Intraperitoneal drug delivery systems for peritoneal carcinomatosis: Bridging the gap between research and clinical implementation.

Several abdominal-located cancers develop metastasis within the peritoneum, what is called peritoneal carcinomatosis (PC), constituting a clinical challenge in their therapeutical management, often leading to poor prognoses. Current multidisciplinary strategies, including cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC), demonstrate efficacy but have limitations. In response, alternative strategies are explored in the drug delivery field for intraperitoneal chemotherapy. Controlled drug delivery offers a promising avenue, maintaining localized drug concentrations for optimal PC management. Drug delivery systems (DDS), including hydrogels, implants, nanoparticles, and hybrid systems, show potential for sustained and region-specific drug release. The present review aims to offer an overview of the advances and current designs of DDS for PC chemotherapy administration, focusing on their composition, main characteristics, and principal experimental outcomes, highlighting the importance of biomaterial rationale design and in vitro/vivo models for their testing. Moreover, since clinical data for human subjects are scarce, we offer a critical discussion of the gap between bench and bedside in DDS translation, emphasizing the need for further research.

Selection of pharmaceuticals of concern in reclaimed water for crop irrigation in the Mediterranean area.

The reuse of reclaimed water in agriculture is being fostered in areas suffering from water scarcity. However, water pollutants can compromise food safety and pose a risk for the environment. This study aims to select the pharmaceutical compounds worth monitoring and investigating when reclaimed water is used for tomato and lettuce irrigation. A comprehensive study was first conducted to identify the pharmaceuticals frequently detected in secondary wastewater effluents in Catalonia (Northeast Spain). Priority pharmaceuticals were further selected based on their occurrence in secondary effluents, persistence (removal in conventional treatment), bioaccumulation potential, toxicity for aquatic organisms, and the risks they pose to the terrestrial environment and human health (through the consumption of crops). Out of the 47 preselected priority compounds, six could pose a risk to organisms living in soil irrigated with reclaimed water and seven could be potentially taken up by the crops. Nonetheless, no risk for human consumption was foreseen.

Inguinal hernia repair in Spain. A population-based study of 263,283 patients: factors associated with the choice of laparoscopic approach.

PURPOSE: The objective of this study is to evaluate the laparoscopic inguinal hernia repair (IHR) rate in Spain and identify the factors associated with the choice of this surgical approach. METHODS: A retrospective cohort study of 263,283 patients who underwent IHR from January 2016 to December 2018 was conducted. Data were extracted from the Spanish Minimum Basic Data Set (MBDS) of the Health Ministry database. The primary outcome was laparoscopic (LAP) rate utilization. Univariate analysis and multivariable logistic regression analysis were performed to identify factors associated with LAP-IHR. RESULTS: Only 5.7% (15,059) patients underwent LAP-IHR, whereas the remnant 94.3% (248,224 patients) underwent open repair. High variability in the LAP-IHR rate across the country was observed; ranged between provinces from 0 to 19.7%, for a unilateral hernia, and between 0 to 57.4% in the case of bilateral hernias. On multivariate logistic regression analysis, the patient place of residence was the most remarkable factor associated with the likelihood of receiving LAP-IHR (OR 4.96; p < 0.001). There were also significant differences favoring LAP-IHR for bilateral operation (OR 4.596; p < 0.001), insurance coverage (OR 4.439, p < 0.001) and self-pay patients (OR 2.317; p < 0.001), as well as a recurrent hernia (OR 1.780; p < 0.001), age younger than 65 years (OR 1.555; p < 0.001) and male sex (OR 1.162, p < 0.001). CONCLUSION: LAP-IHR remains a not frequent choice among surgeons in Spain, even when dealing with recurrent and bilateral hernias. The results suggest that the choice of LAP-IHR could depend on the surgeon's preference rather than on the indication appropriateness.

Showcasing the potential of wastewater-based epidemiology to track pharmaceuticals consumption in cities: Comparison against prescription data collected at fine spatial resolution.

