Safety and Effectiveness of Perioperative Hyperthermic Intraperitoneal Chemotherapy with Gemcitabine in Patients with Resected Pancreatic Ductal Adenocarcinoma: Clinical Trial EudraCT 2016-004298-41.

BACKGROUND: Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer stem cells. MATERIALS AND METHODS: A randomized trial involving 42 patients. All patients were diagnosed with pancreatic ductal adenocarcinoma. Group I: R0 resection. Group II. R0 resection and HIPEC with gemcitabine (120 mg/m2 for 30 min). Effectiveness was measured with analysis of overall survival, disease-free survival, distant recurrence, locoregional recurrence, and measuring of pancreatic cancer stem cells (EpCAM+CXCR4+CD133+). RESULTS: From 2017 to 2023, 63 patients were recruited for our clinical trial; 21 patients were included in each group, and 21 were excluded. Locoregional recurrence, p-value: 0.022, was lower in the experimental group. There were no significant differences between the two groups in hospital mortality, perioperative complications, or hospital costs. We found a significant decrease in pancreatic cancer stem cells in patients in the experimental group after treatment, p -value of 0.018. CONCLUSIONS: The use of HIPEC with gemcitabine after surgery in patients with resectable pancreatic ductal adenocarcinoma reduces locoregional recurrence and may be associated with a significant decrease in pancreatic cancer stem cells.

The impact of the transversus abdominis plane block (TAP) on stress response measured through the complete blood- derived inflammatory markers.

This study aims to evaluate the effect of the transversus abdominis plane (TAP) block on the blood cells and the inflammatory markers neutrophil- to- lymphocyte ratio (NLR), platelet- to- lymphocyte ratio (PLR), and systemic immune- inflammation index (SII) after the laparoscopic ovariectomy (LapOV) in dogs. 72 healthy bitches undergoing LapOV were randomly allocated to the no- TAP group of dogs under inhaled anesthesia (IA), the TAP- S group (IA and TAP with saline), and the TAP- B group (IA and TAP with bupivacaine). The NLR, PLR, and SII were calculated 1 h before ovariectomy (T0) and at 2-3 h (T1), 6-8 h (T2), and 20-24 h (T3) post- surgery. The number of dogs requiring postoperative analgesic rescue with buprenorphine and the doses administered in each group were recorded. Significant changes were observed in all groups' postoperative NLR, PLR, and SII over time. Between groups, no differences were observed in any of the ratios at any control point (NLR at T0-T3: p = 0.17, 0.36, 0.80, and 0.95; PLR at T0-T3: p = 0.70, 0.62, 0.21, 0.87; SII at T0-T3: p = 0.29, 0.65, 0.09, and 0.34). A significantly lower number of dogs required analgesic rescue in the TAP-B group (p = 0.0001) and a lower number of doses were administered (p = 0.001). There is no difference in the inflammatory response measured through the complete blood- derived inflammatory markers after the LapOV in dogs when the postoperative pain is managed entirely with opioids or with the TAP block with bupivacaine. The hydrodissection associated with the TAP block technique does not increase the inflammatory response.

Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model.

Aims: Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods: pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results: Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion: In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine.

Using complete blood count-derived inflammatory markers to compare postoperative inflammation in dogs undergoing open or laparoscopic ovariectomy.

BACKGROUND: The inflammatory response triggered in dogs after laparoscopic ovariectomy (LapOV) or ovariectomy through mini-celiotomy (COV) has never been compared using the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory index (SII). METHODS: Bitches underwent LapOV (n = 25) or COV (n = 25). NLR, PLR and SII were calculated 1 hour before ovariectomy (T0) and 2-3, 6-8 and 20-24 hours (T1-T3) after surgery. RESULTS: Surgical time was longer in the LapOV group. Changes over time were observed in the NLR, PLR and SII in both groups (p < 0.001). PLR at baseline and T1 (p = 0.03 and 0.01) and NLR, PLR and SII at T2 (p = 0.01, 0.01 and 0.009) were higher in the LapOV group than in the COV group, but they did not differ at T3. LIMITATIONS: The overrepresentation of Greyhounds in the LapOV group and the short-term follow-up are the study's main limitations. CONCLUSION: Although an inflammatory peak was observed 6-8 hours after COV or LapOV, it was higher after the laparoscopy. However, there was no difference in the bitches' inflammatory status 24 hours after surgery.

