[Outcomes of Laparoscopic Liver Resection for Hepatocellular Carcinoma: A Single-Center Experience]. / Resecciones Hepáticas Laparoscópicas por Hepatocarcinoma: Resultados Perioperatorios y Oncológicos.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. Surgery is the treatment of choice in stages 0 and A in the Barcelona Clinic Liver Cancer classification. A minimally invasive technique in this scenario has the advantage of reducing postoperative pain, blood loss, and hospital stay. We present our experience and outcomes in laparoscopic liver resection in HCC. METHODS: Retrospective descriptive analysis from all patients who underwent laparoscopic liver resection for HCC in our center between August 2006 and December 2020. RESULTS: Laparoscopic liver resection for HCC was performed in 20 patients. The median age was 70 years, and the male gender was 75%. Sixteen patients had chronic liver disease, and 87.5% were Child A. The most common liver resection was the non-anatomical (45%). 30-day morbidity was 15%, without the need for reintervention. We had no 30-day mortality and postoperative liver failure. Negative margins were achieved in 90% of patients. Median disease-free survival and overall survival were 25 and 40.5 months, respectively. CONCLUSION: Laparoscopic liver resection for the treatment of HCC in our series is safe, with no 30-day mortality, low incidence of complications, no postoperative liver failure, and suitable medium- and long-term oncological results.

Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile.

BACKGROUND: Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. METHODS: This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. RESULTS: NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (P<.01 or P = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. CONCLUSIONS: Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients. CLINICAL TRIALS REGISTRATION: NCT04888793.

[Liver transplantation for non-resectable colorectal liver metastases: A review]. / Trasplante hepático por metástasis hepáticas irresecables de cáncer colorrectal: revisión de la literatura.

In Chile, colorectal cancer ranks third in incidence and fifth in mortality. Half of these patients have liver metastases at the diagnosis, and only 30% of them are resectable. Despite the development of many complex hepatobiliary procedures to achieve the total resection of metastases, the long-term survival with these techniques is not good. Liver transplantation is an alternative to treat unresectable liver metastasis from colorectal cancer with a good outcome. Several prognostic scores allow the selection of patients with good tumor biology. These patients have better overall and disease-free survival after liver transplantation. The use of immunosuppressive treatment doesn't increase recurrence, and even the pattern of tumor growth is slower in liver transplant recipients. The purpose of this review is to summarize the current evidence in this topic and to highlight the need for a formal protocol for liver transplantation for unresectable colorectal liver metastases, using living donors or marginal grafts to avoid competition with the rest of the national waiting list.

Telemedicine for postoperative follow-up, virtual surgical clinics during COVID-19 pandemic.

Recent coronavirus outbreak and "stay at home" policies have accelerated the implementation of virtual healthcare. Many surgery departments are implementing telemedicine to enhance remote perioperative care. However, concern still arises regarding the safety of this modality in postoperative follow-up after gastrointestinal surgery. The aim of the present prospective study is to compare the use of telemedicine clinics to in-person follow-up for postoperative care after gastrointestinal surgery during COVID-19 outbreak. METHODS: Prospective study that included all abdominal surgery patients operated since the COVID-19 outbreak. On discharge, patients were given the option to perform their postoperative follow-up appointment by telemedicine or by in-person clinics. Demographic, perioperative, and follow-up variables were analyzed. RESULTS: Among 219 patients who underwent abdominal surgery, 106 (48%) had their postoperative follow-up using telemedicine. There were no differences in age, gender, ASA score, and COVID-19 positive rate between groups. Patients who preferred telemedicine over in-person follow-up were more likely to have undergone laparoscopic surgery (71% vs. 51%, P = 0.037) and emergency surgery (55% vs. 41%; P = 0.038). Morbidity rate for telemedicine and in-person group was 5.7% and 8%, (P = 0.50). Only 2.8% of patients needed an in-person visit following the telemedicine consult, and 1.9% visited the emergency department. CONCLUSIONS: In the current pandemic, telemedicine follow-up can be safely and effectively performed in selected surgical patients. Patients who underwent laparoscopic and emergency procedures opted more for telemedicine than in-person follow-up.

