Percutaneous Balloon Dilatation for Hepaticojejunostomy Stricture Following Paediatric Liver Transplantation: Long-Term Results of an Institutional "Three-Session" Protocol.

PURPOSE: The aim of this study was to report the long-term results of an institutional protocol of percutaneous biliary balloon dilatation (PBBD) on paediatric patients with benign anastomotic stricture after liver transplantation. As a secondary objective, we evaluated risk factors associated with post-treatment re-stricture. MATERIALS AND METHODS: Fourteen paediatric, post-liver transplant patients with benign anastomotic stricture of Roux-en-Y hepaticojejunostomy were included. All patients underwent the same treatment protocol of three PBBD procedures with 15-day intervals. Clinical outcome was analysed using the Terblanche classification. Primary patency rate was assessed with the Kaplan-Meier test. RESULTS: All patients had an initial successful result (Terblanche grade, excellent/good) after PBBD. At the end of the follow-up time of 35.7 ± 21.1 months (CI95%, 23.5-47.9), 10 patients persisted with excellent/good grading, while the remaining 4 had re-stricture, all of the latter occurring within the first 19 months. Patency rate after percutaneous treatment at 1, 3, and 5 years were 85.7%, 70%, and 70%, respectively. History of major complication after liver transplantation was associated with 5 times higher risk of re-stricture, HR 5.48 [95% CI, 2.18-8.78], p = 0.018. CONCLUSION: In paediatric patients with benign anastomotic stricture of hepaticojejunostomy after liver transplantation, the "Three-session" percutaneous biliary balloon dilatation protocol is associated with a high rate of long-term success. In this limited series, the history of post-liver transplant major complication, defined as complications requiring a reintervention under general anaesthesia or advanced life support, seems to be an independent risk factor for stricture recurrence.

Impact of Cholestasis on the Sensitivity of Percutaneous Transluminal Forceps Biopsy in 93 Patients with Suspected Malignant Biliary Stricture.

PURPOSE: The aim of this study was to determine the effect of hyperbilirubinemia in the sensitivity of percutaneous transluminal forceps biopsy (PTFB) in patients with suspected malignant biliary stricture. MATERIALS AND METHODS: Ninety-three patients with suspicion of malignant biliary stricture underwent percutaneous transhepatic cholangiography followed by PTFB. Sensitivity, specificity and predictive values were analysed based on the presence or absence of hyperbilirubinemia, defined as total bilirubin equal to, or higher than 5 mg/dL. Variables included demographic and clinical features, laboratory, tumour type and localization, stricture length, therapeutic approach and histopathology. Additionally, major morbidity and mortality were assessed. RESULTS: The overall sensitivity, specificity, positive predictive value and accuracy of PTFB were 61.1%, 100%, 100%, and 62.4%, respectively. Hyperbilirubinemia affected 57% of patients at the time of PTFB. There were 35 (37%) false negative results, none of them related to tumour type or localization, stricture length, or previous biliary intervention (i.e. PBBD (percutaneous biliary balloon dilatation), ERCP (endoscopic retrograde cholangiopancreatography)) (p > 0.05). However, when bilirubin was < 5 mg/dL, false negative results decreased globally (p = 0.024) and sensitivity increased significantly for intrahepatic and hilar localization, as well as for colorectal metastasis, gallbladder carcinoma, and pancreatic carcinoma. No major morbidity occurred. CONCLUSION: The sensitivity of percutaneous transluminal biopsy for diagnosis of malignant stricture may significantly increase if samples are obtained in the absence of hyperbilirubinemia, without adding morbidity to the procedure. LEVEL OF EVIDENCE: Level 3, Case- Control studies.

Fluoroscopy and endoscopy-guided transanastomotic rendezvous: a novel technique for recanalization of a completely obstructed colorectal anastomosis.

