The prognostic significance of lymphovascular space invasion in laparoscopic versus abdominal hysterectomy for endometrioid endometrial cancer.

INTRODUCTION: Recent reports have suggested that uterine manipulators can induce lymphovascular space involvement (LVSI) by endometrial cancer in laparoscopic hysterectomy specimens. The prognostic significance of this phenomenon known as "vascular pseudo invasion" remains elusive. MATERIALS AND METHODS: The authors conducted a retrospective, single institution study of patients who underwent initial surgery for grade 1 and grade 2 endometrioid endometrial cancers with LVSI. Cases were stratified by surgical approach (laparoscopy vs laparotomy). Clinicopathologic and procedure characteristics as well as outcome data were analyzed. Univariate and multivariate analyses were performed. Disease-free survival (DFS) was analyzed using the Kaplan-Meier product limit method. RESULTS: A total of 104 cases (20 laparoscopic, 84 laparotomy) were analyzed. Mean age (65 vs 64 years, respectively), stage distribution, mean number of lymph nodes sampled (18 vs 21, respectively) and use of adjuvant therapy was similar for both groups (p > 0.05). Mean body mass index (BMI) was 30 vs 35 kg/m2, respectively (p = 0.002). Mean follow up was 24 months (range 0.1-102). Univariate analysis demonstrated that LVSI in the laparoscopic setting was associated with worse DFS (p = 0.002). After adjusting for grade the risk of recurrence remained higher for laparoscopic cases (HR: 15.7, 95% CI 1.7-140.0, p = 0.014). CONCLUSIONS: Adjusted risk of recurrence associated with LVSI is higher in cases approached laparoscopically arguing against the concept of "vascular pseudo invasion" associated with the use of uterine manipulators and balloons. LVSI should be regarded as a serious risk factor and taken into account for triage to adjuvant therapies, even in laparoscopically treated early-stage endometrial cancer.

Pelvic exenteration in gynecologic oncology: a single institution study over 20 years.

OBJECTIVE: The profile of women with gynecologic malignancies treated with pelvic exenteration has changed since the initial description of this procedure. We sought to evaluate our experience with pelvic exenteration over the last 20 years. METHODS: Patients who underwent anterior, posterior, or total pelvic exenteration for vulvar, vaginal, and cervical cancer at Barnes-Jewish Hospital between January 1, 1990 and August 1, 2009 were identified through hospital databases. Patient characteristics, the indications for the procedure, procedural modifications, and patient outcomes were retrospectively assessed. Categorical variables were analyzed with chi-square method, and survival data was analyzed using the Kaplan-Meier method and log rank test. RESULTS: Fifty-four patients were identified who had pelvic exenteration for cervical, vaginal, or vulvar cancer. Recurrent cervical cancer was the most common procedural indication. One year overall survival from pelvic exenteration for the entire cohort was 64%, with 44% of patients still living at 2 years and 34% at 50 months. Younger age was associated with improved overall survival after exenteration (p = 0.01). Negative margin status was associated with a longer disease-free survival (p=0.014). Nodal status at the time of exenteration was not associated with time to recurrence or progression, site of recurrence, type of post-operative treatment, early or late complications, or survival. CONCLUSIONS: Despite advances in imaging and increased radical techniques, outcomes and complications after total pelvic exenteration in this cohort are similar to those described historically. Pelvic exenteration results in sustained survival in select patients, especially those that are young with recurrent disease and pathologically negative margins.

Two randomized controlled trials comparing the Hulka and Filshie Clips for tubal sterilization.

To compare the effectiveness and safety of the Filshie Clip System and Hulka Clip System when applied via minilaparotomy and laparoscopy, we conducted 2 multicenter randomized controlled trials of 2126 women (878 in the minilaparotomy study and 1248 in the laparoscopy study) who received either the Filshie or Hulka Clip. A physician other than the operator evaluated patients postoperatively and again at 1, 6, and 12 months after surgery. We compared the cumulative incidence of pregnancy and the frequency of safety related events for the device groups. Twenty-four month follow-up was planned for a subset of 599 women in the laparoscopy study. One woman who received the Filshie Clip and 6 women who received the Hulka Clip became pregnant within one year. The 12-month life-table pregnancy probability was 1.1 per 1000 women in the Filshie Clip group and 6.9 per 1000 women in the Hulka Clip group. The difference in the risk of pregnancy through 12 months between device groups neared statistical significance (p = 0.06). Among the extended follow-up subset, the 12- and 24-month cumulative pregnancy probabilities were 3.9 and 9.7 per 1000 women for the Filshie Clip group and 11.7 and 28.1 per 1000 women for the Hulka Clip group (p = 0.16 for comparison through 24 months). Both the Filshie and Hulka Clips are effective and safe for use in tubal occlusion.

