Prepacked Take-Home Analgesia in Outpatient Hand Surgery Reduces Opioid Dispensation.

BACKGROUND: Adequate postoperative pain treatment is important for quality of life, patient satisfaction, rehabilitation, function, and total opioid consumption, and might lower both the risk of chronic postoperative pain and the costs for society. Prolonged opioid consumption is a well-known risk factor for addiction. Previous studies in upper extremity surgery have shown that total opioid consumption is a third of the amount prescribed, which can be explained by package size. The aim of this study was to examine whether implementation of prepacked takehome analgesia bags reduced the quantity of prescribed and dispensed opioids. MATERIAL AND METHODS: We introduced prepacked take-home analgesia bags for postoperative pain treatment in outpatient surgery. The bags came in two sizes, each containing paracetamol, etoricoxib, and oxycodone. The first 147 patients who received the prepacked analgesia bags were included in the study, and received a questionnaire one month after surgery covering self-assessed pain (visual analog scale of 0-10) and satisfaction (0-5), as well as opioid consumption. Prescription data after introducing the analgesia bags were compared with data before the bags were introduced. RESULTS: Of the 147 patients included in the study, 58 responded. Compared to standard prescription (small bag group: 14 oxycodone immediate release capsules (5 mg), large bag group: additional 28 oxycodone extended release tablets (5 mg), based on the smallest available package), the patients in the small analgesia bag group received 50% less oxycodone and 67% less for the large bag group. Patients with small bags consumed a median of 0.0 mg oxycodone and those with large bags consumed a median of 25.0 mg oxycodone. The median satisfaction was 5.0 (range: 2-5) and the median pain score was acceptable at the first postoperative day. Prescription data showed a significant reduction of 60.0% in the total amount of prescribed opioids after the introduction of prepacked analgesia bags. CONCLUSIONS: The introduction of prepacked analgesia bags dramatically reduced the quantity of opioids prescribed after outpatient hand surgery. Patient satisfaction was high and the postoperative pain level was acceptable. KEY WORDS: analgesia, hand surgery, opioids, outpatint surgery, wrist surgery.

Predictors of progression free survival, overall survival and early cessation of chemotherapy in women with potentially platinum sensitive (PPS) recurrent ovarian cancer (ROC) starting third or subsequent line(≥3) chemotherapy - The GCIG symptom benefit study (SBS).

BACKGROUND: Potentially platinum sensitive recurrent ovarian cancer (PPS ROC) is defined by a platinum-free interval of >6 months, and usually treated with platinum-based chemotherapy with variable response and benefit in women who have had 3 or more lines of chemotherapy(≥3). We identified baseline characteristics (health-related quality of life[HRQL] and clinicopathological factors), associated with PFS, OS and early progression (within 8 weeks). The goal is to improve patient selection for chemotherapy based on a nomogram predicting PFS. METHODS: HRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with PFS and OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis were included in multivariable analyses using backward elimination to select those significant. Associations with stopping chemotherapy early were assessed with logistic regression. RESULTS: 378 women were enrolled, with median(m)OS and PFS of 16.6 months and 5.3 months, respectively. The majority had ECOGPS 0-1. Chemotherapy was stopped early in 45/378 participants (12%); with mOS 3.4 months (95% CI: 1.7-7.2). Physical function(PF), role function(RF), cognitive function(CF), social function(SF), Global Health Status(GHS) and abdominal/GI symptoms(AGIS) were significant univariable predictors of PFS(p < 0.030). SF remained significant after adjusting for clinicopathological factors; p = 0.03. PF, RF, CF, SF, GHS and AGIS were significant univariable predictors of OS (p < 0.007); PF, RF, SF and GHS remained significant predictors of OS in multivariable models; p < 0.007. Poor baseline PF and GHS were significant univariable predictors of stopping chemotherapy early (p < 0.007) but neither remained significant after adjusting for clinicopathological factors. CONCLUSION: Baseline HRQL is simple to measure, is predictive of PFS and OS and when used in conjunction with clinicopathological prognostic factors, can assist with clinical decision making and treatment recommendations for women with PPSROC≥3.

Early tumor regrowth is a contributor to impaired survival in patients with completely resected advanced ovarian cancer. An exploratory analysis of the Intergroup trial AGO-OVAR 12.

OBJECTIVE: Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. METHODS: Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. RESULTS: Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. CONCLUSIONS: Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted.

Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register study-On behalf of the Swedish Gynecological Cancer Group.

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not.

Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study.

BACKGROUND: We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women. METHODS: We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records. RESULTS: Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms. CONCLUSION: Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management.

Ki-67 expression predicts locoregional recurrence in stage I oral tongue carcinoma.

Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer associated with poor prognosis. Methods for determining the aggressiveness of OTSCC from analysis of the primary tumour specimen are thus highly desirable. We investigated whether genomic instability and proliferative activity (by means of Ki-67 activity) could be of clinical use for prediction of locoregional recurrence in 76 pretreatment OTSCC paraffin samples (stage I, n=22; stage II, n=33; stage III, n=8; stage IV, n=13). Eleven surgical tumour specimens were also analysed for remnants of proliferative activity after preoperative radiotherapy. Ninety-seven percent of cases (n=72) were characterised as being aneuploid as measured by means of image cytometry. Preoperative radiotherapy (50-68 Gy) resulted in significant reduction of proliferative activity in all patients for which post-treatment biopsies were available (P-value=0.001). Proliferative activity was not associated with response to radiation in stage II patients. However, we report a significant correlation between high proliferation rates and locoregional recurrences in stage I OTSCC patients (P-value=0.028). High-proliferative activity is thus related to an elevated risk of recurrence after surgery alone. We therefore conclude that Ki-67 expression level is a potentially useful clinical marker for predicting recurrence in surgically treated stage I OTSCC.

Lymphedema and bladder-emptying difficulties after radical hysterectomy for early cervical cancer and among population controls.

The aim of the study was to acquire knowledge that can be used to refine radical hysterectomy to improve quality-of-life outcome. Data were collected in 1996-1997 by means of an anonymous postal questionnaire in a follow-up study of two cohorts (patients and population controls). We attempted to enroll all 332 patients with stage IB-IIA cervical cancer registered in 1991-1992 at the seven departments of gynecological oncology in Sweden and 489 population controls. Ninety three (37%) of the 256 women with a history of cervical cancer who answered the questionnaire (77%) were treated with surgery alone. Three-hundred fifty population controls answered the questionnaire (72%). Women treated with radical hysterectomy, as compared with controls, had an 8-fold increase in symptoms indicating lymphedema (25% reported distress due to lymphedema), a nearly 9-fold increase in difficult emptying of the bladder, and a 22-fold increase in the need to strain to initiate bladder evacuation. Ninety percent of the patients were not willing to trade off survival for freedom from symptoms. Avoiding to induce long-term lymphedema or bladder-emptying difficulties would probably improve quality of life after radical hysterectomy (to cure cervical cancer). Few women want to compromise survival to avoid long-term symptoms.

Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer.

The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB-IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (P=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT.

[A Swedish study of women treated for cervix cancer. Gynecologic cancer often affects sexuality]. / Svensk studie av kvinnor som behandlats för cervixcancer. Gynekologisk cancer påverkar ofta sexualiteten.

Gynecological cancer and its treatments are often associated with physical, psychological and social consequences that affect the woman's and the couple's sexuality. Especially due to their impact on sexuality, physical changes distress the women considerably, and warrant consideration for women of all ages. Women with gynecological cancer ask for information about possible side-effects of the disease and treatment that can affect the sexual function. At follow-up visits these issues can be attended to through information, with specific suggestions including advice about topical estrogen and dilators, to alleviate possible long-term sequelae.

Aspects of delayed chemotherapy-induced nausea. Dexamethasone and adrenal response patterns in patients and healthy volunteers.

Delayed chemotherapy-induced nausea is still a clinical problem, and the underlying mechanisms are poorly understood. Previous studies have suggested that corticosteroids are involved, although the mechanisms by which corticosteroids exert their antiemetic effect are largely unknown. We have previously found impaired control of delayed nausea after injection of dexamethasone. The possibility of differences in the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after injection of dexamethasone was investigated in patients (n = 5) with gynaecological cancer being treated with platinum-based chemotherapy and in healthy female volunteers (n = 10). Urinary free cortisol was used to assess the levels of endogenous cortisol. Results showed that in both patients and controls injections of dexamethasone led to a significant decline in endogenous cortisol levels in 24 h and a subsequent significant recovery in the next 24 h. We conclude that the recovery of the HPA axis is rapid after a single dose of dexamethasone in patients and controls. The absence of an abnormal response pattern in patients makes it probable that the suppression and recovery of the HPA axis after injection of dexamethasone does not influence the corticosteroid-induced rebound effect on delayed platinum-induced nausea.

