Solid pseudopapillary neoplasms of the pancreas: Multicenter Vasepa study.

INTRODUCTION: Solid pseudopapillary tumors (SPT) of the pancreas are rare exocrine neoplasms of the pancreas. Correct preoperative diagnosis is not always feasible. The treatment of choice is surgical excision. These tumors have a good prognosis with a high disease-free survival rate. OBJECTIVE: To describe the clinicopathological and radiological characteristics as well as short- and long-term follow-up results of patients who have undergone SPT resection. METHODS: Multicenter retrospective observational study in patients with SPT who had undergone surgery from January 2000-January 2022. We have studied preoperative, intraoperative, and postoperative variables as well as the follow-up results (mean 28 months). RESULTS: 20 patients with histological diagnosis of SPT in the surgical specimen were included. 90% were women; mean age was 33.5 years (13-67); 50% were asymptomatic. CT was the most used diagnostic test (90%). The most frequent location was body-tail (60%). Preoperative biopsy was performed in 13 patients (65%), which was correct in 8 patients. Surgeries performed: 7 distal pancreatectomies, 6 pancreaticoduodenectomies, 4 central pancreatectomies, 2 enucleations, and 1 total pancreatectomy. The R0 rate was 95%. Four patients presented major postoperative complications (Clavien-Dindo > II). Mean tumor size was 81 mm. Only one patient received adjuvant chemotherapy. With a mean follow-up of 28 months, 5-year disease-free survival was 95%. CONCLUSION: SPT are large, usually located in the body-tail of the pancreas, and more frequent in women. The R0 rate obtained in our series is very high (95%). The oncological results are excellent.

Hospitalization Trends for Acute Appendicitis in Spain, 1998 to 2017.

The incidence of acute appendicitis decreased in Western countries from 1930 to at least the early 1990s, when epidemiological data started becoming scarcer. This study aimed to assess the trend in annual hospitalizations for acute appendicitis in all people Spain for a 20-year period between 1998 and 2017. This observational study analyzing direct age-standardized hospital admission rates by gender and age group (0-14 years, 15-34 years, 35-44 years, 45-64 years, and ≥65 years). Joinpoint regression models were fitted to evaluate changes in trends. There were 789,533 emergency hospital admissions for acute appendicitis between 1998 and 2017: 58.9% in boys and men and 41.1% in girls and women. Overall, there was a significant increase in admissions for this cause from 1998 to 2009, with an annual percent change (APC) of 0.6%. Following the peak in 2009, admission rates decreased by around 1.0% annually until 2017. The length of hospital stay gradually decreased from 4.5 days in 1998 to 3.4 days in 2017. The trends in hospital admissions for acute appendicitis in Spain changed over the study period, decreasing from 2009, especially in people younger than 35 years.

Impact of Laparotomy and Intraperitoneal Hyperthermic Instillation (LIHI) on the oxaliplatin pharmacokinetics after intravenous administration in Wistar rats.

PURPOSE: In peritoneal metastasis condition, the fact that most of the disease is limited to the peritoneal cavity laid the foundations for a surgical treatment, including intraperitoneal hyperthermic chemotherapy (HIPEC). The aim of this study was to evaluate the impact of the surgical procedures implied in open HIPEC technique, referred to laparotomy procedures followed by an intraperitoneal hyperthermic instillation (LIHI) on oxaliplatin tissue distribution and elimination. To delimit the influence of this procedure alone, oxaliplatin was administered as an intravenous (iv) bolus in both groups. METHODS: An experimental model in Wistar rats was employed, and LIHI was evaluated as a dichotomous covariate by using a population pharmacokinetic (PK) approach. Rats were randomized in two groups receiving 1.5 mg iv oxaliplatin alone or 1.5 mg iv oxaliplatin under LIHI conditions, carrying out a hyperthermic 5% dextrose instillation. The oxaliplatin plasma concentrations were characterized by an open two-compartment PK model. RESULTS: Results concluded that surgical conditions affect the oxaliplatin elimination and distribution from blood to peripheral tissues, increasing the systemic drug exposure. Concretely, oxaliplatin peripheral volume of distribution, and clearance decreased by 48.6% and 55.3%, respectively, compared to the control group that resulted in a two-fold increase of the area under the concentration time curve. CONCLUSIONS: Comparison in clinical practice of oxaliplatin PK parameters obtained after iv administrations with those obtained after HIPEC interventions must be done carefully. This would limit the use of iv PK parameters to simulate new scenarios for oxaliplatin in HIPEC.