BACKGROUND: Colorectal anastomotic stricture is a frequent complication that may affect up to 30% of patients. However, a complete obstruction is rare. Endoscopic balloon dilation is the first-line therapy, but it invariably requires being able to cross the stricture with the dilation device. When this is not possible, surgical revision is the alternative, but it is associated with higher morbidity. CASE PRESENTATION: A 76-year-old male patient underwent an urgent high anterior resection with transverse loop colostomy for an occlusive high rectal tumor. On postoperative day 8, he presented with anastomotic leakage and abscess formation, requiring percutaneous drainage. Ten months after surgery, a colonoscopy revealed a complete stricture of the anastomosis, refractory to negotiation of a guide wire, thus precluding balloon dilation. Hence, a modified rendezvous technique was planned. Simultaneously, a flexible endoscope and a rigid rectoscope were progressed through the distal loop colostomy, and the anus, respectively. A needle device was introduced through the rectoscope and used to pierce the colonic stump. A guide wire was progressed, and the stricture was dilated with a controlled radial expansion balloon catheter. Finally, a 12-Fr Foley catheter was left through the anastomosis. A total of three endoscopic balloon dilation sessions were completed, and successful colostomy reversal was carried out 10 days after the last session. CONCLUSION: Fluoroscopy-endoscopy-guided recanalization is an effective and safe treatment option for complete colorectal anastomotic stricture.

Early pancreatic cancer in IgG4-related pancreatic mass: A case report.

BACKGROUND: IgG4-related disease can manifest diversely, including autoimmune pancreatitis and IgG4-related cholangiopathy. We are reporting a very unusual cause of pancreatic cancer triggered in a previously unknown IgG4-related disease. CASE SUMMARY: A 75-year-old man was diagnosed with a 43 mm × 33 mm pancreatic head tumor after consulting for abdominal pain and jaundice. A pancreaticoduodenectomy was carried out uneventfully, and the histopathology report showed an early stage of acinar-cell pancreatic cancer. The patient reconsulted on the 30th postoperative day with fever, jaundice and asthenia. Magnetic resonance cholangiopancreatography evidenced an extense bile duct stricture. A percutaneous biliary drainage proved to be ineffective, even after exchanging it with larger bore drainage. Reviewing the surgical specimen, features compatible with IgG4-related disease were observed. Consequently, empiric treatment with steroids was initiated achieving excellent results. CONCLUSION: IgG4-related disease may cause chronic inflammation of the pancreas and can condition pancreatic malignancies.

Percutaneous Patency Recovery and Biodegradable Stent Placement in a Totally Occluded Hepaticojejunostomy After Paediatric Living Donor Liver Transplantation.

Biliary complications after living donor liver transplantation (LDLT) cause severe morbidity and mortality, with biliary anastomotic stricture being the most common form of presentation. Surgical revision is risky, and it is avoided whenever possible. When a Roux-en-Y hepaticojejunostomy (RYHJ) is used for bilioenteric reconstruction, endoscopic approach is more difficult, if not impracticable. Therefore, percutaneous approach remains as a first-line treatment in these patients. In this case presentation, a percutaneous approach was used to recover patency in an intractable, totally occluded RYHJ stricture in an LDLT paediatric recipient, using a Rösch-Uchida needle to access to the collapsed jejunal loop from the bile duct. Once recanalization of the RYHJ was achieved, a biodegradable stent was placed with middle-term patency at follow-up.

Risk factors and outcomes of pyogenic liver abscess in adult liver recipients: a matched case-control study.

BACKGROUND: Adult liver recipients (ALR) differ from the general population with pyogenic liver abscess (PLA) as they exhibit: reconstructed biliary anatomy, recurrent hospitalizations, poor clinical condition and are subjected to immunosuppression. The aim of this study was to identify risk factors associated with PLA in ALR and to analyze the management experience of these patients. METHODS: Between 1996 and 2016, 879 adult patients underwent liver transplantation (LT), 26 of whom developed PLA. Patients and controls were matched according to the time from transplant to abscess in a 1 to 5 relation. A logistic regression model was performed to establish PLA risk factors considering clusters for matched cases and controls. Risk factors were identified and a multivariate regression analysis performed. RESULTS: Patients with post-LT PLA were more likely to have lower BMI (p = 0.006), renal failure (p = 0.031) and to have undergone retransplantation (p = 0.002). A history of hepatic artery thrombosis (p = 0.010), the presence of Roux en-Y hepatojejunostomy (p < 0.001) and longer organ ischemia time (p = 0.009) were independent predictors for the development of post-LT PLA. Five-year survival was 49% (95%CI 28-67%) and 89% (95%CI 78%-94%) for post-LT PLA and no post-LT PLA, respectively (p < 0.001). CONCLUSION: history of hepatic artery thrombosis, the presence of hepatojejunostomy and a longer ischemia time represent independent predictors for the development of post-LT PLA. There was a significantly poorer survival in patients who developed post-LT PLA compared with those who did not.

