Víctor Molina

Outcome after laparoscopic enucleation for non-functional neuroendocrine pancreatic tumours

BACKGROUND Non-functional endocrine pancreatic tumours (NPT) of more than 2 cm have an increased risk of malignancy. The aim of the present study was: (i) to define the guidelines for laparoscopic enucleation (LapEn) in patients with a non-functional NPT ≤3 cm in diameter; (ii) to evaluate pancreas-related complications; and (iii) to present the long-term outcome. METHODS Between April 1998 and September 2010, 30 consecutive patients underwent laparoscopic surgery for a non-functional NPT (median age 56.5 years, range 44-83). Only 13 patients with tumours ≤3 cm in size underwent LapEn. Local lymph node dissection to exclude lymph node involvement was performed in all patients. RESULTS The median tumour size, operative time and blood loss were 2.8 cm (range 2.8-3), 130 min (range 90-280) and 220 ml (range 120-300), respectively. A pancreatic fistula occurred in five patients: International Study Group of Pancreatic Fistula (ISGPF) A in two patients and ISGPF B in three patients. The median follow-up was 48 months (12-144). Three patients with well-differentiated carcinoma are free of disease 2, 3 and 4 years after LapEn and a regional lymphadenectomy. One patient, 5 years after a LapEn, presented with lymph node and liver metastases. CONCLUSIONS The present study confirms the technical feasibility and acceptable morbidity associated with LapEn. Intra-operative lymph node sampling and frozen-section examination should be performed at the time of LapEn; when a malignancy is confirmed, oncologically appropriate lymph node dissection should be performed.

Prospective validation of ab initio liver transplantation in hepatocellular carcinoma upon detection of risk factors for recurrence after resection.

A decade ago we proposed to enlist for transplantation those patients with resected hepatocellular carcinoma in whom pathology registered pejorative histological markers (microvascular invasion and/or satellites; ab initio indication) and not wait for the appearance of recurrence. This study evaluates the outcome of this approach. From 1995 to 2012, 164 patients with hepatocellular carcinoma underwent resection. Eighty‐five patients were potential candidates for liver transplantation and were considered for it upon detection of pejorative histological markers. Patients without these markers were followed, and salvage liver transplantation was considered upon development of tumor recurrence/liver function impairment. Thirty‐seven patients were at high risk and 48 at low risk of recurrence at pathology. Twenty‐three out of 37 high‐risk patients recurred during follow‐up, but in nine of them the tumor burden extent contraindicated liver transplantation. Seventeen were finally transplanted: 10 of them presented recurrence at imaging/explant. After a median posttransplant follow‐up of 50.9 months, hepatocellular carcinoma had recurred in two patients and five patients had died, the 5‐year survival being 82.4%. Twenty‐six of the 48 low‐risk patients developed recurrence, and 11 of them were transplanted. After a median posttransplant follow‐up of 59 months, two patients developed recurrence and five died, their 5‐year survival being 81.8%. Conclusion: Enlistment of patients at high risk of HCC recurrence after resection but before recurrence development seems a valid strategy and is associated with excellent long‐term outcome; as early (<6 months) recurrence reflects an aggressive tumor behavior leading to tumor extent exceeding transplant criteria, we propose to wait at least 6 months before enlistment; however, once included on the waiting list, priority strategies should be implemented in order to reach effective transplantation prior to the appearance of recurrence. (Hepatology 2016;63:839–849)

CA 19–9 in pancreatic cancer: retrospective evaluation of patients with suspicion of pancreatic cancer

CA 19.9 serum levels were prospectively determined in 573 patients admitted to hospital for suspicion of pancreatic cancer. The final diagnosis was 77 patients with no malignancy, 389 patients with pancreatic cancer, 37 neuroendocrine pancreatic cancer, 28 cholangiocarcinomas, 4 gallbladder cancer, 27 ampullary carcinomas, and 11 periampullary carcinomas. CA 19.9 was determined using a commercial assay from Roche Diagnostics, and 37 U/ml was considered as the upper limit of normality. Abnormal CA 19.9 serum levels were found in 27%, 81.5%, 85.7%, 59.3%, 63.6%, and 18.9% of patients with benign diseases, pancreatic cancer, cholangiocarcinomas, and ampullary, periampullary, or neuroendocrine tumors. Significantly higher concentrations of CA 19.9 were found in patients with than in those without malignancy or with neuroendocrine tumors. CA 19.9 serum levels were higher in pancreatic cancer or cholangiocarcinoma than in other malignancies (p < 0.0001). CA 19.9 serum levels were also correlated with tumor stage, treatment (significantly lower concentrations in resectable tumors), and tumor location (the highest in those located in the body, the lowest in those in the tail or uncinate) and site of metastases (highest in liver metastases). A trend to higher CA 19.9 serum concentrations was found in patients with jaundice, but only with statistical significance in the early stages. Using 50 or 100 U/ml in patients with jaundice, CA 19.9 was useful as an aid in the diagnosis of pancreatic cancer (sensitivity 77.9%, specificity 95.9%) as well as tumor resectability in pancreatic cancer with different cutoffs according to tumor location and bilirubin serum levels with specificities ranging from 90% to 100%. CA 19.9 is the tumor marker of choice in pancreatic adenocarcinomas, with a clear relationship with tumor location, stage, and resectability.