[Adverse events in ambulatory surgical procedures]. / Efectos adversos en cirugía mayor ambulatoria.

OBJECTIVE: To assess the incidence of adverse events and patients with adverse events in ambulatory surgical procedures and to compare it with that of other studies. MATERIAL AND METHOD: Historical cohort study. The scope of the study was the ambulatory surgical procedures unit of a university hospital. All general surgery department patients seen in this unit during the year 2005 were included. RESULTS: The incidence of patients with adverse events directly related to hospital care was of 3% (95% CI, 0.9-5). Of the adverse events identified 5 were considered slight, 3 moderate and none were considered serious. All the moderate ones were considered unavoidable and of slight, only the one was avoidable. Six of the adverse events were associated to a procedure, one due to hospital infections and one with other causes. There was an increase in hospital stay due to 75% of the adverse events, and 25% of them affected admission. CONCLUSIONS: The incidence of adverse events related to medical care in the Spanish hospitals is similar to those found in the studies carried out in American and European countries using the same methodology. The surgical area is considered a high risk unit. However, ambulatory surgical procedures reduce these risks, in such a way that the incidence is far below that of surgery department. Therefore, besides improving the technical efficiency of the clinical services, it is safer for the patients.

Brain cholinergic impairment in liver failure.

The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (~30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, remains unaffected. In agreement with the human data, AChE activity in brain cortical extracts of bile duct ligated (BDL) rats was increased (~20%) compared to controls. A hyperammonemic diet did not result in any further increase of AChE levels in the BDL model, and no change was observed in hyperammonemic diet rats without liver disease. Portacaval shunted rats which display increased levels of cerebral ammonia did not show any brain cholinergic abnormalities, confirming that high ammonia levels do not play a role in brain AChE changes. A selective increase of tetrameric AChE, the major AChE species involved in hydrolysis of acetylcholine in the brain, was detected in both cirrhotic humans and BDL rats. Histological examination of BDL and non-ligated rat brains shows that the subcellular localization of both AChE and choline acetyltransferase, and thus the accessibility to their substrates, appears unaltered by the pathological condition. The BDL-induced increase in AChE activity was not parallelled by an increase in mRNA levels. Increased AChE in BDL cirrhotic rats leads to a pronounced decrease (~50-60%) in the levels of acetylcholine. Finally, we demonstrate that the AChE inhibitor rivastigmine is able to improve memory deficits in BDL rats. One week treatment with rivastigmine (0.6 mg/kg; once a day, orally, for a week) resulted in a 25% of inhibition in the enzymatic activity of AChE with no change in protein composition, as assessed by sucrose density gradient fractionation and western blotting analysis. In conclusion, this study is the first direct evidence of a cholinergic imbalance in the brain as a consequence of liver failure and points to the possible role of the cholinergic system in the pathogenesis of hepatic encephalopathy.

Reelin is overexpressed in the liver and plasma of bile duct ligated rats and its levels and glycosylation are altered in plasma of humans with cirrhosis.

