N-acetylcysteine: a novel approach to methaemoglobinaemia in normothermic liver machine perfusion.

Extended duration of normothermic machine perfusion (NMP) provides opportunities to resuscitate suboptimal donor livers. This intervention requires adequate oxygen delivery typically provided by a blood-based perfusion solution. Methaemoglobin (MetHb) results from the oxidation of iron within haemoglobin and represents a serious problem in perfusions lasting > 24 h. We explored the effects of anti-oxidant, N-acetylcysteine (NAC) on the accumulation of methaemoglobin. NMP was performed on nine human donor livers declined for transplantation: three were perfused without NAC (no-NAC group), and six organs perfused with an initial NAC bolus, followed by continuous infusion (NAC group), with hourly methaemoglobin perfusate measurements. In-vitro experiments examined the impact of NAC (3 mg) on red cells (30 ml) in the absence of liver tissue. The no-NAC group sustained perfusions for an average of 96 (range 87-102) h, universally developing methaemoglobinaemia (≥ 2%) observed after an average of 45 h, with subsequent steep rise. The NAC group was perfused for an average of 148 (range 90-184) h. Only 2 livers developed methaemoglobinaemia (peak MetHb of 6%), with an average onset of 116.5 h. Addition of NAC efficiently limits formation and accumulation of methaemoglobin during NMP, and allows the significant extension of perfusion duration.

Situación actual del trasplante hepático pediátrico por hepatopatías crónicas en Chile: Inequidades asociadas a la priorización por sistema MELD/PELD

Background: The Chilean allocation system for liver transplantation (LT) uses the MELD/PELD score to prioritize candidates on the waiting list. Aim: To assess if the Chilean allocation system for LT is equitable for pediatric candidates compared to their adult counterparts. Material and Methods: We used the Public Health Institute's registry between October 2011 and December 2017. We analyzed candidates with chronic hepatic diseases listed for LT. The primary outcome was the cadaveric liver transplantation (CLT) rate. Secondary outcomes were death or disease progression in the waiting list and living donor liver transplant (LDLT) rate. Results: We analyzed 122 pediatric and 735 adult candidates. Forty one percent of pediatric candidates obtained a CLT compared to 48% of adults (p = NS). Among patients aged under two years of age, the access to CLT on the waiting list there was 28% of CLT, compared to 48% in adults (p = 0.001). Fifty-seven percent of candidates aged under two years were listed for cholestatic diseases, obtaining a CLT in 18% and requiring a LDLT in 49%. The median time in the waiting list for CLT was 5.9 months in pediatric candidates and 5.1 in adults, while the median time to death in the waiting list was 2.8 and 5.6 months, respectively. The mortality rate at one year in candidates under two years old was 38.1% compared to 32.5% in adults. Conclusions: Pediatric candidates with chronic liver diseases, especially under two years of age, have greater access difficulties to CLT than adults. Half of the pediatric candidates die on the waiting list before three months. The mortality among candidates under two years of age in the waiting list is excessively high.

[Current situation of pediatric liver transplantation in Chile. Inequities associated with the MELD/PELD prioritization system]. / Situación actual del trasplante hepático pediátrico por hepatopatías crónicas en Chile: Inequidades asociadas a la priorización por sistema MELD/PELD.

BACKGROUND: The Chilean allocation system for liver transplantation (LT) uses the MELD/PELD score to prioritize candidates on the waiting list. AIM: To assess if the Chilean allocation system for LT is equitable for pediatric candidates compared to their adult counterparts. MATERIAL AND METHODS: We used the Public Health Institute's registry between October 2011 and December 2017. We analyzed candidates with chronic hepatic diseases listed for LT. The primary outcome was the cadaveric liver transplantation (CLT) rate. Secondary outcomes were death or disease progression in the waiting list and living donor liver transplant (LDLT) rate. RESULTS: We analyzed 122 pediatric and 735 adult candidates. Forty one percent of pediatric candidates obtained a CLT compared to 48% of adults (p = NS). Among patients aged under two years of age, the access to CLT on the waiting list there was 28% of CLT, compared to 48% in adults (p = 0.001). Fifty-seven percent of candidates aged under two years were listed for cholestatic diseases, obtaining a CLT in 18% and requiring a LDLT in 49%. The median time in the waiting list for CLT was 5.9 months in pediatric candidates and 5.1 in adults, while the median time to death in the waiting list was 2.8 and 5.6 months, respectively. The mortality rate at one year in candidates under two years old was 38.1% compared to 32.5% in adults. CONCLUSIONS: Pediatric candidates with chronic liver diseases, especially under two years of age, have greater access difficulties to CLT than adults. Half of the pediatric candidates die on the waiting list before three months. The mortality among candidates under two years of age in the waiting list is excessively high.