Results of laparoscopic radiofrequency ablation for HCC. Could the location of the tumour influence a complete response to treatment? A single European centre experience

INTRODUCTION In selected patients, radiofrequency ablation (RFA) is a well-established treatment for hepatocellular carcinoma (HCC). However, subcapsular or lesions close to adjacent viscera preclude a percutaneous approach. In this setting laparoscopic-RFA (LRFA) is a potential alternative. The aim of this study was to analyse the safety and feasibility of LRFA in patients with HCC. PATIENTS AND METHODS Retrospective study of patients with HCC meeting strict inclusion criteria who underwent LRFA at a single Institution from December 2000 to March 2013. RESULTS Forty-one patients underwent 42 LRFA of 51 nodules. The median size of the nodule was 2.5 (range 1.2-4.7) cm. Thirty-one tumours were subcapsular and 17 located near the gallbladder. Major complications occurred in 17 patients. The initial complete response (ICR) rate was 94% and was lower among tumours located adjacent to the gallbladder. At the end of the follow-up period, the sustained complete response (SCR) rate was 70% and was lower in tumours adjacent to the gallbladder while increased for subcapsular tumours. The 1-, 3- and 5-year overall survival rate was 92.6%, 64.5% and 43%, respectively. CONCLUSION LRFA of HCC is safe, feasible and achieves excellent results in selected patients. LRFA should be the first-line technique for subcapsular lesions as it minimizes the risk of tumoural seeding and improves ICR. Proximity to gallbladder interferes in treatment efficacy (lower rate of ICR and lower rate of SCR).

Successful conversion from twice-daily to once-daily tacrolimus in liver transplantation: observational multicenter study

Dopazo C, Rodriguez R, Llado L, Calatayud D, Castells L, Ramos E, Molina V, García R, Fabregat J, Charco R. Successful conversion from twice‐daily to once‐daily tacrolimus in liver transplantation: observational multicenter study. 
Clin Transplant 2012: 26: E32–E37. 
© 2011 John Wiley & Sons A/S.

Beneficial Effect of a Resorbable Biliary Stent in Living Donor Liver Transplantation

Background: Living donor liver transplantation (LDLT) entails a significant number of bile duct complications. We aimed to diminish the biliary complication rate with the use of a resorbable biliary stent (RBS) during LDLT. The objective of this study is to describe the surgical techniques and the associated outcomes, especially in terms of safety, of RBS use in LDLT. Methods: From 2011 to 2014, 12 LDLT recipients were enrolled in a clinical trial with the use of a specifically designed RBS. These patients were followed according to the clinical protocol. Specific complications derived from RBS as well as biliary complications were recorded. Results: One patient underwent early retransplantation due to a small-for-size syndrome. None of the patients had a complication attributable to the placement, remaining in place, or degradation of the stent. Four of the remaining patients presented with a biliary complication: 1 (9.1%) with a biliary leak alone, 1 (9.1%) with a biliary stenosis alone, and 2 (18.2%) with both. However, none of the leaks could be directly attributed to the RBS. Patient and graft 1-year survival was 100 and 91.7%, respectively. Conclusion: The use of an RBS in LDLT is not associated with complications, and initial results regarding efficacy and safety are encouraging. The need for a larger and prospective study is warranted.

Surgical treatment of perihilar cholangiocarcinoma: early results of en bloc portal vein resection

ObjectiveThe objective of this study was to analyse the safety, feasibility and survival outcomes of our treatment of perihilar cholangiocarcinoma (PHC) since the introduction of more aggressive approaches (en bloc, vascular and extended liver resections) in 2007.Patients and methodsFrom July 2007 to December 2014, 32 consecutive patients with PHC underwent surgery with curative intent. Surgery with resection and reconstruction of the portal vein bifurcation and right hepatic artery was performed if necessary for a complete removal of the tumour. Perioperative data and postoperative histological findings, tumour recurrence rates and survival rates were recorded. Seventeen (53%) of the patients presented with stage IIIb or IV according to the UICC classification system.ResultsThe 5-year survival rate in our series was 45%, and this percentage increased to 65% when patients with advanced stage cancer (stage IIIb or higher) were excluded. We performed 3 arterials and 23 portal vein reconstruction. Twelve patients underwent extended hemihepatectomy. We achieved cancer-free margins in 19 patients (60%). Tumour stage and nodal involvement were the most important prognostic factors. The perioperative morbidity and mortality rates of this cohort were 72% (23) and 15.6% (5), respectively; these results were similar to data published by other groups.ConclusionsAn aggressive approach involving en bloc or extended liver resection combined with vascular reconstruction provides acceptable morbidity and mortality and increases the 5-year survival rate of PHC.