[Liver transplantation: development, learning curve and results after the first 300 cases]. / Trasplante hepático: evolución, curva de aprendizaje y resultados después de los primeros 300 casos.

BACKGROUND: Liver transplantation (LT) is an option for people with liver failure who cannot be cured with other therapies and for some people with liver cancer. AIM: To describe, and analyze the first 300 LT clinical results, and to establish our learning curve. MATERIAL AND METHODS: Retrospective cohort study with data obtained from a prospectively collected LT Program database. We included all LT performed at a single center from March 1994 to September 2017. The database gathered demographics, diagnosis, indications for LT, surgical aspects and postoperative courses. We constructed a cumulative summation test for learning curve (LC-CUSUM) using 30-day post-LT mortality. Mortality at 30 days, and actuarial 1-, and 5-year survival rate were analyzed. RESULTS: A total of 281 patients aged 54 (0-71) years (129 women) underwent 300 LT. Ten percent of patients were younger than 18 years old. The first, second and third indications for LT were non-alcoholic steatohepatitis, chronic autoimmune hepatitis and alcoholic liver cirrhosis, respectively. Acute liver failure was the LT indication in 51 cases (17%). The overall complication rate was 71%. Infectious and biliary complications were the most common of them (47 and 31% respectively). The LC-CUSUM curve shows that the first 30 patients corresponded to the learning curve. The peri-operative mortality was 8%. Actuarial 1 and 5-year survival rates were 82 and 71.4%, respectively. CONCLUSIONS: Outcome improvement of a LT program depends on the accumulation of experience after the first 30 transplants and the peri-operative mortality directly impacted long-term survival.

Renal outcomes following left renal vein harvest for venous reconstruction during pancreas and liver surgery.

BACKGROUND: The left renal vein (LRV) may be used for venous reconstruction during hepato-pancreato-biliary (HPB) surgery, although concerns exist about compromising renal function. This study aimed to determine renal outcomes following LRV harvest during HPB resections. METHODS: Circumferential PV/SMV resections from 2008 to 2014 were included within two groups (LRV harvest, Control). Absolute and change in Creatinine (Cr) and estimated GFR (eGFR), and rates of acute kidney injury (AKI) and chronic kidney disease (CKD), were compared. Multivariate logistic regression analyses were performed. RESULTS: 76 patients were included (LRV n = 17, Control n = 59). Median Cr and eGFR did not change within groups, although change in eGFR differed between groups at postoperative day (POD) 3 (-4.3 vs. 12.8, p = 0.0035) and 7 (-1.8 vs. 12.4, p = 0.0074). AKI occurred more frequently in the LRV group at POD1 (5/17 vs. 4/59, p = 0.023) and POD3 (5/17 vs. 3/59, p = 0012), with no difference in CKD between groups (2/11 vs. 5/33 at 3 months, p = 0.99). LRV harvest was an independent risk factor for AKI at POD1 and POD3, but not thereafter. CONCLUSIONS: Patients who undergo LRV harvest experience a higher rate of AKI in the first three post-operative days. LRV harvest during pancreas resection does not impact on long-term renal function.

The Volume-outcome Relationship in Deceased Donor Kidney Transplantation and Implications for Regionalization.