Analgesic efficacy of liquid ketoprofen compared to liquid dipyrone and placebo administered orally as drops in postepisiotomy pain.

OBJECTIVE: The objective of this single-center, single-dose, double-blind randomized parallel group study was to evaluate the analgesic efficacy of a new liquid formulation of ketoprofen at two dose levels (25 mg or 50 mg) compared to a commercially available liquid form of dipyrone 500 mg and placebo with all treatments administered as drops to patients with severe postepisiotomy pain. METHODS: The study was designed with a sample size of 69 patients per treatment for a total of 276 patients. However, due to administrative changes at the site, the study was prematurely terminated; thus only 108 patients (26 to 28 patients per treatment), 18 years or older, with severe postepisiotomy pain were randomized to one of the four treatments. Treatments were assessed over a 6-hour period using standard scales for pain intensity and pain relief and a number of derived variables based on these data. Since the study medications were not identical in appearance, the preparation and administration of the study medication, and the observation of the patient, were carried out by two different individuals to maintain double-blind conditions. RESULTS: All active treatments were significantly superior to placebo for several measures of analgesia including 4-hour and 6-hour SPID and TOTPAR scores. The global rating was assessed as "good" or "excellent" by over 75% of the patients in the active treatment groups compared to 7.4% of the patients in the placebo group. Reduction in pain intensity was very similar for the two-dose levels of ketoprofen and the comparator dipyrone 500 mg. CONCLUSION: Ketoprofen 25 mg or 50 mg, and dipyrone 500 mg seem to be equally suited for use as pain relief medication after minor surgery, as well as episiotomy. This study did not demonstrate a need for more than 25 mg of ketoprofen in postepisiotomy pain. All treatments were well tolerated. No adverse events were reported.

A food interaction study of bromfenac, naproxen sodium, and placebo in cesarean section patients.

Objective: This double-blind study was to compare the effect of food on the analgesic response to bromfenac, naproxen sodium, and placebo.Methods: Single doses of bromfenac (BRO) 25 mg, naproxen Na (NAP) 550 mg, or placebo (PLA) were given to 284 patients with moderate or severe pain following cesarean section. A standard breakfast was provided for the "fed" patients. "Fasted" patients received no food 3 h before and 1 h after the dose. Treatments were compared over 8 h using standard scales for pain intensity and pain relief. Plasma levels of BRO were measured in 7 fasted and 12 fed patients.Results: BRO and NAP were significantly superior to PLA; food did not affect the response to any treatment: As expected, mean peak plasma levels of bromfenac were reduced by food by about 65%.Conclusion: Food reduces the bioavailability of bromfenac but has no effect on the analgesic response.

Onset and duration of analgesia of diclofenac potassium in the treatment of postepisiotomy pain.