Tumor de Klatskin: Diagnóstico, evaluación preoperatoria y consideraciones quirúrgicas

Hiliar cholangiocarcinoma is the most common type of cholangiocarcinoma, an represent around 10% of all hepatobiliary tumors. It is an aggressive malignancy, resectable in around 47% of the patients at diagnosis. Complete resection is the most effective and only potentially curative therapy, with a survival rate of less than 12 months in unresectable cases. Axial computerized tomography and magnetic resonance are the most useful image techniques to determine the surgical resectability. Clinically, jaundice and pruritus are the most common symptoms at diagnosis;preoperative biliary drainage is recommended using endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography. Surgery using extended liver resections with an en bloc resection of the liver with vascular reconstruction is the technique with the highest survival. Complete resection with histologically negative resection margins (R0), nodal involvement and metastases are the most important prognostic factors.

Liver Regeneration Rate Analysis in Living Donor Liver Transplantation

Introduction and Aim Liver surgery has had an exponential development making possible the use of partial liver grafts for living donor liver transplantation (LDLT). Nonetheless, LDLT indication still depends on the graft size used for the recipient, due to the development of “small for size syndrome” (SFSS) which can be better understood through the study of hepatocellular regeneration. The aim of this study is to analyze the liver regeneration rate (LRR, grams/day) of a healthy human liver after a major liver resection such as donation of the right hepatic lobe (RHL). We have also evaluated the LRR in the recipients of this RHL and the different factors that can affect it. Materials and Methods In between January 2005 to December 2015 fifty LDLT were performed in our institution, 46 donors with their respective recipients were included being the ones de RHL was used (92%). A MRI was performed during follow up at the first, third and twelve months to all donors and recipients. With this MRI, the LRR was calculated within 3 periods of time (1 month, 1-3m and 12m after donation). Results and Discusion The median age of the donors and recipients was 35 (r=20-46) and 57 years old (r=49-66) respectively. Fifty two percent of the donors and 84.8% of the recipients were male. Intraoperative baseline biopsy of the donor was normal in almost all cases except 7 (15%) in which we found mild steatosis (<10%). Liver transplant indication was due to end stage liver disease in 20 patients (9 alcohol related, 28 with HCV infection and 9 of other causes) and the other 26 recipients the indication was due to HCC. The liver remnant volume in the donors was approximately 36.5% (r=30.5-45.2) of the total liver volume (1588g, r=1065-2079). The body to graft weigh ratio in the recipient had a median of 1.2 (r= 0.7-2.0). The median of the LRR in donors was of 14.5 g/d the first month, 0.47 g/d between 1-3m and of 0.49 g/d between 3-12m. The liver volume at the end of follow up (1 year) was 1196 g (r=864-2229). In the recipients, the LRR for the same periods of time was 13.42 g/d, 2.74 g/d and-0.26 g/d respectively and the graft volume at the end was 1503 g (r=931-2042). Interestingly the LRR in patients with HCV infection was diminished with statistical difference in the first month and in the 3-12m period after transplantation (22,19 vs 13,4 y 1,23 vs 0,14, p=0.044 y p=0.035 respectively). Conclusions We have confirmed how liver regeneration is an acute process that mainly develops in the first month after liver resection in a healthy liver when leaving and adequate liver remnant. This LR is similar in the context of LDLT when the graft has a correct volume, even though this regeneration can be affected by HCV re-infection.

Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications: ORTEGA-RIBERA et al.

Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture, endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver‐resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured with functional LSEC maintained morphology and showed high albumin and urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4) activity, and maintained expression of hepatocyte nuclear factor 4 alpha (hnf4α) and transporters, showing delayed hepatocyte dedifferentiation. In addition, differentiated hepatocytes cultured within this liver‐resembling device responded to acute treatment with known hepatotoxic drugs significantly different from those seen in conventional culture platforms. In conclusion, this study describes a new bioengineered device that mimics the human sinusoid in vitro, representing a novel method to study liver diseases and toxicology.