Liver-targeted nanoparticles delivering nitric oxide reduce portal hypertension in cirrhotic rats.

Nitric oxide (NO) is a small vasodilator playing a key role in the pathogenesis of portal hypertension. Here, we assessed the potential therapeutic effect of a NO donor targeted to the liver by poly(beta-amino ester) nanoparticles (pBAE NPs) in experimental cirrhosis. Retinol-functionalized NO donor pBAE NPs (Ret pBAE NPs) were synthetized with the aim of actively targeting the liver. Administration of Ret pBAE NPs resulted in uptake and transfection by the liver and spleen. NPs were not found in other organs or the systemic circulation. Treatment with NO donor Ret pBAE NPs (30 mg/ kg body weight) significantly decreased aspartate aminotransferase, lactate dehydrogenase and portal pressure (9.75 ± 0.64 mmHg) compared to control NPs (13.4 ± 0.53 mmHg) in cirrhotic rats. There were no effects on mean arterial pressure and cardiac output. Liver-targeted NO donor NPs reduced collagen fibers and steatosis, activation of hepatic stellate cells and mRNA expression of profibrogenic and proinflammatory genes. Finally, Ret pBAE NPs displayed efficient transfection in human liver slices. Overall, liver-specific NO donor NPs effectively target the liver and mitigated inflammation and portal hypertension in cirrhotic rats. The use of Ret pBAE may prove to be an effective therapeutic strategy to treat advanced liver disease.

Validation of the Back-table Graft Arterial Anastomosis between the Splenic Artery and Superior Mesenteric Artery: Arterial Complications after a 21-year Single-center Experience of Pancreas Transplantation.

OBJECTIVE: To determine the role of the arterial splenomesenteric anastomosis (ASMA) vascular reconstruction technique in terms of arterial vascular complications in pancreas transplant (PT) recipients. SUMMARY BACKGROUND DATA: The ASMA technique was first described in 1992 by Hospital Clínic Barcelona group. Regardless that the iliac Y-graft technique is the most frequently used worldwide, evidence of arterial complications and implications of using a different back-table reconstruction is conspicuously absent in the literature. METHODS: Descriptive review of 407 PTs performed at a single center (1999-2019) by analyzing the type of arterial reconstruction technique, focusing on ASMA. The endpoints were the management of arterial complications and long-term patient and graft survival. RESULTS: ASMA was performed in 376 cases (92.4%) and a Y-graft in 31 cases (7.6%). A total of 34 arterial complications (8.3%) were diagnosed. In the ASMA group (n=30, 7.9%) they comprised: 15 acute thrombosis; 4 stenosis; 1 pseudoaneurysm and 10 diverse chronic arterial complications while in the Y-graft group (n=4, 12.9%) 3 acute thrombosis and 1 chronic artery-duodenal fistula occurred. Graft salvage was achieved in 16 patients (53.3%) from the ASMA group and in 2 (50%) from the Y-graft. After a median follow-up of 129.2 (IQR 25-75%, 77.2 -182) months the overall graft and patient survival for the whole cohort at 1, 5, and 10 years was 86.7%, 79.5%, 70.5%, and 98.5%, 95.3%, 92.5%, respectively. CONCLUSIONS: The ASMA proves to be a safe and more easily reproducible technique and should therefore be considered for first-line back-table reconstruction in the PT population.

Current Trends in Organ Preservation Solutions for Pancreas Transplantation: A Single-Center Retrospective Study.

Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000-2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 7.5% for University of Wisconsin (UW) group (n = 267), 10.8% of Celsior (CS) group (n = 83), 28.5% of Histidine-Tryptophan-Ketoglutarate (HTK) group (n = 7), and none for Institut Georges Lopez-1 (IGL-1) group (n = 23). The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1 year using UW and IGL-1, and at 3 and 5 years using IGL-1 (p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions.

Physical Bases, Indications, and Results of the Use of Magnets in Digestive Surgery: A Narrative Review.

Background: The use of magnetic devices in digestive surgery has been a matter of debate in recent years. The aim of this review was to describe the physical bases, indications, and results of the use of magnets in digestive surgery. Methods: A review of the literature was performed using Scopus, PubMed, ScienceDirect, and SciELO databases considering as inclusion criteria all articles published since 2007 to date, describing the physical basis of magnetic assisted surgery and those that describe the surgical procedure, including case reports, as well as, articles on humans and experimental animals. Results: Sixty-four studies were included, 15 detailing aspects on the physical basis and 49 about indications and results. Magnets are currently used to perform fixed traction, mobilizing structures, and anastomosis in humans and experimental animals. Conclusions: The use of magnets in digestive surgery has shown good results, and no complications arising from their use have been reported. However, more prospective and randomized studies that compare magnetic surgery and conventional techniques are needed.

