"Pelvic neuro-visualization: an anatomical illustration of the autonomic pelvic nervous network in gynecologic surgery".

OBJECTIVE: During radical pelvic surgeries fibers of the autonomic pelvic nervous network can be accidentally damaged leading to significant visceral sequelae, which dramatically affect women's quality of life because of urinary, anorectal, and sexual postoperative dysfunctions.1,2 Direct visualization is one way to preserve hypogastric nerves(HNs), pelvic splanchnic nerves(PSNs), and the bladder branches from the inferior hypogastric plexus(IHP). However, the literature lacks critical photos and/or illustrations that are necessary to understand the precise anatomy needed to preserve the pelvic autonomic fibers. DESIGN: Narrated laparoscopic video footage for identifying, dissecting, and preserving the autonomic nerve bundles during pelvic surgery. SETTING: Tertiary level hospital - "IRCCS Istituto Nazionale dei Tumori", Milano, Italy. INTERVENTIONS: Visceral pelvic innervation is established by the superior hypogastric plexus(SHP) located anteriorly to the aortic bifurcation and the median sacral vessels and carries mostly sympathetic fibers. SHP divides in front of the sacrum into the right and left HN. At the level of the paracervix, the HNs join the parasympathetic PSNs coming out from sacral root S2, S3, S4 to form the IHP.2-5 Here, we performed laparoscopic surgery, before "Laparoscopic Approach to Cervical Cancer" trial (LACC) era, identifying key anatomic landmarks useful to highlight the path of the most commonly encountered autonomic pelvic nerves in gynecologic radical surgery: during the narration we describe and illustrate the procedure to identify all autonomic pelvic nerves, the sympathetic fibers, the PSNs, and the bladder branch emerging from the IHP in order to preserve their anatomic and functional integrity. This technique is anatomically and surgically indicated for adequate removal of the parametrial issues and vagina while preserving the total pelvic nervous system. CONCLUSION: Nerve-sparing surgery reduces bowel-, bladder- and sexual- dysfunction without decreasing surgical efficacy.1,2 To accomplish safe and effective surgery, comprehension of the three dimensional structure of the vascular and nerve anatomy in the pelvis is essential. This video provides a great resource to educate surgeons, especially the youngest ones, about the retroperitoneal nervous networking: we identified the autonomic nerve pathway from adjacent tissues along the pathway consisting of cardinal, sacro-uterine, rectouterine/vaginal, and vesico-uterine ligaments.

Are biomarkers expression and clinical-pathological factors predictive markers of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer?

INTRODUCTION: To predict the overall pathologic response to neoadjuvant chemotherapy (NACT) of patients with locally advanced cervical cancer (LACC) creating a prediction model based on clinical-pathological factors and biomarkers (p53, Bcl1 and Bcl2) and to evaluate the prognostic outcomes of NACT. MATERIALS AND METHODS: This is a retrospective study of 88 consecutive patients with LACC who underwent NACT followed by nerve sparing surgery with retroperitoneal lymphadenectomy at National Cancer Institute of Milan, between January 2000 and June 2013. Clinical pathologic data were retrieved from the institutional database. Biomarkers (p53, Bcl1 and Bcl2) were evaluated before and after NACT in the specimen. To investigate their role as predictors of response, we tried several statistical machine learning algorithms. RESULTS: Responders to NACT showed a 5-years survival between 100%(CR) and 85.7%(PR). Clinical factors were the most important predictor of response. Age, BMI and grade represented the most important predictors of response at random forest analysis. Tree-based boosting revealed that after adjusting for other prognostic factors, age, grade, BMI and tumor size were independent predictors of response to NACT, while p53 was moderately related to response to NACT. Area under the curve (crude estimate): 0.871. Whereas Bcl1 and Bcl2, were not predictors for response to NACT. The final logistic regression reported that grade was the only significant predictor of response to NACT. CONCLUSION: Combined model that included clinical pathologic variables plus p53 cannot predict response to NACT. Despite this, NACT remain a safe treatment in chemosensitive patients avoiding collateral sequelae related to chemo-radiotherapy.

Endometriosis-associated ovarian cancer: a different clinical entity.