Reelin is an extracellular matrix protein secreted by a variety of cell types in both embryonic and adult tissues, including the liver. However, the physiological significance of Reelin in normal and cirrhotic liver has thus far not been elucidated. We have investigated Reelin levels in the liver and plasma of bile duct ligated (BDL) rats. We observe a 115% increase in full-length Reelin and its 310- and 180-kDa fragments in liver extracts from BDL rats, compared to sham-operated controls (p = 0.005). The overall increase in protein levels was associated with a 30% increase of Reelin transcripts (p = 0.03). Immunohistochemical analysis demonstrated that hepatic stellate cells are the major source of Reelin in the injured liver. Increased liver Reelin in BDL rats leads to a pronounced 165% increase in the plasma levels (p < 0.001), particularly in the less abundant 180-kDa fragment (300% increase; p < 0.001). The data provides evidence that a fraction of plasma Reelin is synthesized in the liver. In human subjects suffering liver cirrhosis the level of the 180-kDa fragment was also increased by 140% in the plasma (p < 0.001). Analysis of Reelin glycosylation by lectin binding demonstrated that the 180- and predominant 310-kDa Reelin fragments in the plasma of cirrhotic patients are differentially glycosylated compared to non-diseased control subjects. The data show that Reelin is up-regulated in experimental liver cirrhosis and that its levels and glycosylation are altered in plasma from patients with cirrhosis, thereby supporting that Reelin is involved in the pathogenesis of liver disease.

Effectiveness of a physician-oriented feedback intervention on inappropriate hospital stays.

OBJECTIVE: To evaluate the effectiveness of a combined intervention to reduce inappropriate hospital stays. DESIGN: Quasi-experimental pre-test/post-test with a non-equivalent control group. SETTING: Three teaching hospitals in the National Health System in Alicante, Spain. STUDY PARTICIPANTS: Intervention group (2 Surgical Units with 1451 hospital stays) and control group (1 Surgical Unit with 1268 hospital stays). INTERVENTION: Structured oral presentation followed by direct feedback to surgeons about their own percentages of inappropriate stays and daily evaluation of appropriateness by the surgeons during their rounds. MAIN OUTCOME MEASURES: Reduction in the percentage of inappropriate stays identified by the Appropriateness Evaluation Protocol during the intervention period compared to the basal period. RESULTS: The intervention group reduced its percentage of inappropriate stays from 14.3% to 7.9% (absolute reduction: -6.40; 95% CI -10.7 to -2.14; relative reduction: 44.8%), while no changes occurred in the control group. The reduction was in the number of inappropriate stays attributable to the patients' medical management that went from 12.7% to 5.8% (absolute reduction: -6.92; 95% CI -10.90 to -2.92), while no significant changes occurred in inappropriate stays due to other causes. CONCLUSIONS: A combined intervention of feedback and physician participation in appropriateness evaluations is effective in reducing the percentage of inappropriate hospital stays, particularly those attributable to conservative medical patterns at discharge.

Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis.

Studies of the pathogenesis of hepatic encephalopathy are hampered by the lack of a satisfactory animal model. We examined the neurological features of rats after bile duct ligation fed a hyperammonemic diet (BDL+HD). Six groups were studied: sham, sham pair-fed, hyperammonemic, bile duct ligation (BDL), BDL pair fed, and BDL+HD. The BDL+HD rats were made hyperammonemic via an ammonia-containing diet that began 2 weeks after operation. One week later, the animals were sacrificed. BDL+HD rats displayed an increased level of cerebral ammonia and neuroanatomical characteristics of hepatic encephalopathy (HE), including the presence of type II Alzheimer astrocytes. Both BDL and BDL+HD rats showed activation of the inflammatory system. BDL+HD rats showed an increased amount of brain glutamine, a decreased amount of brain myo-inositol, and a significant increase in the level of brain water. In coordination tests, BDL+HD rats showed severe impairment of motor activity and performance as opposed to BDL rats, whose results seemed only mildly affected. In conclusion, the BDL+HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances.

Changes in liver and plasma acetylcholinesterase in rats with cirrhosis induced by bile duct ligation.