Breaking the limits of experimental pancreas transplantation: Working toward the clinical ideal graft.

Pancreas transplantation is, at present, the only curative treatment for type-1 diabetes that maintains normoglycemia thus avoiding complications arising from poor glycemic control. Despite its great benefits, the number of pancreas transplants has decreased significantly since its inception in the late 1960s, largely due to demographic changes and the consequent suboptimal quality of donors. The selection criteria for pancreas donors mainly depend on morphological variables such as fatty infiltration, fibrosis, or edema, as well as both functional (amylase and lipase) and clinical variables of the donor. However, the final criterion in the decision-making process is the somewhat subjective assessment of a trained surgeon. That being said, the recent incorporation of graft perfusion machines into clinical practice seems to be changing the work dynamics of the donor organ retrieval team, facilitating decision-making based on objective morphological and functional criteria. Normothermic perfusion using perfusate with supplemental oxygen replicates near physiological parameters thus being a promising strategy for organ preservation. Nevertheless, optimum perfusion parameters are difficult to establish in pancreas transplantation given its complex vascular anatomy combined with an intrinsically low blood flow. The objective of this work is to analyze the results published in the recent literature relating to the considerations of ex-vivo normothermic graft perfusion machines and their usefulness in the field of pancreas transplantation.

Missing colorectal liver metastases: the surgical challenge.

BACKGROUND: New chemotherapy schemes have allowed for a better radiological response of unresectable colorectal liver metastases, leading to an interesting scenario known as a complete radiological response. The aim of this study was to review the current management of missing liver metastases (MLM) from the liver surgeon's point of view. METHODS: A systematic search was conducted on all publications of PubMed and Embase between 2003 and 2018. Meta-analysis was performed on MLM resected/unresected. Residual tumor or regrowth and relapse-free survival were used as evaluation indices. RESULTS: After literature search, 18 original articles were included for analysis. The predictive factors for MLM are type and duration of chemotherapy and size and number of lesions. Magnetic resonance is the most sensitive preoperative technique. Regarding clinical management, liver surgery is deemed the fundamental pillar in the therapeutic strategy of these patients. Meta-analysis due to data heterogeneity was inconclusive. CONCLUSIONS: Depending on the clinical context, MLM monitoring appears to be a valid therapeutic alternative. Nevertheless, prospective randomized clinical studies are needed.

Laparoscopic versus open hemihepatectomy: comprehensive comparison of complications and costs at 90 days using a propensity method.

Laparoscopic hemihepatectomy (LHH) may offer advantages over open hemihepatectomy (OHH) in blood loss, recovery, and hospital stay. The aim of this study is to evaluate our recent experience performing hemihepatectomy and compare complications and costs up to 90 days following laparoscopic versus open procedures. Retrospective evaluation of patients undergoing hemihepatectomy at our center 01/2010-12/2018 was performed. Patient, tumor, and surgical characteristics; 90-day complications; and costs were analyzed. Inverse probability of treatment weighting (IPTW) was used to balance covariates. A total of 141 hemihepatectomies were included: 96 OHH and 45 LHH. While operative times were longer for LHH, blood loss and transfusions were less. At 90 days, there were similar rates of liver-specific and surgical complications but fewer medical complications following LHH. Medical complications that arose with greater frequency following OHH were primarily pulmonary complications and urinary and central venous catheter infections. Complications at 90 days were lower following LHH (Clavien-Dindo grade ≥ III OHH 23%, LHH 11%, p = 0.130; Comprehensive Complication Index OHH 20.0 ± 16.1, LHH 10.9 ± 14.2, p = 0.001). While operating costs were higher, costs for hospital stay and readmissions were lower with LHH. Patients undergoing LHH experience a significant reduction in postoperative medical complications and costs, resulting in 90-day cost equity compared with OHH.

Hemoperitoneum and giant hepatic hematoma secondary to nasal melanoma metastases.

