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The role of inflammation in malignant cell proliferation has been well described. High values of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation have shown associations with unfavorable long-term outcomes. The purpose of this study was to determine values of NLR and PLR evaluated prior to and after surgery and their associations with mortality and recurrence rates of liver transplant patients with hepatocellular carcinoma (HCC).A total of 105 patients with HCC who underwent orthotopic liver transplantation (OLT) were retrospectively reviewed. NLR and PLR values were obtained from complete blood counts prior to and after surgery. Overall survival (OS) and recurrence-free survival (RFS) in relation with delta NLR and PLR were estimated.Serum alpha-fetoprotein levels100 ng/mL (The analysis of PLR as a continuous variable may predict recurrence outcomes in patients undergoing OLT for HCC. It is more representative than isolated values.

Hepatocellular carcinoma is the most common primary liver tumor, with 905 677 diagnosed cases and 830 180 deaths, in 2020 worldwide. In Argentina, it accounts for the 9th cause of death for cancer in men and the 10th in women. Unlike other highly-prevalent tumors, scientific evidence for most therapeutic options is limited mainly to small cohorts and retrospective studies. The aim of this study is to characterize and describe epidemiologically patients with diagnosis of hepatocellular carcinoma in the Italian Hospital of Buenos Aires during a 12-year period. Overall survival for our cohort was 58%, 46%, and 36% at 1, 3 and 5 years respectively. Average survival for patients receiving palliative treatment was 5 months, while for those who received either non-curative or curative treatment was 23 and 75 months respectively. Recurrence-free survival for those patients who underwent a curative treatment was 89%, 76% y 61% at 1, 3 and 5 years. A thorough analysis of etiology, risk factors, incidence, mortality and treatment was made. The study's importance lies in its large sample size, quantity and quality of data, and will most certainly stimulate the development of local studies in hepatocellular carcinoma.El carcinoma hepatocelular (HCC) es el tumor primario más frecuente del hígado, con 905 677 casos diagnosticados en 2020, en todo el mundo, y 830 180 muertes. Es responsable de la novena causa de muerte por cáncer en los hombres y la décima en mujeres en Argentina. A diferencia de otros tumores de alta prevalencia, la evidencia científica acerca del HCC se limita principalmente a pequeñas cohortes y estudios retrospectivos. El objetivo de este estudio fue describir epidemiológicamente a aquellos pacientes con diagnóstico de HCC en el Hospital Italiano de Buenos Aires en un periodo de 12 años. La supervivencia global para nuestra cohorte fue de 58, 46 y 36% a 1, 3 y 5 años respectivamente. El promedio de supervivencia en pacientes con tratamiento paliativo fue de 5 meses, 23 para aquellos que recibieron tratamientos no curativos y 75 meses para los que recibieron tratamientos curativos. El porcentaje de pacientes libres de enfermedad a 1, 3 y 5 años fue de 89%, 76% y 61% respectivamente. Se realizó un estudio minucioso de la etiología, factores de riesgo, incidencia, mortalidad y tratamientos realizados. Su importancia yace en su tamaño muestral, calidad y cantidad de información disponible.

To explore potential sex differences in outcomes and regenerative parameters post major hepatectomies.Although controversial, sex differences in liver regeneration have been reported for animals. Whether sex disparity exists in human liver regeneration is unknown.Data from consecutive hepatectomy patients (55 females, 67 males) and from the international ALPPS (Associating-Liver-Partition-and-Portal-vein-ligation-for-Staged-hepatectomy, a two stage hepatectomy) registry (449 females, 729 males) were analyzed. Endpoints were severe morbidity (≥3b Clavien-Dindo grades), Model for End-stage Liver Disease (MELD) scores, and ALPPS interstage intervals. For validation and mechanistic insight, female-male ALPSS mouse models were established. t , χ 2 , or Mann-Whitney tests were used for comparisons. Univariate/multivariate analyses were performed with sensitivity inclusion.Following major hepatectomy (Hx), males had more severe complications ( P =0.03) and higher liver dysfunction (MELD) P =0.0001) than females. Multivariate analysis established male sex as a predictor of complications after ALPPS stage 1 (odds ratio=1.78; 95% confidence interval: 1.126-2.89; P =0.01), and of enhanced liver dysfunction after stage 2 (odds ratio=1.93; 95% confidence interval: 1.01-3.69; P =0.045). Female patients displayed shorter interstage intervals (2 weeks, 64% females versus 56% males, P =0.01), however, not in postmenopausal subgroups. In mice, females regenerated faster than males after ALPPS stage 1, an effect that was lost upon estrogen antagonism.Poorer outcomes after major surgery in males and shorter ALPPS interstage intervals in females not necessarily suggest a superior regenerative capacity of female liver. The loss of interstage advantages in postmenopausal women and the mouse experiments point to estrogen as the driver behind these sex disparities. Estrogen's benefits call for an assessment in postmenopausal women, and perhaps men, undergoing major liver surgery.