Evaluation of the Two-Point Ultrasound-Guided Transversus Abdominis Plane Block for Laparoscopic Canine Ovariectomy.

The transversus abdominis plane (TAP) block causes desensitization of the abdominal wall and peritoneum. Of all the approaches proposed to perform it, the two-injection-point TAP showed the best results in terms of the area reached by the anesthetic solution. However, to date, no clinical data exist. The aim of this study was to evaluate the intra- and postoperative analgesic efficacy of a two-injection-point TAP block in dogs undergoing laparoscopic ovariectomy. A total of 26 animals were assigned to receive general inhalation anesthesia (control group), and 26 dogs were assigned to general inhalation anesthesia combined with TAP block (TAP group). The ultrasound-guided TAP block was carried out with a subcostal and cranial-to-ilium injection per hemiabdomen. The end-tidal concentration of isoflurane (EtISO) was recorded at different moments during the surgery. Postoperative pain was assessed at different time points during the first 24 h after surgery. The control group required significantly higher EtISO concentration during the ovarian resection and showed higher postoperative pain scores than the TAP group. Fewer dogs in the TAP group required intra- or postoperative rescue analgesia. TAP block can be implemented to improve postoperative pain management after laparoscopy, reducing the dosage of the systemic drugs used and, hence, their possible side effects.

Mycosis fungoides: A rare cause of giant cardiac mass.

Mycosis fungoides is the most common cutaneous T-cell lymphoma. Although myocardial infiltration is frequent in advanced stages, symptomatic cardiac involvement is rare. We report an unusual case of rapidly progressing acute heart failure due to cardiac affection by mycosis fungoides manifested as an intracavitary mass in the right atrium. The patient received cytoreductive surgery and adjuvant radiotherapy, presenting an excellent cardiovascular outcome during follow-up. Learning objectives: •Recognize mycosis fungoides as a potential cause of cardiac mass due to its visceral progression.•Note the role of cytoreductive surgery with adjuvant radiotherapy in order to relieve heart failure symptoms and improve the prognosis of the disease in the exceptional case of mycosis fungoides presenting as an isolated cardiac mass.

Development and psychometric properties of the human papillomavirus-quality of life (HPV-QoL) questionnaire to assess the impact of HPV on women health-related-quality-of-life.

PURPOSE: The HPV-Quality-of-Life (HPV-QoL) questionnaire was developed to determine the impact of Human-Papillomavirus (HPV) infection and related interventions on women health-related quality-of-life. This study provides the development and preliminary psychometric properties of a novel HPV-QoL questionnaire for adult women with HPV. METHODS: After reviewing literature and cognitive debriefing interviews in women who had experienced HPV-related conditions, instrument items and domains were developed. A draft questionnaire was pilot tested for comprehension and ease of completion. Psychometric evaluation of the final HPV-QoL scale was conducted in a psychometric study including 252 adult women derived to our centre by a positive HPV test in the cervical cancer screening program and/or presenting genital warts. RESULTS: The present study reveals that the HPV-QoL questionnaire, structured in four domains: general well-being [including psychological well-being and social well-being subdomains], health, contagiousness and sexuality, showed good metric properties of feasibility irrespective of age or educational level, and time to administer was less than 5 min. Internal consistency and temporal stability (reliability) showed values above the acceptable standards. The instrument showed its concurrent validity by means of a significant correlation with mental and sexual existing instruments; GHQ-12 and FSFI questionnaires, respectively, and also known groups validity showing significant differences among the subgroups regarding either sexual dysfunction or mental deterioration. CONCLUSION: This study provides an HPV-QoL questionnaire with an innovative patient-reported outcomes specific measurement tool to assess HRQoL in women with HPV infection. The present study suggests this questionnaire has satisfactory psychometric properties, including validity and reliability. Results support the use of the HPV-QoL questionnaire as a HRQoL measurement instrument for daily medical practice and clinical research.

