Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome : a prospective randomized multinational study

BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment. METHODS: Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR. RESULTS: Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95 confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI. CONCLUSIONS: Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.peer-reviewe

Developing and assessing a cadaveric training model for transanal total mesorectal excision: initial experience in the UK and USA.

AIM: Transanal Total Mesorectal Excision (taTME) has become one of the most promising technical advancement in the surgical treatment of rectal cancer, with rising numbers of surgeons seeking training. We describe our experience with human cadaveric courses for taTME delivered in two countries. METHOD: Four fresh human cadaveric workshops conducted in Oxford, UK in 2015 and two in Chicago, USA in 2013-2014, trained a total of 52 surgeons. Parameters of operative performance for each delegate were recorded. Previous surgical experience and uptake of taTME in the surgeons&apos; clinical setting were surveyed. RESULTS: 47 taTME cases were performed on cadaveric models. Participating surgeons had previous experience in laparoscopic TME surgery and transanal approaches but limited taTME exposure. The purse-string remained occluded throughout in 93% of UK and 60% of USA cases. Operative timings for key procedural steps were similar between the two countries with mean time from start of circumferential dissection to peritoneal entry of 79.5 minutes (range=25-155). 96% of surgeons dissected transanally to a level S2 or above. The TME specimen quality was complete or near complete in 81%, with improvements noted between the first and second procedure performed. 81% of surgeons surveyed are currently performing taTME in their local hospitals. CONCLUSION: Fresh frozen cadavers provide excellent teaching models for complex pelvic surgery. A structured training curriculum including reading material, dry-lab purse-string practice and post-course mentorship will provide surgeons a more complete training package and ongoing support, to ultimately ensure the safe introduction of taTME in the clinical setting

Outcomes following completion and salvage surgery for early rectal cancer: A systematic review

Objectives To establish outcomes after completion and salvage surgery following local excision in literature published since 2005, to inform decision-making when offering local excision. Background Local excision of early rectal cancer aims to offer cure while maintaining quality of life through organ preservation. However, some patients will require radical surgery, prompted by unexpected poor pathology or local recurrence. Consistent definition and reporting of these scenarios is poor. We propose the term “salvage surgery” for recurrence after local excision and “completion surgery” for poor pathology. Methods Electronic databases were searched in February 2016. Studies since 2005 describing outcomes for radical surgery following local excision of rectal cancer were included. Pooled and average values were obtained. Results A total of 23 studies included 262 completion and 165 salvage operations. Most completion operations were done within 4 weeks; local recurrence rate was 5% and overall disease recurrence rate was 14%. The majority of salvage operations for local recurrence were within 15 months of local excision, often following adjuvant treatment. Re-do local excision was used in 15%; APR was the most common radical procedure. Further local recurrence was uncommon (3%) but overall disease recurrence rate was 13%. Estimated 5-year survival was in the order of 50%. Heterogeneity was high among the studies. Conclusions Patients undergoing local excision must be informed of risks and expected outcomes, but better data on completion and salvage surgery are required to achieve this

Water Management Solution of Reservoir Storage Function Under Condition of Measurement Uncertainties in Hydrological Input Data

AbstractThe paper describes a possible procedure of the rate uncertainty implementation to the continuous water stage measurement and uncertainties of state - discharge rating curve point positions, which the stage -discharge rating curves were fitted into the uncertainties of the real discharge series members. Then the members of discharge series under uncertainty impact were tested on the calculated values of the reservoir storage volume. The next step was the implementation of the uncertainties of the real discharge series members on the generation of the artificial discharge series of mean monthly discharge using the AR and ARMA generators and the determination of their impact on the calculated values of the reservoir storage volume