Smartphone application supplements laparoscopic training through simulation by reducing the need for feedback from expert tutors.

BACKGROUND: Simulation training is a validated, highly effective tool for learning laparoscopy. Feedback plays a crucial role in motor skills training. We present an app to guide students during advanced laparoscopy simulation training and evaluate its effect on training. METHODS: A smartphone(iOS)-app was developed. A group of trainees were randomized to use the app (YAPP) or not use the app (NAPP). We used blinded analysis with validated rating scales to assess their performance before and after the training. The number of requests for tutor feedback per session was recorded. Finally, the participants in the YAPP group completed a survey about their experience with the app. RESULTS: Fifteen YAPP and 10 NAPP completed the training program. There were no statistically significant differences between their skills performance scores (P = .338). The number of tutor feedback requests in the YAPP and NAPP was of 4 (3-6) and 13 (10-14) (P < .001), respectively. All participants in the YAPP group found the app was useful. CONCLUSION: The use of a smartphone app reduces the need for expert tutor feedback without decreasing the degree of skills acquisition.

Utilidad pronóstica del PET/CT en cáncer de páncreas / Prognostic value of PET/CT in pancreatic cancer

Background: Pancreatic cancer is the tenth most prevalent cancer in world, and represents the fourth cause of cancer death. It has a five year-survival of 5%. Aim: To assess the prognostic value of PET/CT in pancreatic cancer. Material and Methods: Sixty-nine patients with pancreatic adenocarcinoma who underwent staging 18F-fluorodeoxyglucose (FDG) PET/CT between December 2008 and July 2016 were selected. Gender, age, body-mass index, laboratory tests (Ca 19-9, hemoglobin, erythrocyte sedimentation rate, liver enzymes, lactate dehydrogenase), histological differentiation of tumor, American Joint Committee on Cancer (AJCC) stage, size and 18F-FDG uptake (maximal stan-dardized uptake value [SUVmax]) of the primary tumor, nodal involvement and distant metastasis detected by PET/CT were registered. Survival was assessed using Kaplan-Meier curves, Log Rank test and Cox multivariable analysis. Results: Mortality was 66.7%, during a mean observation time of 18 months (range 20 days-66 months). Curative surgery, lack of metastases detected by PET/CT, histologically well differentiated tumors, and SUVmax ≤ 4.3 were significantly associated with a better specific survival, determined by the Log Rank test. Histological differentiation was the only variable that had a statistically significant prognostic value in the multivariable analysis. Conclusions: The detection of distant metastases and the intensity of primary tumor 18F-FDG uptake during PET/CT provide useful prognostic information in pancreatic cancer patients.

Simulation-trained junior residents perform better than general surgeons on advanced laparoscopic cases.