IMPORTANCE: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon’s direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width. OBJECTIVE: To determine the optimal margin width in CRLM by using artificial intelligence–based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics. DESIGN, SETTING, AND PARTICIPANTS: The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité–University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021. EXPOSURES: Hepatectomy. MAIN OUTCOMES AND MEASURES: Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence–based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory–based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values. RESULTS: This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort. CONCLUSIONS AND RELEVANCE: This cohort study used artificial intelligence–based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.

Background: The aim of this study is to analyze the role of neutrophil-lymphocyte ratio and its variation pre and post-operatively (delta NLR) in overall survival after pancreatectomy for pancreatic ductal adenocarcinoma at a single centre and to identify factors associated with overall survival.Methods: A retrospective study of consecutive patients undergoing pancreatic resection due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 was performed. Association between evaluated factors and overall survival were analyzed using a log-rank test and Cox proportional hazard regression model.Results: Overall, 242 patients underwent complete pancreatic resection for PDAC or undifferentiated carcinoma. OS was 22.8 months (95% CI: 19.5-29) and survival rates at 1, 3 and 5 years were 72%, 32.5% and 20.8% respectively. NLR and delta NLR were not significantly associated with survival (HR=1.14, 95%CI: 0.77-1.68, p=0.5). Lymph node ratio was significantly associated (HR=1.66, 95%CI: 1.21-2.26, p=0.001) in the bivariate analysis. In multivariable analysis the only factors that were significantly associated with survival were perineural invasion (HR=1.94, 95%CI: 1.21-3.14, p=0.006), surgical margin (HR=1.83, 95%CI: 1.10-3.02, p=0.019), tumor size (HR=1.01, 95%CI: 1.003-1.027, p=0.16), postoperative CA 19-9 level (HR=1.001, pConclusion: Neutrophil-lymphocyte ratio and delta NLR were not associated with overall survival in this cohort. Risk factors such as perineural invasion, surgical margins, CA19-9 level and tumor size showed worse survival in this study, whereas completing adjuvant treatment was a protective factor.

Almost 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastasis (LM). Although their only long-term curative treatment is surgery, less than half of these patients can be eventually resected. Therefore, palliative chemotherapy is offered as a definitive option, though with poor results. Recently, the University of Oslo group has published encouraging results in the treatment of these patients with liver transplantation (LT), whereby worldwide interest in this option has been renewed. A literature review of LT for patients with unresectable colorectal metastasis was performed. This included information regarding patient selection, complications, overall survival (OS) and disease-free survival (DFS), immunosuppression, chemotherapy, and description of the ongoing trials. Improvements in OS and DFS have been observed in consecutive published prospective trials, as patient selection has been refined. Papers reporting OS of patients who randomly presented similar selection criteria also exhibited good results. LT within the available therapeutic options in patients with CRC-LM seems to be a compelling alternative in carefully selected patients. The ongoing trials will provide valuable information regarding selection criteria, immunosuppressive therapy and different modalities of adjuvant chemotherapy, which are, to our knowledge, the vital platform of LT in CRC-LM. Although some of the developing techniques involve living donors, graft availability for these patients remains a matter of major concern.

The surgical strategy to resolve the underlying biliary pathology in patients with acute gallstone pancreatitis (AGP) remains controversial. The aim of this study was to evaluate the safety and effectiveness of early laparoscopic cholecystectomy (ELC) in patients with mild AGP. A retrospective cohort of consecutive patients diagnosed with mild AGP according to the Atlanta Guidelines from January 2009 to July 2019 was selected. Patients were assigned to surgery on the first available surgical shift, 48 h after the symptoms onset. Univariate analysis was performed to determine the association between AGP and grades of Balthazar (A, B and C) with time to surgery, days of hospitalization and postoperative complications. From 239 patients evaluated, 238 (99.58%) were operated by laparoscopic approach. Intraoperative cholangiogram was performed routinely. Choledocholithiasis, if present, was successfully treated by laparoscopic common bile duct exploration in all cases. A significant association was found between Balthazar grades and time to surgery (median of 3 days, p = 0.003), with length hospitalization and from surgery to discharge, with median of 4 days (p = 0.0001) and 2 days (p = 0.003), respectively. Mild postoperative complications (CD I/II) were observed in 22/239 patients (9.2%). This represents 2% of patients with grade A of Balthazar, 9% of grade B and 14% of grade C (p = 0.016). We observed no severe complications or mortality. ELC with routine intraoperative cholangiogram, performed on the first available surgical shift 48 h after the symptoms of pancreatitis onset, is a viable, effective and safe strategy for the resolution of mild AGP and its underlying biliary pathology in a single procedure.