Percutaneous Biliary Balloon Dilation: Impact of an Institutional Three-Session Protocol on Patients with Benign Anastomotic Strictures of Hepatojejunostomy.

BACKGROUND: Percutaneous biliary balloon dilation (PBBD) stands as a safe, useful, and inexpensive treatment procedure performed on patients with benign anastomotic stricture of Roux-en-Y hepatojejunostomy (BASH). However, the optimal mode of application is still under discussion. METHODS: A retrospective cohort study was conducted including patients admitted between 2008 and 2015 with diagnosis of BASH. Patients were divided into 2 groups: group I (n = 22), included patients treated after the implementation of an institutional protocol of 3 PBBD sessions within a fixed time interval and group II (n = 24) consisted of our historical control of patients who underwent one or 2 dilation sessions. Patency at one-year post procedure was assessed with the classification proposed by Schweizer. Symptomatic response to treatment was analyzed using the Terblanche classification. RESULTS: Patients in group I exhibited more excellent/good results (90 vs. 50%, p = 0.003) and less poor results (5 vs. 42%, p = 0.005) according to the Schweizer classification and more grade I/excellent results according to Terblanche classification (p = 0.003). Additionally, group I showed lower serum total bilirubin (p = 0.001), direct bilirubin (p = 0.002), alkaline phosphatase (p = 0.322), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.006). CONCLUSION: A protocol of 3 consecutive PBBD sessions within a fixed time interval may yield a high rate of patency, with a positive clinical, biochemical, and radiological impact on patients with BASH.

Pyogenic liver abscess: current status and predictive factors for recurrence and mortality of first episodes.

BACKGROUND: In times of modern surgery, transplantation and percutaneous techniques, pyogenic liver abscess (PLA) has essentially become a problem of biliary or iatrogenic origin. In the current scenario, diagnostic approach, clinical behavior and therapeutic outcomes have not been profoundly studied. This study analyzes the clinical and microbiological features, diagnostic methods, therapeutic management and predictive factors for recurrence and mortality of first episodes of PLA. METHODS: A retrospective single-center study was conducted including 142 patients admitted to the Hospital Italiano de Buenos Aires, between 2005 and 2015 with first episodes of PLA. RESULTS: Prevailing identifiable causes were biliary diseases (47.9%) followed by non-biliary percutaneous procedures (NBIPLA, 15.5%). Seventeen patients (12%) were liver recipients. Eleven patients (7.8%) died and 18 patients (13.7%) had recurrence in the first year of follow up. The isolation of multiresistant organisms (p = 0.041) and a history of cholangitis (p < 0.001) were independent risk factors for recurrence. Mortality was associated with serum bilirubin >5 mg/dL (p = 0.022) and bilateral involvement (p = 0.014) in the multivariate analysis. CONCLUSION: NBPLA and PLA after transplantation may be increasing among the population of PLA in referral centers. History of cholangitis is a strong predictor for recurrence. Mortality is associated to hiperbilirrubinemia and anatomical distribution of the lesions.

Skin fibroblasts from patients with type 1 diabetes (T1D) can be chemically transdifferentiated into insulin-expressing clusters: a transgene-free approach.

The conversion of differentiated cells into insulin-producing cells is a promising approach for the autologous replacement of pancreatic cells in patients with type 1 diabetes (T1D). At present, cellular reprogramming strategies encompass ethical problems, epigenetic failure or teratoma formation, which has prompted the development of new approaches. Here, we report a novel technique for the conversion of skin fibroblasts from T1D patients into insulin-expressing clusters using only drug-based induction. Our results demonstrate that skin fibroblasts from diabetic patients have pancreatic differentiation capacities and avoid the necessity of using transgenic strategies, stem cell sources or global demethylation steps. These findings open new possibilities for studying diabetes mechanisms, drug screenings and ultimately autologous transgenic-free regenerative medicine therapies in patients with T1D.

