Individual patient data meta-analysis of randomized evidence to assess the effectiveness of laparoscopic uterosacral nerve ablation in chronic pelvic pain.

BACKGROUND: There have been conflicting results in randomized trials of the effects of laparoscopic uterosacral nerve ablation (LUNA) in chronic pelvic pain. Our objective was to perform a meta-analysis using individual patient data (IPD) to provide the most comprehensive and reliable assessment of the effectiveness of LUNA. METHODS: Electronic searches were conducted in the Medline, Embase, PsycInfo and Cochrane Library databases from database inception to August 2009. The reference lists of known relevant papers were searched for any further articles. Randomized trials comparing LUNA with no additional intervention were selected and authors contacted for IPD. Raw data were available from 862 women randomized into five trials. Pain scores were calibrated to a 10-point scale and were analysed using a multilevel model allowing for repeated measures. RESULTS: There was no significant difference between LUNA and No LUNA for the worst pain recorded over a 12 month time period (mean difference 0.25 points in favour of No LUNA on a 0-10 point scale, 95% confidence interval: -0.08 to 0.58; P = 0.1). CONCLUSIONS: LUNA does not result in improved chronic pelvic pain.

Communication of adenomyosis with the endometrial cavity: visualization with saline contrast sonohysterography.

We report four cases of a finding of communication between the endometrial cavity and adenomyotic lesions observed during saline contrast sonohysterography. In each case there was a saline-filled defect extending from the endometrial cavity into the myometrium in the region of previously suspected adenomyosis. We believe this finding represents the sonohysterographic correlate of endometrium invading the myometrium, as has been described histologically.

A six-month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia.

OBJECTIVE: A subset of fibromyalgia (FM) patients have a dysfunctional hypothalamic-pituitary-insulin-like growth factor 1 (IGF-1) axis, as evidenced by low serum levels of IGF-1 and a reduced growth hormone (GH) response to physiologic stimuli. There is evidence that pyridostigmine (PYD) improves the acute response of GH to exercise in FM patients. The purpose of this study was to evaluate the clinical effectiveness of 6 months of PYD and group exercise on FM symptoms. METHODS: FM patients were randomized to 1 of the following 4 groups: PYD plus exercise, PYD plus diet recall but no exercise, placebo plus exercise, and placebo plus diet recall but no exercise. The primary outcome measures were the visual analog scale (VAS) score for pain, tender point count, and total myalgic score. Secondary outcome measures were the total score on the Fibromyalgia Impact Questionnaire (FIQ) and FIQ VAS scores for individual symptoms (fatigue, poor sleep, stiffness, and anxiety), as well as quality of life (QOL) and physical fitness (lower body strength/endurance, upper and lower body flexibility, balance, and time on the treadmill). RESULTS: A total of 165 FM patients completed baseline measurements; 154 (93.3%) completed the study. The combination of PYD and exercise did not improve pain scores. PYD groups showed a significant improvement in sleep and anxiety in those who completed the study and in QOL in those who complied with the therapeutic regimen as compared with the placebo groups. Compared with the nonexercise groups, the 2 exercise groups demonstrated improvement in fatigue and fitness. PYD was generally well tolerated. CONCLUSION: Neither the combination of PYD plus supervised exercise nor either treatment alone yielded improvement in most FM symptoms. However, PYD did improve anxiety and sleep, and exercise improved fatigue and fitness. We speculate that PYD may have improved vagal tone, thus benefiting sleep and anxiety; this notion warrants further study.

Meta-analysis using individual patient data from randomised trials to assess the effectiveness of laparoscopic uterosacral nerve ablation in the treatment of chronic pelvic pain: a proposed protocol.

BACKGROUND: Currently, there are a number of clinical trials, but no international collaboration for collating research on effectiveness of laparoscopic uterosacral nerve ablation (LUNA) for alleviating chronic pelvic pain. OBJECTIVE: Meta-analysis was used by collecting individual patient data (IPD) from the existing trials, to provide a comprehensive assessment of the effectiveness of LUNA that will be generalisable in various clinical contexts. METHODS: IPD will be sought and collected from all relevant (both already finished and continuing) randomised trials identified through previous systematic reviews. After obtaining raw data and cleaning the database, analysis will be of all patients ever randomised based on the intention-to-treat principle using endpoints measured at 12 months following randomisation. PROPOSAL: We will update searches, contact all authors, obtain data in whatever form it can be provided, build a single database, produce results for individual studies, have them verified by original authors, explore of any heterogeneity and reasons behind it and finally pool all raw data in to a meta-analysis using appropriate statistical methods. The project will test the effectiveness of LUNA for women with chronic pelvic pain. It will also motivate collaborating primary investigators to undertake new primary studies to corroborate or improve upon the conclusions derived from the retrospective analysis.

