Joaquim Balsells

Influence of anti-HLA antibodies and positive T-lymphocytotoxic crossmatch on survival and graft rejection in human liver transplantation

BACKGROUND/AIMS The role of crossmatching in liver transplantation is controversial. The aim of this study was to investigate retrospectively the effect of sensitization and IgG lymphocytotoxic crossmatching on liver transplantation. METHODS/RESULTS Over 5 years, 20 of 243 (8.2%) first liver transplants were performed with a positive crossmatch and their outcome was compared with the remaining 223 performed with a negative crossmatch. Women had a higher incidence of positive crossmatch than men (p < 0.001). Significant differences in mean panel reactive antibody of 2.7% and 43.3% were found in negative and positive crossmatch patients, respectively (p < 0.001). Severe early rejection resulting in graft loss occurred in eight of 20 positive crossmatch patients, and only one of 223 negative crossmatch patients (p < 0.001). Five of the remaining positive crossmatch patients suffered several acute rejection episodes some months after liver transplantation. Two of 20 in the positive crossmatch group developed chronic rejection (10%) compared with ten of 223 negatives (4.4%) (N.S). Nine of 16 positive crossmatch female recipients suffered graft loss and seven died, representing 1-year graft and patient survival of 56% and 43%, respectively. Fifteen of 68 negative crossmatch female recipients presented graft loss and 12 died, accounting for 1-year patient and graft survival of 82% and 78% (p < 0.005), respectively. Five patients (20%) displayed positive crossmatch at the time of retransplantation, compared with 24 (10%) who were negative (N.S). CONCLUSION Our experience confirms the adverse impact of a positive crossmatch in liver transplantation, particularly in female recipients. Candidates with high panel reactive antibody are more likely to display a positive crossmatch, and therefore to develop early severe rejection and graft failure.

Outcome of patients following hepatic resection for metastatic cutaneous and ocular melanoma

Background/purposeThe aim of this study was to analyze the outcome of patients undergoing hepatic resection for melanoma liver metastases.MethodsPatients undergoing liver resection for melanoma metastases at the Hospital Vall d’Hebron and Hospital Clinic, Barcelona, were reviewed. Selection criteria were: good performance status, feasibly complete and safe resection, and absence of visceral extrahepatic metastases.ResultsBetween 1994 and 2007, 14 liver resections were performed for melanoma liver metastases. The primary tumor was cutaneous in 8 patients and ocular in 6. Two patients underwent urgent liver surgery due to tumor bleeding. In these patients, complete melanoma staging was not performed and extrahepatic metastases were found during surgery or during the postoperative course. Six of 13 patients (46.2%) developed liver recurrence during follow-up. One- and 3-year actuarial patient survivals were 77 and 49%, respectively. Excluding the patients who underwent urgent liver surgery, the 1- and 3-year actuarial patient survivals in those with primary ocular and cutaneous melanoma were 83 and 56% and 80 and 60%, respectively.ConclusionsLiver resection may be considered as part of oncosurgical treatment in patients with melanoma liver metastases, since prolonged survival was observed, albeit with a high recurrence rate. Nevertheless, it should be taken into account that our study included only a small number of patients.

Pancreatitis aguda durante la gestación, experiencia de 7 años en un centro de tercer nivel

INTRODUCTION Acute pancreatitis is a common cause of acute abdomen in pregnant women. The purpose of this study was to determine the frequency at our institution and its management and outcomes. METHODS A retrospective analysis of a database of cases presented in 7 consecutive years at a tertiary center was performed. RESULTS Between December 2002 and August 2009, there were 19 cases of acute pancreatitis in pregnant women, 85% with a biliary etiology. The highest frequency was in the third trimester of pregnancy (62.5% cases). In cases of gallstone pancreatitis, 43.6% of pregnant women had had previous episodes before pregnancy. A total of 52.6% of the patients were readmitted for a recurrent episode of pancreatitis during their pregnancy. Overall, 26.3% of the patients received antibiotic treatment and 26.3% parenteral nutrition. Laparoscopic cholecystectomy was performed during the 2nd trimester in two patients (10.5%). There was no significant maternal morbidity. CONCLUSION Acute pancreatitis in pregnant women usually has a benign course with proper treatment. In cases of biliary origin, it appears that a surgical approach is suitable during the second trimester of pregnancy.

