Robotic platforms in gynaecological surgery: past, present, and future.

Background: More than two decades ago, the advent of robotic laparoscopic surgery marked a significant milestone, featuring the introduction of the AESOP robotic endoscope control system and the ZEUS robotic surgery system. The latter, equipped with distinct arms for the laparoscope and surgical instruments, was designed to accommodate remote connections, enabling the practice of remote telesurgery as early as 2001. Subsequent technological progress has given rise to a range of options in today's market, encompassing multi-port and single-port systems, both rigid and flexible, across various price points, with further growth anticipated. Objective: This article serves as an indispensable guide for gynaecological surgeons with an interest in embracing robotic surgery. Materials and methods: Drawing insights from the experience of the Strasbourg training centre for minimally invasive surgery (IRCAD), this article offers a comprehensive overview of existing robotic platforms in the market, as well as those in development. Results: Robotic surgical systems not only streamline established operative methods but also broaden the scope of procedures, including intra- and transluminal surgeries. As integral components of the digital surgery ecosystem, these robotic systems actively contribute to the increasing integration and adoption of advanced technologies, such as artificial intelligence-based data analysis and support systems. Conclusion: Robotic surgery is increasingly being adopted in clinical practice. With the growing number of systems available on the marketplace, the primary challenge lies in identifying the optimal platform for each specific procedure and patient. The seamless integration of robotic systems with artificial intelligence, image-guided surgery, and telesurgery presents undeniable advantages, enhancing the precision and effectiveness of surgical interventions. What is new?: This article provides a guide to the robotic platforms available on the market and those in development for gynaecologists interested in robotic surgery.

Primary flap closure of perineal defects to avoid empty pelvis syndrome after pelvic exenteration in gynecologic malignancies: An old question to explore a new answer.

Pelvic exenteration (PE) is a radical oncological surgical procedure proposed in patients with recurrent or persistent gynecological cancers. The radical alteration of pelvic anatomy and of pelvic floor integrity can cause major postoperative complications. Fortunately, PE can be combined with reconstructive procedures to decrease complications and functional and support problems of pelvic floor, reducing morbility and mortality and increasing quality of life. Many options for reconstructive surgery have been described, especially a wide spectrum of surgical flaps. Different selection criteria have been proposed to select patients for primary perineal defect flap closure without achieving any strict indication of the best option. The aim of this review is to focus on technical aspects and the advantages and disadvantages of each technique, providing an overview of those most frequently used for the treatment of pelvic floor defects after PE. Flaps based on the deep inferior epigastric artery, especially vertical rectus abdominis musculocutaneous (VRAM) flaps, and gracilis flaps, based on the gracilis muscle, are the most common reconstructive techniques used for pelvic floor and vaginal reconstruction. In our opinion, reconstructive surgery may be considered in case of total PE or type II/III PE and in patients submitted to prior pelvic irradiation. VRAM could be used to close extended defects at the time of PE, while gracilis flaps can be used in case of VRAM complications. Fortunately, numerous choices for reconstructive surgery have been devised. As these techniques continue to evolve, it is advisable to adopt an integrated, multi-disciplinary approach within a tertiary medical center.

Is the sarcomatous component (homologous vs heterologous) the prognostic "driving force" in early-stage uterine carcinosarcomas? A retrospective multicenter study.

PURPOSE: Uterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a carcinomatous/epithelial component and a sarcomatous/mesenchymal counterpart. The aim of this study was to evaluate the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS). METHODS: This is a multicenter observational retrospective study conducted in patients with stage I and II UCSs. RESULTS: Ninety-five women with histological diagnosis of early-stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207-4.623, p value = 0.012) and on OS (HR 1.950, 95% CI 1.032-3.684, p = 0.040). CONCLUSION: Carcinomatous and sarcomatous components both played a role in tumor progression and patients' survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early-stage UCSs.

Surgical and functional impact of nerve-sparing radical hysterectomy for parametrial deep endometriosis: a single centre experience.