OBJECTIVE: The aim of this study was to investigate the volume-outcome relationship in kidney transplantation by examining graft and patient outcomes using standardized risk adjustment (observed-to-expected outcomes). A secondary objective was to examine the geographic proximity of low, medium, and high-volume kidney transplant centers in the United States. SUMMARY OF BACKGROUND DATA: The significant survival benefit of kidney transplantation in the context of a severe shortage of donor organs mandates strategies to optimize outcomes. Unlike for other solid organ transplants, the relationship between surgical volume and kidney transplant outcomes has not been clearly established. METHODS: The Scientific Registry of Transplant Recipients was used to examine national outcomes for adults undergoing deceased donor kidney transplantation from January 1, 1999 to December 31, 2013 (15-year study period). Observed-to-expected rates of graft loss and patient death were compared for low, medium, and high-volume centers. The geographic proximity of low-volume centers to higher volume centers was determined to assess the impact of regionalization on patient travel burden. RESULTS: A total of 206,179 procedures were analyzed. Compared with low-volume centers, high-volume centers had significantly lower observed-to-expected rates of 1-month graft loss (0.93 vs 1.18, P<0.001), 1-year graft loss (0.97 vs 1.12, P<0.001), 1-month patient death (0.90 vs 1.29, P=0.005), and 1-year patient death (0.95 vs 1.15, P=0.001). Low-volume centers were frequently in close proximity to higher volume centers, with a median distance of 7 miles (interquartile range: 2 to 75). CONCLUSIONS: A robust volume-outcome relationship was observed for deceased donor kidney transplantation, and low-volume centers are frequently in close proximity to higher volume centers. Increased regionalization could improve outcomes, but should be considered carefully in light of the potential negative impact on transplant volume and access to care.

The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study.

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer-related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5-year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long-term follow-up (10-years) using an intention-to-treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow-up from listing was 59.7 (26.8-103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10-year actuarial survival from transplant between groups. On an intention-to-treat basis, the dropout rate was higher in the M+ group and the 5-year and 10-year survival rates from listing were decreased in the M+ group. An alpha-fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups. CONCLUSION: Tumor differentiation and cancer-related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha-fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077-2088).

CT volumetry is superior to nuclear renography for prediction of residual kidney function in living donors.

Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology.

Technique and outcomes of robot-assisted median arcuate ligament release for celiac artery compression syndrome.

OBJECTIVE: Celiac artery compression by the median arcuate ligament (MAL) is a potential cause of postprandial abdominal pain and weight loss that overlaps with other common syndromes. Robotic technology may alter the current paradigm for surgical intervention. Open MAL release is often performed with concurrent bypass for celiac stenosis due to the morbidity of reintervention, whereas the laparoscopic approach is associated with high rates of conversion to open due to bleeding. We hypothesized that a robot-assisted technique might minimize conversion events to open, decrease perioperative morbidity, and defer consideration of vascular bypass at the initial operative setting. METHODS: We retrospectively analyzed patients treated for MAL syndrome by a multidisciplinary team at a tertiary medical center between September 2012 and December 2013. Diagnosis was based on symptom profile and peak systolic velocity (PSV) >200 cm/s during celiac artery duplex ultrasound imaging. All patients underwent robot-assisted MAL release with simultaneous circumferential neurolysis of the celiac plexus. Postoperative celiac duplex and symptom profiles were reassessed longitudinally to monitor outcomes. RESULTS: Nine patients (67% women) were evaluated for postprandial pain (100%) and weight loss (100%). All patients had celiac stenosis by mesenteric duplex ultrasound imaging (median PSV, 342; range, 238-637 cm/s), and cross-sectional imaging indicated a fishhook deformity in five (56%). Robot-assisted MAL release was completed successfully in all nine patients (100%) using a standardized surgical technique. Estimated blood loss was <50 mL, with a median hospital stay of 2 days (range, 2-3 days). No postoperative complications of grade ≥3, readmissions or reoperations were observed. All patients (100%) improved symptomatically at the 25-week median follow-up. Three patients experienced complete resolution on postoperative celiac duplex ultrasound imaging, and six patients showed an improved but persistent stenosis (PSV >200 cm/s) compared with preoperative velocities (P < .05 by Wilcoxon signed rank). No patients required additional treatment. CONCLUSIONS: Robot-assisted MAL release can be performed safely and effectively with avoidance of conversion events and minimal morbidity. Potential factors contributing to success are patient selection by a multidisciplinary team and replication of the open surgical technique by means of robot-assisted dexterity and visualization. The need for delayed reintervention for persistently symptomatic celiac stenosis is uncertain.