While the extent of pharmaceutical consumption within a society/community is of high relevance to its health, economy and general wellbeing, this data is often not readily available. Herein, we strengthen a wastewater-based epidemiology (WBE) approach as a way to track the consumption of pharmaceuticals within the sampled community. This method is less laborious than established questionnaire or databases approaches and allows a higher temporal and spatial resolution. The WBE approach was conducted by sampling influent wastewater from two wastewater treatment plants of different size. A total of 39 targeted compounds were quantified by liquid chromatography coupled with tandem mass spectrometry. The number of prescriptions and the defined daily doses for each prescription was obtained from the reference database of The Catalan Health System to validate the wastewater-based approach. The wastewater sampling and the data inquiry were both executed during the same period (October 2019) and standardised for comparison to treatments per 1,000 inhabitants per day. The back-calculation parameters were improved from previous studies by including the faecal excretion rate of the pharmaceuticals. For prescription only pharmaceuticals, where prescription numbers are expected to be a good estimate of consumption, our WBE approach agreed with 27 out of 32 (<0.7 order of magnitude). Common over-the-counter pharmaceuticals such as acetaminophen, ibuprofen and naproxen showed much higher values for treatments per day per 1,000 inhabitant in wastewater than prescribed, reflecting the usefulness of WBE in obtaining an estimate of the total consumption i.e. with and without a prescription.

Long-term incisional hernia rate after single-incision laparoscopic cholecystectomy is significantly higher than that after standard three-port laparoscopy: a cohort study.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is a feasible technique that provides comparable results to standard laparoscopic cholecystectomy (LC). However, despite the theoretical advantages of minor wound complications and cosmetic results, SILC usually requires a larger incision, which may increase the incidence of incisional hernias. This study evaluated SILC and standard multiport cholecystectomy with respect to perioperative outcomes, hospital stay, cosmetic results, and postoperative complications, including the 5-year incisional hernia rate. METHODS: A cohort study was performed with patients who underwent elective laparoscopic surgery for noncomplicated cholelithiasis at our hospital between July 2009 and June 2011. During the study period, there were 45 nonselected patients who underwent SILC, and these patients were compared with a control group of 140 patients who underwent LC using the standard three-trocar technique during the same period. Both patient groups were comparable in age, gender, BMI and ASA classification. RESULTS: The mean follow-up was 58.7 ± 10.9 (range 3-80) months. There were no differences between groups in terms of hospital stay, rate and severity of complications, wound infection, and patient cosmetic satisfaction. However, the operating time (57.8 versus 35.2 min) and long-term incisional hernia rate (13.3% versus 4.7%) were significantly higher in the SILC group. CONCLUSION: SILC is associated with a statistically significantly higher long-term incisional hernia rate at the umbilical port site than the standard multiport laparoscopic cholecystectomy. Our data show there was no relevant advantage regarding the postoperative course, hospital stay or cosmetic satisfaction. To date, widespread use of SILC cannot be recommended. Registration number: NCT03768661 (https://www.clinicaltrials.gov). TRIAL REGISTRATION: This study has been registered at www.clinicaltrials.gov. The clinicaltrials.gov ID number is: NCT03768661.

Long-term follow-up (at 5 years) of midline incisional hernia repairs using a primary closure and prosthetic onlay technique: recurrence and quality of life.

INTRODUCTION AND OBJECTIVES: The recurrence rate of incisional hernia (IH) repair is usually underestimated due to a lack of long-term follow-up. The objective of this study was to evaluate recurrence rate for patients operated on midline IH surgery, using a primary closure and prosthetic onlay technique, 5 years after the procedure. MATERIALS AND METHODS: From January 2009 to January 2011, all 92 patients operated on elective midline IH repair by primary closure and prosthetic onlay technique in a General Surgery Department were retrospectively included in the study. Exclusion criteria were absence of follow-up or death. Recurrence rate and quality of life were assessed. Demographic, surgical data and quality of life in patients with and without 5-year recurrence were compared. RESULTS: Mean follow-up was 64 months. Ultimately, 76 patients were included in the study, representing 82% of the selected patients during the study period (76/92), of whom 24 presented a recurrence (32%). Half (12) were diagnosed for recurrence more than 3 years after the surgery. Patients who developed a recurrence had more percentage of obesity (64 vs. 29%, p = 0.016), which denoted an odds ratio (OR) for recurrence of 4.4 (1.2-15.7; p = 0.01) and they punctuated lower in quality of life (6.0 ± 2.9 vs. 7.6 ± 2.6, p = 0.006). CONCLUSIONS: Recurrence rate on midline IH repair is still a concern (32% at 5 years). It is advisable to look for other strategies and more efficient surgical techniques for IH surgery, especially in obese patients.

Imaging-Guided Preoperative Localization of Intra-Abdominal Local Recurrences of Colorectal Cancer Using the Harpoon Technique.

