Clinical Impact of Preoperative Biliary Drainage in Patients with Ductal Adenocarcinoma of the Pancreatic Head.

Our aim was to study the association between preoperative biliary drainage (PBD) and morbidity following cephalic pancreaticoduodenectomy (CPD) for pancreatic ductal adenocarcinoma (PDAC) and its prognostic impact, which is still controversial in the literature. A retrospective study was conducted, which included 128 patients who underwent CPD for PDAC, divided into two groups: those who underwent PBD (group 1) and those who did not undergo this procedure (group 2). Group 1 was subdivided according to the drainage route: endoscopic retrograde cholangiopancreatography (ERCP), group 1.1, and percutaneous transhepatic cholangiography (PTC), group 1.2. 34.4% of patients underwent PBD, and 47.7% developed PBD-related complications, with 37% in group 1.1 and 64.7% in group 1.2 (p = 0.074). There was a significant difference between group 1 and 2 regarding bacterial colonization of the bile (45.5% vs. 3.6%, p < 0.001), but no difference was found in the colonization by multidrug-resistant bacteria, the development of Clavien-Dindo ≥ III complications, clinically relevant pancreatic fistula and delayed gastric emptying (DGE), intra-abdominal abscess, hemorrhage, superficial surgical site infection (SSI), and readmission. Between groups 1.1 and 1.2, there was a significant difference in clinically relevant DGE (44.4% vs. 5.9%, p = 0.014) and Clavien-Dindo ≥ III complications (59.3% vs. 88.2%, p = 0.040). There were no significant differences in median overall survival and disease-free survival (DFS) between groups 1 and 2. Groups 1.1 and 1.2 had a significant difference in DFS (10 vs. 5 months, p = 0.017). In this group of patients, PBD was associated with increased bacterial colonization of the bile, without a significant increase in postoperative complications or influence in survival. ERCP seems to contribute to the development of clinically significant DGE. Patients undergoing PTC appear to have an early recurrence.

Tumor Stroma Area and Other Prognostic Factors in Pancreatic Ductal Adenocarcinoma Patients Submitted to Surgery.

Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, responsible for up to 80% of its volume. The amount of stroma can be associated with prognosis, although there are discrepancies regarding its concrete impact. The aim of this work was to study prognostic factors for PDAC patients submitted to surgery, including the prognostic impact of the tumor stroma area (TSA). A retrospective study with PDAC patients submitted for surgical resection was conducted. The TSA was calculated using QuPath-0.2.3 software. Arterial hypertension, diabetes mellitus, and surgical complications Clavien-Dindo>IIIa are independent risk factors for mortality in PDAC patients submitted to surgery. Regarding TSA, using >1.9 × 1011 µ2 as cut-off value for all stages, patients seem to have longer overall survival (OS) (31 vs. 21 months, p = 0.495). For stage II, a TSA > 2 × 1011 µ2 was significantly associated with an R0 resection (p = 0.037). For stage III patients, a TSA > 1.9 × 1011 µ2 was significantly associated with a lower histological grade (p = 0.031), and a TSA > 2E + 11 µ2 was significantly associated with a preoperative AP ≥ 120 U/L (p = 0.009) and a lower preoperative AST (≤35 U/L) (p = 0.004). Patients with PDAC undergoing surgical resection with preoperative CA19.9 > 500 U/L and AST ≥ 100 U/L have an independent higher risk of recurrence. Tumor stroma could have a protective effect in these patients. A larger TSA is associated with an R0 resection in stage II patients and a lower histological grade in stage III patients, which may contribute to a longer OS.

Clinicopathological prognostic factors for gallbladder carcinoma: a retrospective study.