[Cell therapy for diabetes mellitus: beyond stem cells]. / Terapia celular para el tratamiento de la diabetes: Más allá de las células madre.

Type 1 diabetes is an autoimmune disease of unknown etiology characterized by destruction of pancreatic beta cells, leading to absolute insulin deficiency. Standard therapy includes the use of exogenous insulin. However, due to the difficulty to achieve a tight metabolic control, a number of patients will present severe complications, including vascular, renal and ophthalmologic disease. On the other hand, a more strict metabolic control is often associated with episodes of life threatening hypoglycemia. This motivated the research and development of new alternative treatments, such as the transplantation of insulin producing beta cells, obtained from cadaveric pancreatic islets. Best results with this therapy were observed with consecutive islet injection from more than one donor and immunosuppressive therapy without steroids. However, the scarcity of organs as well as an increased immune reaction derived from the use of pancreas from different donors have limited this therapy to markedly selected patients and highly experienced centers. Furthermore, lifelong administration of immunosuppressive drugs may produce undesired secondary effects. Regenerative medicine opens the possibility of using stem cells capable of differentiating into insulin-producing cells after stimulation by diverse trophic factors that may act over stem cells located within a specific tissue.

Terapia celular para el tratamiento de la diabetes: Más allá de las células madre / Cell therapy for diabetes mellitus: Beyond stem cells

La diabetes tipo 1 es una enfermedad de etiología autoinmune que se caracteriza por la destrucción de las células ß pancreáticas, produciendo un déficit absoluto de insulina. El tratamiento clínico estándar consiste en la aplicación de insulina. Sin embargo, en un número importante de pacientes y debido a la dificultad en lograr un control metabólico preciso, generalmente se asocia con complicaciones graves a nivel vascular con repercusión renal y ocular entre otras. Por otra parte, un estricto control metabólio, a menudo se asocia con hipoglucemias con riesgo de muerte. Esto motivó la investigación y el desarrollo de alternativas de tratamiento. Una de ellas es el trasplante de células productoras de insulina, las células ß, obtenidas por medio del aislamiento y trasplante de islotes de un páncreas cadavérico. Los mejores resultados con esta modalidad de trasplante se obtuvieron con la inyección sucesiva de islotes pancreáticos de diferentes donantes y terapia inmunosupresora exenta de corticoides. Sin embargo, la escasez de órganos por un lado, y el hecho de que cada implante de islotes de otro páncreas aumenta las posibilidades de rechazo inmunológico, hace que este tratamiento se vea limitado a centros de alta experiencia y pacientes muy seleccionados. Asimismo, las drogas inmunosupresoras que deben administrarse de por vida, pueden producir efectos no deseados en el organismo. La medicina regenerativa abre la posibilidad de utilizar células madre con capacidad de diferenciarse en células productoras de insulina, utilizando de manera conjunta factores tróficos que serían capaces de estimular a las propias células madre de cada parénquima.

Type 1 diabetes is an autoimmune disease of unknown etiology characterized by destruction of pancreatic beta cells, leading to absolute insulin deficiency. Standard therapy includes the use of exogenous insulin. However, due to the difficulty to achieve a tight metabolic control, a number of patients will present severe complications, including vascular, renal and ophthalmologic disease. On the other hand, a more strict metabolic control is often associated with episodes of life threatening hypoglycemia. This motivated the research and development of new alternative treatments, such as the transplantation of insulin producing beta cells, obtained from cadaveric pancreatic islets. Best results with this therapy were observed with consecutive islet injection from more than one donor and immunosuppressive therapy without steroids. However, the scarcity of organs as well as an increased immune reaction derived from the use of pancreas from different donors have limited this therapy to markedly selected patients and highly experienced centers. Furthermore, lifelong administration of immunosuppressive drugs may produce undesired secondary effects. Regenerative medicine opens the possibility of using stem cells capable of differentiating into insulin-producing cells after stimulation by diverse trophic factors that may act over stem cells located within a specific tissue.

Effect of the embolization of completely unpurified islets on portal vein pressure and hepatic biochemistry in clinical practice.

