Efficacy of hydrodynamic interleukin 10 gene transfer in human liver segments with interest in transplantation.

Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. The use of immunosuppressant drugs generally improve organ transplantation, but they cannot completely solve the problem. Also, their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required. The local expression of interleukin (IL) 10 protein in transplanted livers mediated by hydrodynamic gene transfer could improve the organ acceptance by the host because it presents the natural ability to modulate the immune response at different levels. In the organ transplantation scenario, IL10 has already demonstrated positive effects on graft tolerance. Hydrodynamic gene transfer has been proven to be safe and therapeutically efficient in animal models and could be easily moved to the clinic. In the present work, we evaluated efficacy of human IL10 gene transfer in human liver segments and the tissue natural barriers for gene entry into the cell, employing gold nanoparticles. In conclusion, the present work shows for the first time that hydrodynamic IL10 gene transfer to human liver segments ex vivo efficiently delivers a human gene into the cells. Indexes of tissue protein expression achieved could mediate local pharmacological effects with interest in controlling the immune response triggered after liver transplantation. On the other hand, the ultrastructural study suggests that the solubilized plasmid could access the hepatocyte in a passive manner mediated by the hydric flow and that an active mechanism of transportation could facilitate its entry into the nucleus. Liver Transplantation 23:50-62 2017 AASLD.

Laparoscopy may decrease morbidity and length of stay after elective colon cancer resection, especially in frail patients: results from an observational real-life study.

BACKGROUND: Advantages of laparoscopic approach in colon cancer surgery have been previously demonstrated in controlled, randomized trials and in retrospective analysis of large administrative databases. Nevertheless, evidence of these advantages in prospective, observational studies from real-life settings is scarce. METHODS: This is a prospective, observational study, including a consecutive series of patients that underwent elective colonic resection for cancer in 52 Spanish hospitals. Pre-/intraoperative data, related to patient, tumor, surgical procedure, and hospital, were recorded as well as 60-day post-operative outcomes, including wound infection, complications, anastomotic leak, length of stay, and mortality. A univariate and multivariate analysis was performed to determine the influence of laparoscopy on short-term post-operative outcome. A sub-analysis of the effect of laparoscopy according to patients' pre-operative risk (ASA Score I-II vs. III-IV) was also performed. RESULTS: 2968 patients were included: 44.2% were initially operated by laparoscopy, with a 13.9% conversion rate to laparotomy. At univariate analysis, laparoscopy was associated with a decreased mortality (p = 0.015), morbidity (p < 0.0001), wound infection (p < 0.0001), and post-operative length of stay (p < 0.0001). At multivariate analysis, laparoscopy resulted as an independent protective factor for morbidity (OR 0.7; p = 0.004), wound infection (OR 0.6; p < 0.0001), and length of post-operative stay (Effect-2 days; p < 0.0001), compared to open approach. These advantages were more relevant in high-risk patients (ASA III-IV), even if the majority of them were operated by open approach (67.1%). CONCLUSIONS: In a real-life setting, laparoscopy decreases wound infection rate, post-operative complications, and length of stay, especially in ASA III-IV patients.

Rectal cancer at the peritoneal reflection. Preoperative MRI accuracy and histophatologic correlation. Prospective study.

INTRODUCTION: To investigate magnetic resonance imaging (MRI) accuracy for determining the location of rectal tumors with respect to the peritoneal reflection (PR) and its potential involvement. METHODS: Prospective study of 161 patients ongoing surgery for rectal cancer. A double-ink method has been aplied to examine surgical specimen, orange ink for the serosal surface and indian ink for the mesorrectal margin, and assess preoperative MRI accuracy. RESULTS: Twenty-two tumors were located above, 65 at and 74 below PR. MRI accuracy was 90.6% for determining tumor's location with respect to the PR and 80.5% for defining peritoneal involvement. For classifying tumors according to their intra or extraperitoneal location an accuracy of 92.5% was set for MRI. Histophatologic peritoneal involvement was found in 28.7% of tumors located above or at the PR. CONCLUSIONS: Magnetic resonance imaging accurately predicts the location of rectal tumors with respect to the PR and its potential involvement. The double-ink method is useful to assess serosal involvement (pT4a) and to distinguish mesorrectal fascia from the peritonealized surface.

Importance of some technical aspects of the procedure of percutaneous posterior tibial nerve stimulation in patients with fecal incontinence.

