Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

Influence of initial clinical suspicion on the diagnostic yield of laboratory enzymatic testing in lysosomal storage disorders. Experience from a multispecialty hospital.

Lysosomal storage disorders (LSD) are a group of inherited metabolic diseases mainly caused by a deficiency of lysosomal hydrolases, resulting in a gradual accumulation of non-degraded substrates in different tissues causing the characteristic clinical manifestations of such disorders. Confirmatory tests of suspected LSD individuals include enzymatic and genetic testing. A well-oriented clinical suspicion can improve the cost-effectiveness of confirmatory tests and reduce the time expended to achieve the diagnosis. Thus, this work aims to retrospectively study the influence of clinical orientation on the diagnostic yield of enzymatic tests in LSD by retrieving clinical, biochemical, and genetic data obtained from subjects with suspicion of LSD. Our results suggest that the clinical manifestations at the time of diagnosis and the initial clinical suspicion can have a great impact on the diagnostic yield of enzymatic tests, and that clinical orientation performed in specialized clinical departments can contribute to improve it. In addition, the analysis of enzymatic tests as the first step in the diagnostic algorithm can correctly guide subsequent confirmatory genetic tests, in turn increasing their diagnostic yield. In summary, our results suggest that initial clinical suspicion plays a crucial role on the diagnostic yield of confirmatory enzymatic tests in LSD.

Human Metabotropic Glutamate Receptor 5 Antibodies Alter Receptor Levels and Behavior in Mice.

Ophelia syndrome or encephalitis with antibodies against the metabotropic glutamate receptor 5 (mGluR5) manifests with behavioral changes, memory deficits, and anxiety. To study the antibody pathogenicity, mice received continuous cerebroventricular infusion of patients' or controls' immunoglobulin G (IgG) for 14 days, followed by a 15-day washout. The effects on hippocampal mGluR5 clusters were determined by confocal microscopy. Animals infused with patients' IgG, but not controls' IgG, showed memory impairment, increased anxiety, and decreased neuronal surface mGluR5 clusters. After antibody clearance, both behavioral and molecular changes reversed to baseline conditions. These findings support the pathogenicity of these antibodies in anti-mGluR5 encephalitis. ANN NEUROL 2022;92:81-86.

Human CASPR2 Antibodies Reversibly Alter Memory and the CASPR2 Protein Complex.

OBJECTIVE: The encephalitis associated with antibodies against contactin-associated proteinlike 2 (CASPR2) is presumably antibody-mediated, but the antibody effects and whether they cause behavioral alterations are not well known. Here, we used a mouse model of patients' immunoglobulin G (IgG) transfer and super-resolution microscopy to demonstrate the antibody pathogenicity. METHODS: IgG from patients with anti-CASPR2 encephalitis or healthy controls was infused into the cerebroventricular system of mice. The levels and colocalization of CASPR2 with transient axonal glycoprotein 1 (TAG1) were determined with stimulated emission depletion microscopy (40-70µm lateral resolution). Hippocampal clusters of Kv1.1 voltage-gated potassium channels (VGKCs) and GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) were quantified with confocal microscopy. Behavioral alterations were assessed with standard behavioral paradigms. Cultured neurons were used to determine the levels of intracellular CASPR2 and TAG1 after exposure to patients' IgG. RESULTS: Infusion of patients' IgG, but not controls' IgG, caused memory impairment along with hippocampal reduction of surface CASPR2 clusters and decreased CASPR2/TAG1 colocalization. In cultured neurons, patients' IgG led to an increase of intracellular CASPR2 without affecting TAG1, suggesting selective CASPR2 internalization. Additionally, mice infused with patients' IgG showed decreased levels of Kv1.1 and GluA1 (two CASPR2-regulated proteins). All these alterations and the memory deficit reverted to normal after removing patients' IgG. INTERPRETATION: IgG from patients with anti-CASPR2 encephalitis causes reversible memory impairment, inhibits the interaction of CASPR2/TAG1, and decreases the levels of CASPR2 and related proteins (VGKC, AMPAR). These findings fulfill the postulates of antibody-mediated disease and provide a biological basis for antibody-removing treatment approaches. ANN NEUROL 2022;91:801-813.