Background: Deep endometriosis (DE) usually creates a distortion of the retroperitoneal anatomy and may infiltrate the parametria with an oncomimetic pathway similar to cervical cancer. The condition represents a severe manifestation of endometriosis that may result in a functional impairment of the inferior hypogastric plexus. An extensive surgical resection may be required with an associated risk of increased neurogenic postoperative pelvic organ dysfunction. Objectives: To evaluate the post-operative function and complications following hysterectomy with posterolateral parametrial resection for DE. Materials and Methods: In total, 23 patients underwent radical hysterectomy for DE with the parametria involved. The severity of pain was assessed by the Visual Analogue Scale (VAS) score. The KESS, GQLI, BFLUTS and FSFI were used to examine the gastrointestinal, urinary and sexual functions respectively. Intra and post-operative complications were recorded. Main outcome measures: The main outcomes were gastrointestinal, urinary and sexual function and intra and post-operative complications. Results: Dyschezia, dyspareunia and chronic pelvic pain were significantly reduced following hysterectomy. Furthermore, an improvement of gastrointestinal function was observed, while sexual functions, examined by FSFI and urinary symptoms, examined by BFLUTS, was not shown to be significant. Conclusion: The modified nerve-sparing radical hysterectomy for DE results in an improvement of symptoms. Nevertheless, despite the nerve-sparing approach, this procedure may be associated with a not-negligible risk of post-operative bladder voiding deficit. What is new?: This is the first study that focuses on parametrial endometriosis using validated questionnaires to assess functional outcomes following radical hysterectomy for DE.

4K versus 3D total laparoscopic hysterectomy by resident in training: a prospective randomised trial.

Background: The introduction of ultra-high-definition laparoscopic cameras (4K), by providing stronger monocular depth perception, could challenge the existing 3D technology. There are few available studies on this topic, especially in gynaecological setting. Objectives: Prospective, single institution, randomised clinical trial (NCT04209036). Materials and Methods: The two laparoscopes utilised were the 0°ULTRA Telescopes with 4K technology and the 0°3D-HD by Olympus. The surgeons were all trainees and in their last year of residency and who had obtained the certificate of first or second level of the Gynaecological Endoscopic Surgical Education and Assessment program - GESEA program. Twenty-nine patients with benign uterine pathology were enrolled. Main outcome measures: To compare if the use three-dimensional (3D) versus ultra-high-definition laparoscopic vision system (4K) for total laparoscopic hysterectomy performed by trainees was associated with a shorter operative time. Results: The 3D vision system did not prove to be superior to the 4K vision system. Operators reported significantly more vision-related side effects when using 3D than 4K. Completing the GESEA training program was the only factor with a positive and statistically significant impact on the overall time of the procedure, especially when greater dexterity and tissue handling were required. Conclusions: Neither technology used proved superior to the other, although operators showed a preference for 4K over 3D due to the lower number of visual side effects. Attendance at courses on laparoscopic simulators and training programs allowed trainees to demonstrate excellent surgical skills.

Optimizing the number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma: A propensity-score matching analysis.

OBJECTIVE: Neoadjuvant chemotherapy and interval debulking surgery are now widely offered in ovarian cancer patients unsuitable for surgery; the number of preoperative NACT cycles to be given is still an issue. Our aim was to compare survival outcomes of patients with advanced ovarian cancer treated with ≤4 or more NACT cycles. METHODS: A cohort of AEOC patients with stage III-IV epithelial OC who underwent NACT followed by IDS was identified. Patients were classified in group A (≤4 cycles) and group B (>4 cycles). Selection bias from the heterogeneity of demographic and clinical characteristics was avoided using propensity score matching (2:1 ratio). RESULTS: 140 (group A) and 70 (group B) patients were included. After the propensity score matching, there were no imbalances in baseline characteristics. BRCA status was associated to improved OS (HR = 0.41; 95%CI 0.18.0.92, p = 0.032) and residual tumor to decreased OS (HR = 1.93; 95%CI 1.08-3.46, p = 0.026). Statistically significant differences were not observed in OS (2-year OS 82.4% for group A versus 77.1% for group B, p = 0.109) and PFS (2-year PFS 29.7% for group A versus 20.0% for group A, p = 0.875). In group B, the administration of >4 cycles was related to an additional chance of achieving complete (12.9%) and partial (34.3%) responses compared to responses after 3-4 cycles. CONCLUSIONS: Receiving more than 4 cycles of NACT is no detrimental in terms of OS and PFS in advanced ovarian cancer. Response rates can increase following further cycles administration.

Rectosigmoid Mesorectal-Sparing Resection in Advanced Ovarian Cancer Surgery.