Nontraumatic hepatic haemorrhage is a rare emergency situation (< 1 %) that requires rapid diagnosis and treatment. Hepatocarcinoma and adenoma are the most common causes representing metastatic lesions a very small percentage. CT angiography is the gold standard to establish the diagnosis, allowing ruling out active bleeding. We report the case of a 58-year-old male presented at our emergency department with abdominal pain and a palpable mass in the epigastrium without a traumatic history or another clinic.

Normothermic perfusion and outcomes after liver transplantation.

Ischemia has been a persistent and largely unavoidable element in solid organ transplantation, contributing to graft deterioration and adverse post-transplant outcomes. In liver transplantation, where available organs arise with greater frequency from marginal donors (i.e., ones that are older, obese, and/or declared dead following cardiac arrest through the donation after circulatory death process), there is increasing interest using dynamic perfusion strategies to limit, assess, and even reverse the adverse effects of ischemia in these grafts. Normothermic perfusion, in particular, is used to restore the flow of oxygen and other metabolic substrates at physiological temperatures. It may be used in liver transplantation both in situ following cardiac arrest in donation after circulatory death donors or during part or all of the ex situ preservation phase. This review article addresses issues relevant to use of normothermic perfusion strategies in liver transplantation, including technical and logistical aspects associated with establishing and maintaining normothermic perfusion in its different forms and clinical outcomes that have been reported to date.

Role of Kupffer cells in the progression of CRC liver metastases after the first stage of ALPPS.

Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been suggested as a potential therapy for extensive bilobar liver tumors, although in some circumstances this technique may induce tumor progression, a fact still not well studied. Our aim was to study tumor hepatic progression induced by the first step of ALPPS in a WAG/Rij rat syngenic model of metastatic colorectal carcinoma by subcapsular CC531 cell line inoculation. ALPPS induced: tumor progression on deportalized lobe and metastases; expression of hepatic vasculogenic factors (HIF1-α and VEGF); and a dramatic increase of Kupffer cells (KCs) and tumor-associated macrophages (TAMs). Interestingly, KCs expressed COX-2 (M1 polarization), while TAMs expressed mainly arginase-1 (M2 polarization). ALPPS also induced a decrease of tumor-infiltrating lymphocytes and an increase of intrahepatic T lymphocytes. Thus, ALPPS technique seems to induce a hypoxic environment, which enhances hepatic HIF1-α and VEGF expression and may promote KCs and TAMs polarization. Consequently, the regenerative stimulus seems to be driven by a pro-inflammatory and hypoxic environment, in which M1 intrahepatic macrophages expressing COX-2 and T-Lymphocytes play a key role, facts which may be related with the tumor progression observed.

Histopathological and Immunohistochemical Analysis of the Use of Collagen Dressing as a Reinforcement of Esophagic Anastomosis in a Rat Experimental Model. / Análisis histopatológico e inmunohistoquímico del uso del apósito de colágeno como refuerzo de anastomosis esofágica en un modelo experimental en rata.

INTRODUCTION: One of the most severe complications after esophaguectomy is anastomotic dehiscence. The use of collagen sponges could be an effective way to resolve this complication. Our objective was to perform an experimental model of esophageal anastomosis in rats to study these mechanisms. METHODS: A total of 50 Sprague-Dawley rats were used divided into 2 groups, Tachosil® group (n=25) and control group (n=25). After the section of the abdominal esophagus a single-layer esophago-gastric anastomosis was performed reinforced with 1cm of Tachosil® wrapping the anastomosis in group 1. A functional study was performed using manometry as well as histopathological and immunohistochemical studies for angiogenic, fibrogenic and growth factors. RESULTS: The mortality in our series was 8% in the collagen dressing group, compared to 36% in the control group. When esophageal manometry was performed, the dehiscence pressure was higher in the reinforced anastomosis, On microscopical analysis, in the collagen dressing group a profuse inflammatory reaction with abundant neutrophils and macrophages surrounded by a connective matrix with fibroblasts and blood vessels was observed, The expression of VEGF, FGF1 and FGF2 was noticeably higher in the collagen dressing group. CONCLUSIONS: These results show that the application of collagen dressing facilitates tissue reparation phenomena, and therefore could be very useful as a reinforcement of esophago-gastric anastomosis to prevent dehiscence.

Giant symptomatic pancreatic cyst mimicking a malignant tumor.