Here we report on the impact of completely unpurified islet transplantation on the portal vein pressure (PVP) and the hepatic biochemistry in the peritransplant period and on follow-up. Type I diabetic patients underwent simultaneous kidney and islet transplantation. Islets were not purified from the acinar tissue to prevent loss of endocrine mass. Each patient received a mean 521,846 +/- 201,539.4 islet equivalents (7812.1 islet equivalents/kg/recipient). Immunosuppression and peritransplant medication were given according to the Giessen protocol. The islets were injected into the left hepatic lobe through the umbilical vein. PVP was recorded at time 0 and every 5 min throughout cell infusion. Liver function was assessed daily for the first 10 days, and on follow-up. Basal, peak, and final PVP were 12 +/- 3.8, 25.1 +/- 7.9, and 19.5 +/- 6.2 mmHg, respectively (basal vs. final, p < 0.05). Bilirubin, alkaline phosphatase, prothrombin time, and APTT stayed within normal range. Peak aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum amylase were 109.4 +/- 61.2 IU/L (basal vs. peak, not significant), 79.5 +/- 56.9 IU/L (basal vs. peak, not significant), and 887.5 +/- 153.6 IU/L (basal vs. peak, p = 0.02), respectively. In all cases AST, ALT, and amylase normalized within 6 days posttransplant and remained so on follow-up (longest control, 33 months posttransplant). Although the intrahepatic infusion of unpurified pancreatic islets affects both the portal vein pressure and the hepatic biochemical profile, this effect is transient and does not compromise the safety of the procedure.

Autoinmunidad de las células beta del páncreas y riesgo de progresión a diabetes tipo I / Pancreatic beta cell autoimmunity and the risk of progression to type 1 diabetes

La diabetes tipo 1 es una enfermedad autoinmune, caracterizada por la carencia absoluta de insulina. Si bien muchos aspectos de la fisiopatología aún no están resueltos, se sabe que en el período prodrómico, cuando todavía no hay síntomas de la enfermedad, se encuentran autoanticuerpos contra diferentes estructuras de las células betapancreáticas. Hasta el momento se cuenta con métodos bioquímicos para dosar ICA (anticuerpo contra células del islote), GADA (anticuerpo contra glutamato decarboxilasa), IA-2 (anticuerpo contra tirosin fosfatasa), e IAA (anticuerpo anti insulina), siendo el riesgo significativamente mayor cuando tres o cuatro autoanticuerpos resultan positivos. El dosaje de estos autoanticuerpos y los alelos HLA-DQB 0203/0302 permiten identificar a las personas con alto riesgo de desarrollar DBT-1 durante los siguientes 5 a 10 años. Por el contrario, el hallazgo de HLA-DQB1 0602/0603 funciona de alguna manera con alelos protectores. En estudios más recientes, se ha investigado la utilidad del dosaje de anticuerpos en pacientes con trasplante de páncreas o de islotes para evaluar el comportamiento de las células trasplantadas y como predictores de rechazo

Autoinmunidad de las células beta del páncreas y riesgo de progresión a diabetes tipo I / Pancreatic beta cell autoimmunity and the risk of progression to type 1 diabetes

La diabetes tipo 1 es una enfermedad autoinmune, caracterizada por la carencia absoluta de insulina. Si bien muchos aspectos de la fisiopatología aún no están resueltos, se sabe que en el período prodrómico, cuando todavía no hay síntomas de la enfermedad, se encuentran autoanticuerpos contra diferentes estructuras de las células betapancreáticas. Hasta el momento se cuenta con métodos bioquímicos para dosar ICA (anticuerpo contra células del islote), GADA (anticuerpo contra glutamato decarboxilasa), IA-2 (anticuerpo contra tirosin fosfatasa), e IAA (anticuerpo anti insulina), siendo el riesgo significativamente mayor cuando tres o cuatro autoanticuerpos resultan positivos. El dosaje de estos autoanticuerpos y los alelos HLA-DQB 0203/0302 permiten identificar a las personas con alto riesgo de desarrollar DBT-1 durante los siguientes 5 a 10 años. Por el contrario, el hallazgo de HLA-DQB1 0602/0603 funciona de alguna manera con alelos protectores. En estudios más recientes, se ha investigado la utilidad del dosaje de anticuerpos en pacientes con trasplante de páncreas o de islotes para evaluar el comportamiento de las células trasplantadas y como predictores de rechazo