PUVA and cancer risk: the Swedish follow-up study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16-centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow-up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15-21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4. 4-7.1) for men and 3.6 (95% CI 2.1-5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.

Vaginal changes and sexuality in women with a history of cervical cancer.

BACKGROUND: In women with cervical cancer, treatment causes changes in vaginal anatomy and function. The effect of these changes on sexual function and the extent, if any, to which they distress women are not known. METHODS: In 1996 and 1997, we attempted to contact 332 women with a history of early-stage cervical cancer (age range, 26 to 80 years) who had been treated in 1991 and 1992 at the seven departments of gynecological oncology in Sweden and 489 women without a history of cancer (controls) to ask them to answer an anonymous questionnaire about vaginal changes and sexual function. RESULTS: We received completed questionnaires from 256 of the women with a history of cervical cancer and 350 of the controls. A total of 167 of 247 women with a history of cancer (68 percent) and 236 of 330 controls (72 percent) reported that they had regular vaginal intercourse. Twenty-six percent of the women who had cancer and 11 percent of the controls reported insufficient vaginal lubrication for sexual intercourse, 26 percent of the women who had cancer and 3 percent of the controls reported a short vagina, and 23 percent of the women who had cancer and 4 percent of the controls reported an insufficiently elastic vagina. Twenty-six percent of the women who had cancer reported moderate or much distress due to vaginal changes, as compared with 8 percent of the women in the control group. Dyspareunia was also more common among the women who had cervical cancer. The frequency of orgasms and orgasmic pleasure was similar in the two groups. Among the women who had cervical cancer, the type of treatment received had little if any effect on the prevalence of specific vaginal changes. CONCLUSIONS: Women who have been treated for cervical cancer have persistent vaginal changes that compromise sexual activity and result in considerable distress.

Biological activity of human epidermal interleukin-1beta: comparison with recombinant human interleukin-1beta.

We have recently presented evidence that human plantar stratum corneum and psoriatic scales contain biologically active interleukin-1beta (IL-1beta) which has been activated in a process not involving interleukin-1beta-converting-enzyme. The aim of the present study was to compare this form of native IL-1beta with recombinant mature human IL-1beta as regards activity and the effects of inhibitors. In an assay based on the ability of IL-1 to induce the expression of E-selectin in cultured endothelial cells, the maximal activity of IL-1beta partially purified from plantar stratum corneum and recombinant IL-1beta was approximately the same. The specific activity was slightly higher for recombinant IL-1beta, although this difference was within one order of magnitude. An antibody to IL-1beta caused total inhibition of both forms of IL-1beta with no significant differences in the dose-response curves for the antibody. Immunochemical analyses and experiments with neutralising antibodies specific for IL-1alpha and tumor necrosis factor-alpha (TNF-alpha) verified that the observed activity in the partially purified preparation was due to IL-1beta, and not to IL-1alpha or TNF-alpha. There were no significant differences between the two forms of IL-1beta as regards the inhibitory effects of recombinant IL-1 receptor antagonist. Partially purified IL-1beta from plantar stratum corneum and from psoriatic scales were both highly active in the D10 proliferation assay. This activity could be totally inhibited with an IL-1beta specific antibody. This work thus confirms the presence of biologically active IL-1beta in plantar stratum corneum and psoriatic scales. Alternatively activated IL-1beta in the epidermis should be considered in future studies on skin biology and pathophysiology.

Similarities and differences in assessing nausea on a verbal category scale and a visual analogue scale.

The use of verbal category scales in assessing patient symptoms is evolving, but the extent to which reliability and precision are lost in using them as opposed to a visual analogue scale (VAS) remains uncertain. The present study analyzed the concordance between a four-point verbal category scale and a VAS in assessing nausea intensity in patients undergoing chemotherapy. The analysis of a total of 348 simultaneous ratings by 104 women over four cycles revealed good concordance between the scales. The means of the VAS ratings (range 0-100 mm) corresponding to the four verbal categories divided the scale in four almost equally large parts (no nausea = 0.7, mild = 24.8, moderate = 48.3, severe = 75.1). However, the VAS ranges were wide. On an individual level a one-step change in the verbal category was associated with an average change of 20 mm on the VAS. The choice of scale to use should be based on the need in the particular situation. When measuring intensity of nausea in patients, the VAS is a reasonable choice due to its possibly greater ability to detect changes over time. On the group level, findings on a four-point category scale and a VAS on the average seem similar.