[The Research Network on Preventive Activities and Health Promotion (redIAPP): a reference network and promoter of primary care research]. / La Red de Investigación en Actividades Preventivas y Promoción de la Salud (redIAPP): una red de referencia e impulsora de la investigación en atención primaria.

The Research Network on Preventive Activities and Health Promotion (redIAPP), a reference network and promoter of primary care research was created in 2003 thanks to the program Thematic Networks for Cooperative Research in Health (RETICS) of the Instituto de Salud Carlos III (ISCIII). Its creation has meant a radical change in the situation of research in primary care. Throughout its 19 years (2003-2021), different research groups and autonomous communities have participated, and different lines of research have been developed with numerous projects and publications. Despite the difficulties suffered, it has created a collaborative research experience between different autonomous communities with great vitality and with important results for primary care. The redIAPP, therefore, has been a great reference for research in primary care and for the deepening of its area of knowledge. Several lines of improvement are suggested for the future of primary care research.

Donor-derived acute myeloid leukemia in solid organ transplantation.

We report the transmission of acute myeloid leukemia (AML) undetected at donation from a deceased organ donor to two kidneys and one liver recipients. We reviewed the medical records, and performed molecular analyses and whole exome sequencing (WES) to ascertain AML donor origin and its molecular evolution. The liver recipient was diagnosed 11 months after transplantation and died from complications 2 months later. The two kidney recipients (R1 and R2) were diagnosed 19 and 20 months after transplantation and both received treatment for leukemia. R1 died of complications 11 months after diagnosis, while R2 went into complete remission for 44 months, before relapsing. R2 died 10 months later of complications from allogenic bone marrow transplantation. Microsatellite analysis demonstrated donor chimerism in circulating cells from both kidney recipients. Targeted molecular analyses and medical records revealed NPM1 mutation present in the donor and recipients, while FLT3 was mutated only in R1. These findings were confirmed by WES, which revealed additional founder and clonal mutations, and HLA genomic loss in R2. In conclusion, we report the first in-depth genomic analysis of AML transmission following solid organ transplantation, revealing distinct clonal evolution, and providing a potential molecular explanation for tumor escape.

Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: the NEXT-in-CML study.

In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms.

Allosteric modulation of NMDA receptors prevents the antibody effects of patients with anti-NMDAR encephalitis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disease characterized by a complex neuropsychiatric syndrome in association with an antibody-mediated decrease of NMDAR. About 85% of patients respond to immunotherapy (and removal of an associated tumour if it applies), but it often takes several months or more than 1 year for patients to recover. There are no complementary treatments, beyond immunotherapy, to accelerate this recovery. Previous studies showed that SGE-301, a synthetic analogue of 24(S)-hydroxycholesterol, which is a potent and selective positive allosteric modulator of NMDAR, reverted the memory deficit caused by phencyclidine (a non-competitive antagonist of NMDAR), and prevented the NMDAR dysfunction caused by patients' NMDAR antibodies in cultured neurons. An advantage of SGE-301 is that it is optimized for systemic delivery such that plasma and brain exposures are sufficient to modulate NMDAR activity. Here, we used SGE-301 to confirm that in cultured neurons it prevented the antibody-mediated reduction of receptors, and then we applied it to a previously reported mouse model of passive cerebroventricular transfer of patient's CSF antibodies. Four groups were established: mice receiving continuous (14-day) infusion of patients' or controls' CSF, treated with daily subcutaneous administration of SGE-301 or vehicle (no drug). The effects on memory were examined with the novel object location test at different time points, and the effects on synaptic levels of NMDAR (assessed with confocal microscopy) and plasticity (long-term potentiation) were examined in the hippocampus on Day 18, which in this model corresponds to the last day of maximal clinical and synaptic alterations. As expected, mice infused with patient's CSF antibodies, but not those infused with controls' CSF, and treated with vehicle developed severe memory deficit without locomotor alteration, accompanied by a decrease of NMDAR clusters and impairment of long-term potentiation. All antibody-mediated pathogenic effects (memory, synaptic NMDAR, long-term potentiation) were prevented in the animals treated with SGE-301, despite this compound not antagonizing antibody binding. Additional investigations on the potential mechanisms related to these SGE-301 effects showed that (i) in cultured neurons SGE-301 prolonged the decay time of NMDAR-dependent spontaneous excitatory postsynaptic currents suggesting a prolonged open time of the channel; and (ii) it significantly decreased, without fully preventing, the internalization of antibody-bound receptors suggesting that additional, yet unclear mechanisms, contribute in keeping unchanged the surface NMDAR density. Overall, these findings suggest that SGE-301, or similar NMDAR modulators, could potentially serve as complementary treatment for anti-NMDAR encephalitis and deserve future investigations.