BACKGROUND: Multiple simulation training programs have demonstrated that effective transfer of skills can be attained and applied into a more complex scenario, but evidence regarding transfer to the operating room is limited. OBJECTIVE: To assess junior residents trained with simulation performing an advanced laparoscopic procedure in the OR and compare results to those of general surgeons without simulation training and expert laparoscopic surgeons. METHODS: Experimental study: After a validated 16-session advanced laparoscopy simulation training program, junior trainees were compared to general surgeons (GS) with no simulation training and expert bariatric surgeons (BS) in performing a stapled jejuno-jejunostomy (JJO) in the OR. Global rating scale (GRS) and specific rating scale scores, operative time and the distance traveled by both hands measured with a tracking device, were assessed. In addition, all perioperative and immediate postoperative morbidities were registered. RESULTS: Ten junior trainees, 12 GS and 5 BS experts were assessed performing a JJO in the OR. All trainees completed the entire JJO in the OR without any takeovers by the BS. Six (50 %) BS takeovers took place in the GS group. Trainees had significantly better results in all measured outcomes when compared to GS with considerable higher GRS median [19.5 (18.8-23.5) vs. 12 (9-13.8) p < 0.001] and lower operative time. One morbidity was registered; a patient in the trainees group was readmitted at postoperative day 10 for mechanical ileus that resolved with medical treatment. CONCLUSION: This study demonstrated transfer of advanced laparoscopic skills acquired through a simulated training program in novice surgical residents to the OR.

Allowing New Opportunities in Advanced Laparoscopy Training Using a Full High-Definition Training Box.

INTRODUCTION: Simulated laparoscopy training is limited by its low-quality image. A high-definition (HD) laparoscopic training box was developed under the present necessity of simulating advanced surgery. OBJECTIVE: To describe and test a new HD laparoscopic training box for advanced simulation training. METHODS: We describe the features and image quality of the new training box. The simulator was tested and then evaluated by a group of 76 expert surgeons using a 4-item questionnaire. To assess the effectiveness of training using this simulation box, 15 general surgery residents were trained to perform a laparoscopic jejuno-jejunostomy in a validated simulation program. They were assessed with objective rating scales before and after the training program, and their results were compared with that of experts. RESULTS: The training box was assembled using high-density fiberglass shaped as an insufflated abdomen. It has an adapted full-HD camera with a LED-based illumination system. A manually self-regulated monopod attached to the camera enables training without assistance. Of the expert surgeons who answered the questionnaire, 91% said that the simulation box had a high-quality image and that it was very similar to real laparoscopy. All residents trained improved their rating scores significantly when comparing their initial versus final assessment ( P < .001). Their performance after completing the training in the box was similar to that of experts ( P > .2). CONCLUSIONS: This novel laparoscopic training box presents a high-resolution image and allows training different types of advanced laparoscopic procedures. The simulator box was positively assessed by experts and demonstrated to be effective for laparoscopy training in resident surgeons.

Effectiveness of learning advanced laparoscopic skills in a brief intensive laparoscopy training program.

BACKGROUND: Intensive training programs arose from limitations in access to simulation centers. The aim of this study is to evaluate the effect and associated factors involved in an intensive course for learning advanced laparoscopic skills, which include validated teaching techniques. METHODS: General surgeons and final-year residents were analyzed after completing an intensive 5-session advanced laparoscopy course. Initial (IA) and final assessment (FA) consisted in performing a jejunojejunal anastomosis in a live porcine model, measured using objective structured assessment of technical skill (OSATS) (GRS and SRS, that is, global rating scale and specific rating scale, respectively) and operative time (OT). The 3-session training was structured in a bench model with an ex vivo bowel. For the demographic analysis, 3 groups were defined according to the presentation of relevant changes in OSATS and in OT between IA and FA: group A, no changes; group B, change in 1 variable; and group C, change in both variables. RESULTS: After the course, all 114 participants presented a significant improvement in OT (37 vs 24.6min, p < 0.001) and in OSATS; global rating scale (10.5 vs 16 points; p < 0.001) and Specific Rating Scale (8.5 vs 12.7 points; p < 0.001). In the IA, 70 (61%) participants completed the jejunojejunal anastomosis and 105(92%) in the FA (p < 0.01). In the FA, 56% of participants presented relevant changes in both variables (group C). This group was significantly younger (34 vs 45 vs 40y old; p < 0.001), had fewer years of surgical experience (2 vs 9 vs 5y; p < 0.001), and had a proportionally higher concentration of residents (p = 0.01). CONCLUSIONS: This intensive course is set out as a viable alternative to teach basic skills in advanced laparoscopy in a short period of time, which is ideal for surgeons with difficult access to training centers. It remains necessary to establish the participant profile for which this type of course is most beneficial.