Specific activin receptor-like kinase 3 inhibitors enhance liver regeneration.

Pharmacologic agents to enhance liver regeneration after injury would have wide therapeutic application. Based on previous work suggesting inhibition of bone morphogenetic protein (BMP) signaling stimulates liver regeneration, we tested known and novel BMP inhibitors for their ability to accelerate regeneration in a partial hepatectomy (PH) model. Compounds were produced based on the 3,6-disubstituted pyrazolo[1,5-a] pyrimidine core of the BMP antagonist dorsomorphin and evaluated for their ability to inhibit BMP signaling and enhance liver regeneration. Antagonists of the BMP receptor activin receptor-like kinase 3 (ALK3), including LDN-193189 (LDN; 4-[6-[4-(1-piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-quinoline), DMH2 (4-(2-(4-(3-(quinolin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)phenoxy)ethyl)morpholine; VU0364849), and the novel compound VU0465350 (7-(4-isopropoxyphenyl)-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridine; VU5350), blocked SMAD phosphorylation in vitro and in vivo, and enhanced liver regeneration after PH. In contrast, an antagonist of the BMP receptor ALK2, VU0469381 (5-(6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinolone; 1LWY), did not affect liver regeneration. LDN did not affect liver synthetic or metabolic function. Mechanistically, LDN increased serum interleukin-6 levels and signal transducer and activator of transcription 3 phosphorylation in the liver, and modulated other factors known to be important for liver regeneration, including suppressor of cytokine signaling 3 and p53. These findings suggest that inhibition of ALK3 may be part of a therapeutic strategy for treating human liver disease.

Endovascular management of critical limb ischemia in renal transplant patients.

BACKGROUND: End-stage renal disease is a significant negative predictor of limb salvage and patient survival in patients with limb ischemia, but little is known of the overall effects of renal transplantation. Endovascular management may be less morbid than open surgery, but technical success and durability in these patients is not well established. METHODS: All patients with functioning renal transplants and critical limb ischemia (CLI) treated with endovascular techniques between 2003 and 2010 were retrospectively reviewed for limb salvage, reintervention, pre- and postprocedure creatinine, and estimated glomerular filtration rate (eGFR), and overall survival. Contralateral common femoral access, low-profile techniques, and isosmolar contrast were standard for all interventions. RESULTS: Endovascular interventions were performed on 57 limbs in 28 patients with renal transplants. Mean age was 54 years, 78% were male, 85% were diabetic, 100% were hypertensive, and 64% had a positive smoking history. All patients were treated for CLI. Treated regions included 16 iliac, 19 superficial femoral, 16 popliteal, and 12 tibial arteries, as well as 1 bypass graft with initial technical success of 100% and 0% 30-day mortality. Of all lesions, 43% required reintervention during the follow-up period, the majority in the first year. There was no significant change in eGFR or creatinine comparing pre- and post-angiogram value. Limb salvage and 1-year survival were 83% and 82%, respectively. CONCLUSIONS: Endovascular management of CLI in renal transplant patients results in good technical success and can be accomplished without a measurable change in transplant kidney function, although it requires repeat interventions. Endovascular therapy is a reasonable first-line treatment option for this high-risk group.

Portosystemic shunt surgery for severe portal hypertension due to portal thrombosis after bariatric surgery.

Portal vein thrombosis is a rare complication after laparoscopic sleeve gastrectomy, a widely performed bariatric surgery procedure. Occasionally, the development of portal vein thrombosis can progress to more severe conditions, including portal hypertension and cavernomatosis, thereby presenting a complex and challenging clinical scenario. The management of such complications often requires careful consideration; however, surgical intervention in the form of a splenorenal shunt is an exceptional indication. We present the case of a 33-year-old female patient who had previously undergone laparoscopic sleeve gastrectomy in 2014 and subsequently developed portal thrombosis, followed by cavernomatosis and associated complications of portal hypertension. A proximal splenorenal shunt procedure and splenectomy were successfully performed to manage portal hypertension. The presentation of this clinical case aims to contribute to the available evidence and knowledge surrounding this rare and challenging pathology.