A double-blind, placebo-controlled, parallel group study was performed to compare the analgesic efficacy of diclofenac potassium (25, 50, or 100 mg) with that of aspirin (650 mg), or placebo. Two hundred fifty-five inpatients with severe postepisiotomy pain were randomly assigned to receive a single oral dose of one of the four active treatments or placebo. Analgesia was assessed over an 8-hour period. Treatments were compared on the basis of standard scales for pain intensity and relief and a number of derived variables based on these data, as well as two global ratings of the study medication. All active treatments were effective analgesics statistically superior to placebo for many hourly and summary measures, including the global ratings. Diclofenac potassium (50 and 100 mg) was statistically significantly superior to aspirin at half-hour and for many other hourly scores from hour 3 on. The 4- and 8-hour sum of the pain intensity difference and total pain relief scores reflected the superiority of diclofenac potassium to aspirin. In addition, the 100-mg dose was significantly more efficacious than the 25-mg dose of diclofenac potassium. The probability of obtaining onset was significantly better for all active treatments than for placebo; however, the median onset times were similar for all treatments. The duration of effect, as measured by mean pain intensity difference and relief scores, was better for diclofenac potassium than aspirin, and these differences were significant for the 50- and 100-mg doses. The probability of pain returning to baseline was significantly less for the diclofenac groups than for placebo or aspirin groups. In addition, significantly fewer patients treated with diclofenac (25, 50, or 100 mg) or aspirin (650 mg) required remedication during the 8-hour study period as compared with those treated with placebo. Diclofenac potassium is an effective analgesic in the range of aspirin (650 mg) at the 25-mg dose and superior in efficacy and longer lasting than aspirin at the 50- and 100-mg doses. The onset of analgesia was similar for aspirin and diclofenac potassium.

[Induced and spontaneous labor: its duration and hourly frequency]. / Parto inducido y espontáneo: su duración y frecuencia horaria.

A retrospective randomized paired study was performed of 200 electively induced labor by means of artificial rupture of membranes and oxytocin infusion and 200 spontaneous labor. It was found that labor length was significantly shorter (p < 0.5) in the study group tan the control group (2.02 +/- 3 h and 6.2 +/- 3 h respectively). Delivery was accomplished in the majority of the induced group (50.2%) between 12:00 and 17:59 h (p < 0.001), while in the control group it occurred randomly during the 24 hours (p > 0.05).

Ketoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain.

Ketoprofen (Orudis) is a nonsteroidal anti-inflammatory drug that is currently approved in the United States for the management of mild to moderate pain. The objective of this trial was to determine the effectiveness of orally administered ketoprofen in the management of severe postoperative pain. This randomized, double-blind parallel study compared the efficacy and safety of single doses of 100 mg or 50 mg ketoprofen, the combination of 650 mg acetaminophen plus 10 mg oxycodone hydrochloride, 650 mg acetaminophen, or placebo in 240 patients with severe postoperative pain after cesarean section. Analgesia for the first dose was assessed over an 8-hour period. Multiple doses of 100 mg or 50 mg ketoprofen and the combination at half the dose (325 mg acetaminophen plus 5 mg oxycodone) were also assessed for up to 7 days. The 100 and 50 mg doses of ketoprofen and the combination were statistically superior to acetaminophen and placebo for many analgesic measures. A dose response was observed between the two doses of ketoprofen, with the 100 mg dose providing significantly greater analgesia over the lower dose. Ketoprofen, 100 mg, was at least as effective as the combination and its effects lasted longer, with the exception of hour 1 when the combination was superior. Remedication time for the group receiving 100 mg ketoprofen was significantly longer than for the other treatment groups. Significantly more patients who took repeated doses of the combination (84%) than those who took either dose of ketoprofen (70%) had adverse effects. Ketoprofen at both dose levels was shown to be effective, long-lasting, and well tolerated, and it should be considered as a viable option for the management of moderate to severe postoperative pain.

Analgesic oral efficacy of tramadol hydrochloride in postoperative pain.

Tramadol hydrochloride is a synthetic opiate agonist with a plasma elimination half-life of 5 to 6 hours and peak plasma levels at about 1 1/2 hours. It derives its activity from attachment to the mu-receptor and blockage of norepinephrine reuptake. The purpose of this single-dose, double-blind, placebo-controlled study was to determine the analgesic effectiveness of an oral administration of two dose levels of tramadol hydrochloride (75 or 150 mg) compared with the combination of 650 mg acetaminophen plus 100 mg propoxyphene napsylate in 161 patients with severe postoperative pain after cesarean section. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard scales for pain intensity and relief and a number of derived variables based on these data. A global rating of the study medication was also used to compare treatments. The three active treatments were effective analgesics, statistically superior to placebo for many hourly and summary measures. A dose response was seen between the two tramadol doses, with the 150 mg dose providing significantly greater analgesia over the lower dose. The 75 mg dose of tramadol was generally more effective than the acetaminophen-propoxyphene combination after hour 2, and significantly so for some hourly time points, as well as for the global rating of the medication. The 150 mg dose of tramadol was significantly more effective than the acetaminophen-propoxyphene combination from hour 2 through hour 6 for the sum of pain intensity differences and total pain relief scores, as well as for the global rating of the medication. Tramadol hydrochloride at both dose levels is an effective analgesic agent and at 150 mg is statistically superior to the acetaminophen-propoxyphene combination. No serious adverse effects were observed; however, dizziness was more frequently reported with 150 mg tramadol.