Fracture of the Distal Radius by Tuberculous Osteomyelitis: A Case Report and Review of Literature.

We report a 94-year-old patient with a fractured radius that was being managed conservatively. At 2 months, an abscess was observed overlying the fracture site. An MRI scan was done and samples obtained for microbiological and pathological analyses. The patient was diagnosed with tuberculous osteomyelitis. Surgical debridement of the fracture site was performed, and the bone defect was filled with bone cement impregnated with gentamicin and rifampicin. Anti-tuberculosis therapy was administered for 9 months and the patient made an uneventful recovery. Early diagnosis and correct medical treatment depend on sound evidence of tuberculous osteomyelitis. Surgical debridement is essential if abscesses are present in the bone. Level of Evidence: Level V (Therapeutic).

Delayed hemorrhage after pediatric stereo-electroencephalography: delayed occurrence or delayed diagnosis?

BACKGROUND: Stereo-electroencephalography (SEEG) is a well-known invasive diagnostic method for drug-resistant epilepsy (DRE). Its rate of complications is relatively low, being the intracranial hemorrhage (ICH) the most relevant. Most centers perform immediate imaging studies after SEEG to rule out complications. However, delayed intracranial hemorrhages (DIH) can occur despite normal imaging studies in the immediate postoperative period. METHODS: We performed a retrospective review of DRE pediatric patients operated on SEEG between April 2016 and December 2020 in our institution. After implantation, an immediate postoperative CT was performed to check electrode placement and rule out acute complications. An additional MRI was performed 24 h after surgery. We collected all postoperative hemorrhages and considered them as major or minor according to Wellmer´s classification. RESULTS: Overall, 25 DRE patients were operated on SEEG with 316 electrodes implanted. Three ICHs were diagnosed on postoperative imaging. Two of them were asymptomatic requiring no treatment, while the other needed surgical evacuation after clinical worsening. The total risk of hemorrhage per procedure was 12%, but just one third of them were clinically relevant. Two hemorrhages were not visible on immediate postoperative CT, being incidentally diagnosed in the 24 h MRI. We recorded them as DIH and are reported in detail. CONCLUSION: Few reports of DIH after SEEG exist in the literature. It remains unclear whether these cases are late occurring hemorrhages or immediate postoperative hemorrhages undiagnosed on initial imaging. According to our findings, we recommend to perform additional late postoperative imaging to diagnose these cases and manage them accurately.

Clinical Relevance of Persistent Off-Track Hill-Sachs Lesion After Arthroscopic Latarjet Procedure.

BACKGROUND: The Latarjet procedure is often used to address off-track Hill-Sachs lesions (OFF-HS) in shoulders with anterior instability. There are concerns as to whether the Latarjet procedure is able to convert all OFF-HS into on-track Hill-Sachs lesions (ON-HS) and whether this limitation could explain the cases of recurrent postoperative instability. HYPOTHESIS: Latarjet surgery converts many preoperative OFF-HS lesions, but not all of them, and there is a difference in the failure rate between shoulders with converted lesions and those with persistent OFF-HS lesions. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with anterior shoulder instability and an OFF-HS lesion treated with an arthroscopic classic Latarjet procedure between January 2010 and September 2017 were retrospectively evaluated. Patients with moderate or severe shoulder arthrosis, rotator cuff tears, or age older than 50 years were excluded. Glenoid track (GT), HS, HS interval (HSI), and the difference between HSI and GT (ΔHSI-GT) were measured preoperatively. A postoperative computed tomography scan and a clinical evaluation, including the Rowe and Western Ontario Shoulder Instability scores, were performed at a minimum 1- and 2-year follow-up, respectively. Postoperatively, 2 groups of patients were obtained: (1) patients with postoperative persistent OFF-HS; (2) patients with postoperative ON-HS. Clinical and imaging data were compared between the 2 groups. RESULTS: A total of 51 patients (n = 51 shoulders), with a mean age of 29.8 ± 8.4 years (range, 15-50 years), met the inclusion criteria. Six shoulders (11.8%) still showed OFF-HS lesions despite Latarjet surgery. There were no postoperative dislocations, but 3 patients reported subluxations. The subluxation rate was significantly higher in the postoperative persistent OFF-HS group (2 [33%] vs 1 [2.2%]; P = .033). There was a wider preoperative HSI (29.8 ± 2.4 mm vs 22.9 ± 3.5 mm; P < .001) and a larger preoperative ΔHSI-GT (12.2 ± 3.8 mm vs 4.82 ± 3.2 mm; P < .001) in the persistent OFF-HS group. A receiver operating characteristic curve was performed based on preoperative ΔHSI-GT values. A preoperative ΔHSI-GT value ≥7.45 mm predicted a persistent OFF-HS after Latarjet surgery (sensitivity, 100%; specificity, 87%; positive predictive value, 50%; and negative predictive value, 100%). CONCLUSION: Latarjet surgery converted many preoperative OFF-HS lesions into ON-HS lesions, but not all of them. Six patients (11.8%) retained an OFF-HS and had a statistically significantly higher failure rate after Latarjet surgery compared with those with postoperative ON-HS lesions. Because there were few postoperative OFF-HS lesions and few recurrences, findings are statistically fragile and should be confirmed with larger series.