Risk factors for readmission after a cholecystectomy: a case-control study.

OBJECTIVE: The aim of this study was to assess the risk factors associated with 30-day hospital readmissions after a cholecystectomy. METHODS: We conducted a case-control study, with data obtained from UC-Christus from Santiago, Chile. All patients who underwent a cholecystectomy between January 2015 and December 2019 were included in the study. We identified all patients readmitted after a cholecystectomy and compared them with a randomized control group. Univariate and multivariate analyses were conducted to identify risk factors. RESULTS: Of the 4866 cholecystectomies performed between 2015 and 2019, 79 patients presented 30-day hospital readmission after the surgical procedure (1.6%). We identified as risk factors for readmission in the univariate analysis the presence of a solid tumor at the moment of cholecystectomy (OR = 7.58), high pre-operative direct bilirubin (OR = 2.52), high pre-operative alkaline phosphatase (OR = 3.25), emergency admission (OR = 2.04), choledocholithiasis on admission (OR = 4.34), additional surgical procedure during the cholecystectomy (OR = 4.12), and post-operative complications. In the multivariate analysis, the performance of an additional surgical procedure during cholecystectomy was statistically significant (OR = 4.24). CONCLUSION: Performing an additional surgical procedure during cholecystectomy was identified as a risk factor associated with 30-day hospital readmission.

OBJETIVO: El objetivo de este estudio fue evaluar los factores de riesgo asociados al reingreso hospitalario en los primeros 30 días post colecistectomía. MÉTODOS: Estudio de casos-controles con datos obtenidos del Hospital Clínico de la UC-Christus, Santiago, Chile. Se ­incluyeron las colecistectomías realizadas entre los años 2015-2019. Se consideraron como casos aquellos pacientes que reingresaron en los 30 primeros días posterior a una colecistectomía. Se realizó un análisis univariado y multivariado de diferentes posibles factores de riesgo. RESULTADOS: De un total de 4866 colecistectomías, 79 pacientes presentaron reingreso hospitalario. Los resultados estadísticamente significativos en el análisis univariado fueron; tumor sólido al momento de la colecistectomía (OR = 7.58) bilirrubina directa preoperatoria alterada (OR = 2.52), fosfatasa alcalina preoperatoria alterada (OR = 3.25), ingreso de urgencia (OR = 2.04), coledocolitiasis al ingreso (OR = 4.34) realización de otros procedimientos (OR = 4.12) y complicaciones postoperatorias. En el análisis multivariado sólo la realización de otro procedimiento durante la colecistectomía fue estadísticamente significativa (OR = 4.24). CONCLUSIÓN: La realización de otros procedimientos durante la colecistectomía es un factor de riesgo de reingreso hospitalario en los 30 días posteriores a la colecistectomía.

Roux-en-Y biliary reconstruction as a definitive treatment for serious complications of portal biliopathy. Case series.

INTRODUCTION AND IMPORTANCE: Portal biliopathy (PB) is an abnormality of the biliary tree wall due to extrahepatic portal hypertension. Among the complications of portal biliopathy are digestive bleeding, jaundice, and cholangitis. Surgical treatment is an exception when medical management is not possible. CASE PRESENTATION: This is a case series study of four patients with severe PB complications requiring surgical management in our center from 2005 to 2016. Two of them had previous surgical procedures related to portal hypertension. All presented with severe biliary stenosis and recurrent cholangitis, and two also had massive upper gastrointestinal bleeding. Because of endoscopic management failure, a Roux-en-Y hepaticojejunostomy was performed in all cases. Two patients presented morbidity Clavien-Dindo>IIIA, requiring reoperation. During follow-up, no one developed other complications related to PB. DISCUSSION: Surgical treatment for PB complications is a challenge and mainly implies a portosystemic shunt as a first step. When it fails, an alternative is perform a biliodigestive anastomoses, with high risk of bleeding given the prominent collaterals present in the hepatoduodenal pedicle secondary to portal cavernomatosis. CONCLUSION: Our patients after YRGB didn't present new complications due to PB. The surgery could be a definite solution for PB complications. It has only been made for selective cases because it implies high complexity and risk.