Background: Gallbladder carcinoma (GBC) is an uncommon neoplasm with poor long-term survival. Worldwide the incidence rates vary according to geographic area. The multifactorial aetiology and the rarity of the disease limits the studies to improve outcomes in patients, since the treatment remains mostly surgical. The aim of this study was to identify clinicopathological prognostic factors for survival in patients with GBC submitted to surgery in our institution-a tertiary centre in Portugal. Also, to assess the expression of possible biomarkers (HER2, CD44 and ALDH1) in GBC, as well as the frequency of microsatellite instability (MSI) tumours. Methods: Clinicopathological characteristics of 41 consecutive patients that underwent surgical resection for GBC (2008-2019) at our hospital were retrospectively reviewed. Clinicopathological factors were assessed and an immunohistochemical (IHC) analysis was done. Microsatellite stability (MSS) was considered if there was maintenance of nuclear expression of MLH1, MSH2, MSH6 and PMS2. Human epidermal growth factor receptor 2 (HER2) expression was evaluated according to the rules applied for gastric cancer and expression of CD44 and ALH1 was evaluated in order to detect cancer stem cells (CSC). Survival analysis was conducted using Kaplan-Meier and Cox regression was used to find prognostic factors. Results: Incidence of GBC in our cohort of patients was 0.45%, most commonly affecting females. Median overall survival (OS) was 23 months with a 39.6% 5-year survival rate. Stage > II [hazard ratios (HR) =8.58; P=0.007], lymphovascular invasion (LVI) (HR =4.06; P=0.045) and hepatic resection (HR =0.288; P=0.034) independently influenced survival. HER2 positivity and high expression of CD44 or ADLH1 did not show significant influence in survival (P=0.649, P=0.868 and P=0.914, respectively), although HER2 and ALDH1 positive patients showed a tendency to a shorter OS, compared to negative patients. We found no relation between these biomarkers expression and disease stage. All analysed samples had MSS. Conclusions: GBC patients with a worse prognosis can be identified. The overexpression of HER2 could select patients for targeted therapy and prompt tissue sampling in unresectable patients.

Extensive thrombosis after COVID-19 vaccine: cause or coincidence?

A 62-year-old Caucasian female patient presented with abdominal pain, vomiting and fever 1 day after administration of COVID-19 vaccine. Bloodwork revealed anaemia and thrombocytosis. Abdominal CT angiography showed a mural thrombus at the emergence of the coeliac trunk, hepatic and splenic arteries, and extensive thrombosis of the superior and inferior mesenteric veins, splenic and portal veins, and the inferior vena cava, extending to the left common iliac vein. The spleen displayed extensive areas of infarction. Aetiological investigation included assessment of congenital coagulation disorders and acquired causes with no relevant findings. Administration of COVID-19 vaccine was considered a possible cause of the extensive multifocal thrombosis. After reviewing relevant literature, it was considered that other causes of this event should be further investigated. Thrombosis associated with COVID-19 vaccine is rare and an aetiological relationship should only be considered in the appropriate context and after investigation of other, more frequent, causes.

Prognostic Factors After Hepatectomy for Gastric Adenocarcinoma Liver Metastases: Desmoplastic Growth Pattern as the Key to Improved Overall Survival.

PURPOSE: Hepatectomy (Hp) is an alternative approach for the treatment of gastric carcinoma liver metastases (GCLM). However, prognostic factors that may assist patient selection are still controversial. Several pathologic features, such as the growth pattern (GP), associated with prognosis in colorectal cancer liver metastases, were never investigated in GCLM. Our principal aim was to assess if the GP has prognostic impact on GCLM. PATIENTS AND METHODS: Review of the clinical and pathological characteristics of 19 consecutive patients submitted to surgical resection of GCLM with curative intent at our department. Major potential prognostic factors considered were patients' gender, age, timing and extent of Hp, postoperative course, as well as histopathological characteristics of primary and secondary tumors. RESULTS: Major morbidity occurred in four patients, mortality in one. Median and 5-year overall survival were 17 months and 26.7%, respectively. Ten patients developed recurrent disease and two patients survived more than 10 years. Factors independently associated with overall survival were the absence of major morbidity, distal location of the primary tumor, and desmoplastic GP (p<0.05). CONCLUSION: The selection of patients is crucial for the improvement of survival rates of GCLM. Consequently, we demonstrate for the first time that the desmoplastic GP of GCLM is associated with improved outcomes, prompting further research on tumor-host interactions.

Advanced hepatic vasculobiliary imaging segmentation and 3D reconstruction as an aid in the surgical management of high biliary stenosis.

BACKGROUND: Three-dimensional (3D) models are increasingly used to help surgeons, guiding them through the complex hepatic vasculobiliary anatomy. The biliary tract is a relatively untapped territory with only a few case reports described in medical literature. Our aim is to present an innovative 3D reconstruction methodology for biliary imaging and surgical planning, applied to a case of iatrogenic biliary stricture, with fusion of segmented CT and MRI images. CASE PRESENTATION: A selected case of Bismuth type III iatrogenic biliary stenosis for 3D planning. CT and MR studies were acquired with dedicated protocols for segmentation. Two radiologists performed segmentation and 3D model post-processing, fusing both imaging techniques to faithfully render the anatomical structures. Measurements of anatomical landmarks were taken in both the CT/MRI and the 3D model to assure its accuracy and differences in measurement were calculated. The 3D model replicates anatomical structures and pathology with high accuracy, with only 2.2% variation between STL, CT and MRI measurements. The model was discussed with the surgical team and used in the surgical planning, improving confidence in this delicate procedure, due to the detailed prior knowledge of the patient's anatomy. CONCLUSION: Three-dimensional reconstructions are a rapidly growing area of research with a significant impact in the personalized and precision medicine. The construction of 3D models that combine vascular and biliary anatomy, using different imaging techniques, respectively CT and MRI, will predictably contribute to a more rigorous planning of complex liver surgeries.