Intracoronary injection of haematopoietic precursor cells regenerates the borders, but not the core, of old myocardial scars.

AIMS: Cell therapy regenerative potential is hindered by cell access to the infarct zone. We studied function recovery at the scar zone and its impact in global left ventricular function after intracoronary injection of haematopoietic precursor cells. METHODS AND RESULTS: Haematopoietic precursor cells were obtained by blood apheresis in patients with an old myocardial infarction, and the presence of CD34+ and CD133+ cells was quantified. Left ventricular function, volumes, and infarct zone segmental motion were measured by magnetic resonance imaging (MRI) and echo left ventricular segmental strain (LVSS). The aphaeresis product was administered to 20 patients in the coronary artery responsible for the myocardial infarction. High cell yield in blood aphaeresis product allowed us to inject a high number of cells in most patients. Three patients were excluded because of insufficient CD133+ cell number, and one more patient was excluded because of artefacts in MRI images. The remaining 16 patients were compared with 16 controls. After 1 year, infarct zone reduction was related to the number of CD133+ (R = 0.53; P %3C 0.05) and CD34+ (R = 0.63; P %3C 0.01) cells injected. The number of CD133+ cells injected was also related to an improvement in LVSS (R = 0.62; P %3C 0.01). In turn, scar zone reduction was related to an improvement in LVSS (R = 0.64; P %3C 0.01). End-diastolic volume showed a reduction at follow-up in the treated group when compared with control patients. MRI infarct area segments systolic thickness increase improved after treatment in treated patients [expressed as median (interquartile range)] [0.42 (-0.38 to 1.14) vs. 1.06 (-0.10 to 2.12) mm; P %3C 0.01], but not in controls [2.02 (0.75 to 3.4) vs. 1.91 (0.77-3.17) mm; P = not significant (n.s.)]. In cell therapy patients, the borders of the infarct zone, but not the core, showed a significant recovery [proximal rim: 0.48 (-0.18 to 1.33) vs. 1.07 (0.22-2.40) mm; P %3C 0.05, distal rim: 0.75 (0.26-1.40) vs. 1.76 (0.65-2.86) mm; P %3C 0.05, and core: 0.36 (-0.33 to 1.20) vs. 0.60 (-0.18 to 1.62) mm; P = n.s.]. That improvement was not observed in the control group [proximal rim: 1.20 (0.33-2.53) vs. 0.82 (-0.13 to 1.65) mm; P = n.s., distal rim: 1.24 (0.80-1.72) vs. 0.96 (0.19-1.81) mm; P = n.s., and core: 0.30 (-0.42 to 1.64) vs. 0.07 (-0.60 to 1.20) mm; P = n.s.]. Only small size infarcts showed a complete recovery in the cell therapy patients [systolic thickness increase post-treatment increment in infarcts ≤6 segments vs. >6 segments affected: 0.28 (-0.19 to 0.71) vs. -1.21 (-2.60 to -0.53) mm; P %3C 0.01]. CONCLUSIONS: Intracoronary injection of peripheral blood-derived haematopoietic precursor cells produces a complete recovery of the borders and partial regeneration of the infarct core, which is directly related to the number of CD133+ and CD34+ cells injected. Cell therapy infarct zone regeneration prevents ventricular remodelling by preserving segmental contractility and halting left ventricular dilatation.