Overexpression of Yes Associated Protein 1, an Independent Prognostic Marker in Patients With Pancreatic Ductal Adenocarcinoma, Correlated With Liver Metastasis and Poor Prognosis

Objectives Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Overexpression of Yes associated protein 1 (YAP1), a downstream target of Hippo pathway, implicated in regulation of cell growth and apoptosis, has been reported in several human tumor types. The objective of this study was to investigate YAP1 expression in patients with PDAC and its prognostic values. Methods We evaluated YAP1 expression in 64 PDAC and 15 chronic pancreatitis (CP) cases and its related pancreatic intraepithelial neoplasia (PanIN) lesions and in 5 control subjects. Yes associated protein 1 expression was determined by immunohistochemistry. Association of YAP1 with clinicopathologic features in PDAC, disease-free survival, and overall survival was analyzed. Results We found a higher positive rate of nuclear expression of YAP1 in PDAC than in CP (P = 0.000) and lower expression of YAP1 in PanIN lesions in CP in contrast with expression in PanIN lesions in PDAC. Nuclear overexpression of YAP1 in PDAC is associated with hepatic metastasis (P = 0.0280) and is a prognostic factor (P = 0.0320), as well as surgical margin involvement (P = 0.0013) and tumoral stage (P = 0.0109). Conclusions Overexpression of YAP1 may occur as a part of tumorigenesis of PDAC. Yes associated protein 1 is an independent prognostic marker for overall survival of PDAC and associated with liver metastasis, being a potential therapeutic target.

Autoimmune pancreatitis type-1 associated with intraduct papillary mucinous neoplasm: report of two cases.

Chronic pancreatitis lesions usually embrace both intraduct papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC). Patients at genetically-determined high risk of PDAC often harbor IPMN and/or chronic pancreatitis, suggesting IPMN, chronic pancreatitis and PDAC may share pathogenetic mechanisms. Chronic autoimmune pancreatitis (AIP) may also herald PDAC. Concurrent IPMN and AIP have been reported in few patients. Here we describe two patients with IPMN who developed type-1 AIP fulfilling the Honolulu and Boston diagnostic criteria. AIP diffusively affected the whole pancreas, as well as peripancreatic lymph nodes and the gallbladder. Previous pancreatic resection of focal IPMN did not show features of AIP. One of the patients carried a CFTR class-I mutation. Of notice, serum IgG4 levels gradually decreased to normal values after IPMN excision. Common risk factors to IPMN and AIP may facilitate its coincidental generation.

Resultados a largo plazo de la duodenopancreatectomía cefálica con resección de la vena mesentérica superior y vena porta por adenocarcinoma de la cabeza de páncreas

INTRODUCTION The benefit of pancreaticoduodenectomy (PD) with superior mesenteric-portal vein resection (PVR) for pancreatic adenocarcinoma (PA) is still controversial in terms of morbidity, mortality and survival. We conducted a retrospective study to analyze outcomes of PD with PVR in a Spanish tertiary centre. METHODS Between 2002 and 2012, 10 patients underwent PVR (PVR+ group) and 68 standard PD (PVR- group). Morbidity, mortality, overall survival (OS) and disease-free survival (DFS) were compared between PVR+ and PVR- group. Prognostic factors were identified by a Cox regression model. RESULTS Postoperative mortality was 5% (4/78), all patients in PVR- group. Morbidity was higher in the PVR- group compared to PVR+ (63 vs. 30%, P=.004). OS at 3 and 5 years was 43 and 43% in PVR+ group, 35 and 29% in PVR- group (P=.07). DFS at 3 and 5 years DFS were 28 and 15% in PVR+ group, 25 and 20% in PVR- group (P=.84). Median survival was 23.1 months in PVR- group, and 22.8 months in PVR+ group (P=.73). Factors related with OS were absence of adjuvant treatment (OR 2.9, 95%IC: 1.39-6.14, P=.003), R1 resection (OR 2.3, 95%IC: 1.2-4.43, P=.006), preoperative CA 19.9 level ≥ 170 UI/mL (OR 2.3, 95%IC: 1.22-4.32, P=.01). DFS risk factors were R1 resection (OR 2.6, 95%IC: 1.41-4.95, P=.002); moderate or poor tumor differentiation grade (OR 2.7, 95%IC: 1.23-6.17, P=.01); N1 lymph node status (OR 1.8, 95%IC: 1.02-3.19, P=.04); CA 19.9 level ≥ 170 UI/mL (OR 2.4, 95%IC: 1.30-4.54, P=.005). CONCLUSIONS PVR for PA can be performed safely. Patients with PVR have a comparable survival to patients undergoing standard PD if disease-free margins can be obtained.