BACKGROUND AND AIMS: Intra-abdominal local recurrences of colorectal cancer can be difficult to localize and excise because they are not easily visible or palpable. MATERIALS AND METHODS: We report on our experience using the computed tomography-guided harpoon technique to locate and resect these nodules in seven patients. RESULTS: No complications were recorded during the procedures. Six nodes were malignant and all margins were tumor free. CONCLUSIONS: Harpoon placement for intra-abdominal local recurrences of colorectal cancer is a feasible and useful technique that provides direct localization and complete excision of lesions.

Randomized clinical trial of mesh fixation with glue or sutures for Lichtenstein hernia repair.

BACKGROUND: Pain is the most likely reason for delay in resuming normal activities after groin hernia repair. The primary aim of this study was to determine whether the use of glue to fix the mesh instead of sutures reduced acute postoperative pain after inguinal hernia repair. Secondary objectives were to compare postoperative complications, chronic pain and early recurrence rates during 1-year follow-up. METHODS: Some 370 patients who underwent Lichtenstein hernia repair were randomized to receive either glue (Histoacryl®) or non-absorbable polypropylene sutures for fixation of lightweight polypropylene mesh. Postoperative complications, pain and recurrence were evaluated by an independent blinded observer. RESULTS: Postoperative pain at 8 h, 24 h, 7 days and 30 days was less when glue was used instead of sutures for all measures (P < 0·001). The operation was significantly quicker using glue (mean(s.d.) 35·3(8·7) min versus 39·9(11·1) min for sutures; P < 0·001). There were no significant differences between the groups in terms of postoperative complications, chronic pain and early recurrence at 1-year follow-up. CONCLUSION: Atraumatic mesh fixation with glue was quicker and resulted in less acute postoperative pain than sutures for Lichtenstein hernia repair. Registration number: NCT02632097 (http://www.clinicaltrials.gov).

Comparative study of dental anomalies assessed with panoramic radiographs of Down syndrome and non-Down syndrome patients.

AIM: The aim of this study was to compare the prevalence of dental anomalies from panoramic radiographs of age-matched individuals with and without Down Syndrome (DS). STUDY DESIGN: This is a retrospective cross-sectional study. A group of 41 patients (19 female and 22 male) with Down Syndrome (DS), mean age 10.6 ± 1.4 and a control group of 42 non- DS patients (26 female and 16 male), mean age 11.1 ± 1.3 were studied. METHODS: This study examined the medical history and a panoramic radiograph of each patient. The dental anomalies studied were agenesis of permanent teeth (except third molars), size and shape maxillary lateral anomalies and maxillary canine eruption path anomalies. STATISTICS: The groups were compared using Mann-Whitney and Wilcoxon non-parametric tests (p<0.05). Rho Spearman correlation coefficient was applied for associations. Results Agenesis of one permanent tooth was found in 73.17% of DS subjects and two or more permanent teeth in more than 50% (p<0.001). Maxillary lateral incisor was the most frequently absent tooth followed by mandibular second premolar, mandibular lateral incisor, maxillary second premolar and mandibular central incisor. No significant differences were detected between maxilla and mandible on either side. No differences in gender were observed. Significant differences were found for size and shape anomalies of maxillary lateral incisors, as well as for canine eruption anomalies (p<0.05). No gender differences were observed for either variable. No association was found between these two variables in the DS group. CONCLUSIONS: More dental anomalies were present in the DS group than in the control group, which implied that DS patients need periodical dental and orthodontic supervision so as to prevent or control subsequent oral problems.

[Are treatments with statins that are considered unsuitable really unsuitable?]. / ¿Son realmente inadecuados los tratamientos con estatinas considerados como inadecuados?

In the Catalonian Institute of health there are 2 well-established circumstances for indicating lipid-lowering drug treatment with statins in the primary prevention of ischaemic heart disease. These are, severe hypercholesterolaemia, with a low density lipoprotein cholesterol equal to or greater than 240mg/dL, or above 130mg/dL when the coronary risk is equal to or greater than 10% at 10 years. There are data that suggest that these 2 criteria are not the only ones used in routine clinical practice, as such that the majority of patients to whom it is indicated, do not meet either of these 2 conditions. This study aims to determine the characteristics of the patients when statins are indicated outside the aforementioned circumstances. It is concluded that around 40% of patients have clinical characteristics that could justify the treatment. The level of suitability could not be established in about 33% of the patients, due to not being able to determine the coronary risk.