Ovarian cancer is the most lethal of all gynecologic cancers.1 Primary debulking surgery (PDS) with achievement of no residual tumor (RT, 0) still is the recommended treatment, and the one with the greatest prognostic impact.2,3 Given the usual disease spread, several surgical procedures often are needed, and one of the most frequent is rectosigmoid resection.4 Anastomotic leak is the most feared complication. Other common complications are persistent urinary, defecatory, and sexual dysfunction due to autonomic nervous system injuries during surgery.5 Even if mesorectal resection is not deemed part of the treatment paradigm for advanced ovarian cancer (AOC), total mesorectal excision (TME) is the most common surgical technique used. However, for selected cases, with detection of no lymphadenopathies at the origin of the of the inferior mesenteric artery and a favorable ratio between the length of the left colon and the extent of the bowel carcinomatosis, a mesorectal-sparing resection with the preservation of the superior rectal artery and the mesorectal tissue should be pursued. This report presents the case of a 54-year-old woman with a diagnosis of FIGO stage 3C AOC who underwent PDS. The video (video 1) provides a step-by-step description of the surgical technique adopted for colorectal resection with mesorectal-sparing technique. Rectosigmoid mesorectal-sparing resection is feasible and could be a viable option for selected cases of AOC, maximizing the blood supply to colorectal anastomosis while minimizing the risk of both anastomotic leak and pelvic autonomic nervous system dysfunction.6.

Hormone replacement therapy and cervical cancer: a systematic review of the literature.

Gynecological tumor treatment, including cervical cancer (CC) treatment, often leads to iatrogenic premature menopause. This highlights the critical importance of investigating indications for hormone replacement therapy (HRT), as most patients, thanks to the improvement in diagnosis and treatment, have to deal with the sequelae of their cancer treatments for many years. This systematic review aims to provide an overview of the current knowledge regarding the risks of HRT and CC. In particular, we aim to investigate whether the use of HRT can increase CC incidence, and evaluate its risk in CC survivors. A systematic review, in agreement with PRISMA guidelines, of the English literature present in PubMed and SCOPUS has been performed. A total of 2805 articles have been screened, of which 10 were considered eligible. Several studies reported a significantly reduced risk of developing cervical squamous cell carcinoma in postmenopausal women treated with HRT, while a weak increase in the incidence of adenocarcinoma has been shown. No evidence reports a harmful effect of HRT on CC oncological outcome, while several benefits, in terms of reduced metabolic risk and increased quality of life, have been described, thus concluding that HRT should be offered to young CC survivors for the management of early menopause.

Secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer before olaparib maintenance: Still getting any benefit? A case-control study.

OBJECTIVE: The role of secondary cytoreductive surgery (SCS) in platinum-sensitive recurrent ovarian cancer (PSROC) is still controversial. We investigated the role of SCS in PSROC patients with BRCA1/2 mutation (BRCAmut) who received platinum-based chemotherapy followed by olaparib maintenance. METHODS: This is a case-control study. Patients with first PSROC admitted to our Gynecologic Oncology Unit between 2014 and 2018 were identified. Main eligibility criteria: positive BRCA1/2 germline or somatic mutation status and olaparib maintenance at primary recurrence after response to platinum-based chemotherapy. Cases were those who received SCS followed by medical treatment (SCS-CT-OLA, group 1), controls were those who received medical treatment alone (CT-OLA, group 2). RESULTS: Overall, 46 patients were identified; 23 (50%) BRCAmut women undergoing SCS followed by platinum-based chemotherapy and olaparib maintenance were matched with 23 (50%) BRCAmut women who only received medical treatment. Groups were well balanced: no statistical differences were found with regard of age, mutational status, treatment's approach at diagnosis, timing and patterns of disease presentation at recurrence. Median time to first subsequent therapy (TFST) was significantly longer in the SCS-CT-OLA than in the CT-OLA group (42 months vs 16 months; p = 0.05). Also, SCS-CT-OLA patients had the best post-recurrence survival (PRS), with a 3-year PRS of 79% in SCS-CT-OLA group versus 42% in CT-OLA group (p = 0.02). CONCLUSIONS: SCS increases TFST and PRS in PSROC patients with BRCAmut candidate for olaparib maintenance after platinum-based chemotherapy. Prospective studies are needed. In the era of personalized medicine, indication to SCS should be individualized.

Robotic Single-Port Platform in General, Urologic, and Gynecologic Surgeries: A Systematic Review of the Literature and Meta-analysis.