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives

Background Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

The role of extra-pancreatic infections in the prediction of severity and local complications in acute pancreatitis

BACKGROUND The aim of our study was to determine the risk factors for extrapancreatic infection (EPI) occurrence and its predictive power for assessing severity and local complications in acute pancreatitis including infected pancreatic necrosis (IPN). METHODS Clinical data of 176 AP patients prospectively enrolled were analysed. EPI analysed were bacteraemia, lung infection, urinary tract infection and catheter line infection. Risk factors analysed were: Leukocyte count, C-reactive protein, liver function test, serum calcium, serum glucose, Blood urea nitrogen, mean arterial pressure at admission, total parenteral nutrition (TPN), enteral nutrition, hypotension, respiratory, cardiovascular and renal failure at admission, persistent systemic inflammatory response (SIRS) and intrapancreatic necrosis. Severity outcomes assessed were defined according to the Atlanta Criteria definition for acute pancreatitis. The predictive accuracy of EPI for morbidity and mortality was measured using area-under-the-curve (AUC) receiver-operating characteristics. RESULTS Forty-four cases of EPI were found (25%). TPN (OR:9.2 CI95%: 3.3-25.7), APACHE-II>8 (OR:6.2 CI95%:2.48-15.54) and persistent SIRS (OR:2.9 CI95%: 1.1-7.8), were risk factors related with EPI. Bacteraemia, when compared with others EPI, showed the best accuracy in predicting significantly persistent organ failure (AUC:0.76, IC95%:0.64-0.88), ICU admission (AUC:0.80 IC95%:0.65-0.94), and death (AUC:0.73 CI95%:0.54-0.91); and for local complications including IPN (AUC:0.72 CI95%:0.53-0.92) as well. Besides, it was also needed for an interventional procedure against necrosis (AUC:0.74 IC95%: 0.57-0.91). When bacteraemia and IPN occurs, bacteraemia preceded infected necrosis in all cases. On multivariate analysis, risk factor for IPN were lung infection (OR:6.25 CI95%1.1-35.7 p = 0.039) and TPN (OR:22.0CI95%:2.4-205.8, p = 0.007), and for mortality were persistent SIRS at first week (OR: 22.9 CI95%: 2.6-203.7, p = 0.005) and Lung infection (OR: 9.7 CI95%: 1.7-53.8). CONCLUSION In our study, EPI, played a role in predicting the severity and local complications in acute pancreatitis.

Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches: Autoimmune diseases and pancreatic cancer risk

Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene‐disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case–control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58–0.93) which decreased in subjects having ≥2 AIDs (OR = 0.39, 95%CI 0.21–0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19–0.89, and OR = 0.73, 95%CI 0.53–1.00, respectively). Several inflammatory‐related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC.

Initial experience in sentinel lymph node detection in pancreatic cancer

BACKGROUND The local recurrence of pancreatic cancer is around 30% when complete resection can be achieved. Extended lymphatic resections may improve survival, but increases severe morbidity. As accurate patient selection should be mandatory, a new method is presented for pancreatic sentinel lymph node (SLN) detection with lymphoscintigraphy and gamma probe. MATERIALS AND METHODS Seven patients with cT2N0M0 pancreatic head cancer were enrolled between 2009 and 2012 in this prospective study. One day prior to surgery, preoperative lymphoscintigraphy with echoendoscopic intratumoural administration of Tc(99m)-labelled nanocolloid was performed, with planar and SPECT-CT images obtained 2h later. Gamma probe detection of SLN was also carried out during surgery. RESULTS Radiotracer administration was feasible in all patients. Scintigraphy images showed inter-aortocaval lymph nodes in 2 patients, hepatoduodenal ligament lymph nodes in 1, intravascular injection in 3, intestinal transit in 5, and main pancreatic duct visualisation in 1. Surgical resection could only be achieved in 4 patients owing to locally advanced disease. Intraoperative SLN detection was accomplished in 2 patients, both with negative results. Only in one patient could SLN be confirmed as truly negative by final histopathological analysis. CONCLUSIONS This new method of pancreatic SLN detection is technically feasible, but challenging. Our preliminary results with 7 patients are not sufficient for clinical validation.