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STUDY QUESTION: What is the cost-effectiveness of in vitro fertilization(IVF) with conventional ovarian stimulation, single embryotransfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?. SUMMARY ANSWER: Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy. Whether IVF-SET is cost-effective depends on society's willingness to pay for an additional healthy child. WHAT IS KNOWN ALREADY: IUI-COH and IVF, either after conventional ovarian stimulation or in a MNC, are used as first-line treatments for couples with unexplained or mild male subfertility. As IUI-COH is less invasive, this treatment is usually offered before proceeding to IVF. Yet, as conventional IVF with SET may lead to higher pregnancy rates in fewer cycles for a lower multiple pregnancy rate, some have argued to start with IVF instead of IUI-COH. In addition, IVF in the MNC is considered to be a more patient friendly and less costly form of IVF. STUDY DESIGN, SIZE, DURATION: We performed a cost-effectiveness analysis alongside a randomized noninferiority trial. Between January 2009 and February 2012, 602 couples with unexplained infertility and a poor prognosis on natural conception were allocated to three cycles of IVF-SET including frozen embryo transfers, six cycles of IVF-MNC or six cycles of IUI-COH. These couples were followed until 12 months after randomization. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected data on resource use related to treatment, medication and pregnancy from the case report forms. We calculated unit costs from various sources. For each of the three strategies, we calculated the mean costs and effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated for IVF-SET compared with IUI-COH and for IVF-MNC compared with IUI-COH. Nonparametric bootstrap resampling was used to investigate the effect of uncertainty in our estimates. MAIN RESULTS AND THE ROLE OF CHANCE: There were 104 healthy children (52%) born in the IVF-SET group, 83 (43%) the IVF-MNC group and 97 (47%) in the IUI-COH group. The mean costs per couple were (sic)7187 for IVF-SET, (sic)8206 for IVF-MNC and (sic)5070 for IUI-COH. Compared with IUI-COH, the costs for IVF-SET and IVF-MNC were significantly higher (mean differences (sic)2117; 95% CI: (sic)1544-(sic)2657 and (sic)3136, 95% CI: (sic)2519-(sic)3754, respectively). The ICER for IVF-SET compared with IUI-COH was (sic)43 375 for the birth of an additional healthy child. In the comparison of IVF-MNC to IUI-COH, the latter was the dominant strategy, i.e. more effective at lower costs. LIMITATIONS, REASONS FOR CAUTION: We only report on direct health care costs. The present analysis is limited to 12 months. WIDER IMPLICATIONS OF THE FINDINGS: Since we found no evidence in support of offering IVF as a first-line strategy in couples with unexplained and mild subfertility, IUI-COH should remain the treatment of first choice

Modern management of T1 rectal cancer by TEM:a ten-year single-centre experience.

Aim Minimally-invasive, organ-sparing surgery has been used increasingly for early rectal cancer in recent years. However local recurrence remains a concern. This study presents a ten-year single-centre experience of recurrence after local excision for T1 rectal cancer. Method Data are collected prospectively on all patients undergoing local excision by transanal endoscopic microsurgery (TEM) in a single institution. Data covering a 10-year period were analysed. Results 192 patients underwent TEM for rectal cancer; 70 of these had T1 tumour in the TEM specimen and did not have pre-operative radiotherapy. Four were managed with completion surgery following TEM and a further six had radiotherapy, 60 underwent surveillance alone. Local recurrence occurred in six patients, three underwent salvage surgery. Estimated local recurrence at 3 years was 7.2% for the surveillance alone group. Conclusions Local recurrence rates were lower than previous studies. Better pre-operative assessment, more effective local excision surgery and post-operative radiotherapy may be contributory factors to a better-than-predicted outcome. Local excision should be offered as part of standard of care for T1 rectal cancer in the presence of good pre-operative selection and meticulous surveillance

Intraoperative identification and analysis of lymph nodes at laparoscopic colorectal cancer surgery using fluorescence imaging combined with rapid OSNA pathological assessment