OBJECTIVE: To compare survival outcomes and patterns of recurrence between endometriosis-associated ovarian cancer patients and non-endometriosis-associated ovarian cancer patients. METHODS: This retrospective study included data of consecutive patients with endometrioid or clear cell ovarian cancer treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano between January 2010 and June 2021. Patients were assigned to one of two groups according to the absence or presence of endometriosis together with ovarian cancer at final histological examination. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Proportions in recurrence rate and pattern of recurrence were evaluated using the Fisher exact test. RESULTS: Overall, 83 women were included in the endometriosis-associated ovarian cancer group and 144 in the non-endometriosis-associated ovarian cancer group, respectively. Patients included in the non- endometriosis-associated ovarian cancer group had a shorter disease-free survival than those in the endometriosis-associated ovarian cancer group (23.4 (range 2.0-168.9) vs 60.9 (range 4.0-287.8) months; p<0.001). Univariable and multivariable analyses showed that the association with endometriosis, previous hormonal treatment, early stage at presentation, and endometrioid histology were related to better disease-free survival in the entire study population. Similarly, patients in the non-endometriosis-associated ovarian cancer group had a shorter median (range) overall survival than those in the endometriosis-associated ovarian cancer group (54.4 (range 0.7-190.6) vs 77.6 (range 4.5-317.8) months; p<0.001). Univariable and multivariable analyses showed that younger age at diagnosis, association with endometriosis, and early stage at presentation were related to better overall survival. The recurrence rate was higher in the non-endometriosis-associated ovarian cancer group (63/144 women, 43.8%) than in the endometriosis-associated ovarian cancer group (17/83 women, 20.5%; p<0.001). CONCLUSIONS: Endometriosis-associated ovarian cancer patients had significantly longer disease-free survival and overall survival than non-endometriosis-associated ovarian cancer patients, while the recurrence rate was higher in non-endometriosis-associated ovarian cancer patients.

Endovenous laser ablation (EVLA) for vein insufficiency: two-year results of a multicenter experience with 1940-nm laser diode and a novel optical fiber.

Thermoablative techniques currently represent, in accordance with international guidelines, the most used methods in the treatment of varicose veins. From some years, lasers with a wavelength greater than 1900 nm have been introduced for EndoVenous Laser Ablation (EVLA) treatment. However, currently, few clinical studies regarding this new technology are reported in the medical literature. The aim of this study is to evaluate outcomes at a 2-year follow-up (mid-term) of EVLA of varicose veins of the lower limbs using a 1940-nm laser and a new cylindric monoring fiber. This clinical trial was conducted as a multicenter, retrospective, non-randomized, non-blind clinical study. Ninety-three patients were enrolled for a total of one hundred consecutive procedures performed in the period between January 2021 and May 2021 in two Italian facilities. The primary efficacy endpoint was the occlusion rate of the treated vein immediately after surgery and at the follow-up (24 months). The secondary efficacy endpoint was the evaluation of the parameters of energy delivered during the procedure (power and linear energy density or LEED). The primary safety endpoints were the incidence of pain (1 day and 7 days after surgery) and the rate of intraoperative and postoperative complications. The precepted pain was evaluated with the visual analog scale (VAS). The secondary safety endpoint was the evaluation of the improvement of the patient's symptoms related to venous disease. This evaluation was conducted by recording the changes in clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification. All procedures were carried out regularly on an outpatient basis, and no intraoperative complications occurred. The occlusion rate of the target veins was 100% at 7- and 30-day controls. At follow-up controls, performed at 6 months, 1 and 2 years carried out showed an occlusion rate respectively of 99% (97 to 100), 96.9% (93.6 to 100), and 95.9% (92.1 to 99.9). The secondary efficacy endpoint was the evaluation of the parameters of energy delivered during the procedure (power watt and linear energy density): As regards the power parameters, we report an average of watts of 4.5 ± 0.8 [2.5 to 6] and linear energy density delivered (LEED) of 41.2 ± 8.6 [(21.1 to 66.7)]. The pain reported (with VAS scale) on 1 day of the procedure was 2 [1; 3] and 1 [0 to 4] at 7 days. All patients showed improved symptoms related to venous disease, with reduction of the individual CEAP class to which they belong. This study demonstrates that EndoVascular Laser Ablation (EVLA) treatment of varicose veins with a wavelength > 1900 nm is safe and effective. The overall occlusion rate was high. The reported results suggest that using lower parameters, such as output power (watts) and LEED (linear energy density), do not reduce the success rate of the treatment when used over 35 J/cm.

Sentinel lymph node biopsy in endometrial cancer: When, how and in which patients.