Correction to: Outcome quality standards in advanced ovarian cancer surgery.

An amendment to this paper has been published and can be accessed via the original article.

Outcome quality standards in advanced ovarian cancer surgery.

INTRODUCTION: Advanced ovarian cancer surgery (AOCS) frequently results in serious postoperative complications. Because managing AOCS is difficult, some standards need to be established that allow surgeons to assess the quality of treatment provided and consider what aspects should improve. This study aimed to identify quality indicators (QIs) of clinical relevance and to establish their acceptable quality limits (i.e., standard) in AOCS. MATERIALS AND METHODS: We performed a systematic search on clinical practice guidelines, consensus conferences, and reviews on the outcome and quality of AOCS to identify which QIs have clinical relevance in AOCS. We then searched the literature (from January 2006 to December 2018) for each QI in combination with the keywords of advanced ovarian cancer, surgery, outcome, and oncology. Standards for each QI were determined by statistical process control techniques. The acceptable quality limits for each QI were defined as being within the limits of the 99.8% interval, which indicated a favorable outcome. RESULTS: A total of 38 studies were included. The QIs selected for AOCS were complete removal of the tumor upon visual inspection (complete cytoreductive surgery), a residual tumor of < 1 cm (optimal cytoreductive surgery), a residual tumor of > 1 cm (suboptimal cytoreductive surgery), major morbidity, and 5-year survival. The rates of complete cytoreductive surgery, optimal cytoreductive surgery, suboptimal cytoreductive surgery, morbidity, and 5-year survival had quality limits of < 27%, < 23%, > 39%, > 33%, and < 27%, respectively. CONCLUSION: Our results provide a general view of clinical indicators for AOCS. Acceptable quality limits that can be considered as standards were established.

Family caregiver mistreatment of the elderly: prevalence of risk and associated factors.

BACKGROUND: The detection of elder mistreatment is emerging as a public health priority; however, abusive behaviors exercised by caregivers are little known and rarely detected among primary health care professionals. This study aims to estimate the prevalence of risk of abuse against community-residing elderly with moderate to severe dependency whose caregivers are relatives. In addition, we aim to describe the association between such a risk and socio-demographic variables, cognitive and dependency state of the victim, and the scale of the caregiver's anxiety, depression, and burden. METHODS: Cross-sectional study developed in 72 Primary Health Care teams from Barcelona, Spain. Participants were caregivers and their dependent care recipients (N = 829). Home interviews included the Caregiver Abuse Screen (CASE); self-reported abuse from care recipient; activities of daily living and cognitive state of the care recipient; anxiety and depression in caregivers and Caregiver Burden Scale. The relationship prior to the dependency, positive aspects of caregiving, and social support for the caregiver were also assessed. Multivariate analysis was performed using logistic regression with risk of abuse as dependent variable. RESULTS: Caregivers were mainly women (82.8%) with a mean age of 63.3 years. Caregivers and care recipients lived in the same household in 87.4% of cases, and 86.6% had enjoyed a good previous relationship. Care recipients were women (65.6%), with a mean age of 84.2 years, and 64.2% had moderate to severe cognitive impairment. CASE demonstrated a prevalence of 33.4% (95% CI: 30.3-36.7) of abuse risk by the caregiver. Logistic regression showed as statistically significant: caregiver burden (OR = 2.75; 95% CI: 1.74-4.33), caregiver anxiety (OR = 2.06; 95% CI: 1.40-3.02), caregiver perception of aggressive behavior in the care recipient (OR = 7.24; 95% CI: 4.99-10.51), and a bad previous relationship (OR = 4.66; 95% CI: 1.25-17.4). CONCLUSIONS: Prevalence of risk of abuse is high among family caregivers. Our study has found risk factors in family caregivers that are preventable to an extent, namely: anxiety and feelings of burden. It is essential to become aware of these risk factors and their causes to intervene and help primary as well secondary prevention.