Purity Determines the Effect of Extracellular Vesicles Derived from Mesenchymal Stromal Cells.

Extracellular vesicles (EVs) have been recently identified as vital components of cell-based therapies based on the observation that conditioned media from cultured stromal cells reproduce some of the beneficial effects of intact cells. In order to obtain clinically active EVs derived from Mesenchymal Stromal Cells (MSCs) different procedures have been reported in the literature. Usually, non-confluent cells are incubated with culture medium for 48 h either with EV-depleted Fetal Bovine Serum (FBS) or without FBS. Our aim was to compare the effects of EVs isolated by ultracentrifugation from human umbilical cord MSC conditioned media obtained using these two conditions: with EV-depleted FBS (UC) or without FBS (UCw/o) on the mRNA expression levels of extracellular matrix related genes using the mouse chondrogenic cell line ATDC-5. We observed a deleterious effect on chondrogenic cells treated with UCw/o, showing higher mRNA expression levels of different metalloproteinases and decorin (Dcn) and lower collagen (Col1a1 and Col2a1) and aggrecan (Acan) mRNA levels. To elucidate whether this deleterious effect was induced by the EVs or by any proteins co-purified in the EV pellet, we used size exclusion chromatography (SEC) to further purify the EV pellet, obtaining an EV enriched fraction (EV or EVw/o) and a protein enriched fraction (Prot or Protw/o). Our results pointed that the negative effect on the chondrogenic cell line was due to the contaminant proteins coisolated with the EVs by ultracentrifugation and not from the EVs themselves. Thus, these results highlight the importance of working with well purified EV preparations to specifically achieve their therapeutic effect.

Multinodular and vacuolating neuronal tumor associated with focal cortical dysplasia in a child with refractory epilepsy: a case report and brief review of literature.

Multinodular and vacuolating neuronal tumor (MVNT) is a rare newly identified benign lesion, firstly included in the World Health Organization classification of tumors of the central nervous system in 2016, whose neoplastic or dysplastic nature remains unclear but with a distinctive cytoarchitectural pattern and radiological features. It is usually discovered as late-onset refractory epilepsy, headache related, or an incidental lesion of adulthood. As it is typically a stable disease, many opt for follow-up, as long as it keeps remaining asymptomatic, leaving surgery for refractory epilepsy, neurological deficits, or intracranial hypertension symptoms. A subtotal or complete resection seems to control seizures and neurological manifestations. We herein present the case of a child with refractory epilepsy related to MVNT and focal cortical dysplasia, a dual pathology case in a less frequent age group and without the typical radiological imaging. We report its radiologic features, histologic description, and management, and we present a brief literature review on MVNT focusing on the pediatric cases reported. MVNT should now be another probable low-grade epilepsy-associated lesion (LEAT) in patients of all ages, with a benign and stable course as it constitutes a curable cause of focal epilepsy. As all the refractory cases, surgery should be indicated after a comprehensive evaluation of a multidisciplinary epilepsy surgery team.

Traumatic kidney injuries: A systematic review and meta-analysis.