BACKGROUND: Pancreatic cystic lesions found in the literature are estimated between 2.6-19.6%. These neoplasms are almost exclusively benign tumors, and rarely become malignant. The aim of this paper was to report a feasible total pancreatectomy with portal resection in a giant pancreatic serous cystadenoma mimicking a malignant tumor. CASE PRESENTATION: A healthy 52-year-old female patient presented to us with a giant pancreatic cyst with unknown preoperative diagnosis and a secondary dilatation of the Wirsung duct, and unclear vascular invasion. The imaging assessment was not conclusive for malignancy. Furthermore, it was decided to perform a total pancreatectomy with portal vein resection and splenectomy. The pathological findings revealed a microcystic serous cystadenoma of 10 cm with abundant myxoid stromal degeneration and focal papillary proliferation without atypia. CONCLUSION: Unless the diagnosis of serous cystadenoma is certain, cystic tumors with inconclusive clinical and imaging features should be radically treated.

Utility of 18 fludeoxyglucose in preoperative positon-emission tomography-computed tomography (PET-CT) in the early diagnosis of exocrine pancreatic cancer: A study of 139 resected cases. / Utilidad de la 18-fluorodeoxiglucosa en la tomografía por emisión de positrones-tomografía computarizada (PET-TC) preoperatoria en el diagnóstico precoz del cáncer de páncreas exocrino: estudio en 139 casos resecados.

INTRODUCTION: In pancreatic ductal adenocarcinoma (PDA), surgical resection is the only curative treatment, but due to its late clinical presentation only 15-25% patients are candidates for curative resection. The aim of this prospective, single-center study is to determine the diagnostic utility of preoperative PET-CT for early detection of PDA and early panIN lesions. METHODS: We studied the histopathological features of PDA and different panIN lesions in 139 surgical samples from patients undergoing pancreatic resection (from 2010-2014), comparing these results with preoperative PET-CT and MDCT study. For tumor diagnosis in PET-CT maximum standard SUV 2.5 was used. Pancreatic baseline SUVmax is the maximum uptake of the radiotracer 18-2FDG on the ROI curve determined for the area of the normal pancreas after pathological reassessment with areas not affected by tumours or preneoplastic lesions. Tumour Uptake Index is the ratio between the tumour SUVmax and pancreatic baseline SUVmax. RESULTS: Using an standard maximum SUV value of 2.5, PET-CT sensitivity was 77.7% (108 of the 139 cases) against 75.5% (105 of the 139 cases) of MDCT. But when we combined this value with maximum SUV of normal pancreatic tissue from each patient, PET-CT sensitivity improved its value to 94.9%. CONCLUSION: A combination of studies of PET-CT in tumor and non-tumor tissue of each patient might be a very useful diagnostic tool not only for preoperative diagnosis of PDA, but also for early panIN lesions.

Associated Liver Partition and Portal Vein Ligation (ALPPS) vs Selective Portal Vein Ligation (PVL) for Staged Hepatectomy in a Rat Model. Similar Regenerative Response?

Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage hepatectomy technique which can be associated with a hypertrophic stimulus on the future liver remnant (FLR) stronger than other techniques--such as portal vein ligation (PVL). However, the reason of such hypertrophy is still unclear, but it is suggested that liver transection combined with portal vein ligation (ALPPS) during the first stage of this technique may play a key role. The aim of this study is to compare the hypertrophic stimulus on the FLR and the clinical changes associated with both ALPPS and PVL in a rat surgical model. For this purpose, three groups of SD rats were used, namely ALPPS (n = 30), PVL (n = 30) and sham-treated (n = 30). The second stage of ALPPS (hepatectomy of the atrophic lobes), was performed at day 8. Blood and FLR samples were collected at 1, 24, 48 hours, 8 days and 12 weeks after the surgeries. ALPPS provoked a greater degree of hypertrophy of the FLR than the PVL at 48 hours and 8 days (p<0.05). The molecular pattern was also different, with the highest expression of IL-1ß at 24h, IL-6 at 8 days, and HGF and TNF-α at 48 hours and 8 days (p<0.05). ALPPS also brought about a mild proliferative stimulus at 12 weeks, with a higher expression of HGF and TGF-ß (p<0.05) than PVL. Clinically, ALPPS caused a significant liver damage during the first 48 hours, with a recovery of liver function at day 8. In conclusion, ALPPS seems to induce higher functional hypertrophy on the FLR than PVL at day 8. Such regenerative response seems to be leaded by a complex interaction between pro-mitogenic (IL-6, HGF, TNF-α) and antiproliferative (IL1-ß and TGF-ß) cytokines.