INTRODUCTION: The results of percutaneous posterior tibial nerve stimulation (PTNS) in the treatment of fecal incontinence (IF) are modest. The aim of the study is to assess the relationship of some technical aspects with the clinical response: location of the nerve, distal response (motor or sensory) and accommodation. METHODS: Prospective study of patients with FI undergoing PTNS therapy. The clinical response was assessed using the Wexner scale, defecation diary and anorectal manometry. RESULTS: 32 patients were studied. The intensity of localization (proximity to the nerve) was not correlated with clinical or manometric changes. Motor response was associated with a decrease on the Wexner scale [12.12 (±5.39) to 7.71 (±4.57) P < .005], the number of episodes of passive incontinence [8.78 (±9.64) to 4.11 (±7.11) P = .025], the total number of incontinence episodes [16.11 (±16.03) to 7.78 (±11.34) P = .009] and the number of days with fecal soiling [6.89 (±5.53) to 2.56 (±4.13) P = .002] and with an increase in the length of the manometric anal canal at rest [4.55 (±0.596) to 4.95 (±0.213) P = .004]. The increase in stimulation (accommodation) was inversely correlated with the decrease in the Wexner scale (r = -0.677 P < .005) and the number of days with soiling (r = -0.650 P = .022). CONCLUSIONS: The motor response during PTNS seems to be related to a better clinical response. The accommodation phenomenon could be associated with worse results. The proximity of the electrode to the nerve does not seem to be important as long as a good distal response is achieved.

Rectal cancer at the peritoneal reflection. Preoperative MRI accuracy and histophatologic correlation. Prospective study. / Cáncer de recto a nivel de la reflexión peritoneal. Exactitud de la RM preoperatoria y correlación anatomopatológica. Estudio prospectivo.

INTRODUCTION: To investigate magnetic resonance imaging (MRI) accuracy for determining the location of rectal tumors with respect to the peritoneal reflection (PR) and its potential involvement. METHODS: Prospective study of 161 patients ongoing surgery for rectal cancer. A double-ink method has been aplied to examine surgical specimen, orange ink for the serosal surface and indian ink for the mesorrectal margin, and assess preoperative MRI accuracy. RESULTS: Twenty-two tumors were located above, 65 at and 74 below PR. MRI accuracy was 90.6% for determining tumor's location with respect to the PR and 80.5% for defining peritoneal involvement. For classifying tumors according to their intra or extraperitoneal location an accuracy of 92.5% was set for MRI. Histophatologic peritoneal involvement was found in 28.7% of tumors located above or at the PR. CONCLUSIONS: Magnetic resonance imaging accurately predicts the location of rectal tumors with respect to the PR and its potential involvement. The double-ink method is useful to assess serosal involvement (pT4a) and to distinguish mesorrectal fascia from the peritonealized surface.

Importance of some technical aspects of the procedure of percutaneous posterior tibial nerve stimulation in patients with fecal incontinence. / Importancia de algunos aspectos técnicos del procedimiento de estimulación percutánea del nervio tibial posterior en pacientes con incontinencia fecal.

INTRODUCTION: The results of percutaneous posterior tibial nerve stimulation (PTNS) in the treatment of fecal incontinence (IF) are modest. The aim of the study is to assess the relationship of some technical aspects with the clinical response: location of the nerve, distal response (motor or sensory) and accommodation. METHODS: Prospective study of patients with FI undergoing PTNS therapy. The clinical response was assessed using the Wexner scale, defecation diary and anorectal manometry. RESULTS: 32 patients were studied. The intensity of localization (proximity to the nerve) was not correlated with clinical or manometric changes. Motor response was associated with a decrease on the Wexner scale [12.12 (± 5.39) to 7.71 (± 4.57) p < 0.005], the number of episodes of passive incontinence [8.78 (± 9.64) to 4.11 (± 7.11) p = 0.025], the total number of incontinence episodes [16.11 (± 16.03) to 7.78 (± 11.34) p = 0.009] and the number of days with faecal soiling [6.89 (± 5.53) to 2.56 (± 4.13) p = 0.002] and with an increase in the length of the manometric anal canal at rest [4.55 (± 0.596) to 4.95 (± 0.213) p = 0.004]. The increase in stimulation (accommodation) was inversely correlated with the decrease in the Wexner scale (r = -0.677 p < 0.005) and the number of days with soiling (r = -0.650 p = 0.022). CONCLUSIONS: The motor response during PTNS seems to be related to a better clinical response. The accommodation phenomenon could be associated with worse results. The proximity of the electrode to the nerve does not seem to be important as long as a good distal response is achieved.

Feeding Jejunostomy after esophagectomy cannot be routinely recommended. Analysis of nutritional benefits and catheter-related complications.

BACKGROUND: Patients undergoing esophagectomy for cancer usually deal with malnourishment which increases postoperative morbimortality. The objective of this paper is to analyze the nutritional benefits of feeding jejunostomy (FJ) for early postoperative enteral nutrition (EN) and directly-related complications. MATERIAL AND METHODS: Retrospective study of 100 patients undergoing esophagectomy for cancer between 2008 and 2016. RESULTS: FJ was placed in 47 patients. 82.98% reached EN requirements in FJ group, with a median EN re-start of 1.9 days and median days to objective requirements of 5 days. 51.06% developed directly-related FJ complication, 91.66% of them mild ones (gastrointestinal or catheter-related). 2 patients (4.25%) required re-intervention. No significant differences were shown in total protein and albumin seric levels during first postoperative week and in anastomotic leak rate between both groups (p > 0.05). CONCLUSIONS: Feeding jejunostomies are associated with a great number of complications although most are not life-threatening. Since its nutritional benefit is not proven FJ cannot routinely recommended after esophagectomy. However, the optimal pathway for EN reintroduction, including direct oral intake, is still a matter of debate.