BACKGROUND: Traumatic kidney injury is an infrequent event with a wide range of injury patterns. The aim of this paper is to review the incidence, mechanisms of injury, diagnostic methods, and therapeutic indications of renal injury according to the most recent evidence and to perform an analysis of mortality rates on these patients. OBJECTIVES: To perform a systematic review of the literature and a meta-analysis on traumatic kidney injuries. DATA SOURCES: A literature search was performed using PubMed, Embase, and Scopus databases. Articles published in English, French and Spanish were selected from 1963 to 2018. MeSH terms utilized were renal trauma, kidney trauma, blunt renal trauma, and penetrating renal trauma. STUDY PARTICIPANTS: The eligibility criteria included only original and human subject articles. Articles not involving human patients, cancer related, review articles, surveys, iatrogenic injuries, pediatric patients, and case reports were excluded from this search. RESULTS: Forty-six articles met the inclusion criteria of which 48,660 patients were identified and included in this review. Gender was reported in 32,918 cases, of which 75.3% of patients were male with a mean age of 33 years. Of the 44,865 patients where the mechanism of injury was described, we identified 36,086 (80.5%) patients that sustained blunt trauma, while 8,779 (19.5%) were due to penetrating mechanisms. Twenty one series with a total of 31,689 patients included the mortality rate. Overall mortality rate with exact binomial 95% confidence interval estimated via random effects model was 6.4% (4.8%-8.4%). CONCLUSIONS: Non-operative management has become the standard in renal trauma management with good results in morbidity and mortality. This has resulted in a decrease in the number of unnecessary iatrogenic nephrectomies and potential improvement in a patient's quality of life. When an invasive treatment is necessary, angioembolization for active bleeding or nephrorrhaphy is usually sufficient.

Biological Treatment Patterns in Patients with Inflammatory Joint Diseases. Retrospective Study with 4 Years Follow-up. / Patrones de tratamiento biológico en pacientes con enfermedades articulares inflamatorias. Estudio retrospectivo de 4 años de seguimiento.

OBJECTIVES: To describe the therapeutic management of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) in patients initiating treatment with biological agents. MATERIALS AND METHODS: Observational, retrospective, longitudinal study in 33 Spanish hospitals. Patients with RA, PsA and AS starting treatment with biological agents between September 2009 and August 2010 and a follow-up longer than 3 years were included. Clinical-demographic characteristics, drugs, biological therapy survival, and reasons for discontinuation or switching were analyzed. RESULTS: Four hundred and sixty-three patients were included (183 RA, 119 PsA and 161 AS), with a mean follow-up of 3.8 years. At the end of follow-up, a high proportion continued with the first biological prescribed (41.0% of RA, 59.7% of PsA and 51.6% of AS), 31.1%, 47.9% and 42.9% of RA, PsA and AS patients requiring dosage adjustments, respectively. There was temporary discontinuation in 8.2%, 8.4% and 15.5% of patients, and a switch of biologic agent was required in 37.7%, 26.1% and 24.2%. Definitive discontinuation occurred in 13.1%, 5.9% and 8.7% of RA, PsA and AS patients, respectively. Mean time to discontinuation or switching was 30.1 months for RA and 35.7 months for PsA and AS. CONCLUSIONS: Our results suggest that, in practice, half of patients with RA and two thirds with PsA or AS maintained the first biological, but with frequent dose adjustments.

Size-Dependent Transport and Cytotoxicity of Mitomycin-Gold Nanoparticle Conjugates in 2D and 3D Mammalian Cell Models.

This work aims at learning how the size of gold nanocarriers influences the transport of DNA-alkylating antitumoral drugs. For this purpose, we devised conjugates of mercaptoethylmitomycin C (MEMC), a DNA alkylating agent, with gold nanoparticles of different sizes (2, 5, and 14 nm), and studied how size affects drug cytotoxicity, tumor penetrability, cellular uptake, and intracellular localization using two-dimensional (2D) and three-dimensional (3D) cell models. We show that only small, 2 nm, nanoparticles can transport MEMC efficiently to the cell nucleus, whereas MEMC cell uptake is much lower when delivered by these small nanoparticles than with the larger ones. 3D cellular models showed that smaller nanoparticles can transport MEMC toward deeper areas of tumor spheroids as compared to larger nanoparticles. We discuss the insights of this work toward the efficient delivery of DNA-targeting drugs.

Mechanical Reinforced Terminolateral Ileo-Transverse Anastomosis: An Option After Right Hemicolectomy-A 452 Patients Study.