The role of nodal dissection in patients with endometrial cancer has been intensively studied in several studies. Historically, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess potential nodal involvement and consequently define the appropriate stage of the tumor. Over the last years, sentinel node biopsy (SLNB) has been introduced as a more targeted alternative to lymph node dissection for lymph node staging and it has become popular among gynecologic oncologists. However, no level A evidence is still available, and several features of the SLNB technique have been matter of discussion among clinicians and a universally accepted methodology is still not currently available. This narrative review aims to summarize the body of knowledge on SLNB to offer the reader a complete picture about the evolution of this technique over the last decades.

Alzheimer's Disease Evaluation Through Visual Explainability by Means of Convolutional Neural Networks.

Background and Objective: Alzheimer's disease is nowadays the most common cause of dementia. It is a degenerative neurological pathology affecting the brain, progressively leading the patient to a state of total dependence, thus creating a very complex and difficult situation for the family that has to assist him/her. Early diagnosis is a primary objective and constitutes the hope of being able to intervene in the development phase of the disease. Methods: In this paper, a method to automatically detect the presence of Alzheimer's disease, by exploiting deep learning, is proposed. Five different convolutional neural networks are considered: ALEX_NET, VGG16, FAB_CONVNET, STANDARD_CNN and FCNN. The first two networks are state-of-the-art models, while the last three are designed by authors. We classify brain images into one of the following classes: non-demented, very mild demented and mild demented. Moreover, we highlight on the image the areas symptomatic of Alzheimer presence, thus providing a visual explanation behind the model diagnosis. Results: The experimental analysis, conducted on more than 6000 magnetic resonance images, demonstrated the effectiveness of the proposed neural networks in the comparison with the state-of-the-art models in Alzheimer's disease diagnosis and localization. The best results in terms of metrics are the best with STANDARD_CNN and FCNN with accuracy, precision and recall between 98% and 95%. Excellent results also from a qualitative point of view are obtained with the Grad-CAM for localization and visual explainability. Conclusions: The analysis of the heatmaps produced by the Grad-CAM algorithm shows that in almost all cases the heatmaps highlight regions such as ventricles and cerebral cortex. Future work will focus on the realization of a network capable of analyzing the three anatomical views simultaneously.

Explainable Convolutional Neural Networks for Brain Cancer Detection and Localisation.

Brain cancer is widely recognised as one of the most aggressive types of tumors. In fact, approximately 70% of patients diagnosed with this malignant cancer do not survive. In this paper, we propose a method aimed to detect and localise brain cancer, starting from the analysis of magnetic resonance images. The proposed method exploits deep learning, in particular convolutional neural networks and class activation mapping, in order to provide explainability by highlighting the areas of the medical image related to brain cancer (from the model point of view). We evaluate the proposed method with 3000 magnetic resonances using a free available dataset. The results we obtained are encouraging. We reach an accuracy ranging from 97.83% to 99.67% in brain cancer detection by exploiting four different models: VGG16, ResNet50, Alex_Net, and MobileNet, thus showing the effectiveness of the proposed method.

Real-time Fluorescent ICG and 99m-Tc Nanocolloid Tracer Navigation in Bilateral Sentinel Lymph Node Mapping of Vulvar Cancer.

STUDY OBJECTIVE: The effectiveness of sentinel lymph node (SLN) biopsy has been validated by 2 prospective trials, GROINS VI and GOG 173 [1,2]. According to the European Society of Gynaecological Oncology guideline in patients with unifocal tumors with a diameter of <4 cm, in the absence of suspected inguinal lymph nodes, SLN biopsy is recommended. The use of a radioactive tracer is mandatory [2]. Using indocyanine green (ICG) increases the detection of the vulvar sentinel node from 89.7% to 100% [3]. This video aimed to share our experience about the feasibility, safety, and usefulness of the surgical identification of SLN in vulvar cancer using real-time fluorescent ICG with 99m-technetium (Tc) nanocolloid. DESIGN: A stepwise demonstration of the technique with narrated video footage. SETTING: Tertiary level hospital "IRCCS Istituto Nazionale dei Tumori," Milano, Italy. INTERVENTIONS: A 50-year-old woman was diagnosed as having vulvar cancer on biopsy of 1.5 cm size vulvar lesion under the clitoris area and referred to our operative unit. F-18 fluorodeoxyglucose positron emission tomography computed tomography showed no extravulvar disease. The patient was scheduled for radical vulvectomy and bilateral inguinal SLN biopsy. (Video still 1) In this video, the surgical procedure involved double location of SLN, first with the 99m-Tc detector followed by ICG identification. We used an ICG dilution of 2.5 mg/mL in sterile water and injected 4 mL around the tumor 5 to 10 minutes before visualization. First a handheld gamma probe used to identify the location of the SLNs with 99m-Tc. The fluorescence imaging was performed by the quest imaging system (FLUOPTICS, Middenmeer, The Netherlands) that combines autofluorescence and fluorescence perfusion imaging (Video Still 2). Second, we performed the SLN biopsy using a dark mode procedure to identify the IGC tracer (Video Still 3). The fluorescence imaging enables the detection of these markers through some millimeters of tissue, and ICG has the advantage that is visible through the skin [4]. CONCLUSION: This video shows a successful combined 99m-Tc and ICG fluorescence image-guided bilateral SLN biopsy in a vulvar cancer patient using a near-infrared optical imaging system (FLUOPTICS). ICG for SLN mapping seems to be safe in women with vulvar cancer with a satisfactory detection rate. This may help in retaining surgical radicality while minimizing operative complications.