The morphology of the koniocellular axon pathway in the macaque monkey.

The key objective of this study was to determine the distribution and morphology of koniocellular (K) lateral geniculate nucleus (LGN) axons in primary visual cortex (V1) of the macaque monkey. In particular, we were interested in understanding whether subpopulations of K axons exist in this species and, if so, if these subpopulations arise from different K layers of the LGN. Restricted injections of the tracers, biotinilated dextran amine, or Phaseolus vulgaris leucoagglutinin were targeted to specific LGN K layers under electrophysiological guidance and immunocytochemistry was used to visualize labeled axons in cortex that were subsequently reconstructed through serial sections. A total of 36 complete axons and 166 axon segments were reconstructed. Our results identified at least 2 main subpopulations of K axons in macaque V1 based on branching patterns and bouton distribution. Axons that arise primarily from LGN layers K1 and K2 are morphologically simple and tend to branch in cortical layers 1 and 3A. These axons give rise to fewer boutons than seen in axons arising from the dorsal K LGN layers K3-K6. Axons that arise from LGN layers K3-K6 terminate as complex, focused arbors in the cytochrome oxidase (CO) blobs in layer 3Balpha, with only occasional simple projections to the more superficial layers of cortex. Combined with previous observations, our data suggest that there are at least 3 subclasses of K LGN axons in macaque monkey that are similar to K axons identified earlier in both nocturnal simian owl monkeys (Ding and Casagrande 1997) and in prosimian, bush babies (Lachica and Casagrande 1992) suggesting that the LGN K channels that terminate in the CO blobs and in layer 1 are not unique to macaque monkeys but are a common primate feature.

Obstipation as a paraneoplastic presentation of small cell lung cancer: case report and literature review.

Paraneoplastic symptoms caused by abnormal gastrointestinal motility may be the initial manifestation of small cell lung cancer (SCLC). We report a case of a 63-year-old woman who presented with progressive constipation culminating in obstipation, and associated symptoms of more widespread dysmotility. A paraneoplastic syndrome was suspected. The only abnormality on chest computed tomography was a minimally enlarged paratracheal lymph node. Positron emission tomography demonstrated increased activity in the lymph node. The antinuclear neuronal antibody titer was elevated. Bronchoscopy with transtracheal biopsy confirmed the diagnosis of SCLC. One year after diagnosis, the patient had progressive symptoms of intestinal obstruction, and ultimately feculent vomiting. On abdominal radiography, colonic sitz markers ingested a year earlier were in virtually the same positions as after ingestion. Palliative colectomy with ileostomy was performed. The myenteric plexus in the terminal ileum and colon showed infiltration by a mixture of B-cell and T-cell lymphocytes and plasma cells, and no gross neuronal abnormalities. We review the clinical and pathologic features, clinical course, and management of paraneoplastic pseudoobstruction.

Genomic progression in mouse models for liver tumors.

The principal cause of human liver cancer is infection with hepatitis viruses B and C, but tumor progression is fueled by ensuing perturbations that confer gain of function on proto-oncogenes or loss of function on tumor suppressor genes. Frequent among these perturbations is overexpression of the proto-oncogene MET. We have modeled the pathogenesis of liver tumors by expressing conditional transgenes of MET in the hepatocytes of inbred mice. The response to the MET transgene varied with both the magnitude and timing of its expression but included hyperplasia of hepatic progenitor cells, as well as benign and malignant tumors that display both phenotypic and genotypic resemblances to human counterparts. The results reveal MET to be a crucial switch in the development of the liver; dramatize how different cellular compartments within a developmental lineage can give rise to distinctive tumor stem cells; delineate rules of tumor progression; provide evidence that the experimental tumors in mice are authentic models for human tumors; and support a role for MET in the genesis of human liver tumors. The models should be useful in elucidating the mechanisms of tumorigenesis and in the preclinical testing of new therapeutics.

Screening for gestational diabetes: a retrospective audit.