A cadaveric porcine model for assessment in laparoscopic bariatric surgery--a validation study.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is the most effective surgical therapy for morbid obesity. It is an advanced laparoscopic surgical procedure and has a protracted learning curve. Therefore, it is important to develop innovative ways of training and assessing surgeons. The aim of this study is to determine if a cadaveric porcine jejuno-jejunostomy model is an accurate way of assessing a surgeon's technical skills by determining if a correlation exists with how he performs in the operating room. METHODS: Eight surgeons of varying experience performed a side-to-side stapled jejuno-jejunostomy on a cadaveric bench model before proceeding to perform the procedure on a real patient scheduled for LRYGBP. Performance was assessed using a motion tracking device, the Imperial College Surgical Assessment Device. Each procedure was recorded in video and scored by two blinded expert surgeons using procedure-specific rating scales. RESULTS: The cadaveric bench model demonstrated concurrent validity with significant correlations between performance on the cadaveric model and patient for dexterity measures. Left-hand path length, r = 0.857 (median, 27, 41.3; P = 0.007), right-hand path length, r = 0.810 (median, 31.5, 60; P = 0.015) and total number of movements, r = 0.743 (median, 422, 637; P = 0.035). This correlation in performance was also demonstrated in the video rating scales, r = 0.727 (median, 13.2, 14.8; P = 0.041). No correlation was found in operative time (median, 541, 742; P = 0.071). CONCLUSIONS: This study demonstrates the concurrent validity of the cadaveric porcine model, showing similar performances in surgeons completing a jejuno-jejunostomy on the cadaveric model and the patient.

Significant transfer of surgical skills obtained with an advanced laparoscopic training program to a laparoscopic jejunojejunostomy in a live porcine model: feasibility of learning advanced laparoscopy in a general surgery residency.

BACKGROUND: Simulation may provide a solution to acquire advanced laparoscopic skills, thereby completing the curriculum of residency programs in general surgery. This study was designed to present an advanced simulation-training program and to assess the transfer of skills to a live porcine model. METHODS: First-year residents were assessed in a 14-session advanced laparoscopic training program followed by performing a jejunojejunostomy in a live porcine model. Previous and after training assessments at the bench model were compared to a single performance of six expert laparoscopic surgeons. Results obtained by trainees at the porcine model assessment were compared to those of 11 general surgeons without any laparoscopic lab-simulation training and 6 expert laparoscopic surgeons. In all assessments, global and specific OSATS scores, operative time, and covered path length of hands were registered. RESULTS: Twenty-five residents improved significantly their global and specific OSATS score median at the bench model [7 (range, 6-11) vs. 23 (range, 21-24); p < 0.05 and 7 (range, 4-8) vs. 18 (range, 18-19); p < 0.05, respectively] and obtained significantly better scores on the porcine model compared with general surgeons with no lab-simulation training [21 (range, 20.5-21) vs. 8 (range, 12-14); p < 0.05]. The results were comparable to those achieved by expert certificated bariatric surgeons. Total path lengths registered for trainees were more efficient post-training and significantly lower compared with general surgeons on the porcine model [7 (range, 6-11) vs. 23 (range, 21-24); p < 0.05] with no statistical difference compared with experts. CONCLUSIONS: Trainees significantly improved their advanced laparoscopic skills to a level compared with expert surgeons. More importantly, these acquired skills were transferred to a more complex live model.

[Simultaneous kidney and pancreas transplantation (SKPT) in patients with type 1 diabetes and chronic renal failure: experience in 12 patients in Chile]. / Trasplante simultáneo de páncreas y riñon en diabetes mellitus tipo 1: Experiencia de un centro en Chile.