Clinical experience with the GYNE-T 380 postpartum intrauterine device.

OBJECTIVE: The insertion of conventional intrauterine devices (IUDs) during the 1st 10 days after delivery is associated with a high rate of expulsions. DESIGN: The GYNE-T 380 (Ortho Pharmaceutical [Canada] Ltd., Toronto, Ontario, Canada) IUD was modified by the addition of a loose loop of knotted biodegradable no. 2 catgut to the top of the IUD (GYNE-T 380 postpartum IUD). After delivery, a special inserter was used to imbed the knotted portion of the loop into the myometrium of the uterine fundus. PATIENTS, PARTICIPANTS: This modified IUD was evaluated in a phase II trial involving 190 women at four clinical sites. MAIN OUTCOME MEASURES: There were no pregnancies during the 1st year of the study. The continuation rate was 74 per 100 women and a life table expulsion rate of 9.6 and 13.3 per 100 women was observed at 6 and 12 months, respectively. RESULTS: Complications associated with the insertion and the use of this IUD were minimal. Large scale trials evaluating this IUD are in progress.

PIP: The insertion of conventional IUDs during the 1st 10 days after delivery is associated with a high rate of expulsions. The Gyne T 380 (Ortho Pharmaceutical, Canada Ltd., Toronto, Ontario, Canada) IUD was modified by the addition of a loose loop of knotted biodegradable no.2 catgut to the top of the IUD (Gyne T 380 postpartum IUD). After delivery, a special inserter was used to imbed the knotted portion of the loop into the myometrium of the of the uterine fundus. This modified IUD was evaluated in a phase II trial involving 190 women at 4 clinical sites; continuation rate was 74/100 women, the life table expulsion rate as 9.6 and 13.3/100 women observed at 6 and 12 months, respectively. There were no pregnancies during the 1st year of study. Complications associated with the insertion and use of this IUD were minimal and largescale trials evaluating this IUD are now in progress.

Augmentation of acetaminophen analgesia by the antihistamine phenyltoloxamine.

A double-blind, placebo-controlled, parallel-group study was performed to compare the analgesic activity of the combination of 650 mg acetaminophen plus 60 mg phenyltoloxamine citrate with that of 650 mg acetaminophen alone. Two hundred female inpatients who had severe pain associated with a recent episiotomy procedure were randomly assigned to receive a single dose of one of the two active treatments or a placebo. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard subjective scales for pain intensity and relief, a number of derived variables based on these data and two global measures. For essentially all measures, the two active treatments were significantly superior to the placebo control. The combination was significantly superior to acetaminophen alone for all analgesic measures including SPID, TOTAL, and global ratings. The results of this study demonstrate that 60 mg phenyltoloxamine produces significant augmentation of the analgesic activity of 650 mg acetaminophen in postepisiotomy pain.

A double-blind, parallel comparison of ketoprofen, aspirin, and placebo in patients with postpartum pain.

Our purpose was to evaluate the analgesic efficacy of single oral doses of ketoprofen 25, 50, and 100 mg compared with aspirin 650 mg and placebo in the relief of moderate to severe postepisiotomy, uterine cramping, or cesarean section pain. One hundred and fifty-six patients participated in a randomized, double-blind, stratified, parallel-group study. They were observed over a six-hour period by one nurse-observer. Several of the standard summary measures of analgesia were derived from the interview data, including the sum of pain intensity differences (SPID) and the sum of the hourly relief values (TOTAL). The study showed significant differences between aspirin and placebo for four-hour SPID and several other parameters and between ketoprofen at all dose levels and placebo for the four- and six-hour SPID and many other parameters. The two higher doses of ketoprofen were significantly more effective than aspirin as as assessed by the four- and six-hour SPID, TOTAL, and other summary measures. The low dose of ketoprofen, although not significantly different from aspirin for SPID and TOTAL, showed a significantly faster onset of relief and had a better global rating. This study suggests that 50 mg of ketoprofen may be the clinical dose of choice as an analgesic. There were no adverse effects reported.