Background: While ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR). Methods: This cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyse the influence of demographic, tumour type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in millilitre and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula. Results: A total of 734 patients were included from 99 centres. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18–0.28) and 0.39 (IQR: 0.31–0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p =.02), height ˃1.76 m (p ˂.01), weight ˃83 kg (p ˂.01), BMI˃28 (p ˂.01), male gender (p ˂.01), antihypertensive therapy (p ˂.01), operation time ˃370 minutes (p ˂.01) and hospital stay˃14 days (p ˂.01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared with 50% of female, and female present 15.3% in group ˃14 days compared with 20.6% of male. Conclusions: Height, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage.

Pancreatic cancer is an aggressive disease associated with poor results regarding long term survival. Surgical treatment along with new oncologic treatments have improved the survival of these patients in international experience reports. The aim of this study was to describe overall survival and disease-free survival after pancreatectomy for pancreatic ductal adenocarcinoma. A retrospective study of consecutive patients undergoing pancreatic resection due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 in a single tertiary center was performed. Overall, 242 patients underwent complete pancreatic resections for pancreatic ductal adenocarcinoma or undifferentiated carcinoma. Median overall survival was 22.8 months (95% CI: 19.5-29) and survival at 1, 3 and 5 years were 72%, 32.5% and 20.8% respectively. The median disease-free survival was 13.8 months (95% CI: 12-17.6) and 1, 3- and 5-years disease-free survival were 56.1%, 21.8% and 19.4% respectively. The groups of patients that completed adjuvant treatment showed a better overall survival (p0.0001).El adenocarcinoma ductal de páncreas es una enfermedad agresiva asociada con pobres resultados de supervivencia a largo plazo. La resección quirúrgica y los nuevos tratamientos oncológicos perioperatorios han logrado mejorar la supervivencia de estos pacientes en la experiencia internacional. En este estudio retrospectivo se analiza la supervivencia global y la libre de enfermedad de todos los pacientes operados por cáncer de páncreas en el Hospital Italiano de Buenos Aires de enero 2010 a enero 2020. Se identificaron 242 pacientes con resecciones pancreáticas por adenocarcinoma de páncreas o carcinoma indiferenciado. La supervivencia global mediana fue de 22.8 meses (IC 95%: 19.5-29) y la tasa de supervivencia global a 1, 3 y 5 años fue de 72%, 32.5% y 20.8% respectivamente. La supervivencia libre de enfermedad mediana fue de 13.8 meses (IC 95%: 12-17.6) y la tasa de supervivencia libre de enfermedad a 1, 3 y 5 años fueron de 56.1%, 21.8% y 19.4% respectivamente. El grupo de pacientes que logró completar el tratamiento adyuvante mostró una mayor supervivencia global (p0.0001).

BACKGROUND Hepatocellular adenoma (HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception. Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications CASE SUMMARY A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging (MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up. CONCLUSION HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated.

To evaluate short- and long-term outcomes after live-donor liver transplantation (LT) with hyper-reduced grafts in low-weight pediatric recipients. LT is an established curative therapy for children with end-stage chronic liver disease or acute liver failure. A major problem in pediatric LT has been the lack of size-matched donor organs. The disadvantage of the use of large-for-size grafts is the insufficient tissue oxygenation and graft compression, which result in poor outcomes. The shortage of suitable donors is most notable in children under 10 kg. To overcome such obstacle, in situ hyper-reduced live-donor liver grafts have been introduced. Available articles in the literature are based on small samples and are deficient in long-term follow-up. A single-cohort, retrospective analysis was conducted including 59 pediatric patients under 10 kg who underwent hyper-reduced (in situ “a la carte” left lateral segment reduction) live-donor LT (LDLT) between February 1994 and February 2018. The most frequent cause of liver failure was biliary atresia (70%). Median recipient weight was 8 kg. Vascular complications were confirmed in 15% of the sample, while 45% presented biliary complications. Median follow-up time was 40.3 months. Ten-year overall survival rate was 74%. Pediatric end-stage liver disease score > 23 was associated with a higher risk of post-operative complications. LDLT can be undertaken in children with body weight