Social media ambassadors and collaboration with OncoAlert: a European Network of Young Gynae Oncologists study of comparative Twitter analysis of #ESGO2021 and #ESGO2022.

OBJECTIVE: The primary objective was to reveal the impact of social media ambassadors and the collaboration between the European Society of Gynaecological Oncology (ESGO) and the OncoAlert Network on Twitter during the ESGO 2022 Congress by comparing it with the ESGO 2021 Congress. We also aimed to share our experience on how to organize a social media ambassador program and evaluate the potential benefits for the society and the ambassadors. METHODS: We defined the impact as promoting the congress, sharing the knowledge, change in follower count, and change in tweet, retweet, and reply counts. We used the Academic Track Twitter Application Programming Interface to retrieve data from ESGO 2021 and ESGO 2022. We used the keywords of ESGO2021 and ESGO2022 to retrieve data for each of the conferences. The time range in our study captured interactions from before, during, and after conferences. We collected the ambassadors', ESGO's, and the European Network of Young Gynae Oncologists' (ENYGO's) follower data on Twitter from November 2021 to November 2022 for comparative analysis. RESULTS: There was a 7.23-fold increase in the use of the official congress hashtag in 2022 compared with 2021. Compared with #ESGO2021 data, the main interventions of the Social Media Ambassadors and OncoAlert partnership determined 7.79-, 17.36-, 5.50-, 10.58-, and 8.50-fold increases with #ESGO2022 data in the mentions, mentions in retweet, tweet, retweet, and replies, respectively. Similarly, all other most commonly used hashtags in the top 10 list indicated a range from 2.56- to 7.00-fold increase. Compared to the ESGO 2021 congress month, ESGO and the majority (83.3%, n=5) of ambassadors gained more followers during ESGO 2022 congress month. CONCLUSIONS: An official social media ambassadors program and collaboration with influential accounts in the field of interest are beneficial for congress-related engagement on a social media platform (Twitter). Individuals participating in the program can also benefit from gaining higher visibility among specific audience.

Diagnostic Accuracy of Magnetic Resonance Imaging in the Pre-Operative Staging of Cervical Cancer Patients Who Underwent Neoadjuvant Treatment: A Clinical-Surgical-Pathologic Comparison.

Magnetic resonance imaging (MRI) has been proven to ensure high diagnostic accuracy in the identification of vaginal, parametrial, and lymph node involvement in patients affected by cervical cancer (CC), thus playing a crucial role in the preoperative staging of the disease. This study aims to compare the accuracy of MRI for the preoperative staging of patients with CC who underwent neoadjuvant treatment (NAT) or direct surgery. Retrospective data analysis of 126 patients with primary CC International Federation of Gynecology and Obstetrics stage IB3-IIB who underwent NAT before radical surgery (NAT group = 94) or received surgical treatment alone (control arm = 32) was prospectively performed. All enrolled patients were clinically assessed with both a pelvic examination and MRI before surgical treatment. Data from the clinical examination were compared with the histopathological findings to assess the accuracy of MRI for staging purposes after NAT or before direct surgery. MRI showed an overall accuracy of 46.1%, proving it to be not superior to pelvic and physical examination. The overall MRI accuracy for the evaluation of parametrial, vaginal, and lymph node status was 65.8%, 79.4%, and 79.4%, respectively. In the NAT group, the accuracy for the detection of parametrial, lymph node, and vaginal involvement was lower than the control group; however, the difference was not significant (p ≥ 0.05). The overall accuracy of MRI for the preoperative staging of CC after NAT is shown to be not unsatisfactory. The limits of MRI staging are especially evident when dealing with pre-treated patients.

Lymphatic mapping and sentinel node biopsy in vulvar melanoma: the first multicenter study and systematic review.