¿Son realmente inadecuados los tratamientos con estatinas considerados como inadecuados? / Are treatments with statins that are considered unsuitable really unsuitable?

Las circunstancias que están bien establecidas, en el ámbito del Institut Català de la Salut, para indicar un tratamiento farmacológico hipolipidemiante con estatinas en la prevención primaria de la cardiopatía isquémica son 2: una hipercolesterolemia severa, con valores de colesterol transportado por las lipoproteínas de baja densidad iguales o superiores a 240 mg/dL, o por encima de 130 mg/dL cuando el riesgo coronario es igual o mayor al 10% a los 10 años. Hay datos que indican que en la práctica habitual estos 2 criterios no son los únicos utilizados, de forma que la mayoría de los pacientes a quienes se indica, de novo, una estatina, no reúnen ninguna de estas 2 condiciones. Este estudio pretende conocer las características que tienen los pacientes cuando estas son indicadas fuera de los supuestos mencionados. Se concluye que cerca del 40% de los pacientes tienen características clínicas que pueden explicar la indicación del tratamiento. En una tercera parte no puede establecerse el grado de adecuación por no poderse determinar el riesgo coronario

In the Catalonian Institute of health there are 2 well-established circumstances for indicating lipid-lowering drug treatment with statins in the primary prevention of ischaemic heart disease. These are, severe hypercholesterolaemia, with a low density lipoprotein cholesterol equal to or greater than 240 mg/dL, or above 130 mg/dL when the coronary risk is equal to or greater than 10% at 10 years. There are data that suggest that these 2 criteria are not the only ones used in routine clinical practice, as such that the majority of patients to whom it is indicated, do not meet either of these 2 conditions. This study aims to determine the characteristics of the patients when statins are indicated outside the aforementioned circumstances. It is concluded that around 40% of patients have clinical characteristics that could justify the treatment. The level of suitability could not be established in about 33% of the patients, due to not being able to determine the coronary risk

Precision optical trapping via a programmable direct-digital-synthesis-based controller for acousto-optic deflectors.

We describe a simple-to-construct programmable direct-digital-synthesis-based controller for use with acousto-optic deflectors. Our controller corrects for nonlinear diffraction efficiency versus diffraction angle, provides superior stability, functionality, and configurability, and costs a fraction of commercially available systems. Using this instrument, we move a 1 mum diameter bead by 1-nm-sized steps and resolve these steps.

Laparoscopic low rectal anastomosis using a new stapling device: early experience with the Contour stapler.

Rectal cancer was initially considered a contraindication for the laparoscopic approach to low rectal resection due to the greater difficulty of deep pelvic dissection, but several studies have demonstrated its potential clinical advantages. The currently accepted technique for this intervention includes total mesorectal excision, which entails complete dissection of the mesorectum followed by low transection of the rectum. The laparoscopic approach provides good visualization and magnification of the operative field, but transection of the rectum may be more difficult. This is illustrated by the conversion rate of around 15% in most series, mainly due to technical difficulties. Contour placement may overcome these difficulties. Two key points support the interest in the use of devices with the features of the Contour. First, the current feeling and evidence indicate that with presently available laparoscopic devices, the section of the low rectum in selected patients (males and mid-third rectal tumors) is often difficult. Secondly, although the Contour device was designed for open surgery, surgeons have the intuitive perception that it perfectly accomplishes the functions an ideal laparoscopic stapler should include. There is clearly a need for more appropriate laparoscopic instruments for low rectal transection. The Contour device could be considered a prototype because it meets the surgeon's requirements when operating on the low rectum, providing one shot, simultaneous sewing and cutting function and a symmetric rectum section. However, a number of technical modifications would enhance the utility of the instrument in this setting.

Unusual upper gastrointestinal diseases associated with achalasia: laparoscopic approach.