Factor XI (FXI) deficiency is a rare congenital hemostatic disorder associated with increased bleeding tendency in trauma, surgery or when other hemostatic defects are present. Perioperative hemostatic management of a patient with a severe FXI deficiency undergoing major oncological liver and colorectal surgery with therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP) is reported.A 54-year-old male with severe FXI deficiency was scheduled for resection of synchronous rectal cancer and multiple liver metastases. Baseline prothrombin time (PT) was 97 %, activated partial thromboplastin time (aPTT) 89 s(s) and FXI levels1 IU/dL. The rotational thromboelastometry (ROTEM™) presented a prolonged INTEM clotting time (CT) = 443 s (RV 100-240 s) and a clot formation time (CFT) = 110 s (RV 30-100 s). TPE with FFP was carried out achieving FXI levels up to 46 IU/dL and an aPTT of 33 s, normalizing thromboelastometry parameters to an INTEM CT = 152 s and a CFT = 86 s before the procedure. After surgery, the patient received daily FFP to maintain FXI levels above 30 IU/dL until discharge on the eighth day. A total of 30 FFP units were transfused during hospital stay. No significant bleeding events neither transfusion related complications were observed during the perioperative period.Given the lack of correlation between FXI levels and bleeding risk, a multidisciplinary approach based on daily FXI levels monitoring, close clinical assessment and factor supplementation is mandatory. In conclusion, TPE with FFP is an efficacious alternative strategy to correct severe FXI deficiency in patients undergoing major surgery.

Liver resection represents the curative treatment of choice for patients with colorectal liver metastases (CRLM). Laparoscopic hepatectomy in CRLM is considered a safe approach. However, the information on their oncological results in the different series is deficient. This study aimed to compare the surgical margin, overall survival (OS), and disease-free survival (DFS) in patients with oncological resections of CRLM according to the type of surgical approach performed.Between April 2007 and June 2017, 263 patients with CRLM underwent hepatic resection. Inclusion criteria were initial resectability, tumor size ≤ 50 mm, 3 or less metastases, no bilobar involvement, and absence of extrahepatic disease. A propensity score was performed to adjust the indication bias.Eighty-two patients were included (56 open and 26 laparoscopic). Twenty-eight (50%) patients had synchronous presentation in the open approach and 6 (23%) in the laparoscopic approach (p = 0.021), with more frequent simultaneous open resections (p = 0.037). The resection margin was positive (R1) in 5 patients with an open approach and 2 with a laparoscopic approach (8.9% and 7.6% respectively; p = 0.852). Nine patients (16%) with conventional approach and 2 (7.7%) with laparoscopic approach had local complications (p = 0.3). There was one death in the open group and none in the laparoscopic. There were no significant differences in OS and DFS rate between both groups (1-3 years, OS: 92-77% and 96-75% respectively; 1-3 years, DFS: 63-20% and 73-36% respectively).There were no significant differences in terms of surgical margin, OS rate, and DFS rate between the laparoscopic and open approach in patients with CRLM.

Introduction Two novel clinical risk scores (CRS) that incorporate KRAS mutation status (modified CRS (mCRS) and GAME score) were developed. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS. Methods Patients undergoing hepatectomy for CRLM (2000-2018) in ten centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrel's C-index and Akaike's Information Criterion. Results In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14405, 14447, and 14319, respectively. Conclusion In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS.

Acute biliary pancreatitis (ABP) is often associated with persistent common bile duct (CBD) stones. The best strategy in terms of timing of surgery is still controversial. The aim of the current study is to describe the prevalence of persistent common bile duct (CBD) stones in ABP during the first week of symptoms at a high-volume referral center. Single-institution retrospective analysis of a prospectively collected database. Patients with diagnosis of ABP who underwent laparoscopic cholecystectomy (LC) between January 2009 and December 2019 were extracted. Two hundred thirty-one patients were included. Cholecystectomy was performed laparoscopically in 230 (99.57%) patients. Intraoperative cholangiogram was performed in all patients. Two hundred nine (90%) patients had surgery within the first 7 days. Global prevalence of persistent CBD stones during IOC was 19.91% (95% CI 14.96–25.65). No significant association between timing to surgery and presence of CBD stones was found for the first week since the initial attack (p=0.28). Prevalence of CBD stones was significantly higher after day 7 (p=0.007 and 0.005). Positive findings in preoperative MRCP are significantly related to intraoperative CBD stones (p=0.0001). Mild postoperative complications (CD I/II) were present in 21 patients (9.09%). No difference was found in morbidity between CBD stones group and non-CBD stones group (p=0.48). We observed no severe complications nor mortality. In patients with mild acute biliary pancreatitis, the prevalence of persistent CBD stones does not change within the first 7 days since the onset of symptoms. This fact may have major clinical relevance when deciding the optimal therapeutic strategy in this population.