There are various indications for screening pregnant women for gestational diabetes. Screening is then often carried out by performing a timed random blood sugar (t-RBS). In this unit a raised t-RBS is an indication to perform a glucose tolerance test (GTT), and if this is abnormal, the patient is managed with dietary modification or insulin therapy. A t-RBS is considered abnormal if the fasting value (> 2 hours since last meal) is > 5.7 mmol/l, or the non-fasting value (<2 hours since last metal) is > 6.3 mmol/l. However, higher t-RBS values have been recommended by the Diabetic Pregnancy Study Group. This group considers a t-RBS abnormal if the fasting value is > 6.1 mmol/l, or the non-fasting value is > 7.0 mmol/l. A retrospective audit was carried out to determine if cases of gestational diabetes would have been missed if the new guidelines were adopted. There were 112 patients with a fasting t-RBS of 5.8 to 6.1 mmol/l, inclusive, and 196 patients with a non-fasting t-RBS of 6.4 to 7.0 mmol/l, inclusive; 45 patients did not have a GTT result. Therefore 263 patients were included in the study. The number of patients with a normal GTT result was 257 (97.7%), and 6 (2.30%) patients had an abnormal GTT result. Only 4 (1.52%) were labelled as gestational diabetics, and all these cases were managed with diet alone with no adverse obstetric outcome. A large number of GTTs are performed unnecessarily in our unit, and the values recommended by the Diabetic Pregnancy Study Group should be adopted.

Recurrence of chocolate cysts after laparoscopic ablation.

STUDY OBJECTIVE: To estimate the recurrence rate of chocolate cysts 3 to 12 months after ablative laparoscopic surgery. The secondary outcome measure was the need for a repeat surgical procedure. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: Tertiary referral center for laparoscopic treatment of endometriosis. PATIENTS: Seventy-three consecutive women with chocolate cysts larger than 2 cm. INTERVENTION: Laparoscopy at which cyst capsules were vaporized or coagulated with the potassium-titanyl-phosphate (KTP) laser or Bicap bipolar diathermy. MEASUREMENTS AND MAIN RESULTS: There were 96 cysts (23 bilateral) in 73 women (1 patient underwent a two-stage procedure). Their mean diameter was 4.79 cm (range 2-25 cm). The median r-AFS score was 56 (range 22-128), and 55 patients (75.3%) had stage 4 disease. The KTP laser was used in 50 women (68.5%) and bipolar diathermy in 23 (31.5%). At 12 months, 5 patients (6.9%) were lost to follow-up, and 12 had a recurrent cyst. Therefore, the cyst recurrence rate/patient was 16.4% (12/73) and the rate/cyst was 12.5% (12/96). Women who had recurrences were significantly more likely to have bilateral cysts, 7/12 (58.3%), than those with single cysts, 16/61 (26.2%, p =0.032). Bicap bipolar diathermy was associated with a recurrence rate of 20.8% (5/24). The rate in women who had KTP laser ablation was 14.3% (7/49, NS). Eighteen patients had repeat operations (including on recurrent cysts). Therefore the reoperation rate was 24.6% (18/73). No major surgical complications occurred. One woman had a postoperative wound infection after a second procedure to remove an ovary with a recurrent cyst. CONCLUSION: Laparoscopic cyst fenestration followed by capsule ablation is safe and effective treatment for preventing recurrence of chocolate cysts.

Laser laparoscopy for endometriosis and endometriotic cysts.

BACKGROUND: Endometriosis is a common and debilitating condition involving women during their reproductive years. It is characterized by the occurrence of endometrial glands and stroma outside the uterine cavity. Presenting symptoms include chronic nonmenstrual pelvic pain, dysmenorrhea, dyspareunia, and subfertility. The condition is diagnosed at laparoscopy, and operative laparoscopic surgery for endometriosis is also possible. METHODS: This article critically evaluates the evidence for the laparoscopic management of endometriosis and endometriotic cysts. It focuses on laser laparoscopy and reviews the contribution made by the Minimal Access Therapy Training Unit, Guildford, UK, to the treatment of this condition. RESULTS: Few randomized controlled trials have been undertaken to evaluate the surgical management of endometriosis. The studies that have been done show that laparoscopic surgery, including laser laparoscopy, is effective in the management of painful symptoms and subfertility and preventing cyst recurrence. Several of the landmark studies in this area have been carried out in Guildford. CONCLUSION: Laparoscopic surgery is the treatment of choice for patients with endometriosis and endometriotic cysts.

The ovarian endometrioma: why is it so poorly managed? Indicators from an anonymous survey.

