Expression levels of circulating miRNAs as biomarkers during multimodal treatment of rectal cancer - TiMiSNAR-mirna: a substudy of the TiMiSNAR Trial (NCT03962088).

BACKGROUND: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading and lymph node status helped to visualize individual tumor sensitivity to chemoradiotherapy, retrospectively. As the response to neoadjuvant chemoradiotherapy is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed. MicroRNAs are currently under investigation to serve as blood-based biomarkers. To date, no screening approach to identify relevant miRNAs as biomarkers in blood of patients with rectal cancer was undertaken. The aim of the study is to investigate the role of circulating miRNAs as biomarkers in those patients included in the TiMiSNAR Trial (NCT03465982). This is a biomolecular substudy of TiMiSNAR Trial (NCT03962088). METHODS: All included patients in the TiMiSNAR Trial are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery, and after adjuvant chemotherapy whenever indicated. DISCUSSION: TiMiSNAR-MIRNA will evaluate the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pathological complete response. Moreover, the study will evaluate the role of liquid biopsies in the monitoring of treatment, correlate changes in expression levels of miRNA following complete surgical resection with disease-free survival, and evaluate the relation between changes in miRNA during surveillance and tumor relapse. TRIAL REGISTRATION: Clinicaltrials.gov NCT03962088 . Registered on 23 May 2019.

Correction to: Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR).

Following publication of the original article [1], the authors reported that the family name of the author, Ludovica Baldari, was misspelled.

Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR).

BACKGROUND: The optimal timing of surgery in relation to chemoradiation is still controversial. Retrospective analysis has demonstrated in the recent decades that the regression of adenocarcinoma can be slow and not complete until after several months. More recently, increasing pathologic Complete Response rates have been demonstrated to be correlated with longer time interval. The purpose of the trial is to demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathologic Complete Response and reflects on disease-free survival and overall survival rather than standard timing. METHODS: The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and forty patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8 weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12 weeks. DISCUSSION: To date, it is well-know that pathologic Complete Response is associated with excellent prognosis and an overall survival of 90%. In the Lyon trial the rate of pCR or near pathologic Complete Response increased from 10.3 to 26% and in retrospective studies the increase rate was about 23-30%. These results may be explained on the relationship between radiation therapy and tumor regression: DNA damage occurs during irradiation, but cellular lysis occurs within the next weeks. Study results, whether confirmed that performing surgery after 12 weeks from neoadjuvant treatment is advantageous from a technical and oncological point of view, may change the current pathway of the treatment in those patient suffering from rectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT3465982.

Male-to-Female (MtoF) gender affirming surgery: Modified surgical approach for the glans reconfiguration in the neoclitoris (M-shape neoclitorolabioplasty).

PURPOSE: The aim of this article is to describe our modified surgical technique for the reconfiguration of the glans in the clitoris and the labia minora, known as the "M-shape neoclitorolabioplasty". METHODS: The glans with all its neurovascular bundle is isolated from the corpora cavernosa, incised in Y-shape mode and spread in order to obtain an M-shape glandular flap. The "belly" of the M-shape glans will constitute the triangular neoclitoris meanwhile the lateral flaps will constitute the labia minora. The inferior apex of the neoclitoris is fixed to the superior apex of the previously spatulated urethra. The two glans flaps are incised transversally to increase their length and sutured to the sides of the spatulated urethra forming the labia minora. Our technique permits to create an aesthetically pleasing neovagina preserving all the glandular erogenous sensitivity. RESULTS: 94 patients have been treated with our modified technique of male-to-female (MtoF) gender affirming surgery. At median follow-up of 27.57 months, 81 (86.1%) patients reported vaginal intercourse and 78 (82.9%) patients referred presence of erogenous sensitivity during dilatations, intercourse or masturbations. All the glandular tissue is preserved and reconfigured forming the neoclitoris and the labia minora. The M-shape reconfiguration permit to create an aesthetically pleasant neoclitoris. CONCLUSIONS: This technique could be applied safely and easily to patients undergoing gender affirming surgery, allowing the creation of a neovagina with the best possible erogenous sensitivity without losing aesthetical results.

Systematic review of studies reporting perioperative and functional outcomes following male-to-female gender assignment surgery (MtoF GAS): a call for standardization in data reporting.

INTRODUCTION: The aim of this study is to accomplish a systematic review on the surgical techniques available for male-to-female gender assignment surgery (MtoF GAS) published in the last 15 years, from January 2002 to May 2017, assessing advantages and disadvantages. EVIDENCE ACQUISITION: A specific search on MEDLINE, Scopus and Web of Science databases included vaginoplasty for gender exchange. Preoperative (age, gender, body mass index, prior surgery), intraoperative (mean operating time, intraoperative complications, transfusion rate, conversion rate), postoperative (hospital stays, readmission rate, early and late complication rate), postoperative sexual activity, subjective satisfaction, vaginal depth, and long-term outcomes (vaginal stenosis, prolapse, dyspareunia and labial abscess) data of vaginoplasty for sexual exchange were collected. 29 articles were included (2.402 patients). EVIDENCE SYNTHESIS: Out of the 29 papers, 19 studies assessed penile skin inversion and 10 evaluated intestinal vaginoplasty. No comparative studies were found. Penile skin inversion vaginoplasty reported slightly shorter operative time compared to intestinal vaginoplasty (109-420 vs 145-420 minutes). Intraoperative complications for penile skin inversion vaginoplasty not exceeded an incidence of 10%. No significant differences in terms of postoperative complications or hospitalization time were reported. Intestinal vaginoplasty provides a deeper neovagina. Female Sexual Function Index score was significantly higher in patients undergoing intestinal vaginoplasty. CONCLUSIONS: A standardized data collection may allow a better understanding of effectiveness and outcomes of different techniques.