BACKGROUND: Simultaneous kidney and pancreas transplantation (SKPT) is the best alternative for end stage renal disease among patients with insulin dependent diabetes mellitus. AIM: To report our experience with SKPT. MATERIAL AND METHODS: Retrospective analysis of 12 recipients of SKPT transplanted in one center starting in 1994, with a mean follow-up period of 6.8 years (2-15). RESULTS: Eleven of 12 recipients were in chronic hemodialysis before SKPT. Mean A, B, DR and HLA mismatch was 4.3. Mean preformed anti HLA antibodies was 3.3 %. Mean cold ischemia times for pancreas and kidney were 6 and 10 hours, respectively. In the first eight cases, the pancreas was drained to the bladder, and in the last four, an enteric drainage was performed. Eleven recipients were induced with antibodies, and maintenance immunosuppression consisted of cyclosporin or tacrolimus plus an antiproliferative agent. Ten year patient survival was 70%. Pancreas and kidney survival, defined by insulin and dialysis independence, were 72 and 73% respectively. Fifty percent of recipients experienced acute graft rejection (cellular or humoral), with good response to treatment except in one case. CONCLUSIONS: This experience shows that SKPT is associated with an excellent patient survival associated to insulin and dialysis independence in 70% of patients at 10 years.

Acute and fulminant hepatitis induced by flutamide: case series report and review of the literature.

Flutamide is a non-steroidal anti-androgenic drug, commonly used in the treatment of advanced prostate cancer, acne and hirsutism. This drug may induce various degrees of liver injury, including acute liver failure (ALF), with further need for liver transplantation. Here, we present a report of 10 consecutive patients seen in a period of 14 years, with acute liver toxicity induced by flutamide (in most cases severe hepatotoxicity): 3 men and 7 women, with a mean age of 75 and 29 years old, respectively. All men received flutamide as treatment of advanced prostate carcinoma and they developed hepatotoxicity without ALF, and three months after withdrawal of the drug, they recovered completely. In contrast, in 7 young female with liver toxicity caused by flutamide as treatment of various hyperandrogenic conditions (acne and hirsutism), ALF was observed in 5 patients, all of them requiring urgent liver transplantation, with excellent outcome and survival in 4 of them. Based on the above, we believe that flutamide treatment should be preferentially avoided in young female patients with benign pathologies, or if it is used, patients should be warned of its potential severe complications. Also, serial liver tests should be closely monitored and, in case of elevations, the drug should be immediately withdrawn.

Trasplante simultáneo de páncreas y riñon en diabetes mellitus tipo 1: Experiencia de un centro en Chile / Simultaneous kidney and pancreas transplantation (SKPT) in patients with type 1 diabetes and chronic renal failure: Experience in 12 patients in Chile

Background: Simultaneous kidney and páncreas transplantation (SKPT) is the best alternative for end stage renal disease among patients with insulin dependent diabetes mellitus. Aim: To report our experience with SKPT. Material andMethods: Retrospective analysis ofl2 recipients of SKPT transplanted in one center starting in 1994, with a meanfollow-upperiod of6.8years (2-15). Results: Eleven ofl2 recipients were in chronic hemodialysis before SKPT. Mean A, B, DR and HLA mismatch was 4.3. Mean preformed anti HLA antibodies was 3.3 percent. Mean cold ischemia times for páncreas and kidney were 6 and 10 hours, respectively. In the first eight cases, the páncreas was drained to the bladder, and in the last four, an enteric drainage was performed. Eleven recipients were induced with antibodies, and maintenance immunosuppression consisted ofCyclosporine or Tacrolimusplus an antiproliferative agent. Ten year patient survival was 70 percent. Páncreas and kidney survival, defined by insulin and dialysis independence, were 72 and 73 percent respectively. Fifty percent of recipients experienced acute graft rejection (cellular or humoral), with good response to treatment except in one case. Conclusions: This experience shows that SKPT is associated with an excellent patient survival associated to insulin and dialysis independence in 70 percent of patients at 10 years.

[Pancreatic metastasis from renal cell carcinoma: a case report]. / Metástasis pancreáticas tardías secundarias a cáncer de células renales: caso clínico.