Classical studies of cholinesterase activity during liver dysfunction have focused on butyrylcholinesterase (BuChE), whereas acetylcholinesterase (AChE) has not received much attention. In the current study, liver and plasma AChE levels were investigated in rats with cirrhosis induced after 3 weeks of bile duct ligation (BDL). BDL rats showed a pronounced decrease in liver AChE levels (approximately 50%) compared with sham-operated (non-ligated, NL) controls; whereas liver BuChE appeared unaffected. A selective loss of tetrameric (G4) AChE was detected in BDL rats, an effect also observed in rats with carbon tetrachloride-induced cirrhosis. In accordance, SDS-PAGE analysis showed that the major 55-kd immunoreactive AChE band was decreased in BDL as compared with NL. A 65-kd band, attributed in part to inactive AChE, was increased as became the most abundant AChE subunit in BDL liver. The overall decrease in AChE activity in BDL liver was not accompanied by a reduction of AChE transcripts. The loss of G4 was also reflected by changes observed in AChE glycosylation pattern attributable to different liver AChE forms being differentially glycosylated. BDL affects AChE levels in both hepatocytes and Kupffer cells; however, altered AChE expression was mainly reflected in an alteration in hepatocyte AChE pattern. Plasma from BDL rats had approximately 45% lower AChE activity than controls, displaying decreased G4 levels and altered lectin-binding patterns. In conclusion, the liver is an important source of serum AChE; altered AChE levels may be a useful biomarker for liver cirrhosis.

Animal models in the study of episodic hepatic encephalopathy in cirrhosis.

The availability of an animal model is crucial in studying the pathophysiological mechanisms of disease and to test possible therapies. Now, there are several models for the study of liver diseases, but there still remains a lack of a satisfactory animal model of chronic liver disease with hepatic encephalopathy (HE) and abnormalities in nitrogen metabolism, as seen in humans. In rats, two models of chronic HE are widely used: rats after portacaval anastomosis (PCA) and rats with chronic hyperammonemia. The first one mimics the situation induced in cirrhosis by collateral circulation, and has the problem of the absence of hepatocellular injury. The model of hyperammonemia is useful to study the effect of ammonia as a brain toxic substance, but also lacks liver failure. Bile-duct ligation has been used to induce cirrhosis and could also be a model of HE, probably with the addition of a precipitant factor. An ideal model of HE in chronic liver disease must have liver cirrhosis and a precipitant factor of HE; it must also show neuropathological characteristic findings of HE, neurochemical alterations in the main pathways impaired in these complications of cirrhosis, and low-grade brain edema.

[Inappropriate hospitalization use in general surgery wards. Magnitude, associated factors and causes]. / Uso inadecuado de la hospitalización en cirugía general. Magnitud, factores asociados y causas.

OBJECTIVE: To determine the proportion of inappropriate days of hospitalization in the general surgery wards of three university hospitals, its causes, and associated factors. MATERIAL AND METHOD: We concurrently reviewed 596 days of hospitalisation during a 1-week period in 2000, using the Appropriateness Evaluation Protocol (AEP). The association among inappropriate days of hospital stay and independent variables was evaluated using bivariable and multivariable methods. Finally, the causes for inappropriate hospitalization use were analyzed. RESULTS: The percentage of inappropriate days was 17.6%, with no significant differences among the hospitals (21.5%, 12.5% and 17.5%). Inappropriate days were associated with the weekend (odds ratio [OR] = 2.1, scheduled admissions (OR = 2.9), hospital stay of more than 1 week (OR:2.3), the last third of the hospital stay (OR: 3.7), and inappropriate admission (OR: 2.1). The main causes of inappropriate hospital stays were organizational problems in the hospital or in the clinical management of discharge. CONCLUSIONS: Inappropriate days of hospitalization represent a considerable percentage of hospitalization in surgery wards. The main reasons for inappropriate days are problems with surgical and discharge planning and factors that depend on the organization of the surgery departments and other related departments in the hospital.