Control Comparison of the New EndoWrist and Traditional Laparoscopic Staplers for Anterior Rectal Resection with the Da Vinci Xi: A Case Study.

Background: A new robotic stapler for the da Vinci Xi® is directly controlled by the surgeon at the console and equipped with EndoWrist® technology. We evaluated operative and short-term results of the first patients who underwent anterior rectal resection for cancer with the da Vinci Xi and new staplers, and compared the results with those of a comparable group treated with traditional laparoscopic staplers. Methods: From December 2015 to December 2017, 25 patients underwent anterior rectal resection for cancer with robotic EndoWrist staplers (EndoWrist group). Using a case-control method, we compared the results with those of a similar group of patients treated with the same system and a traditional laparoscopic endostapler, controlled by a bedside assistant (Control group). Results: No conversions to laparoscopy or laparotomy were observed, in either group. The mean number of charges was 2.1 ± 0.2 in the EndoWrist group versus 2.7 ± 0.7 in the Control group (P = .0004). The other perioperative results were comparable. During follow-up, the incidence of anastomotic fistula in a contrast enema study was higher in the Control group, although the difference was not statistically significant (two leaks versus two leaks in EndoWrist group; P = .8). The interval between rectal resection and stoma closure was shorter in the EndoWrist group (3.4 ± 2.5 versus 4.2 ± 2.9 months in the Control group; P = .2), although the difference was not significant. Conclusions: Our experience suggests that the new robotic staplers simplify transection, which could reduce the average number of stapler firings used during rectal resection and could decrease the incidence of anastomotic leakage. These findings require confirmation in larger studies.

The role of laparoscopic resection of metastases to adrenal glands.

BACKGROUND: The potential role of the laparoscopic approach for metastases to the adrenal gland is debated. We review here a series of patients consecutively submitted to laparoscopic adrenalectomy (LA) for suspected adrenal metastasis (AM). METHODS: Retrospective study (consecutive series) of LA for AM. We measured parameters associated to primary tumor and metastasis. Statistical analysis: stepwise regression model. RESULTS: Thirty-seven LA were performed on 36 patients. The mean age was 62.1 yrs. The side was right in 13 cases. Primary tumor was in the lung (n=22), breast (n=4), colon-rectum (n=4), kidney (n=3), thyroid, melanoma and ovary (n=1 each). Thirty-three out of 37 were confirmed to be AM (mean diameter 50 mm). Twenty-five were single metastasis. One LA was converted due to cava vein infiltration. Mean operative time was 142 min', median p.o. hospital stay was 3 days. After a mean follow-up of 33 months, 9 patients (25%) were alive free of disease, 6 (17%) were alive with disease. Mean post-adrenalectomy DFI was 19 months (range, 0-97 months), and it was the most predictive variable for survival (P<0.001). CONCLUSIONS: The dimensions and absence of invasion on imaging, the evolutive status of the disease and the performance status of the patient are key factors for LA, which is associated with adequate oncologic results, a quicker postoperative recovery, and potential survival benefits.

Near total parathyroidectomy for the treatment of renal hyperparathyroidism.

BACKGROUND: Different surgical strategies are used to treat medical refractory renal hyperparathyroidism. Our preferred choice in patients with moderate secondary hyperparathyroidism (SHPT) and in patients with low compliance with medical treatment is to leave a very small parathyroid remnant in situ: we name this operation "near total parathyroidectomy" (ntPTX). We report here our results with this technique. METHODS: Retrospective study [2001-2015] of all patients submitted to ntPTX in a single centre. RESULTS: Forty-seven patients were submitted to ntPTX (32 males) aged 47.3 years. Follow-up time is 8.5 years. Thirty-five patients (74%) are alive, 12 are dead. One patient in this series had a functioning renal transplant at time of ntPTX (tertiary hyperparathyroidism), and other 27 subsequently received a renal transplantation (RTx) after ntPTX (still functioning at last follow-up or at death in 19). Amongst the 35 current survivors, the renal graft is functioning in 16 (45.7%). Parathyroid hormone (PTH) at follow-up was 116.1±135.5 pg/mL and calcium 8.6±0.9 mg/dL. Among patients with a functioning RTx PTH was 83 pg/mL and calcium 8.7 mg/dL. There was no persistent disease, and 3 patients (6.4%) had a relapse of hyperparathyroidism at follow-up. CONCLUSIONS: ntPTX is associated to very satisfying rates of normal parathyroid function and of relapse of hyperparathyroidism (6.4%) at long term, either in case of RTx or of maintenance hemodialysis: the concept of "small amount" remnant represents a valuable choice for patients undergoing PTX with a realistic chance of receiving a RTx.