We report the case of a 60-year-old woman with multiple pancreatic nodules found on abdominal computed tomography. Thirteen years earlier she had undergone a left nephrectomy for renal cell carcinoma. The patient underwent surgery with a preoperative diagnosis of multifocal metastatic or neuroendocrine tumor. At surgery, two metastatic nodules of renal cell carcinoma were found and excised. After four years of follow up there is no evidence of recurrence.

Metástasis pancreáticas tardías secundarias a cáncer de células renales: Caso clínico / Pancreatic metastasis from renal cell carcinoma: A case report

We report the case of a 60 year old woman with multiple pancreatic nodules found on abdominal computed tomography. Thirteen years earlier she had undergone a left nephrectomy for renal cell carcinoma. The patient underwent surgery with a preoperative diagnosis of multifocal metastatic or neuroendocrine tumor. At surgery, two metastatic nodules of renal cell carcinoma were found and excised. After four years of follow up there is no evidence of recurrence.

[Accomodation process: ABO-incompatible liver transplantation. Report of one case]. / Fenómeno de acomodación inmunológica: trasplante hepático ABO incompatible. Caso clínico.

We report a 33 year-old female with a diagnosis of halothane-induce fulminant hepatic failure who was subjected to a liver transplant with an ABO-incompatible graft. The patient received a therapeutic protocol that included total plasma exchange, splenectomy and quadruple immunosuppression. After 5 years, the patient remains asymptomatic and with normal liver enzymes, while she has been treated with low dose of immunosuppressive drugs. This case demonstrates an example of how the immunological process of accommodation opens the possibility of using ABO-incompatible organs as a definitive grafts.

[Small-for-size syndrome. Report of one case]. / "Síndrome pequeño para su tamaño", (small-for-size), como complicación de un trasplante hepático con donante vivo adulto relacionado.

Although the use of cadaveric split or living donor liver transplantation is a valid option for liver transplants, they have several complications, being the "small-for-size syndrome" one of the most frequent. This entity is mainly due to the incapacity that the graft has to meet the blood drainage demands. We report a 61 year-old patient with sub-acute liver failure, transplanted with a partial liver graft that developed hyperbilirubinemia, ascites and liver function deterioration. A meso-caval shunt was performed, after which the ascites resolved, serum bilirubin normalized and the synthetic function of the liver improved. After one month, a follow-up CT seen showed the absence of blood flow in the shunt, possible due to the reduction of the hyper-perfusion of the liver. The clinical and biochemical condition of the patient continued improving despite the lack of flow through the shunt.

Fenómeno de acomodación inmunológica: Trasplante hepático ABO incompatible. Caso clínico / Accomodation process: ABO-incompatible liver transplantation. Report of one case

We report a 33 year-old female with a diagnosis of halothane-induce fulminant hepatic failure who was subjected to a liver transplant with an ABO-incompatible graft. The patient received a therapeutic protocol that included total plasma exchange, splenectomy and quadruple immunosuppression. After 5 years, the patient remains asymptomatic and with normal liver enzymes, while she has been treated with low dose of immunosuppressive drugs. This case demonstrates an example of how the immunological process of accomodation opens the possibility of using ABO-incompatible organs as a definitive grafts.

"Síndrome pequeño para su tamaño", (small-for-size), como complicación de un trasplante hepático con donante vivo adulto relacionado / Small-for-size syndrome: report of one case

Although the use of cadaveric split or living donor liver transplantation is a valid option for liver transplants, they have several complications, being the "small-for-size syndrome" one of the most frequent. This entity is mainly due to the incapacity that the graft has to meet the blood drainage demands. We report a 61 year-old patient with sub-acute liver failure, transplanted with a partial liver graft that developed hyperbilirubinemia, ascites and liver function deterioration. A meso-caval shunt was performed, after which the ascites resolved, serum bilirubin normalized and the synthetic function of the liver improved. After one month, a follow-up CT seen showed the absence of blood flow in the shunt, possible due to the reduction of the hyper-perfusion of the liver. The clinical and biochemical condition of the patient continued improving despite the lack of flow through the shunt.