Background Liver transplantation (LT) has been used as a last resort in patients with end-stage liver disease due to bile duct injuries (BDI) following cholecystectomy. Our study aimed to identify and evaluate factors that cause or contribute to an extended liver disease that requires LT as ultimate solution, after BDI during cholecystectomy. Methods Data from 8 high-volume LT centers relating to patients who underwent LT after suffering BDI during cholecystectomy were prospectively collected and retrospectively analyzed. Results Thirty-four patients (16 men, 18 women) with a median age of 45 (range 22-69) years were included in this study. Thirty of them (88.2%) underwent LT because of liver failure, most commonly as a result of secondary biliary cirrhosis. The median time interval between BDI and LT was 63 (range 0-336) months. There were 23 cases (67.6%) of postoperative morbidity, 6 cases (17.6%) of post-transplant 30-day mortality, and 10 deaths (29.4%) in total after LT. There was a higher probability that patients with concomitant vascular injury (hazard ratio 10.69, P=0.039) would be referred sooner for LT. Overall survival following LT at 1, 3, 5 and 10 years was 82.4%, 76.5%, 73.5% and 70.6%, respectively. Conclusion LT for selected patients with otherwise unmanageable BDI following cholecystectomy yields acceptable long-term outcomes. CA extern

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) approach emerged as a promising surgical strategy for rapid and large hypertrophy of the future liver remnant (FLR) when a major liver resection is necessary. Colorectal liver metastasis (CRLM) is their main indication. However, the promising results published so far, are very difficult to interpret since they usually focus on the technique and not on the underlying disease. Moreover, they are usually made up of complex populations, which received different chemotherapy schemes, with the ALPPS technical variations implemented over time and without consistent long-term follow-up results as well. Whereby, its role in CRLM should be analyzed as carefully as possible to indicate and select the best candidates who will benefit the most from this approach. We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to the ALPPS and CRLM.

Biliary fistulas may result as a complication of gallstone disease. According to their tract, abdominal internal biliary fistulas may be classified into cholecystobiliary and bilioenteric fistulas. Surgical treatment is challenging and requires highly trained surgeons with high preoperative suspicion. Conventional surgery is still of choice by most of the authors. However, laparoscopy is emerging as a minimally invasive alternative. We investigated the surgical approach, conversion rate, and outcomes according to the type of biliary fistula. We retrospectively reviewed 11,130 laparoscopic cholecystectomies, 31 open cholecystectomies, and 31 surgeries for gallstone ileus at our institution from May 2007 to May 2020. We diagnosed internal biliary fistula in 73 patients and divided them into two groups according to their fistulous tract: cholecystobiliary fistula and bilioenteric fistula. We described demographic characteristics, preoperative imaging modalities, surgical approach, conversion rates, surgical procedures, and outcomes. We additionally revised the literature and compared our results with 13 studies from the past 10 years. There were 22 and 51 patients in the cholecystobiliary and bilioenteric groups, respectively. Our preoperative suspicion of a fistula was 80%. We started 88% of procedures by laparoscopic approach. The effectiveness of laparoscopy in the resolution of internal biliary fistula was 40% for cholecystobiliary fistula and 55% for bilioenteric fistulas. The most frequent cause for conversion to laparotomy was the difficulty to identify anatomical features, in addition to the need to perform a Roux en-Y hepaticojejunostomy. Choledocholithiasis was not associated with an increase in conversion rates. Laparoscopic resolution of a biliary fistula is still a matter of controversy. Despite the high conversion rates, we believe that a great number of patients benefit from this minimally invasive technique. A high preoperative suspicion and trained surgeons are vital in the treatment of internal biliary fistulas.

Objectives: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. Background: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. Methods: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. Results: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). Conclusions: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Background Repeated liver resections for the recurrence of colorectal liver metastasis (CRLM) are described as safe and have similar oncological outcomes compared to first hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is performed in patients with conventionally non-resectable CRLM. Repeated resections after ALPPS has not yet been described. Methods Patients that underwent repeated liver resection in recurrence of CRLM after ALPPS were included in this study. The primary endpoint was morbidity and secondary endpoints were mortality, resection margin and survival. Results Thirty patients were included in this study. During ALPPS, most of the patients had classical split (60%, n = 18) and clearance of the FLR (77%, n = 23). Hepatic recurrence was treated with non-anatomical resection (57%, n = 17), resection combined with local ablation (13%, n = 4), open ablation (13%, n = 4), segmentectomy (10%, n = 3) or subtotal segmentectomy (7%, n = 2). Six patients (20%) developed complications (10% minor complications). No post-hepatectomy liver failure or perioperative mortality was observed. One-year patient survival was 87%. Five patients received a third hepatectomy. Conclusion Repeated resections after ALPPS for CRLM in selected patients are safe and feasible with low morbidity and no mortality. Survival seems to be comparable with repeated resections after conventional hepatectomy.