As a tertiary referral centre for women with severe endometriosis we see a large number of patients who have endometriotic cysts, and many of these patients have been operated on by gynaecologists elsewhere in the UK. We have been surprised by the variety of approaches to their management. In order to establish the current clinical practices of endometrioma management amongst gynaecologists in the UK, we have carried out an anonymous survey. There appears to be an equal preference for open versus endoscopic surgery, even though there is considerable evidence suggesting that endoscopic surgery is superior. However, the management of endometriomas varies significantly between the two groups. In this article, we have presented the results of our survey and used them as the basis for a debate on the management of endometriomas.

Long term outcome following laparoscopic supracervical hysterectomy.

OBJECTIVES: To assess the long term outcome of laparoscopic supracervical hysterectomy. DESIGN: Retrospective study. SETTING: Minimal Access Surgical Unit, Department of Gynaecology, Royal Surrey County Hospital, Surrey. METHODS: Analysis of patient case records. POPULATION: Seventy consecutive women who had a laparoscopic supracervical hysterectomy. OUTCOME MEASURES Symptoms related to the cervical stump and the need for further surgery. RESULTS: The mean time of patient follow up was 66 months (range 52-84). The mean time from initial procedure to second treatment was 14 months (range 3-53). Seventeen women (24.3%) reported symptoms related to the cervical stump, and all required further surgery. The cervical stump was removed in 16 (22.8%). One patient had laparoscopic adhesiolysis only and two had a laparotomy and trachelectomy because the bowel was adherent to the cervical stump. Nine had a laparoscopically assisted cervical trachelectomy as the sole procedure. Five had laser treatment to endometriotic deposits, and laparoscopically assisted cervical trachelectomy. Histological analysis showed normal cervical tissue in six (35.3%). Endometriosis was detected in four cervical stumps (23.5 %), residual endometrium in another four (23.5 %) cases, and chronic cervicitis, mild CIN and a mucocoele in a further three patients. Of the 17 women who reported cervical stump symptoms, 14 (82.3%) had been treated for endometriosis in the past, compared with 17/53 (32%) who did not have symptoms (P < 0.0002, chi2 test). CONCLUSIONS: Symptoms related to the cervical stump requiring further surgery frequently occur following a laparoscopic supracervical hysterectomy.

Long-term follow-up of a controlled trial of laser laparoscopy for pelvic pain.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the long-term efficacy of laparoscopic laser surgery in the treatment of painful pelvic endometriosis. METHODS: We conducted a long-term follow-up of 56 patients who had participated in a randomized, double-blind controlled study at a tertiary referral center for the laparoscopic treatment of endometriosis. The patients had pelvic pain, minimal-to-moderate endometriosis, and underwent laser laparoscopy. We asked patients whether they had now achieved satisfactory symptom relief or whether they had received any further medical intervention for their endometriosis. The main outcome measure was continued symptom relief after treatment and subsequent medical history. RESULTS: Of the original 56 patients, we were able to contact 38 (67.9%). The mean (range) time since operation was 73 months. Painful symptoms had recurred in 28/38 (73.7%) patients at some point since their operation. The median (range) time for recurrence was 19.7 (5-60) months. At the time of follow-up, satisfactory symptom relief was reported in 21/38 (55.3%) patients. The remaining 17/38 (44.7%) patients continued to experience painful symptoms, and eight eventually had a hysterectomy. CONCLUSIONS: This study suggests that operative laparoscopy can have long-term benefits for the majority of women with pelvic pain due to endometriosis, but because of the small numbers, this study lacks the power to demonstrate this conclusively.

Exercise for patients with fibromyalgia: risks versus benefits.

Although exercise in the form of stretching, strength maintenance, and aerobic conditioning is generally considered beneficial to patients with fibromyalgia (FM), there is no reliable evidence to explain why exercise should help alleviate the primary symptom of FM, namely pain. Study results are varied and do not provide a uniform consensus that exercise is beneficial or what type, intensity, or duration of exercise is best. Patients who suffer from exercise-induced pain often do not follow through with recommendations. Evidence-based prescriptions are usually inadequate because most are based on methods designed for persons without FM and, therefore, lack individualization. A mismatch between exercise intensity and level of conditioning may trigger a classic neuroendocrine stress reaction. This review considers the adverse and beneficial effects of exercise. It also provides a patient guide to exercise that takes into account the risks and benefits of exercise for persons with FM.