Ruptured Hemorrhagic Hepatic Cyst: An Unusual Case Report.

BACKGROUND: Hemorrhagic rupture of a hepatic cyst is rare. To date, very few cases have been reported in the literature. CASE REPORT: A patient with a history of a suspected liver hydatid cyst presented to the emergency department with abdominal pain and fever. She was admitted with the presumptive diagnosis of acute cholecystitis. During hospitalization, the patient presented with hemodynamic instability and abrupt worsening of the abdominal pain. The abdominal angio-chemotherapy scan showed an abundant free peritoneal effusion and an apparent effacement of the anterior wall of a hepatic cyst of 16 cm. The patient underwent an exploratory laparotomy, deroofing of the cyst, and peritoneal lavage. The anatomopathological results showed a simple hepatic cyst. DISCUSSION: Hemorrhagic rupture of simple hepatic cysts is a life-threatening complication and, although rare, should be included in the differential diagnosis of sudden abdominal pain in patients with a history of simple hepatic cysts.

INTRODUÇÃO: A ruptura hemorrágica de um quisto hepático é rara. Até à data, foram descritos poucos casos na literatura. RELATO DE CASO: Uma doente com antecedentes de um provável quisto hidático hepático recorreu ao serviço de urgência por dor abdominal e febre. Foi internada com o diagnóstico presumível de colecistite aguda. Durante o internamento, a doente iniciou um quadro de instabilidade hemodinâmica e agravamento súbito da dor abdominal. A angio-TC abdominal revelou um volumoso derrame peritoneal livre e uma aparente efração da parede anterior de um quisto hepático com 16 cm. A doente foi submetida a uma laparotomia exploradora, excisão da cúpula saliente do quisto e lavagem peritoneal. O exame anatomopatológico foi concordante com um quisto hepático simples. DISCUSSÃO: A ruptura hemorrágica de quistos hepáticos simples é uma complicação com risco de mortalidade, e, embora rara, deve ser incluída no diagnóstico diferencial de abdómen agudo em doentes com história de quistos hepáticos simples.

Pancreatic microcystic serous cystadenoma: a lethal disease? Rare case of a life-threatening haemorrhage.

Serous pancreatic cystadenomas are benign tumours and most cases are detected incidentally. Complications are unusual. A patient with a history of a large pancreatic serous cystadenoma (SCA) presented to the emergency department with abdominal pain and haemodynamic shock. After haemodynamic stabilisation, an urgent abdominal CT scan revealed a large hemoperitoneum but the origin of the bleeding was not found. The patient was submitted to an angiography that revealed a bleeding hypervascular pancreatic mass and an embolisation was done successfully. After 3 weeks, the patient underwent a laparotomic left pancreatectomy with en bloc splenectomy. The anatomopathological results were consistent with a microcystic SCA of the pancreas. Despite the high vascularity of pancreatic SCA, haemorrhage is a very rare but life-threatening complication.

Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival.

INTRODUCTION: Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). PATIENTS AND METHODS: Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). RESULTS: The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. CONCLUSION: The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients.

Bioenergetic adaptations of the human liver in the ALPPS procedure - how liver regeneration correlates with mitochondrial energy status.

BACKGROUND: The Associating Liver Partition and Portal Ligation for Staged Hepatectomy (ALPPS) depends on a significant inter-stages kinetic growth rate (KGR). Liver regeneration is highly energy-dependent. The metabolic adaptations in ALPPS are unknown. AIMS: i) Assess bioenergetics in both stages of ALPPS (T1 and T2) and compare them with control patients undergoing minor (miHp) and major hepatectomy (MaHp), respectively; ii) Correlate findings in ALPPS with volumetric data; iii) Investigate expression of genes involved in liver regeneration and energy metabolism. METHODS: Five patients undergoing ALPPS, five controls undergoing miHp and five undergoing MaHp. Assessment of remnant liver bioenergetics in T1, T2 and controls. Analysis of gene expression and protein content in ALPPS. RESULTS: Mitochondrial function was worsened in T1 versus miHp; and in T2 versus MaHp (p < 0.05); but improved from T1 to T2 (p < 0.05). Liver bioenergetics in T1 strongly correlated with KGR (p < 0.01). An increased expression of genes associated with liver regeneration (STAT3, ALR) and energy metabolism (PGC-1α, COX, Nampt) was found in T2 (p < 0.05). CONCLUSION: Metabolic capacity in ALPPS is worse than in controls, improves between stages and correlates with volumetric growth. Bioenergetic adaptations in ALPPS could serve as surrogate markers of liver reserve and as target for energetic conditioning.

Citrullinemia stimulation test in the evaluation of the intestinal function.

BACKGROUND: Citrullinemia is been reported as a quantitative parameter of the enterocyte mass and function. AIM: The objective of this research is to analyse the value of fasting and stimulated citrullinemias in the intestinal function evaluation. METHODS: A case-control study was undertaken, including 11 patients with short bowel syndrome, 13 patients submitted to malabsorptive bariatric surgery and 11 healthy controls. Plasma levels of amino acids were determined, before and after a stimulation test with oral Lglutamine, by ion exchange chromatography. RESULTS: Citrullinemia was inferior in short bowel patients (28,6 ± 11,3 versus 35,5 ± 11 in operated obese versus 32,2 ± 6,6 µmol/L in controls; n.s.) and lower than 25,5 µmol/L in 54,5% of them (versus 16,7%; p = 0,041; accuracy = 74%; odds ratio = 3, 95%CI 1,2-7,6). ΔCitrullinemia80 (relative variation of citrullinemia at the 80th minute of test) was lower in short bowel patients; its diagnostic accuracy was similar to baseline citrullinemia and also not significant. ΔCitrullinemia80 revealed a high predictive capacity of a short bowel inferior or equal to 50 cm (auR.O.C. = 82,3%; 95%CI 61,7-102,8; p = 0,038). CONCLUSIONS: In short bowel syndrome context, citrullinemia stimulation test with oral L-glutamine is feasible and it may improve the predictive capacity of severity. Further investigation is required to determine its clinical relevance and applicability.

Introducción: Citrulinemia sí ha reportado como un parámetro cuantitativo de la masa y la función del enterocito. Objetivo: El objetivo de esta investigación es analizar el valor de las citrulinemias en ayuno y estimulada en la evaluación de la función intestinal. Métodos: Un estudio de casos y controles se llevó a cabo, incluyendo 11 enfermos con síndrome del intestino corto, 13 pacientes sometidos a cirugía bariátrica de malabsorción y 11 controles sanos. Los niveles plasmáticos de aminoácidos se determinaron, antes y después de la prueba de estimulación oral con L-glutamina, por cromatografía de intercambio iónico. Resultados: Citrulinemia fue menor en los pacientes de intestino corto (28,6 ± 11,3 versus 35,5 ± 11 en los obesos operados versus 32,2 ± 6,6 µmol/L en los controles; n.s.) e inferior a 25,5 µmol/L en el 54,5% de ellos (versus 16,7%; p = 0,041, exactitud = 74%, odds ratio = 3, IC95% 1,2 a 7,6). ?Citrullinemia80 (variación relativa de la citrulinemia a los 80 minutos de la prueba) fue menor en enfermos de intestino corto; su precisión diagnóstica fue similar a la citrulinemia en ayuno y también no significativa. ?Citrullinemia80 reveló una elevada capacidad predictiva de intestino corto inferior o igual a 50 cm (abR.O.C. = 82,3%; IC95% 61,7-102,8; p = 0,038). Conclusiones: En el contexto de lo síndrome de intestino corto, la prueba de estimulación de la citrulinemia con L-glutamina oral es factible y puede mejorar la capacidad predictiva de gravedad. Se requieren nuevas investigaciones para determinar su importancia clínica y aplicabilidad.

Citrullinemia stimulation test in the evaluation of the intestinal function / Citrulinemia prueba de estimulación en la evaluación de la función intestinal

Background: Citrullinemia is been reported as a quantitative parameter of the enterocyte mass and function. Aim: The objective of this research is to analyse the value of fasting and stimulated citrullinemias in the intestinal function evaluation. Methods: A case-control study was undertaken, including 11 patients with short bowel syndrome, 13 patients submitted to malabsorptive bariatric surgery and 11 healthy controls. Plasma levels of amino acids were determined, before and after a stimulation test with oral L-glutamine, by ion exchange chromatography. Results: Citrullinemia was inferior in short bowel patients (28,6 ± 11,3 versus 35,5 ± 11 in operated obese versus 32,2 ± 6,6 μmol/L in controls; n.s.) and lower than 25,5 μmol/L in 54,5% of them (versus 16,7%; p = 0,041; accuracy = 74%; odds ratio = 3, 95%CI 1,2-7,6). ΔCitrullinemia80 (relative variation of citrullinemia at the 80th minute of test) was lower in short bowel patients; its diagnostic accuracy was similar to baseline citrullinemia and also not significant. ΔCitrullinemia80 revealed a high predictive capacity of a short bowel inferior or equal to 50 cm (auR.O.C. = 82,3%; 95%CI 61,7-102,8; p = 0,038). Conclusions: In short bowel syndrome context, citrullinemia stimulation test with oral L-glutamine is feasible and it may improve the predictive capacity of severity. Further investigation is required to determine its clinical relevance and applicability (AU)

Introducción: Citrulinemia sí ha reportado como un parámetro cuantitativo de la masa y la función del enterocito. Objetivo: El objetivo de esta investigación es analizar el valor de las citrulinemias en ayuno y estimulada en la evaluación de la función intestinal. Métodos: Un estudio de casos y controles se llevó a cabo, incluyendo 11 enfermos con síndrome del intestino corto, 13 pacientes sometidos a cirugía bariátrica de malabsorción y 11 controles sanos. Los niveles plasmáticos de aminoácidos se determinaron, antes y después de la prueba de estimulación oral con L-glutamina, por cromatografía de intercambio iónico. Resultados: Citrulinemia fue menor en los pacientes de intestino corto (28,6 ± 11,3 versus 35,5 ± 11 en los obesos operados versus 32,2 ± 6,6 μmol/L en los controles; n.s.) e inferior a 25,5 μmol/L en el 54,5% de ellos (versus 16,7%; p = 0,041, exactitud = 74%, odds ratio = 3, IC95% 1,2 a 7,6). ΔCitrullinemia80 (variación relativa de la citrulinemia a los 80 minutos de la prueba) fue menor en enfermos de intestino corto; su precisión diagnóstica fue similar a la citrulinemia en ayuno y también no significativa. ΔCitrullinemia80 reveló una elevada capacidad predictiva de intestino corto inferior o igual a 50 cm (abR.O.C. = 82,3%; IC95% 61,7-102,8; p = 0,038). Conclusiones: En el contexto de lo síndrome de intestino corto, la prueba de estimulación de la citrulinemia con L-glutamina oral es factible y puede mejorar la capacidad predictiva de gravedad. Se requieren nuevas investigaciones para determinar su importancia clínica y aplicabilidad (AU)

Value of MELD and MELD-based indices in surgical risk evaluation of cirrhotic patients: retrospective analysis of 190 cases.

BACKGROUND: Recent studies have suggested that the Model for End-Stage Liver Disease (MELD) may represent a promising alternative to the Child-Turcotte-Pugh classification as a predictive factor of operative mortality and morbidity. This study was designed to evaluate the value of MELD and four MELD-based indices (iMELD: integrated MELD; MESO: MELD to sodium ratio; MELD-Na: MELD with incorporation of sodium; MELD-XI: MELD excluding the International Normalized Ratio) in the quantification of surgical risk for patients with cirrhosis and compare its prognostic value with the Child-Turcotte-Pugh classification and two derived scores (proposed by Huo and Giannini, respectively). METHODS: A retrospective study of 190 patients with cirrhosis, operated on in our department between 1993 and 2008, was undertaken. RESULTS: Forty-three percent of patients were included in Child-Turcotte-Pugh A class, and their mean MELD score was 12.2 +/- 4.9 (range, 6.4-35.2). Mortality and morbidity rates were 13% and 24%, respectively. In global analysis of mortality, MELD-based indices presented an acceptable prognostic performance (auROC = 71-77%), similar to the three analyzed Child-Turcotte-Pugh-derived scores. iMELD demonstrated the highest prognostic capacity (auROC = 77%; 95% confidence interval (CI), 66-88; p = 0.0001); operative death probability was 4% (95% CI, 3.6-4.4) when the score was inferior to 35, 16.1% (95% CI, 14.4-17.9) between 35 and 45, and 50.1% (95% CI, 42.2-58.1) when superior to 45. In elective surgical procedures, iMELD represented a useful prognostic factor of operative mortality (auROC = 80%; 95% CI, 63-97; p = 0.044) with significant correlation and better accuracy then MELD and Child-Turcotte-Pugh-derived indices. CONCLUSIONS: In this study, iMELD was a useful predictive parameter of operative mortality for patients with cirrhosis submitted to elective procedures. Further studies are necessary to define the relevance of MELD-based indices in the individual surgical risk evaluation.