Liver resection for hepatolithiasis: A multicenter experience in Latin America.

BACKGROUND: Hepatolithiasis is a prevalent disease in Asia but rare in Western countries. An increasing number of cases have been reported in Latin America. Liver resection has been proposed as a definitive treatment for complete stone clearance. The aim of this study was to evaluate the postoperative outcomes of liver resection for the treatment of hepatolithiasis in 2 large hepatobiliary reference centers from South America. METHODS: We conducted a retrospective descriptive analysis from patients with hepatolithiasis who underwent liver resection between November 1986 and December 2018, in 2 Latin-American centers in Chile and Brazil. RESULTS: One hundred forty-nine patients underwent liver resection for hepatolithiasis (72 in Chile, 77 in Brazil). The mean age was 49 years and most patients were female (62.4%). Hepatolithiasis was localized in the left lobe (61.7%), right lobe (24.2%), and bilateral lobe (14.1%). Bilateral lithiasis was associated with higher incidence of preoperative and postoperative cholangitis (81% vs 46.9% and 28.6% vs 6.1%) and need for hepaticojejunostomy (52.4%). In total, 38.9% of patients underwent major hepatectomy and 14.1% were laparoscopic. The postoperative stone clearance was 100%. The 30-day morbidity and mortality rates were 30.9% and 0.7%, respectively. Cholangiocarcinoma was seen in 2 specimens, and no postoperative malignancy were seen after a median follow-up of 38 months. Fourteen patients (9.4%) had intrahepatic stones recurrence. CONCLUSIONS: Liver resection is an effective and definitive treatment for patients with hepatolithiasis. Bilateral hepatolithiasis was associated with perioperative cholangitis, the need for hepaticojejunostomy, and recurrent disease. Resection presents a high rate of biliary tree stone clearance and excellent long-term results, with low recurrence rates and low risk of malignancy.

BMP4 is a novel paracrine inhibitor of liver regeneration.

Transforming growth factor (TGF)-ß family members exert strong effects on restoration of liver mass after injury. Bone morphogenetic proteins (BMPs) are members of the TGF-ß family and are found in the liver, suggesting that these proteins may play a role in liver regeneration. We examined BMP signaling in the liver during hepatectomy. We found that BMP4 is constitutively expressed in the peribiliary stroma and endothelial cells of the liver and that expression is decreased after hepatectomy. Mice driven to maintain BMP4 expression in the liver display inhibited hepatocyte proliferation and restoration of liver mass after hepatectomy, suggesting that reduced BMP4 is necessary for normal regeneration. Consistent with this finding, hepatocyte-specific deletion of the BMP receptor activin receptor-like kinase 3 (Alk3) enhances regeneration and reduces phosphorylation of SMAD1/5/8, a transducer of BMP signaling. In contrast to experiments in wild-type mice, maintaining BMP4 levels has no effect on liver regeneration in hepatocyte-specific Alk3 null mice, providing evidence that BMP4 signals through Alk3 to inhibit liver regeneration. Consistent with these findings, the BMP4 antagonist Noggin enhances regeneration. Furthermore, high-dose BMP4 inhibits proliferation of primary hepatocytes and HepG2 cells in culture. These findings elucidate a new, potentially clinically relevant paradigm in which a constitutively expressed paracrine inhibitory factor plays a critical role in liver regeneration.