Background Surgery is the most effective treatment option for neuroendocrine liver metastases (NELM). This study investigated the role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a novel strategy in treatment of NELM. Methods The International ALPPS Registry was reviewed to study patients who underwent ALPPS for NELM. Results From 2010 to 2017, 954 ALPPS procedures from 135 international centers were recorded in the International ALPPS Registry. Of them, 24 (2.5%) were performed for NELM. Twenty-one patients entered the final analysis. Overall grade ≥3b morbidity was 9% after stage 1 and 27% after stage 2. Ninety-day mortality was 5%. R0 resection was achieved in 19 cases (90%) at stage 2. Median follow-up was 28 (19–48) months. Median disease free survival (DFS) was 17.3 (95% CI: 7.1–27.4) months, 1-year and 2-year DFS was 73.2% and 41.8%, respectively. Median overall survival (OS) was not reached. One-year and 2-year OS was 95.2% and 95.2%, respectively. Conclusions ALPPS appears to be a suitable strategy for inclusion in the multimodal armamentarium of well-selected patients with neuroendocrine liver metastases. In light of the morbidity in this initial series and a high rate of disease-recurrence, the procedure should be taken with caution.

Annals of surgical oncology (2020). doi:10.1245/s10434-019-08192-z, Published by Springer, Berlin [u.a.]

Purpose Pancreatic cancer (PC) has not changed overall survival in recent years despite therapeutic efforts. Surgery with curative intent has shown the best long-term oncological results. However, 80%-85% of patients with these tumors are unresectable at the time of diagnosis. In those patients, first therapeutic attempts are minimally invasive or surgical procedures to alleviate symptoms. The addition of radiotherapy (RT) to standard chemotherapy, ergo chemoradiation, in patients with locally advanced pancreatic cancer (LAPC) is still controversial. The study aims to compare outcomes in patients with a double bypass surgery due to LAPC treated or not with RT. Materials and methods A retrospective cohort study of patients with double bypass for LAPC were registered and divided into two groups: treated or not with postoperative RT. Baseline characteristics, postoperative complications, those related to RT and their relation to the main event (mortality) were compared. Results Seventy-four patients were included. Surgical complications between the groups did not offer significant differences. Complications related to RT were mostly mild, and 86% of patients completed the treatment. Overall survival at 1 and 2 years for patients in the exposed group was 64% and 35% vs. 50% and 28% in the non-exposed group, respectively (p = 0.11; power 72%; hazard ratio = 0.53; 95% confidence interval, 0.24-1.18). Conclusion We observed a tendency for survival improvement in patients with postoperative RT. However, we've not had enough power to demonstrate this difference, possibly due to the small sample size. It is indispensable to develop randomized and prospective trials to guide more specific treatment lines in this patients.

Background Various, often conflicting, estimates for post-operative morbidity and mortality following ALPPS have been reported in the literature, suggesting that considerable center-level variation exists. Some of this variation may be related to center volume and experience. Methods Using data from seventeen centers who were early adopters of the ALPPS technique, we estimated the variation, by center, in standardized 90-day mortality and comprehensive complication index (CCI) for patients treated between 2012 and 2018. Results We estimated that center-specific 90-day mortality following treatment with ALPPS varied from 4.2% (95% CI: 0.8, 9.9) to 29.1% (95% CI: 13.9, 50.9), and that center-specific CCI following treatment with ALPPS varied from 17.0 (95% CI: 7.5, 26.5) to 49.8 (95% CI: 38.1, 61.8). Declines in estimated 90-day mortality and CCI were observed over time, and almost all individual centers followed this trend. Patients treated at centers with a higher number of ALPPS cases performed over the prior year had a lower risk of post-operative mortality. Conclusion Despite considerable center-level variation in ALPPS outcomes, perioperative outcomes following ALPPS have improved over time and treatment at higher volume centers results in a lower risk of 90-day mortality. Morbidity and mortality remain concerningly high at some centers.

Background Acute calculous cholecystitis (ACC) is the most common complication of cholelithiasis. Laparoscopic cholecystectomy (LC) is the gold standard treatment in mild and moderate forms. Currently there is consensus for the use of antibiotics in the preoperative phase of ACC. However, the need for antibiotic therapy after surgery remains undefined with a low level of scientific evidence. Methods The CHART (Cholecystectomy Antibiotic Randomised Trial) study is a single-center, prospective, double blind, and randomized trial. Patients with mild to moderate ACC operated by LC were randomly assigned to receive antibiotic (amoxicillin/clavulanic acid) or placebo treatment for 5 consecutive days. The primary endpoint was postoperative infectious complications. Secondary endpoints were as follows: (1) duration of hospital stay, (2) readmissions, (3) reintervention, and (4) overall mortality. Results In the per-protocol analysis, 6 of 104 patients (5.8%) in the placebo arm and 6 of 91 patients (6.6%) in the antibiotic arm developed postoperative infectious complications (absolute difference 0.82 (95% confidence interval, −5.96 to 7.61, P = .81). The median hospital stay was 3 days. There was no mortality. There were no differences regarding readmissions and reoperations between the 2 groups. Conclusion Although this trial failed to show noninferiority of postoperative placebo compared to antibiotic treatment after LC for mild and moderate ACC within a noninferiority margin of 5%, the use of antibiotics in the postoperative period does not seem justified, because it was not associated with a decrease in the incidence of infectious and other types of morbidity in the present study.