A comparative oral analgesic study of indoprofen, aspirin, and placebo in postpartum pain.

The purpose of this study was to evaluate the analgesic efficacy and adverse effect liability of single oral doses of indoprofen, 50 mg, 100 mg, and 200 mg, compared with aspirin, 300 mg and 600 mg, and placebo in the relief of moderate to severe postpartum pain. Two hundred-ten patients entered a randomized, double-blind, parallel group study and were evaluated over a six-hour period by a single nurse-observer. There was a significant imbalance in the distribution of pain types across treatments that compromises the interpretation of the results. In addition to analyzing the data from all patients, the subsets with episiotomy/cesarean section pain and uterine cramp pain were examined separately. The latter group had too few patients to permit distinction between drugs. The 100 mg and 200 mg doses of indoprofen were significantly (P less than or equal to .05) more effective than placebo for many variables including the following summary values: sum of pain intensity difference (SPID), sum of hourly relief values (TOTPAR), and % SPID for all patients as well as in the subset of patients with episiotomy/cesarean section pain. Aspirin, 600 mg, was also significantly more effective than placebo for many of the same measures of analgesia in the episiotomy/cesarean section subset. Pairwise differences were also seen between placebo and aspirin, 300 mg, but on fewer variables. Indoprofen, 100 mg, was significantly more effective than aspirin, 600 mg, at hour 6 for pain intensity difference (PID) in the episiotomy/cesarean section subset. The effect of indoprofen appeared to plateau above 100 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Ibuprofen, zomepirac, aspirin, and placebo in the relief of postepisiotomy pain.

Our purpose was to compare the analgesic efficacy of single oral doses of ibuprofen, zomepirac, aspirin, and placebo in severe postepisiotomy pain. One hundred twenty subjects participated in a double-blind, single-dose, parallel-group, 4-hr trial comparing 400 mg ibuprofen, 100 mg zomepirac sodium, 600 mg aspirin, and placebo. For most parameters, including the sum of the pain intensity differences (SPID) and the sum of the hourly pain relief values (TOTAL), which are summary variables, each of the drugs was more effective than placebo. Ibuprofen was more effective than aspirin and zomepirac. Zomepirac and aspirin were equally effective for most of the analgesic variables. There were no adverse effects. Ibuprofen, 400 mg, is an effective oral analgesic and is more effective than 100 mg zomepirac and 600 mg aspirin in most parameters of pain.

Analgesic effect of graded doses of flurbiprofen in post-episiotomy pain.

Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25, 50 and 100 mg, aspirin 600 mg, and placebo in the relief of moderate to severe post-episiotomy pain. One hundred and fifty-two evaluable patients completed a randomized, double-blind, stratified, parallel groups study. They were observed over a six hour period by one nurse-observer. Based upon each of the summary efficacy measures SPID, TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief, each of the four active treatments were statistically superior to placebo. Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg, but the differences were not statistically significant. Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg. There were no observed or reported adverse effects.

Effect of caffeine on acetaminophen analgesia.

Our objective was to determine the value of caffeine in combination with acetaminophen in the relief of pain from uterine cramping, episiotomy, and third molar extraction. In the dental study, 173 patients received two or four tablets of 500 mg acetaminophen or the combination of 500 mg acetaminophen and 65 mg caffeine. In the three postpartum studies, 1345 patients received one, two, or three tablets of acetaminophen, the combination, or a placebo. The mean scores for the summary variable percent sum of the pain intensity differences (% SPID) were higher in all for the combination than for acetaminophen alone, and in two studies the null hypothesis of no differences was rejected. The relative potency estimates for % SPID were 1.9, 1.8, and 1.3 for the three studies in which bioassays could be performed and the pooled relative potency was 1.7 with a 95% confidence interval of 1.1 to 3.1. The results were essentially the same among pain models and among patient groups with similar habitual caffeine consumption. Onset of analgesia was also faster with the combination. We conclude that caffeine enhances the analgesic efficacy of acetaminophen.