[HELLP syndrome with severe liver dysfunction: a presentation of three cases]. / Síndrome de HELLP con disfunción hepática severa: presentación de cuatro casos.

UNLABELLED: HELLP syndrome (HS) occurs in 0.5-0.9% of pregnant women. According to the Tennessee criteria, it is characterised by haemolytic anaemia, thrombopenia and multi-organ dysfunction. The purpose of this article is to present the cases of four pregnant women diagnosed with HS with severe liver involvement. PATIENTS AND METHOD: We present the cases of 4 pregnant women of 24, 27, 28 and 36 weeks gestation, respectively. Pregnancy was terminated by urgent Caesarean section in all 4 cases. The first case required a right hepatectomy, with a good post-operative outcome; the second patient developed fulminant liver failure, dying due to multi-organ failure while waiting for a liver transplant. The third patient progressed satisfactorily with conservative medical treatment. The fourth patient required two livers transplants, being discharged from hospital three months later. CONCLUSIONS: When faced with the clinical suspicion of a HS it is essential to rule out a liver haematoma, since the treatment of choice depends on its clinical-radiological severity. If there is a rupture of the haematoma, urgent surgery is essential and, in the case of severe liver failure, a liver transplant is indicated.

Hemorrhagic cholecystitis and hemobilia: two infrequent complications of systemic lupus erythematosus.

INTRODUCTION: the patients affected by systemic lupus erythematosus (SLE) often suffer gastrointestinal symptoms. The differential diagnosis should contemplate pathology of the gall bladder. We present the case of a patient with hemorrhagic lithiasic cholecystitis and hemobilia. CASE REPORT: 24 year old female diagnosed with SLE under treatment with Sintrom®, Dacortin® and Dolquine® that presented acute lithiasic cholecystitis and hemobilia with a distal calculus. Cholecystectomy and aperture of the ductus choledochus were performed allowing to confirm the hemobilia and to extract the calculus. DISCUSSION: The treatment of cholecystitis in the patients with SLE is controversial due to the fact that most reviewed cases have been solved with cholecystectomy, or in other cases with conservative treatment with corticosteroids. We believe that the presence of cholelithiasis in a patient with SLE with pain on the right hypochondrium and ultrasound confirming the suspicion of cholecystitis demands a surgical treatment since the cause may be vascular, lithiasic or combined. Besides, the possible complications will not respond to pharmaceutical treatment.

[Changes in the diagnosis and therapeutic management of hepatic trauma. A retrospective study comparing 2 series of cases in different (1997-1984 vs. 2001-2008)]. / Cambios en el manejo diagnóstico-terapéutico del traumatismo hepático. Estudio retrospectivo comparando 2 series de casos en periodos diferentes (1997-1984 vs. 2001-2008).

INTRODUCTION: We present a series of 146 cases of hepatic trauma (HT) treated in our hospital over a period of 8 yearsm (2001-2008), and comparing it with a previous series of 92 cases (1977-1984). MATERIAL AND METHOD: The mean age in the current series was 28.6 years and the majority were male. The closed traumas were mainly penetrating, with the most frequent cause being road traffic accidents. RESULTS: The American Association for the Surgery of Trauma (AAST) classification was used to evaluate the grade of the hepatic injury. Associated abdominal and /or extra-abdominal injuries were seen in 79.5% of the patients, with the most frequent being chest trauma, compared to bone fractures in the previous series. The most common associated intra-abdominal injury was the spleen in both series. The most used diagnostic technique in the current series was abdominal CT. Simple peritoneal puncture and lavage (PLP) were the most used examinations used in the previous series. Non-surgical treatment (NST) was given in 98 cases and the surgery was indicated in the remaining 48. In the previous series, 97.8% of patients were operated on. In the current series, on the 15 patients with severe liver injuries, 5 right hepatectomies, 2 segmentectomies and 6 packing compressions were performed, with the remaining two dying during surgery due to hepatic avulsion. The overall mortality was 3.4%, being 1% in the NST group and 8.3% in the surgical patients. In the previous series, the overall mortality was 29.3%. CONCLUSIONS: The key factor for using NST is to control haemodynamic stability, leaving surgical treatment for haemodynamically unstable patients.