The vaginal microcirculation after prolapse surgery.

AIMS: Oxygen plays a crucial role in wound healing after prolapse surgery. Trauma to the vaginal vasculature might limit the delivery of oxygen to the surgical wound, which may negatively affect wound healing and regeneration of connective tissue. This possibly increases the future risk of recurrence. We aimed to determine the effects of vaginal prolapse surgery on the microcirculation of the vaginal wall. METHODS: We evaluated the vaginal microcirculation in healthy participants without known vascular disease undergoing anterior and/or posterior colporrhaphy. We used incident dark-field imaging for in vivo assessment before and after (1 day, 2 weeks, and 6 weeks) surgery. We studied perfusion (microvascular flow index [MFI]), angioarchitecture (morphology/layout of microvessels) and capillary density. RESULTS: Ten women were included. Interindividual differences were observed 1 day postoperatively with regard to perfusion and angioarchitecture. Microvascular flow at the surgical site was absent or significantly reduced in some participants, whereas normal microvascular flow was observed in others (MFI range 0-3). Perfusion and angioarchitecture had been restored in all participants after 6 weeks (MFI range 2-3), regardless of the extent of vascular trauma 1 day postoperatively. CONCLUSIONS: The difference in the extent of vascular trauma between women undergoing seemingly identical surgical procedures suggests that some individuals are more susceptible to vascular trauma than others. Delivery of oxygen to the wound and subsequent wound healing may be compromised in these cases, which could be related to the development of anatomical recurrence. Future studies should investigate whether there is a relationship between the vaginal microvasculature and the recurrence of prolapse.

Comparing cytotoxic backbones for first-line trastuzumab-containing regimens in human epidermal growth factor receptor 2-positive advanced oesophagogastric cancer: A meta-analysis.

According to the Trastuzumab for Gastric Cancer (ToGA) study, trastuzumab plus cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced oesophagogastric cancer. We examined the relative efficacy and safety of alternative trastuzumab-based cytotoxic backbone regimens compared to the standard ToGA regimen using meta-analysis. We searched Medline, EMBASE, CENTRAL and ASCO and ESMO up to March 2017 for studies investigating alternative first-line trastuzumab-based regimens for HER2-positive oesophagogastric cancer, defined as high protein expression IHC3+ or IHC2+ and gene amplification by in situ hybridisation. We compared primary outcome overall survival (OS) of alternative trastuzumab-based regimens to the ToGA regimen. Hazard ratios (HRs) and 95% confidence intervals (95%CI) were calculated by extraction of the published Kaplan-Meier curves. Incidence counts and toxicity sample-sizes were extracted for adverse events and compared using single-arm proportion meta-analysis in R. Fifteen studies (N = 557 patients) were included. OS was significantly longer with regimen trastuzumab plus doublet oxaliplatin and capecitabine/5-FU (median OS = 20.7 months) versus ToGA (16.0 months, HR = 0.75, 95% CI = 0.59-0.99) and was less toxic. Trastuzumab plus doublet cisplatin and S-1 showed no OS difference versus ToGA, but showed a different toxicity profile, including less hand-foot syndrome. Trastuzumab plus cisplatin or capecitabine as singlet backbone showed significantly worse survival and more toxicity versus ToGA regimen. Trastuzumab with triplet cytotoxic backbones or with bevacizumab and doublet cytotoxic backbone showed no survival benefit and more toxicity. In conclusion, trastuzumab plus doublet cytotoxic backbone containing oxaliplatin is preferable over the ToGA regimen with cisplatin. S-1 can substitute capecitabine or 5-FU when specific toxicities are encountered.

Continuation of trastuzumab beyond progression in HER2-positive advanced esophagogastric cancer: a meta-analysis.

INTRODUCTION: After progression on first-line trastuzumab-based therapy, no HER2-targeted agent is available for patients with HER2-positive esophagogastric cancer. However, continuation of trastuzumab after progression is an established strategy in HER2-positive breast cancer. We conducted a meta-analysis to investigate whether continuation of trastuzumab beyond first-line therapy in combination with chemotherapy is more effective compared to chemotherapy-alone. METHODS: PubMed, EMBASE, CENTRAL and meeting abstracts from ASCO and ESMO were searched up to June 2018 for studies (any design) investigating second-line trastuzumab plus chemotherapy compared to chemotherapy-alone for patients with HER2-positive esophagogastric cancer that progressed on first-line trastuzumab-based therapy. Meta-analysis was performed on the primary outcome, overall survival (OS), and on secondary outcomes progression-free survival (PFS), objective-response rate (ORR), and adverse events. RESULTS: Four cohort studies and one randomized controlled trial (RCT) were included with n = 200 patients who received second-line trastuzumab plus chemotherapy and n = 183 who received chemotherapy-alone. Meta-analysis showed that trastuzumab plus chemotherapy did not prolonged OS [HR = 0.72, 95% confidence interval (95% CI) = 0.47-1.08, p=.11). PFS was longer with trastzumab plus chemotherapy compared to chemotherapy-alone (HR = 0.64, 95% CI = 0.45-0.91, p<.05). There was no significant difference in ORR between the trastuzumab plus chemotherapy-group and the chemotherapy-alone group (ORR = 19.1% versus ORR = 13.4%, p=.13) and no significant differences in grade 3/4 and grade 1/2 adverse events. CONCLUSIONS: This meta-analysis showed that patients who progressed on first-line trastuzumab-based therapy but of whom trastuzumab was continued in second-line and added to chemotherapy did not show longer OS or a higher ORR compared to patients receiving second-line chemotherapy-alone. However, PFS was prolonged and trastuzumab was not associated with additional safety concerns. In absence of available second-line HER2-targeted agents, a large prospective RCT should investigate if continuation of trastuzumab might be an attractive strategy, as this meta-analysis was mostly based on non-randomized studies and a RCT with a small sample size.

The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis.

Background: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs). Results: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies, n = 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies, n = 10,761) and 14 for DFS (30 studies, n = 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38⁻0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58⁻1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28⁻0.80). Conclusions: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.