INTRODUCTION: Bowel reconstruction techniques after right hemicolectomy has currently been objective of review, due to the high rate of anastomotic leak. The aim of this study is to analyse our results of the mechanical reinforced terminolateral ileo-transverse anastomosis. MATERIALS AND METHODS: A prospective and descriptive study of a consecutive series of right colonic cancer cases that underwent right hemicolectomy. Mechanical reinforced terminolateral ileo-transverse anastomosis technique was carried out in all patients. Demographics, emergency or elective surgery, surgical management, postoperative complications, rate of anastomotic leak, need for surgical procedure after complication, average stay, and mortality were analysed. RESULTS: A total of 452 patients underwent surgery between 2010 and 2017. Of those, 40.6% were female and 59.4% were male. The average age and body mass index (BMI) was 72±11.3 years old, and 26±7.1, respectively. Elective surgery was carried out in 405 (89.6%) patients. Laparoscopic approach was used in 250 patients (61.7%) and 6% needed conversion. Only 41 patients (10.6%) had major complications (Clavien-Dindo III-IV). The rate of postoperative paralytic ileus reach was up to 13.9%. Reintervention was needed in five patients (1.1%) due to anastomotic leak and three (0.7%) of them from the elective surgery subgroup. There were 10 patients (2.2%) with postoperative gastrointestinal bleeding. The average stay was 8.2±2.8 days and late postoperative mortality in the first 30 days was 2%. CONCLUSIONS: Mechanical reinforced terminolateral ileo-colic anastomosis is a safe technique with a low anastomotic leak rate. Although our results using this approach seem promising, postoperative paralytic ileus is still a high-rate complication.

UHPLC-MS and MALDI-MS study of aluminum phthalocyanine chloride and development of a bioanalytical method for its quantification in nanoemulsions and biological matrices.

Metal phthalocyanines are promising components in photodynamic therapy. Aluminum phthalocyanine chloride (AlClPc) has been used to treat oral cancer in mice, human carious tissue, lung cancer cells and other conditions. To overcome the high hydrophobicity of AlClPc, phthalocyanine is often encapsulated in nanoformulations. Despite increased usage, little is known about the pharmacokinetics and biodistribution of AlClPc. The aim of this study was the development and validation of a UHPLC-MS method for the determination of AlClPc in solution after extraction from nanoformulations and biological matrices such as plasma and tissue. The described method has been assayed as to selectivity, linearity, limits of detection and quantification, precision and recovery. The present study is the first to describe the behavior of AlClPc in biological matrices with mass spectrometry as well as the first to describe the chromatographic behavior of AlClPc contaminants. Molecular mass analysis identified dechlorination of AlClPc by both LC/MS and MALDI-MS and an adduct formation in LC/MS. The parameters observed indicated that the method has applicability and robustness for use in biodistribution studies.

Tratamiento neoadyuvante con imatinib de un tumor gigante del estroma gastrointestinal rectal / Neoadjuvant treatment with imatinib for a giant tumor of the rectal gastrointestinal stroma

Alrededor de 5 % de los tumores del estroma gastrointestinal (GIST) se localizan en el recto. Cuando se encuentran localmente avanzados, el tratamiento neoadyuvante con imatinib ha demostrado buenos resultados para reducir el volumen de este tipo de tumores. Se presenta el caso de un paciente con diagnóstico de GIST rectal gigante, al que se le administró neoadyuvancia con imatinib y, posteriormente, se sometió a resección anterior baja con anastomosis coloanal. Es imprescindible que la evaluación y el tratamiento sean multidisciplinarios en los GIST rectales, para tratar de obtener los mejores resultados ante esta entidad tan poco frecuente, poder evitar la comorbilidad asociada y practicar cirugías menos agresivas tras una buena reacción terapéutica al imatinib

Less than 5% of gastrointestinal stromal tumors (GIST) are located at the rectum. When these tumors are locally advanced, neoadjuvant therapy with imatinib has shown good results, reducing its volume. We present the case of a patient with a giant rectal GIST tumor, who underwent neoadjuvant imatinib therapy, and posterior low anterior resection with coloanal anastomosis. In rectal GIST tumors it is essential the multidisciplinary evaluation and treatment, in order to obtain the best possible results in this rare entity. After a good response to the treatment with imatinib, aggressive surgeries can be avoided, along with the associated morbidity that comes with it