BACKGROUND: Robotic platforms have recently acquired progressive importance in different surgical fields, such as urology, gynecology, and general surgery. Through the years, new surgical robots have become available as single-port robotic platform. The study is aimed to value the single-port robotic platform characteristics in different surgical specialties. METHODS: The terms "LESS" OR "single port" OR "single site" AND "robot" OR "robotic" were systematically used to search the PubMed and Scopus databases. A total of 57 studies were considered eligible for the present review. The articles included were divided according to the surgical field in which the study was conducted: General surgery (29 articles), Gynecology (18 articles), Urology (10 articles). RESULTS: Most part of the articles showed the feasibility of robotic single-port surgical procedures and described advantages in terms of cosmetic, hospital stay, and in some series even cost reduction. A meta-analysis was conducted, showing a significant increment of complications using RSP if compared with SLPS and a trend (P = 0.008) when RSP was compared with LESS. The comparison of different techniques in terms of conversion to laparotomy did not show any significant difference. CONCLUSION: Robotic single port potentially furnishes an important surgical and post-operatory improvement; however, some limits still prolong the surgical time and complication rate.

Total laparoscopic hysterectomy for enlarged uteri: factors associated with the rate of conversion to open surgery.

A hysterectomy for enlarged uteri is considered a challenge for gynaecologic surgeons, due to the limit of exposure to surgical spaces. Our objective is to investigate the different variables that may have an impact on the risk of conversion to open surgery. This is a retrospective cohort study consisting of 133 women who were submitted to surgery for uterine fibroids and who underwent total hysterectomy by laparoscopic approach attempt. The median uterus weight was 622 grams (range 301-3882) and the median maximum diameter of the bigger fibroid was 74 mm (range 33-148). We registered 13 (9.8%) cases of conversion to laparotomy. Minor and major post-operative complications were recorded in 4 (3%) and in 4 (3%) cases, respectively. After multivariable analysis, the surgeon's experience (OR: 0.24; 95% CI: 0.06-0.94, p = .027) and a maximum diameter of the biggest fibroid ≥10 cm (4.7; 1.39-15.87; p = .046), but not the uterus weight were associated with the risk of conversion to open surgery. IMPACT STATEMENT What is already known on this subject? Laparoscopic procedures for enlarged uteri are well described in literature; however, the only parameters that have been studied for the success of a laparoscopic procedure have been the uterus weight and the surgeon's experience. What do the results of this study add? This study aimed to value all the possible variables related to the successful of laparoscopic procedures; in fact, we investigated not only the uterine weight, but in our multivariate analysis, the position of the fibroids, the trocar's setting, etc. were analysed. What are the implications of these findings for clinical practice and/or further research? This study reported novel data about the feasibility of laparoscopic hysterectomy for enlarged uteri. In opposition to the literature, the uterine weight is not a predictive value for laparotomic conversion. Moreover, we discussed the possible reasons of our novel findings. It opens new perspective to create a predictive value of laparoscopic feasibility for the different types of enlarged uteri.

The social cost of chronic kidney disease in Italy.

This study aims to estimate the mean annual social cost per patient with chronic kidney disease (CKD) by stages 4 and 5 pre-dialyses and cost components in Italy. The multicenter cross-sectional study included all adult outpatients in charge of the 14 main Nephrology Centers of Tuscany Region during 7 weeks from 2012 to 2013. Direct medical costs have been estimated using tariffs for laboratory tests, diagnostic exams, visits, hospitalization and prices for drugs. Non-medical costs included expenses of low-protein special foods, travel, and formal and informal care. Patients' and caregivers' losses of productivity have been estimated as indirect costs using the human capital approach. Costs have been expressed in Euros (2016). Totals of 279 patients in stage 4 and 205 patients in stage 5 have been enrolled. The estimated mean annual social cost of a patient with CKD were €7422 (±€6255) for stage 4 and €8971 (±€6503) for stage 5 (p < 0.05). Direct medical costs were higher in stage 5 as compared to stage 4; direct non-medical costs and indirect costs accounted, respectively, for 41 and 5 % of the total social cost of CKD stage 4 and for 33 and 9 % of CKD stage 5. In Italy, the overall annual social cost of CKD was €1,809,552,398 representing 0.11 % of the Gross Domestic Product. Direct non-medical costs and indirect costs were weighted on the social cost of CKD almost as much as the direct medical cost. Patients, their families and the productivity system sustain the burden of the disease almost as much as the healthcare system.

Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study.

PURPOSE: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions. PATIENTS AND METHODS: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline. RESULTS: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue. CONCLUSION: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy.

Dynamic changes of depolarizing GABA in a computational model of epileptogenic brain: Insight for Dravet syndrome.

