Gut Microbiota Signatures with Potential Clinical Usefulness in Colorectal and Non-Small Cell Lung Cancers.

The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.

Gut microbiota profiles in feces and paired tumor and non-tumor tissues from Colorectal Cancer patients. Relationship to the Body Mass Index.

Colorectal Cancer (CRC) and Obesity constitute two of the most common malignancies in the western world, and previously have been associated with intestinal microbial composition alterations. Our main aim in this study is to provide molecular data on intestinal microbiota patterns in subjects with CRC, as well as to establish possible associations with their Body Mass Index (BMI). A total of 113 samples from 45 subjects were collected and submitted to metagenomics analysis for gut microbiota. This study was performed by 16S ribosomal RNA bacterial gene amplification and sequencing using the Ion Torrent™ technology. The same dominant phyla were observed in feces and colorectal tissues, although a greater proportion of Fusobacteriota was found in tumor samples. Moreover, at the genus level, LEfSe analysis allowed us to detect a significant increase in Fusobacterium and Streptococcus in colorectal tissues with respect to fecal samples, with a significant preponderance of Fusobacterium in tumor tissues. Also, our data revealed relevant associations between gut microbiota composition and tumor location. When comparing bacterial profiles between right and left colon cancers, those from the left-sided colon showed a significant preponderance, among others, of the order Staphylococcales. Moreover, phyla Firmicutes and Spirochaetota were more abundant in the group of right-sided CRCs and phylum Proteobacteria was increased in rectal cancers. In relation to BMI of patients, we detected significant differences in beta diversity between the normal weight and the obese groups of cases. Microbiota from obese patients was significantly enriched, among others, in Bacteroidales. Therefore, our results are useful in the molecular characterization of CRC in obese and non-obese patients, with a clear impact on the establishment of diagnostic and prognosis of CRC.

Expression Analysis of hsa-miR-181a-5p, hsa-miR-143-3p, hsa-miR-132-3p and hsa-miR-23a-3p as Biomarkers in Colorectal Cancer-Relationship to the Body Mass Index.

This work aims to investigate the expression levels of four preselected miRNAs previously linked to cancer and/or obesity, with the purpose of finding potential biomarkers in the clinical management of CRC developed by patients showing different BMI values. We analyzed samples from a total of 65 subjects: 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were investigated, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2-∆∆Ct) levels of 4 miRNAs (hsa-miR-181a-5p, hsa-miR-143-3p, has-miR-132-3p and hsa-miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC, serum levels of hsa-miR-143-3p clearly correlated with their levels in both SAT and OAT, independently of the BMI group. Moreover, hsa-miR-181a-5p could be considered as a biomarker in CRC patients with BMI ≥ 25 Kg/m2 and emerges as a tumor location marker. We conclude that both adiposity and CRC induce changes in the expression of the miRNAs investigated, and hsa-miR-143-3p and hsa-miR-181a-5p expression analysis could be useful in the clinical management of CRC.

Telomere Length and Telomerase Activity in Subcutaneous and Visceral Adipose Tissues from Obese and Non-Obese Patients with and without Colorectal Cancer.

To investigate the molecular mechanisms that link obesity and colorectal cancer (CRC), we analyzed parameters related to telomere function in subcutaneous and visceral adipose tissues (SAT and VAT), including subjects with and without CRC, who were classified according to their body mass index (BMI). Adipose tissues were obtained from 147 patients who had undergone surgery. A total of 66 cases corresponded to CRC patients, and 81 subjects were not affected by cancer. Relative telomere length was established by qPCR, and telomerase activity was determined by a method based on the telomeric repeat amplification protocol. Our results indicated longer telomeres in patients affected by CRC, both in SAT and VAT, when compared to the group of subjects without CRC. Tumor local invasion was associated with telomere length (TL) in SAT. Considering the BMI values, significant differences were found in the TL of both adipose tissues between subjects affected by CRC and those without cancer. Overweight subjects showed the greatest differences, with longer telomeres in the group of CRC patients, and a higher number of cases with telomerase reactivation in the VAT of subjects without cancer. In conclusion, parameters related to telomere function in adipose tissue could be considered as potential biomarkers in the evaluation of CRC and obesity.

Obesity and telomere status in the prognosis of patients with colorectal cancer submitted to curative intention surgical treatment.

The risk of colorectal cancer (CRC) development has been associated with telomere dysfunction and obesity. However, clinical relevance of these parameters in CRC prognosis is not clear. Therefore, the aim of the present study was to evaluate the impact of obesity and telomere status in the prognosis of patients affected by CRC and submitted to curative surgical treatment. According to published data, this is the first work in which obesity and telomere status are jointly considered in relation to CRC prognosis. A prospective study including 162 patients with CRC submitted to curative surgical treatment was performed. Subjects were classified according to their BMI. Telomere status was established through telomere length and telomerase activity evaluation. Statistical analyses were performed using the SPSS software package version 22. Telomere shortening was inversely associated with BMI in patients with CRC. Notably, among patients with CRC, subjects with obesity exhibited less shortening of tumor telomeres than non-obese patients (P=0.047). Patients with shorter telomeres, both in the tumor (median telomere length <6.5 kb) and their non-tumor paired tissues (median telomere length <7.1 kb), had the best clinical evolution, regardless of the Dukes' stage of cancers (P=0.025, for tumor samples; P=0.003, for non-tumor samples). Additionally, subjects with a BMI >31.85 kg/m2 showed the worse clinical outcomes compared with subjects with other BMI values. Interestingly, the impact of BMI showed sex dependence, since only the group of men displayed significant differences in CRC prognosis in relation to obesity status (P=0.037). From the results of the present study, based on a multivariate prediction model to establish prognosis, it was concluded that telomere length is a useful biomarker to predict prognosis in patients with CRC. Regardless of BMI values, the improved clinical evolution was associated with shorter telomeres. The impact of BMI seems to be associated with other factors, such as sex.

Systematic review and meta-analysis of fluid therapy protocols in acute pancreatitis: type, rate and route.

BACKGROUND: Adequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols in patients with AP. METHODS: MEDLINE, Embase, Science Citation Index and clinical trial registries were searched for randomised clinical trials published before May 2020, assessing types of fluids, routes and rates of administration. RESULTS: A total 15 trials (1073 participants) were included. Age ranged from 38 to 73 years; follow-up period ranged from 0.5 to 6 months. Ringer lactate (RL) showed a reduced number of severe adverse events (SAE) when compared to normal saline (NS) (OR 0.48; 95%CI 0.29-0.81, p = 0.006); additionally, NS showed reduced SAE (RR 0.38; 95%IC 0.27-0.54, p < 0.001) and organ failure (RR 0.30; 95%CI 0.21-0.44, p < 0.001) in comparison with hydroxyethyl starch (HES). High fluid rate fluid infusion showed increased mortality (OR 2.88; 95%CI 1.41-5.88, p = 0.004), increased number of SAE (RR 1.42; 95%CI 1.04-1.93, p = 0.030) and higher incidence of sepsis (RR 2.80; 95%CI 1.51-5.19, p = 0.001) compared to moderate fluid rate infusion. CONCLUSIONS: In patients with AP, RL should be preferred over NS and HES should not be recommended. Based on low-certainty evidence, moderate-rate fluid infusion should be preferred over high-rate infusion.

Simple liver cyst presenting with clinical signs and symptoms of right-sided heart failure.

Simple hepatic cysts are one of the most common benign lesions in the liver. Despite being frequently asymptomatic, if they reach large sizes in certain anatomical locations, they can appear under atypical symptomatology and cause significant morbidity. We present the case of a giant simple liver cyst as an exceptional cause of right-sided heart failure. Laparoscopic deroofing of the cyst achieved an outstanding improvement of the patient´s cardiac condition. A high diagnostic suspicion, a multidisciplinary approach and adequate treatment are essential for a favourable outcome.

Reactive lymphoid hyperplasia of the liver. A case report.

Reactive lymphoid hyperplasia of the liver is an unusual benign lesion of unknown pathogenesis. The largest reported series to date includes only 7 cases. Reactive lymphoid hyperplasia can be radiologically confused with malignant tumors such as hepatocellular carcinoma or metastases. Histological differential diagnosis should be chiefly made with lymphomas, Castleman disease and primary biliary cirrhosis. We report the clinicopathological findings in a 54-year-old woman with an incidental hepatic lesion when she consulted for hematuria. After histological, immunohistochemical and molecular studies, the diagnosis of reactive lymphoid hyperplasia was made.

Safety and feasibility of cholecystectomy in octogenarians. Analysis of a single center series of 316 patients.

INTRODUCTION: Cholecystectomy is the treatment of choice for symptomatic cholelithiasis. However, outcomes for patients over 80years of age are not well studied. The primary aim of this study was to describe the safety and feasibility of cholecystectomy, including in the acute setting, in a cohort of patients≥80 years of age. MATERIAL AND METHODS: A retrospective study of patients aged≥80 years submitted to cholecystectomy at a single institution from January 2013 to January 2018 was performed. Severity of acute cholecystitis was graded according to the updated Tokyo Guidelines 18. Early cholecystectomy was defined as being performed within the first 48h after admission and delayed when performed beyond 48h of the admission. RESULTS: In total 316 patients underwent cholecystectomy. The indication was acute cholecystitis in 113 (36%) patients. Of the 316 patients 289 (92%) were attempted laparoscopically and 30 (10%) were converted to open. Major complications occurred in 44 patients (14%) and mortality rate was 4%. No bile duct injuries were observed. For those patients with mild or moderate acute cholecystitis (n = 103), there was no differences in outcomes when comparing early vs delayed surgery. CONCLUSION: Cholecystectomy in patients≥80 years of age is safe and feasible. Outcomes did not differ between early and delayed surgery for mild/moderate acute cholecystitis.

Intestinal pneumatosis and pneumoperitoneum in an oncological scenario: a change of attitude.

Pneumoperitoneum and cystic intestinal pneumatosis associated to chemotherapy treatment are rare entities, with non-well stablished etiology and controversial management. We report two cases of oncological patients presenting with this complication as incidental finding in CT scan. Their course was favourable under conservative non-surgical approach associated with interruption of chemoterapy treatment.

Technical options for outflow reconstruction in domino liver transplantation: A single European center experience.

Venous outflow is critical to the success of liver transplantation (LT). In domino liver transplantation (DLT), the venous cuffs should be shared between the donor and the recipient, and the length can be compromised. The aim of this study was to describe and compare the technical options for outflow reconstruction used at our institution. This was a retrospective analysis of 39 consecutive DLT recipients between January 1997 and May 2013. Twenty-seven men and 12 women (mean age, 61.8 ± 4.3 years) underwent LT and consented to receive a liver from a donor with familial amyloid polyneuropathy (FAP). The main indications were hepatocellular carcinoma and hepatitis C virus cirrhosis. All recipients underwent transplantation by a piggyback technique. Liver procurement in the FAP donors was performed with the classic technique in 22 patients and with the piggyback technique in the last 17. In these latter cases, for vascular outflow reconstruction, a cadaveric venous graft was interposed between the hepatic vein (HV) stump of the FAP liver and the recipient HV in 11 cases (28%). Since 2011, we have employed arterial grafts to be interposed between the vessels stumps: a tailored arterial graft in 5 patients and an aortic graft in 1 case. There was no postoperative mortality. Arterial and portal complications presented in 2 (5.1) and 4 patients (10.3), respectively. Postoperative outflow complications (post-LT subacute Budd-Chiari syndrome) occurred in 4 patients, and all of them had received a venous interposed graft for reconstruction. The incidence of outflow complications tended to be higher among patients with venous grafts than those with arterial graft interposition. Overall patient survival at 1, 3, 5, and 10 years was 97%, 79%, respectively. Arterial grafts constitute a feasible and safe option for vascular outflow reconstruction in DLT because they are associated with a relatively low incidence of complications. The recently proposed Bellvitge arterial graft technique should be added to the current range of available surgical modalities.

Results of laparoscopic radiofrequency ablation for HCC. Could the location of the tumour influence a complete response to treatment? A single European centre experience.

INTRODUCTION: In selected patients, radiofrequency ablation (RFA) is a well-established treatment for hepatocellular carcinoma (HCC). However, subcapsular or lesions close to adjacent viscera preclude a percutaneous approach. In this setting laparoscopic-RFA (LRFA) is a potential alternative. The aim of this study was to analyse the safety and feasibility of LRFA in patients with HCC. PATIENTS AND METHODS: Retrospective study of patients with HCC meeting strict inclusion criteria who underwent LRFA at a single Institution from December 2000 to March 2013. RESULTS: Forty-one patients underwent 42 LRFA of 51 nodules. The median size of the nodule was 2.5 (range 1.2-4.7) cm. Thirty-one tumours were subcapsular and 17 located near the gallbladder. Major complications occurred in 17 patients. The initial complete response (ICR) rate was 94% and was lower among tumours located adjacent to the gallbladder. At the end of the follow-up period, the sustained complete response (SCR) rate was 70% and was lower in tumours adjacent to the gallbladder while increased for subcapsular tumours. The 1-, 3- and 5-year overall survival rate was 92.6%, 64.5% and 43%, respectively. CONCLUSION: LRFA of HCC is safe, feasible and achieves excellent results in selected patients. LRFA should be the first-line technique for subcapsular lesions as it minimizes the risk of tumoural seeding and improves ICR. Proximity to gallbladder interferes in treatment efficacy (lower rate of ICR and lower rate of SCR).

Graft and viral outcomes in retransplantation for hepatitis C virus recurrence and HCV primary liver transplantation: a case-control study.

INTRODUCTION: The use of liver retransplantation (ReLT) for hepatitis C virus (HCV) recurrence is controversial because of subsequent viral recurrence after ReLT. METHODS: Case-control analysis between patients undergoing ReLT for HCV reinfection between 1993 and 2012 (ReLT group: 26 patients) and patients undergoing liver transplantation (LT) for HCV infection immediately before and after each ReLT (LT group: 52 patients). RESULTS: ReLT group had worse hepatocellular function, higher preoperative viral load, higher transfusion requirements, and increased number of postoperative complications than LT group. ReLT patients showed a trend toward worse graft survival compared with LT (five-yr graft survival: 42.3% vs. 64.3%, p = 0.145), but the rate of severe HCV recurrence and infection-free survival (IFS) was similar. The use of donors older than 60 yr led to a lower IFS and graft survival in both groups. Early severe HCV infection rate was similar in both groups, but it affected prognosis in ReLT more markedly than in LT (three-yr graft survival: 0% vs. 66.7%, p = 0.003). CONCLUSIONS: ReLT for HCV reinfection has acceptable results when strict selection policies of donor and recipient are applied. However, early severe recurrence more markedly impairs prognosis in ReLT patients than in LT.

The positive financial impact of using an Intensive Care Information System in a tertiary Intensive Care Unit.

INTRODUCTION: In the French healthcare system, the intensive care budget allocated is directly dependent on the activity level of the center. To evaluate this activity level, it is necessary to code the medical diagnoses and procedures performed on Intensive Care Unit (ICU) patients. The aim of this study was to evaluate the effects of using an Intensive Care Information System (ICIS) on the incidence of coding errors and its impact on the ICU budget allocated. PATIENTS AND METHODS: Since 2005, the documentation on and monitoring of every patient admitted to our ICU has been carried out using an ICIS. However, the coding process was performed manually until 2008. This study focused on two periods: the period of manual coding (year 2007) and the period of computerized coding (year 2008) which covered a total of 1403 ICU patients. The time spent on the coding process, the rate of coding errors (defined as patients missed/not coded or wrongly identified as undergoing major procedure/s) and the financial impact were evaluated for these two periods. RESULTS: With computerized coding, the time per admission decreased significantly (from 6.8 ± 2.8 min in 2007 to 3.6 ± 1.9 min in 2008, p<0.001). Similarly, a reduction in coding errors was observed (7.9% vs. 2.2%, p<0.001). This decrease in coding errors resulted in a reduced difference between the potential and real ICU financial supplements obtained in the respective years (€194,139 loss in 2007 vs. a €1628 loss in 2008). CONCLUSION: Using specific computer programs improves the intensive process of manual coding by shortening the time required as well as reducing errors, which in turn positively impacts the ICU budget allocation.

Ischaemic preconditioning of the graft in adult living related right lobe liver transplantation: impact on ischaemia-reperfusion injury and clinical relevance.

BACKGROUND: Ischaemic preconditioning (IPC) of the right liver graft in the donor has not been studied in adult-to-adult living related liver transplantation (LRLT). OBJECTIVE: To assess the IPC effect of the graft on ischaemia reperfusion injury in the recipient and compare recipient and donor outcomes with and without preconditioned grafts. PATIENTS AND METHODS: Alternate patients were transplanted with right lobe grafts that were (n = 22; Group (Precond)) or were not (n = 22; Group (Control)) subjected to IPC in the living donor. Liver ischaemia-reperfusion injury, liver/kidney function, morbidity/mortality rates and outcomes were compared. Univariate and multivariate analyses were performed to identify factors predictive of the aspartate aminotransferase (AST) peak and minimum prothrombin time. RESULTS: Both groups had similar length of hospital stay, morbidity/mortality, primary non-function and acute rejection rates. Post-operative AST (P = 0.8) and alanine aminotransferase (ALT) peaks (P = 0.6) were similar in both groups (307 +/- 189 and 437 +/- 302 vs. 290 +/- 146 and 496 +/- 343, respectively). In univariate analysis, only pre-operative AST and warm ischemia time (WIT) were significantly associated with post-operative AST peak (in recipients). In multivariate analysis, the graft/recipient weight ratio (P = 0.003) and pre-operative bilirubin concentration (P = 0.004) were significantly predictive of minimum prothrombin time post-transplantation. CONCLUSIONS: Graft IPC in the living related donor is not associated with any benefit for the recipient or the donor and its clinical value remains uncertain.

[Intrahepatic cholangiocarcinoma on a hydatidic cyst]. / Colangiocarcinoma intrahepático sobre quiste hidatídico.

Cholangiocarcinomas are malignant tumors arising from the bile ducts. One of the factors associated with the development of malignancy is parasitic infections by helminths trematodes that cause liver fluke infections. This association is very common in south-east Asia, but association with liver hydatidosis has not been reported in the scientific literature. We report a case in which these two diseases were associated and required non-radical surgical treatment, since radiological findings were not suspicious for these entities.