue, and distress. The MDASI-R is valid and reliable for measuring symptom severity and interference in Russian cancer patients.