Objective: The aim of this study was to evaluate interstage liver function in associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) using hepatobiliary scintigraphy (HBS) and whether this may help to predict posthepatectomy liver failure (PHLF). Background: ALPPS remains controversial given the high rate of liver-related mortality after stage 2. HBS combined with single photon emission computed tomography (SPECT) accurately estimates future liver remnant function and may be useful to predict PHLF. Methods: Between 2011 and 2016, 20 of 39 patients (51.3%) underwent SPECT-HBS before ALPPS stage 2 for primary (n = 3) or secondary liver tumors (n = 17) at the Hospital Italiano de Buenos Aires (HIBA). PHLF was defined by the International Study Group of Liver Surgery criteria, 50-50 criteria, or peak bilirubin >7mg/dL. Grade A PHLF was excluded, as it requires no change in clinical management. Receiver-operating characteristic curves were used to determine cutoff for HBS parameters. Results: Interstagely, 3 HBS parameters differed significantly between patients with (n = 4) and without PHLF (n = 16) after stage 2. Among these, the HIBA-index best predicted PHLF, with a cutoff value of 15%. The risk of PHLF in patients with cutoff

Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is an innovative, 2-staged hepatectomy which has elicited controversy within the international hepatobiliary community. Uptake of ALPPS has been limited due to concerns related to evidence of high morbidity and mortality, and scant oncologic and outcome data on quality of life (Qol). Demonstrating reasonable long-term benefits with a short-term risk is necessary to support more widespread endorsement of ALPPS. Our aim was to describe the intermediate-term survival and patient-reported quality of life outcomes after an ALPPS. Methods Prospectively collected data from 2 high-volume ALPPS centers, who were pioneers with the technique, were combined and analyzed for disease-free and overall survival from date of the ALLPS. Only patients treated for colorectal liver metastases with >6 month postoperative follow-up were included. All patients had bilateral colorectal liver metastases with an initially unresectable tumor load, and received preoperative chemotherapy. Information concerning the demographics of the patients, characteristics of the tumor, and treatment were analyzed. The well-validated European Organization for Research and Treatment for Cancer Quality of Life Core Questionnaire version 3.0 questionnaire was used to assess patient quality of life. Results A total of 58 patients underwent ALPPS for colorectal liver metastases, and 47 patients met our inclusion criteria. There were no perioperative mortalities, and the rate of severe complications was 21%. At 3 years post-ALPPS, the overall survival was 50%, while the disease-free survival was 13%. The commonest site of first recurrence was the liver alone (38%). Patient-reported quality of life after ALPPS was similar to reference values for general population. Conclusion In select patients operated at experienced centers, ALPPS results in low perioperative risk, satisfactory overall survival, and excellent quality of life. Hepatic recurrence and not systemic recurrence is the most common site of relapse after ALPPS.

Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows the resection of colorectal liver metastases with curative intent which would otherwise be unresectable and only eligible for palliative systemic therapy. This study aimed to compare outcomes of ALPPS in patients with otherwise unresectable colorectal liver metastases with matched historic controls treated with palliative systemic treatment. Methods All patients with colorectal liver metastases from the international ALPPS registry were identified and analyzed. Survival data were compared according to the extent of disease. Otherwise unresectable ALPPS patients were defined by at least 2 of the following criteria: ≥6 metastasis, ≥2 future remnant liver metastasis, ≥6 involved segments excluding segment 1. These patients were matched with patients included in 2, phase 3, metastatic, colorectal cancer trials (CAIRO and CAIRO2) using propensity scoring in order to compare survival. Results Of 295 patients with colorectal liver metastases in the ALPPS registry, 70 patients had otherwise unresectable disease defined by the proposed criteria. Two-year overall survival was 49% and 72% for patients with ≥2 and

The aim of this study was to use the concept of benchmarking to establish robust and standardized outcome references after the procedure ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy).The recently developed ALPPS procedure, aiming at removing primarily unresectable liver tumors, has been criticized for safety issues with high variations in the reported morbidity/mortality rates depending on patient, disease, technical characteristics, and center experience. No reference values for relevant outcome parameters are available.Among 1036 patients registered in the international ALPPS registry, 120 (12%) were benchmark cases fulfilling 4 criteria: patients ≤67 years of age, with colorectal metastases, without simultaneous abdominal procedures, and centers having performed ≥30 cases. Benchmark values, defined as the 75th percentile of the median outcome parameters of the centers, were established for 10 clinically relevant domains.The benchmark values were completion of stage 2: ≥96%, postoperative liver failure (ISGLS-criteria) after stage 2: ≤5%, ICU stay after ALPPS stages 1 and 2: ≤1 and ≤2 days, respectively, interstage interval: ≤16 days, hospital stay after ALPPS stage 2: ≤10 days, rates of overall morbidity in combining both stage 1 and 2: ≤65% and for major complications (grade ≥3a): ≤38%, 90-day comprehensive complication index was ≤22, the 30-, 90-day, and 6-month mortality was ≤4%, ≤5%, and 6%, respectively, the overall 1-year, recurrence-free, liver-tumor-free, and extrahepatic disease-free survival was ≥86%, ≥50%, ≥57%, and ≥65%, respectively.This benchmark analysis sets key reference values for ALPPS, indicating similar outcome as other types of major hepatectomies. Benchmark cutoffs offer valid tools not only for comparisons with other procedures, but also to assess higher risk groups of patients or different indications than colorectal metastases.