Prediction of suboptimal cytoreductive surgery in patients with advanced ovarian cancer based on preoperative and intraoperative determination of the peritoneal carcinomatosis index.

BACKGROUND: The peritoneal carcinomatosis index (PCI) can be used to quantify the tumor burden in patients with advanced ovarian cancer. The aim of the present study was to establish a predictive model for suboptimal cytoreductive surgery (SCS) (residual tumor of > 1 cm) using preoperative and intraoperative determination of the PCI. METHODS: In total, 110 consecutive patients treated for advanced ovarian cancer during a 4-year period in our institution were assessed. Eighty of these patients were eligible for primary debulking surgery and thus included in the present study. All data were prospectively collected and retrospectively evaluated. We determined the PCI both preoperatively and intraoperatively and assessed postoperative complications. RESULTS: A PCI of > 20 was the best cut-off with which to predict a risk of SCS among all three diagnostic techniques assessed in this study (computed tomography, laparoscopy, and laparotomy). Intraoperative PCI determination was associated with the lowest risk of false negatives for SCS when detecting a PCI of < 20. The combination of preoperative computed tomography and laparoscopy, when both techniques predicted SCS, was associated with the lowest risk of false positives for SCS when detecting a PCI of > 20. CONCLUSION: The combination of computed tomography and laparoscopy to obtain the PCI can help to determine which patients with advanced ovarian cancer are suitable for primary debulking surgery and which should undergo neoadjuvant chemotherapy.

Comparative cytogenetic analysis in two tissues with different lineage in Turner's syndrome patients: correlation with phenotype.

OBJECTIVE: To analyze karyotype of Turner's syndrome (TS) patients in two tissues of different lineage, and to correlate them with phenotype. STUDY DESIGN: An observational study was designed at the Gynaecological Endocrinology Unit of Hospital Clinic in Barcelona. Patients diagnosed with TS by blood karyotype were included, between 20 and 50 years of age. A new 50-cell count blood karyotype and a urethral cell karyotype from urine samples were performed. Data on some TS-related comorbidities were collected. RESULTS: Twenty-seven TS patients were included. Urine cultures of 12 patients were contaminated by microorganisms. With 50-cell count blood karyotype, three cryptic mosaicisms were found. Six patients with mosaicism in blood karyotype showed pure monosomy in urine karyotype. Correlations exist between blood karyotype and phenotype where spontaneous menarche, height, dysmorphology, congenital malformations and hypothyroidism are concerned, whereas they did not appear in urine analysis. CONCLUSIONS: Karyotyping T-lymphocytes in blood samples is the gold standard technique. 50-cell count may be considered if TS or ovarian failure is suspected, in order to detect cryptic mosaicisms. Urethral cell culture from urine samples presents technical difficulties and some limitations, due to the easier lost of abnormal X-chromosome. A partial correlation between blood karyotype and phenotype exists.

Influence of the pilates method on postural balance parameters in older women: An exploratory single-arm trial.

BACKGROUND: Human aging is a natural, biological, progressive, dynamic and complex process that involves morphological, physiological and social changes. Alterations such as decreased postural balance increase the risk of falls and exercise has shown benefits. One of the possible exercise modalities for this population is Pilates. OBJECTIVES: To investigate the effects of Pilates on parameters of static and dynamic postural balance in older women. METHODS: Women aged 60 years or over were evaluated at three time points (pre-training, mid-training, and post-training). Postural balance was assessed using the Short Physical Performance Battery (SPPB), the Timed Up and Go test (TUG), and a force platform. The Pilates exercise protocol consisted of 16 sessions, twice a week, lasting 50 min each. Normality of the data was determined by the Shapiro-Wilk test. Repeated measures ANOVA followed by the Bonferroni post hoc test was used for comparison between assessments. Statistical significance was set at p ≤ 0.05. RESULTS: Fourteen older women were included. Assessment on the force platform revealed no significant differences for most of the variables evaluated. There was a significant difference in SPPB scores and TUG times pre- and post-treatment (p < 0.001). CONCLUSION: Pilates training significantly improved dynamic postural balance evaluated by the TUG and SPPB but did not significantly improve static balance evaluated by the force platform, although the values have decreased in most assessments.