Abnormal reemergence of depolarizing GABAA current during postnatal brain maturation may play a major role in paediatric epilepsies, Dravet syndrome (DS) being among the most severe. To study the impact of depolarizing GABA onto distinct patterns of EEG activity, we extended a neural mass model as follows: one sub-population of pyramidal cells was added as well as two sub-populations of interacting interneurons, perisomatic-projecting interneurons (basket-like) with fast synaptic kinetics GABAA (fast, I1) and dendritic-projecting interneurons with slow synaptic kinetics GABAA (slow, I2). Basket-like cells were interconnected to reproduce mutual inhibition mechanisms (I1➔I1). The firing rate of interneurons was adapted to mimic the genetic alteration of voltage gated sodium channels found in DS patients, SCN1A(+/-). We implemented the "dynamic depolarizing GABAA" mediated post-synaptic potential in the model, as some studies reported that the chloride reversal potential can switch from negative to more positive value depending on interneuron activity. The "shunting inhibition" promoted by GABAA receptor activation was also implemented. We found that increasing the proportion of depolarizing GABAA mediated IPSP (I1➔I1 and I1➔P) only (i.e., other parameters left unchanged) was sufficient to sequentially switch the EEG activity from background to (1) interictal isolated polymorphic epileptic spikes, (2) fast onset activity, (3) seizure like activity and (4) seizure termination. The interictal and ictal EEG patterns observed in 4 DS patients were reproduced by the model via tuning the amount of depolarizing GABAA postsynaptic potential. Finally, we implemented the modes of action of benzodiazepines and stiripentol, two drugs recommended in DS. Both drugs blocked seizure-like activity, partially and dose-dependently when applied separately, completely and with a synergic effect when combined, as has been observed in DS patients. This computational modeling study constitutes an innovative approach to better define the role of depolarizing GABA in infantile onset epilepsy and opens the way for new therapeutic hypotheses, especially in Dravet syndrome.

[Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review]. / Efectividad de la dieta cetogenica en niños con epilepsia refractaria: revision sistematica.

INTRODUCTION: Epilepsy is a brain disorder that affects both children and adults. From the 1920s the ketogenic diet has gained prestige as another treatment option for patients with refractory epilepsy. SUBJECTS AND METHODS: A summary of the evidence will be made through a systematic review of randomized clinical trials that have compared a single ketogenic diet with other diet for the management of these patients. AIM: To determine the effectiveness of the ketogenic diet in reducing episodes of seizures in patients with refractory epilepsy. The search strategy included randomized controlled trials and controlled clinical trials. Databases used were Medline, LILACS, Central and CINAHL. RESULTS: Six articles that met our elegibility criteria. CONCLUSIONS: There is limited evidence that the ketogenic diet compared to the medium-chain triglyceride diet is more effective in reducing the frequency of seizures. There is also moderate evidence that classical ketogenic diet compared to the gradual diet (2.5:1 and 3:1) is more effective in reducing seizures. There is moderate evidence that classical ketogenic diet compared to Atkins diet is more effective in reducing the frequency of seizure. The decision to apply this type of diet should also be based on costs, preferences and safety of treatment. It should also take into account the likelihood that studies have indexing problems have been left out of the review.

TITLE: Efectividad de la dieta cetogenica en niños con epilepsia refractaria: revision sistematica.Introduccion. La epilepsia es una patologia cerebral que afecta tanto a niños como a adultos. Desde los años veinte, la dieta cetogenica ha ganado prestigio como otra opcion de tratamiento en pacientes con epilepsia refractaria. Sujetos y metodos. Se realiza una sintesis de la evidencia a traves de una revision sistematica de ensayos clinicos aleatorizados que hayan comparado una dieta cetogenica sola con otros tipos de dieta para el tratamiento de estos pacientes. Objetivo. Determinar la efectividad de la dieta cetogenica en la disminucion de los episodios de convulsiones en pacientes con epilepsia refractaria. La estrategia de busqueda incluyo ensayos clinicos aleatorizados y ensayos clinicos controlados. Las bases de datos usadas fueron: Medline, LILACS, Central y CINAHL. Resultados. Se obtuvieron seis articulos que cumplian con los criterios de elegibilidad. Conclusiones. Existe evidencia limitada de que la dieta cetogenica en comparacion con la dieta de trigliceridos de cadena media es mas efectiva en disminuir la frecuencia de las convulsiones. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta gradual (2,5:1 y 3:1) es mas efectiva para disminuir las crisis epilepticas. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta Atkins es mas efectiva para disminuir la frecuencia de convulsiones en tres meses. La decision de aplicar este tipo de dietas tambien debe basarse en costes, preferencias y seguridad del tratamiento. Ademas, debe considerarse la probabilidad de que algunos estudios, por problemas de indizacion, hayan quedado fuera de la revision.