Background Standard surgical practice for colorectal cancer involves resection of the primary lesion and all draining lymph nodes. Accurate intraoperative assessment of nodal status could allow stratified resectional extent. One-step nucleic acid (OSNA) can provide a rapid method of interrogating nodal tissue, whilst near-infrared (NIR) laparoscopy together with indocyanine green (ICG) can identify relevant nodal tissue intraoperatively. Methods ICG was administered around the tumour endoscopically prior to the operation. Fluorescent nodes identified by NIR were marked and submitted for whole-node OSNA analysis. Further fresh lymph nodes dissected from the standard resection specimen were examined and analysed by both conventional histology and OSNA. In addition, the status of the fluorescent nodes was compared to that of non-ICG nodes to assess their predictive value. Results Sixteen patients were recruited with a total final lymph node count of 287. 78 fresh lymph nodes were identified on fresh dissection for both histological and OSNA assessment with an analytical concordance rate of 98.7% (77/78). OSNA sensitivity was 1 (0.81–1, 95% CI) and specificity 0.98 (0.91–1, 95% CI). Six patients had a total of nine nodes identified intraoperatively by ICG fluorescence. Of these nine nodes, one was positive for metastasis on OSNA. OSNA analysis of the ICG-labelled node matched the final histological nodal stage in 3/6 patients (two being N0 and one N1). The final pathological nodal stage of the other three was N1 or N2, while the ICG nodes were negative. Conclusion OSNA is highly concordant with standard histology, although only a minority of nodes identifiable by full pathological analysis were found for OSNA on fresh dissection. OSNA can be combined with NIR and ICG lymphatic mapping to provide intraoperative assessment of nodal tissue in patients with colorectal cancer

Transanal total mesorectal excision: a pure NOTES approach for selected patients

Background: The concept of natural orifice transluminal endoscopic surgery (NOTES) has stimulated the development of various “incisionless” procedures. One of the most popular is the transanal approach for rectal lesions. The aims of this study were to report how we standardized NOTES technique for transanal mesorectal excision without abdominal assistance, discuss the difficulties and surgical outcomes of this technique and report its feasibility in a small group of selected patients. Methods: Three consecutive female patients underwent transanal NOTES rectal resection without transabdominal laparoscopic assistance for rectal lesions. Functional results were assessed with the Fecal Incontinence Quality of Life scale and the Wexner score. Results: The technical steps are described in details and complemented with a video. All procedures were completed without transabdominal laparoscopic help. The mesorectal plane was entirely dissected without any disruption, and distal and circumferential margins were tumor-free. No major complications were observed. Functional results show a significant impairment after surgery with improvement at 6 months to levels near those of the preoperative period. Conclusions: The performance and publication of NOTES procedures are subject to much discussion. Despite the small number of patients, this procedure appears feasible and can be accomplished maintaining fecal continence and respecting oncologic principles

Usefulness of CT scan as part of an institutional protocol for proactive leakage management after low anterior resection for rectal cancer

Purpose: Highly selective fecal diversion after low anterior resection (LAR) for rectal cancer requires a strict postoperative protocol for early detection of anastomotic leakage (AL). The purpose of this study was to evaluate C-reactive protein (CRP)–based CT imaging in diagnosis and subsequent management of AL. Methods: All patients that underwent a CT scan for suspicion of AL after transanal total mesorectal excision for rectal cancer in a university center (2015–2020) were included. Outcome parameters were diagnostic yield of CT and timing of CT and subsequent intervention. Results: Forty-four out of 125 patients underwent CT (35%) with an overall median interval of 5 h (IQR 3–6) from CRP measurement. The anastomosis was diverted in 7/44 (16%). CT was conclusive or highly suspicious for AL in 23, with confirmed AL in all those patients (yield 52%), and was false-negative in one patient (sensitivity 96%). CT initiated subsequent intervention after median 6 h (IQR 3–25). There was no or minor suspicion of AL on imaging in all 20 patients without definitive diagnosis of AL. After CT imaging on day 2, AL was confirmed in 0/1, and these proportions were 6/6 for day 3, 7/10 for day 4, 2/4 for day 5, and 9/23 beyond day 5. Conclusion: In the setting of an institutional policy of highly selective fecal diversion and pro-active leakage management, the yield of selective CT imaging using predefined CRP cut-off values was 52% with a sensitivity of 96%, enabling timely and tailored intervention after a median of 6 h from imaging.</p