Background The management of Branch-Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN) is still controversial. Our objective was to assess the long-term follow-up (FU) of patients with “low-risk” BD-IPMN according to the Sendai-International Consensus Guidelines (ICG-I). Methods We retrospectively analyzed a cohort of patients with BD-IPMN and Negative Sendai-Criteria (NSC) from January 2004 to October 2019. A univariate analysis was performed to determine factors associated with conversion to Positive Sendai-Criteria (PSC) and malignancy. Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the IGC-I were assessed for the development of malignancy. Results A total of 219 patients were selected and underwent a median 58-month FU. Thirty-seven (17%) patients developed PSC during FU including 12 (5.5%) with malignant lesions. Conversely, 182 patients (83%) did not develop malignancy. The NPV and PPV of ICG-I for malignancy were 100% and 32.4%, respectively. Among patients who developed PSC, those with cancer were >65years (OR = 3.57;p = 0.015) and had significantly higher serum CA-19-9 levels (OR = 5.27;p = 0.007). Conclusion The ICG-I is a safe strategy for FU of patients with BD-IPMN. The absence of PSC exclude malignancy. Among patients who develops PSC, the risk of cancer remains low and surgery should be decided according to their surgical risk and life expectancy.

Introducción. La prevención temprana de las complicaciones respiratorias en niños con fibrosis quística determina una mayor sobrevida. La aplicación de pruebas de función pulmonar desde los primeros meses de vida permite detectar el compromiso respiratorio, inclusive en niños asintomáticos. Objetivo. Evaluar la evolución de la función pulmonar en niños con fibrosis quística durante los primeros 3 años de vida e identificar aquellos factores que la comprometen. Población y métodos. Estudio analítico, observacional, retrospectivo. Se incluyeron menores de 36 meses con, al menos, dos estudios funcionales respiratorios. Resultados. Entre 2008 y 2016, se incluyeron 48 pacientes, de los cuales el 85 % fue diagnosticado por pesquisa neonatal. La primera evaluación funcional respiratoria fue a los 5 meses. La mediana de puntaje Z de flujo máximo a nivel de la capacidad residual funcional fue de -0,05 (intervalo intercuartil: de -1,09 a 1,08). La mediana de cambio del puntaje Z del flujo máximo entre las evaluaciones fue de -0,32 (intervalo intercuartil: de -1,11 a 0,25), p = 0,045. Los pacientes con infecciones respiratorias por Staphylococcus aureus, especialmente los resistentes a meticilina, evidenciaron una mayor declinación de la función pulmonar comparados con los no infectados. Ni el sexo ni el tipo de mutación genética se asociaron a la evolución respiratoria. Se evidenció una muy buena recuperación nutricional a lo largo del estudio. Conclusión. Los niños con fibrosis quística presentan una función pulmonar que, progresivamente, desmejora durante los primeros 3 años de vida. Estos hallazgos se asocian a las infecciones respiratorias por Staphylococcus aureus. Introduction. The early prevention of respiratory complications in children with cystic fibrosis is determining for a longer survival. The implementation of lung function tests in the first months of life allows to detect respiratory involvement, even in asymptomatic children. Objective. To assess the course of lung function in children with cystic fibrosis in their first 3 years of life and identify the factors affecting it. Population and methods. Observational, retrospective, analytical study. Children younger than 36 months with at least 2 lung function tests were included. Results. Between 2008 and 2016, 48 patients were included; 85 % of them had been diagnosed by newborn screening. The first lung function test was done at 5 months old. The median Z-score of maximal flow at functional residual capacity was -0.05 (interquartile range: -1.09 to 1.08). The median change in the maximal flow Z-score between tests was -0.32 (interquartile range: -1.11 to 0.25), p = 0.045. Patients with Staphylococcus aureus respiratory infections, especially methicillin-resistant SA, evidenced a greater deterioration of lung function compared to those without infection. Neither sex nor the type of genetic mutation were associated with the course of lung function. Nutritional recovery throughout the study was really good. Conclusion. Lung function in children with cystic fibrosis worsens progressively during their first 3 years of life. These findings are associated with Staphylococcus aureus respiratory infections.

Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10–1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1–R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.