IgLON5 deficiency produces behavioral alterations in a knockout mouse model.

Background: Anti-IgLON5 disease is a neurological disorder characterized by autoantibodies against IgLON5 and pathological evidence of neurodegeneration. IgLON5 is a cell adhesion molecule of unknown function that is highly expressed in the brain. Our aim was to investigate the impact of IgLON5 loss-of-function in evaluating brain morphology, social behavior, and the development of symptoms observed in an IgLON5 knockout (IgLON5-KO) mouse model. Methods: The IgLON5-KO mice were generated using CRISPR-Cas9 technology. Immunohistochemistry on fixed sagittal brain sections and Western blotting brain lysates were used to confirm IgLON5 silencing and to evaluate the presence of other cell surface proteins. Two- month-old IgLON5-KO and wild-type (WT) mice underwent a comprehensive battery of behavioral tests to assess 1) locomotion, 2) memory, 3) anxiety, 4) social interaction, and 5) depressive-like behavior. Brain sections were examined for the presence of anatomical abnormalities and deposits of hyperphosphorylated tau in young adult (2-month-old) and aged (22-month-old) mice. Results: Mice did not develop neurological symptoms reminiscent of those seen in patients with anti-IgLON5 disease. Behavioral testing revealed that 2-month-old IgLON5-KO mice showed subtle alterations in motor coordination and balance. IgLON5-KO females exhibited hyperactivity during night and day. Males were observed to have depressive-like behavior and excessive nest-building behavior. Neuropathological studies did not reveal brain morphological alterations or hyperphosphorylated tau deposits. Conclusion: IgLON5-KO mice showed subtle alterations in behavior and deficits in fine motor coordination but did not develop the clinical phenotype of anti-IgLON5 disease.

Oncological outcomes of intraperitoneal chemotherapy in advanced ovarian cancer: BRCA mutation role.

INTRODUCTION: The knowledge of BRCA status offers a chance to evaluate the role of the intraperitoneal route in patients selected by biomolecular profiles after primary cytoreduction surgery in advanced ovarian cancer. MATERIALS AND METHODS: We performed a retrospective, multicenter study to assess oncological outcomes depending on adjuvant treatment (intraperitoneal [IP] vs intravenous [IV]) and BRCA status (BRCA1/2 mutated vs. BRCA wild type [WT]). The primary endpoint was to determine progression-free survival. The secondary objectives were overall survival and toxicity. RESULTS: A total of 288 women from eight centers were included: 177 in the IP arm and 111 in the IV arm, grouped into four arms according to BRCA1/2 status. Significantly better PFS was observed in BRCA1/2-mutated patients with IP chemotherapy (HR: 0.35; 95% CI, 0.16-0.75, p = 0.007), which was not present in BRCA1/2-mutated patients with IV chemotherapy (HR: 0.65; 95% CI, 0.37-1.12, p = 0.14). Significantly better OS was also observed in IP chemotherapy (HR: 0.17; 95% CI, 0.06-043, p < 0.0001), but was not present in IV chemotherapy in relation with BRCA mutation (HR: 0.52; 95% CI, 0.22-1.27, p = 0.15). For BRCA WT patients, worse survival was observed regardless of the adjuvant route used. The IP route was more toxic compared to the IV route, but toxicity was equivalent at the long-term follow-up. CONCLUSION: This retrospective study suggests that BRCA status can help to offer an individualized, systematic treatment after optimal primary surgery for advanced ovarian cancer, but is limited by the small sample size. Prospective trials are essential to confirm these results.

Design and application of a novel PNA probe for the detection at single cell level of JAK2V617F mutation in Myeloproliferative Neoplasms.