OBJECTIVE: This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0). METHODS: Patients who had a proven vulvar melanoma with a Breslow thickness of 1-4 mm, cN0 and underwent a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospectively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients). RESULTS: A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre- and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3-19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6-38.7) and 64.3% (95% CI, 15.5-90.2), respectively. CONCLUSIONS: The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally invasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin relapse and good survival.

The neglected role of preimplantation genetic testing for Lynch syndrome.

Preimplantation genetic testing for monogenic/single-gene disorders (PGT-M) is a procedure employed in the field of assisted reproductive technology to avoid the transmission of genetic diseases to the offspring. Hereditary cancer syndromes represent a diffuse and accepted indication for PGT-M, but take-up differs among the different disorders. Its use is markedly lower for the genes causing Lynch syndrome compared with the breast cancer type 1 or 2 susceptibility genes (BRCA1/2), despite the similar prevalence and severity of the two conditions. Reasons to explain this difference have not been explored. First, Lynch syndrome may be more frequently undiagnosed compared with hereditary breast and ovarian cancer syndrome. In addition, the different take-up may be due to different patient perceptions of the conditions and of the management options. Finally, this distinct attitude may depend on the awareness and sensibility of the professionals caring for affected patients. The authors' considerations are, however, speculative, and specific studies aimed at disentangling the causes of the different receptions of PGT-M are warranted to understand how to tackle this gap. In the meantime, we believe that empowerment regarding PGT-M of all individuals with hereditary cancer syndromes, including Lynch syndrome, is ethically due, and plead for a more active involvement of caregivers.

Analysis of risk factors for recurrence in cervical cancer patients after fertility-sparing treatment: The FERTIlity Sparing Surgery retrospective multicenter study.

BACKGROUND: Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend toward nonradical procedures, such as conization or simple trachelectomy, has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain the safety of such approaches. OBJECTIVE: This study aimed to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in patients with cervical cancer and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures. STUDY DESIGN: Patients aged 18 to 40 years with International Federation of Gynecology and Obstetrics 2018 stage IA1 with positive lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed. RESULTS: A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds of patients were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence, of whom 19 (2.6%) died because of the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was 3 times higher in patients with tumors >2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs 5.7%; hazard ratio, 2.982; 95% confidence interval, 1.383-6.431; P=.005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy and patients who underwent nonradical (conization and simple trachelectomy) cervical procedures (P=.957), regardless of tumor size subcategory (<1 or 1-2 cm) or lymphovascular space invasion. CONCLUSION: Nonradical fertility-sparing cervical procedures were not associated with an increased risk of recurrence compared with radical procedures in patients with tumors ≤2 cm in size in this large, multicenter retrospective study. The risk of recurrence after any type of fertility-sparing procedure was significantly greater in patients with tumors >2 cm in size.

The evolution of endovenous laser ablation (EVLA). A single-center experience with a 1470 nm versus a 1940 nm diode laser.

AIM: To evalue the short-term results obtained in endovenous laser ablation (EVLA) procedure of the varicose insufficiency of the lower limbs with Diode 1470 nm laser compared to Diode 1940 nm laser. MATERIALS OF STUDY: A total of 55 patients were enrolled in the study. The patients were divided into two groups: those subjected to 1470 nm laser treatment in group A and those with 1940 nm laser treatment in group B. The endpoints were: Closure of the target vessel, complications and post-operative pain. RESULTS: There are no intra-and post-operative complications. The occlusion rate of the target veins was 100% at 7- and 60-day controls. The pain perceived in the immediate post-operative and at the controls showed no statistically significant differences between the two groups. However in group B it was necessary to apply lower values of Power (W) and Linear Energy Density (LEED) with a statistically significant difference compared to group A. DISCUSSION: Short-term results demonstrate closure rates comparable to those obtained with 1470 nm lasers. There were no statistically significant differences in the two groups in terms of primary and secondary endpoints. The advantage of using 1940 nm laser technology is that it is possible to dispense a lower linear energy density (LEED) at a lower power (Watt). CONCLUSIONS: Endovenous laser ablation with Diode 1940 nm is particularly suitable and advantageous in the treatment of superficial and small vessels, as well as venous segment adjacent to nerve structures. KEY WORDS: Diode laser, Intravenous ablation, Varicose, Venous insufficiency, Veins.

Vitamin D Status, Cardiovascular Risk Profile, and miRNA-21 Levels in Hypertensive Patients: Results of the HYPODD Study.

The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression.