Ética médica y atención a pacientes en estadio terminal en el nivel primario de atención / Medical Ethics and End-stage Patient Care at the Primary Care Level

Introducción: El artículo reflexiona sobre la naturaleza multidimensional y compleja de la ética y su relación con las ciencias médicas. Objetivo: Reflexionar sobre la atención a pacientes en estadio terminal desde el punto de vista de la ética médica para una atención médica integral en el primer nivel de atención. Métodos: estudio cualitativo; se emplearon análisis documental, sistematización, análisis y síntesis de publicaciones sobre la temática estudiada como métodos teóricos, para ello se valoran los criterios de autores y resultados que se expresan en artículos publicados. Se realizaron búsquedas, tanto en bases de datos estudiadas como en las plataformas de productos del Nacional Council for Biotechnology Information de la Nacional Library of Medicine of United States of America; y de Elsevier, esta última productora de Embase y Scopus, a través del motor de búsqueda Google Académico, en español e inglés, y sin límite de tiempo. Se emplearon los términos: ética médica, deontología médica, relación médico-paciente, paciente terminal y cuidados paliativos. Se excluyeron aquellos artículos que no habían sido revisados por pares o no mostraban el texto completo. Se revisó la información suministrada por cada fuente y se sintetizó. Conclusiones: En Cuba, la bioética avanza en la medida que lo permite la estrategia de Atención Primaria de Salud, con un Programa del Médico y Enfermera de la Familia resiliente y de valores humanos demostrados nacional e internacionalmente. Como reto se plantea estimular el debate entre saberes para generar cambios a favor de los pacientes, las familias, las comunidades y la sociedad(AU)

Introduction: The article reflects on the multidimensional and complex nature of ethics and its relationship to the medical sciences. Objective: To reflect on the care of terminally ill patients from the point of view of medical ethics for comprehensive medical care at the primary level of care. Methods: A qualitative study was carried out using documentary analysis, systematization, analysis and synthesis of publications on the subject studied as theoretical methods. For this purpose, the criteria of authors and results expressed in published articles were evaluated. Searches were carried out in Spanish and English through Google Scholar, and without time limit, both in the databases studied and in the product platforms of the National Council for Biotechnology Information of the National Library of Medicine of the United States of America and Elsevier. The terms: medical ethics, medical deontolog, physician-patient relationship, terminal patient and palliative care were used. Articles that were not peer-reviewed and those that did not show the full text were excluded. The information provided by each source was reviewed and synthesized. Conclusions: In Cuba, bioethics advances to the extent allowed by the Primary Health Care strategy, with a resilient Family Physician and Nurse Practitioner Program and human values demonstrated nationally and internationally. The challenge is to stimulate the debate between knowledge to generate changes in favor of patients, families, communities and society(AU)

Characterization of Mesothelin Glycosylation in Pancreatic Cancer: Decreased Core Fucosylated Glycoforms in Pancreatic Cancer Patients' Sera.

Currently, there are no reliable biomarkers for the diagnosis of pancreatic cancer (PaC). Glycoproteomic approaches that analyze the glycan determinants on specific glycoproteins have proven useful to develop more specific cancer biomarkers than the corresponding protein levels. In PaC, mesothelin (MSLN) is a neo-expressed glycoprotein. MSLN glycosylation has not been described and could be altered in PaC. In this work, we aimed to characterize MSLN glycans from PaC cells and serum samples to assess their potential usefulness as PaC biomarkers. First, we analyzed MSLN glycans from PaC cell lines and then we developed an enzyme-linked lectin assay to measure core fucosylated-MSLN (Cf-MSLN) glycoforms. MSLN glycans from PaC cells were analyzed by glycan sequencing and through Western blotting with lectins. All of the cell lines secreted MSLN, with its three N-glycosylation sites occupied by complex-type N-glycans, which were mainly α2,3-sialylated, core fucosylated and highly branched. The Cf-MSLN glycoforms were quantified on PaC serum samples, and compared with MSLN protein levels. The Cf-MSLN was significantly decreased in PaC patients compared to control sera, while no differences were detected by using MSLN protein levels. In conclusion, Cf-MSLN glycoforms were differently expressed in PaC, which opens the way to further investigate their usefulness as PaC biomarkers.

Microfibril associated protein 4 (MFAP4) is a carrier of the tumor associated carbohydrate sialyl-Lewis x (sLex) in pancreatic adenocarcinoma.

Late diagnosis of pancreatic ductal adenocarcinoma (PDA) is one of the reasons of its low 5-year survival rate and it is due to its unspecific symptoms during the first stages of the disease and the lack of reliable serological markers. Since PDA shows an altered glycan expression, here we have focused on finding novel potential biomarkers, namely glycoproteins that express the tumor associated carbohydrate structure sialyl-Lewis x (sLex), which is described in PDA. Through a glycoproteomic approach, we have analyzed target proteins containing sLex from PDA tissues by 2DE and immunodetection techniques, and have identified by mass spectrometry the protein MFAP4 as a carrier of sLex in PDA. MFAP4 showed a higher expression in PDA tissues compared with pancreatic control tissues. In addition, the colocalization of sLex over MFAP4 was found only in PDA and not in control pancreatic tissues. The analysis of MFAP4 expression in PDA cell lines and their secretome, in combination with immunohistochemistry of pancreatic tissues, revealed that MFAP4 was not produced by PDA cells, but it was found in the pancreatic extracellular matrix. The specificity of MFAP4 glycoform containing sLex in PDA tissues shows its relevance as a potential PDA biomarker. SIGNIFICANCE: Despite advances in the field of cancer research, pancreatic ductal adenocarcinoma (PDA) lacks of a specific and sensitive biomarker for its early detection, when curative resection is still possible before metastases arise. Thus, efforts to discover new PDA biomarkers represent the first line in the fight against the increase of its incidence reported in recent years. Glycan alterations on glycoconjugates, such as glycoproteins have emerged as a rich source for the identification of novel cancer markers. In the present work, we aimed to shed light on novel biomarkers based on altered glycosylation in PDA, in particular those glycoproteins of PDA tissues carrying the tumor carbohydrate antigen sialyl-Lewis x (sLex). Through a glycoproteomic approach, we have shown that the glycoprotein MFAP4 carries sLex in PDA tissues and not in control pancreatic tissues. MFAP4 is found in the extracellular matrix in PDA and although its role in cancer progression is unclear, its sLex glycoform could be a potential biomarker in pancreatic ductal adenocarcinoma.

Evolution of laparoscopic surgery in a high volume hepatobiliary unit: 150 consecutive pure laparoscopic hepatectomies. / Evolución de la cirugía laparoscópica en una unidad hepatobiliar de alto volumen: 150 hepatectomías laparoscópicas consecutivas.

INTRODUCTION: Compared to other surgical areas, laparoscopic liver resection (LLR) has not been widely implemented and currently less than 20% of hepatectomies are performed laparoscopically worldwide. The aim of our study was to evaluate the feasibility, and the ratio of implementation of LLR in our department. METHODS: We analyzed a prospectively maintained database of 749 liver resections performed during the last 10-year period in a single centre. RESULTS: A total of 150 (20%) consecutive pure LLR were performed between 2005 and 2015. In 87% of patients the indication was the presence ofprimary or metastatic liver malignancy. We performed 30 major hepatectomies (20%) and (80%) were minor resections, performed in all liver segments. Twelve patients were operated twice and 2 patients underwent a third LLR. The proportion of LLR increased from 12% in 2011 to 62% in the last year. Conversion rate was 9%. Overall morbidity rate was 36% but only one third were classified as severe. The 90-day mortality rate was 1%. Median hospital stay was 4 days and the rate of readmissions was 6%. CONCLUSIONS: The implementation of LLR has been fast with morbidity and mortality comparable to other published series. In the last 2 years more than half of the hepatectomies are performed laparoscopically in our centre.

[Liver resections as radical surgery for hepatic hydatidosis: results in 50 patients]. / Resultados de las resecciones hepáticas como tratamiento radical de la hidatidosis hepatica en 50 pacientes.

INTRODUCTION: Among several regions in the world hepatic hydatidosis can be considered endemic. Currently there are many available treatments for this disease, been surgery the most effective one. Surgical procedures can be divided in two main groups, radical and non-radical procedures. The goal of this work is to evaluate the morbidity, mortality and percentage of recurrence in patients treated with hepatectomies, comparing them with other publications. MATERIAL AND METHODS: This retrospective study was carried out in a series from Spain and Argentina. We analyzed the following data: sex, age, type of resection, associated surgical gestures, presence of liver disease, operative time, blood transfusion, morbidity, mortality, hospital stay, re-hospitalization, recurrence and follow up. Dindo--Clavien classification was used for complications, and International Hepato-Pancreato-Biliary Association (IHPBA) Brisbane classification for hepatectomies. Mortality was considered until 90 days after surgery. To evaluate the recurence we only included patients followed over 6 months. RESULTS: Indications for liver resections were performed in patients with cysts larger than 5 centimeters, multiple cysts, large cysts, with bile duct communicated or suspicion of this communication. Five patients required blood transfusions (10%) with a median for these 5 patients of 740 ml and 74 ml for the complete series. The median operative time was 186 minutes (range 45 to 1,050 minutes). Median hospital stay was 7.7 days. Monitoring more than 6 months was conducted in 38 patients. CONCLUSIONS: We believe that hepatic hydatid disease is a multifaceted disease and requires more than one therapeutic approach. Hepatectomy with complete resection of the parasite offers the possibility of doing so in a controlled and safe way by experienced hands, ensuring good results in the treatment of this disease.

Pure laparoscopic liver resection reduces surgical site infections and hospital stay. Results of a case-matched control study in 50 patients.

BACKGROUND: Laparoscopic resection is an emerging tool in surgical oncology, but its role in liver tumors is far from being universally accepted. METHODS: We designed a case-matched control study, comparing laparoscopic (LAP) vs. open hepatectomies (OP) performed in the same center during the same period of time. Fifty LAP were performed (34 liver metastases, 7 hepatocellular carcinomas, 2 hydatid cysts, and 5 benign tumors). Cases were compared with 100 OP matched according to: diagnosis, number of lesions, type of resection, age, ASA score, and ECOG performance status. We evaluated intraoperative and postoperative parameters, focusing on morbidity and mortality. RESULTS: Preoperative data were comparable in both groups. Operative features were similar in terms of overall morbidity 18 (36 %) vs. 36 (36 %), p = 1; intraoperative bleeding, 401 (18-2192) vs. 475 (20-2000) mL, p = 0.89; pedicle clamping, 37 (74 %) vs. 88 (88 %), p = 0.55; margin, 0.6 (0-5) vs. 0.65 (0-5) cm, p = 0.94, and mortality p = 0.65 for the LAP and OP groups, respectively. There was a significant decrease in surgical site infections 1 (2 %) vs. 18 (18 %) p = 0.007 in the LAP group. Operative time was longer: 295 (120-600) vs. 200 (70-450) min (p = 0.0001), and hospital stay significantly shorter: 4 (1-60) vs. 7 (3-44) days, p = 0.0001 with less readmissions (0 vs. 7 %) in the LAP. DISCUSSION: In adequately selected patients, laparoscopic hepatectomy is feasible, safe, shortens hospital stay, and decreases surgical site infections.

Resultados de las resecciones hepáticas como tratamiento radical de la hidatidosis hepatica en 50 pacientes / [Liver resections as radical surgery for hepatic hydatidosis: results in 50 patients].

INTRODUCTION: Among several regions in the world hepatic hydatidosis can be considered endemic. Currently there are many available treatments for this disease, been surgery the most effective one. Surgical procedures can be divided in two main groups, radical and non-radical procedures. The goal of this work is to evaluate the morbidity, mortality and percentage of recurrence in patients treated with hepatectomies, comparing them with other publications. MATERIAL AND METHODS: This retrospective study was carried out in a series from Spain and Argentina. We analyzed the following data: sex, age, type of resection, associated surgical gestures, presence of liver disease, operative time, blood transfusion, morbidity, mortality, hospital stay, re-hospitalization, recurrence and follow up. Dindo--Clavien classification was used for complications, and International Hepato-Pancreato-Biliary Association (IHPBA) Brisbane classification for hepatectomies. Mortality was considered until 90 days after surgery. To evaluate the recurence we only included patients followed over 6 months. RESULTS: Indications for liver resections were performed in patients with cysts larger than 5 centimeters, multiple cysts, large cysts, with bile duct communicated or suspicion of this communication. Five patients required blood transfusions (10

) with a median for these 5 patients of 740 ml and 74 ml for the complete series. The median operative time was 186 minutes (range 45 to 1,050 minutes). Median hospital stay was 7.7 days. Monitoring more than 6 months was conducted in 38 patients. CONCLUSIONS: We believe that hepatic hydatid disease is a multifaceted disease and requires more than one therapeutic approach. Hepatectomy with complete resection of the parasite offers the possibility of doing so in a controlled and safe way by experienced hands, ensuring good results in the treatment of this disease.

[Celiac artery stenosis and cephalic duodenopancreatectomy: an undervalued risk?]. / La estenosis del tronco celiaco y duodenopancreatectomía cefálica: ¿un riesgo infravalorado?

INTRODUCTION: Significant celiac trunk or artery stenosis (CAS) is normally asymptomatic. However, when the arteries of the pancreatoduodenal arcade are occluded, it could trigger a visceral ischaemia. The objective of this study is to determine whether preoperative CAS is a risk factor for developing complications in patients subjected to duodenopancreatectomy (DPC). MATERIAL AND METHODS: We have retrospectively analysed 58 consecutive patients subjected to DPC. We have associated significant CAS with post-surgical outcome. In all cases a 16-channel multidetector computed tomography (MDCT) in three hepatic phases was performed. We have reviewed the pre-surgical MDCT focusing on the morphology of the celiac artery (CA), particularly in the presence or absence of significant stenosis (>50%). RESULTS: We found CAS >50% in 13 patients (22%). The overall mortality was 5% (3 patients). Serious complications developed in 16 (28%) patients, 8 (62%) of whom belonged to the group with significant CAS (P=.004). Ten patients (17%) had a pancreatic fistula, 5 (38%) vs. 5 (11%) (P=.036); Fourteen patients (24%) needed new surgery, 7 (54%) vs. 7 (16%) (P=.009); Seven patients (12%) had a haemoperitoneum, 4 (31%) vs. 3 (7%) (P=.038), in the group with and without CAS, respectively. CONCLUSIONS: Significant radiological CAS is a risk factor of serious complications after DPC. The study of the calibre of the superior mesenteric artery (SMA) with MDCT should be routine before a DPC. The correction of a significant CAS should be evaluated preoperatively.

[Major hepatectomies are safe in patients with cholangiocarcinoma and jaundice]. / Las hepatectomías mayores en pacientes con colangiocarcinoma e ictericia son seguras.

BACKGROUND: Surgical resection is the only possibility of long term survival in patients with Klatskin tumours. However, surgical resection is a challenging problem and hepatic resection is often necessary. OBJECTIVE: The aim of our study was to assess the need for biliary drainage, resection rate and outcome of hilar cholangiocarcinoma in a single tertiary referral centre. PATIENTS AND METHODS: From 2005 to 2008, 26 patients with Klatskin tumours were identified and assessed prospectively with multidetector CT and MR cholangiography in special cases. Seven patients (27%) were deemed to be unresectable in pre-operative staging. A total of 19 surgical procedures were performed, 8 left hepatectomies, 5 right hepatectomies and 6 resections exclusively of the biliary tree. RESULTS: Resection rate was 73%, transfusion rate 53% and preoperative biliary drainage was performed only in 7 cases (37%). Major complications occurred in 11 (58%), including two post-operative deaths (10%). There were no differences in the epidemiological data, when we separately analysed the outcomes of the 9 patients with bilirubin<15 mg/dL and the 10 patients with bilirubin>15 mg/dL. Biliary drainage was required in 6 (67%) patients in the group with low bilirubin levels vs. 1(10%) in the other group (P=0.02). The mean bilirubin level in the jaundiced group was 22.1+/-3.9 vs. 4.7+/-4.3 (P<0.001) in the other group. There were no differences in the postoperative outcome between both groups. CONCLUSION: Resection and survival rates have increased recently but still carries the risk of significant morbidity and mortality. Major hepatectomies in selected patients without percutaneous biliary drainage are safe.

[Hepatic angiomyolipoma in two patients infected with hepatitis C virus]. / Angiomiolipoma hepático en dos pacientes con infección por el virus de la hepatitis C.

AIM: The aim of this study is to present our experience with two cases of hepatic angiomyolioma in hepatitis C virus (HCV) positive patients, and to up-date the clinical manage, diagnostic and treatment of this entity. CLINICAL OBSERVATIONS: Both cases were presented in women in their 4-5th decade of life. Clinical presentation was with symptoms in one but incidental in the other. Both were HCV positive. Values of alpha-fetoprotein were normal. Radiological imaging was not diagnostic. Histopathological examination and immunohistochemical findings gave the diagnosis of angiomyolipoma. At time of diagnosis the size of tumours was 4.8 and 8 cm of diameter. Both cases were treated with surgery in order to definetly rule out malignancy. After 6 and 3 years of follow-up, there is no evidence of recurrence. DISCUSSION AND CONCLUSION: The hepatic angiomyolipoma is a rare benign tumour, mimicking other liver tumours. Although no patognomonic features, there are some radiological findings that point out to the diagnosis of angiomy olipoma. Nevertheless, definitive diagnosis is done by his tological and immunohistochemical findings (HMB-45). The hepatic angiomyolipoma consists of varing proportion of three elements, mature fat cells, smooth muscle cells and blood vessels. Although it is a benign tumour, the difficulty in ruling out malignancy, prompted surgical management. It is not described its relation with HCV virus, thus we consider our cases as an coincident finding.