BACKGROUND: Mutation(s) of the JAK2 gene (V617F) has been described in a significant proportion of Philadelphia negative Myeloproliferative Neoplasms (MPN) patients and its detection is now a cornerstone in the diagnostic algorithm. METHODS: We developed a novel assay based on peptide nucleic acid (PNA) technology coupled to immuno-fluorescence microscopy (PNA-FISH) for the specific detection at a single cell level of JAK2-mutation thus improving both the diagnostic resolution and the study of clonal prevalence. RESULTS: Using this assay we found a percentage of mutated CD34+ cells ranging from 40% to 100% in Polycythemia Vera patients, from 15% to 80% in Essential Thrombocythemia and from 25% to 100% in Primary Myelofibrosis. This method allows to distinguish, with a high degree of specificity, at single cell level, between CD34+ progenitor stem cells harbouring the mutated or the wild type form of JAK2 in NPM patients. CONCLUSIONS: This method allows to identify multiple gene abnormalities which will be of paramount relevance to understand the pathophysiology and the evolution of any type of cancer.

Surgery in Recurrent Ovarian Cancer: A Meta-Analysis.

Background: The second cytoreductive surgery performed for a patient who has recurrent ovarian cancer remains controversial. Our study analyzes overall survival (OS) and disease-free survival (DFS) for cytoreductive surgery in addition to chemotherapy in recurrent ovarian cancer instead of chemotherapy alone. Methods: A meta-analysis was conducted using PubMed and the Cochrane database of systematic reviews to select randomized controlled studies. In total, three randomized studies were used, employing a total of 1249 patients. Results: The results of our meta-analysis of these randomized controlled trials identified significant differences in OS (HR = 0.83, IC 95% 0.70-0.99, p < 0.04) and DFS (HR = 0.63, IC 95% 0.55-0.72, p < 0.000001). A subgroup analysis comparing complete cytoreductive surgery and surgery with residual tumor achieved better results for both OS (HR = 0.65, IC 95% 0.49-0.86, p = 0.002) and DFS (HR = 0.67, IC 95% 0.53-0.82, p = 0.0008), with statistical significance. Conclusions: A complete secondary cytoreductive surgery (SCS) in recurrent ovarian cancer (ROC) demonstrates an improvement in the OS and DFS, and this benefit is most evident in cases where complete cytoreductive surgery is achieved. The challenge is the correct patient selection for secondary cytoreductive surgery to improve the results of this approach.

Should We Abandon Intraperitoneal Chemotherapy in the Treatment of Advanced Ovarian Cancer? A Meta-Analysis.

BACKGROUND: Ovarian cancer is the gynaecological malignancy with the highest mortality and diagnosis often occurs in its advanced stages. Standard treatment in these cases is based on complete cytoreductive surgery with adjuvant intravenous chemotherapy. Other types of treatment are being evaluated to improve the prognosis of these patients, including intraperitoneal chemotherapy and antiangiogenic therapy. These may improve survival or time to relapse in addition to intravenous chemotherapy. OBJECTIVE: The aim of this meta-analysis is to determine whether treatment with intravenous chemotherapy remains the gold standard, or whether the addition of intraperitoneal chemotherapy has a benefit in overall survival (OS) and disease-free interval (DFS). MATERIALS AND METHODS: A literature search was carried out in Pubmed and Cochrane, selecting clinical studies and systematic reviews published in the last 10 years. Statistical analysis was performed using the hazard ratio measure in the RevMan tool. RESULTS: Intraperitoneal chemotherapy shows a benefit in OS and DFS compared with standard intravenous chemotherapy. The significant differences in OS (HR: 0.81 CI 95% 0.74-0.88) and in DFS (HR: 0.81 CI 95% 0.75-0.87) are statistically significant (p < 0.00001). There were no clinical differences in toxicity and side-effects. CONCLUSION: Intraperitoneal chemotherapy is an option that improves OS and DFS without significant toxicity regarding the use of intravenous chemotherapy alone. However, prospective studies are needed to determine the optimal dose and treatment regimen that will maintain the benefits while minimising side effects and toxicity and the profile of patients who will benefit most from this treatment.