BACKGROUND: As a result of the high success rate associated with the laparoscopic approach for achalasia, surgery for the disease has become the treatment of choice in recent years. With the greater number of patients undergoing surgery, surgeons may encounter other upper gastroesophageal illnesses associated with achalasia, and these may require evaluation for simultaneous surgical treatment. This study aimed to evaluate the incidence of gastroesophageal diseases associated with achalasia, and to determine the possibility for simultaneous management using the laparoscopic approach. METHODS: From January 1999 to May 2006, 81 patients were referred from the Service of Gastroenterology to the Service of General and Digestive Surgery as candidates for the surgical management of achalasia. Data for this group were recorded prospectively in laparoscopic surgery databases at the Hospital Sant Pau and the Hospital de Igualada. A total of 78 patients underwent laparoscopic Heller myotomy with gastric fundoplication. RESULTS: In 8 of 81 patients, nine additional gastroesophageal diseases (11.1%) were found: three cases of pseudoachalasia (3.7%), three cases of paraesophageal hiatal hernia (3.7%), two cases of esophageal diverticulum (2.5%), and one case of gastric volvulus (1.2%). Pseudoachalasia was diagnosed for three patients. The diagnosis was made preoperatively for one of these patients. For the other two patients, an adenocarcinoma arising from the gastroesophageal junction was diagnosed during the laparoscopy. In three cases, a paraesophageal hiatal hernia was found and treated by laparoscopic Heller myotomy, sac excision, hiatal closure, and posterior fundoplication. Esophageal diverticulectomy was performed for one patient. Another patient presented with an organoaxial gastric volvulus associated with achalasia, for which laparoscopic Heller myotomy, posterior fundoplication, and anterior gastropexy were performed. The median follow-up period was 39 months, with no recurrence. CONCLUSIONS: Despite their infrequency, several gastroesophageal diseases may be found in association with achalasia. Laparoscopic surgery may be useful for the diagnosis and/or treatment of both diseases.

Can we predict immediate outcome after laparoscopic splenectomy for splenomegaly? Multivariate analysis of clinical, anatomic, and pathologic features after 3D reconstruction of the spleen.

The laparoscopic approach is the treatment of choice for splenectomy, but its definitive role in splenomegaly is controversial. Factors that influence immediate outcome are clinical, anatomic, and pathological. The aim of this study was to evaluate the predictive factors on outcome after laparoscopic splenectomy in splenomegaly. We reviewed patients submitted to laparoscopic splenectomy with a final spleen weight superior to 700 g. Three-dimensional reconstruction of the spleen was performed, and spleen volume and diameters were measured. Multivariate analysis showed that factors that predicted for conversion were mediolateral diameter ( P = .039, RR: 1.43) and platelet count (P < .05, RR: 1). For intraoperative bleeding, the predictive factor was spleen volume (P < .03, RR: 1.003). Anteroposterior spleen diameter was related to operative time (P = .011), and the factor related to postoperative morbidity was age (P = .049, RR: 0.941). Local anatomy and clinical factors affect surgical outcome in laparoscopic splenectomy for splenomegaly. These factors should be taken into account when planning this kind of procedure.

Predictive factors for successful laparoscopic splenectomy in immune thrombocytopenic purpura: study of clinical and laboratory data.

BACKGROUND: Laparoscopic splenectomy (LS) offers better short-term results than open surgery for the treatment of immune thrombocytopenic purpura (ITP), but long-term follow-up is required to ensure its efficacy. The remission rate after splenectomy ranges from 49 to 86% and the factors that predict a successful response to surgical management have not been clearly defined. The goal of this study was to determine the preoperative factors that predict a successful outcome following LS. METHODS: From February 1993 to December 2003, LS was consecutively performed in a series of 119 nonselected patients diagnosed with ITP (34 men and 85 women; mean age, 41 years), and clinical results were prospectively recorded. Postoperative follow-up was based on clinical records, follow-up data provided by the referring hematologist, and a phone interview with the patient and/or relative. Univariate and multivariate analyses were performed for clinical preoperative variables to identify predictive factors of success following LS. RESULTS: Over a mean period of 33 months, 103 patients (84%) were available for follow-up with a remission rate of 89% (92 patients, 77 with complete remission with platelet count > 150,000). Eleven patients did not respond to surgery (platelet count < 50,000). Mortality during follow-up was 2.5% (two cases not related to hematological pathology and one case without response to splenectomy). Preoperative clinical variables evaluated to identify predictive factors of response to surgery were sex, age, treatment (corticoids alone or associated with Ig or chemotherapy), other immune pathology, duration of disease, and preoperative platelet count. In a subgroup of 52 patients, we also evaluated the type of autoantibodies and corticoid doses required to maintain a platelet count > 50,000. Multivariate analysis showed that none of the variables evaluated could be considered as predictive factors of response to LS due to the high standard error. CONCLUSION: Long-term clinical results show that LS is a safe and effective therapy for ITP. However, a higher number of nonresponders is needed to determine which variables predict response to LS for ITP.