The Efficacy and Safety of Laparoscopic Single-Anastomosis Duodeno-ileostomy with Sleeve Gastrectomy (SADI-S) in Mid- and Long-Term Follow-Up: a Systematic Review.

This systematic review of 10 studies aimed to investigate the mid- and long-term results of duodeno-ileostomy with sleeve gastrectomy (SADI-S) according to the PRISMA guideline. Related articles, which reported outcomes of laparoscopic SADI-S with follow-up ≥ 3 years, were selected and analyzed. The percentage of excess weight loss (EWL) was 70.9-88.7%, and 80.4% at 6, and 10 years, respectively. The more common late complications were malabsorption (6.3%) and gastroesophageal reflux disease (GERD) (3.6%). The remission rates of hypertension, diabetes, GERD, obstructive sleep apnea, and dyslipidemia were 62.9%, 81.3%, 53.2%, 60.9%, and 69.7%, respectively. In conclusion, SADI-S is a safe and effective surgical technique with durable weight loss and a high rate of comorbidity resolution in mid and long term.

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.

Weight Regain Outcomes After Bariatric Surgery in the Long-term Follow-up: Role of Preoperative Factors.

PURPOSE: Weight regain (WR) compromises the effectiveness of bariatric surgery. The objective of this study was to determine differences in long-term WR prevalence using different definitions and analyze possible preoperative predictors involved. METHODS: Single-center retrospective cohort study including 445 adults who underwent 3 modalities of bariatric surgery between 2009 and 2014. EXPOSURE: age, gender, ethnicity, body mass index (BMI), type 2 diabetes (T2D), hypertension (HTN), and type of surgery. MAIN OUTCOMES: WR at year 6 assessed by 4 definitions and 6 multivariate models based on common thresholds. RESULTS: Our cohort (71.1% female) had a mean age of 44.78 ± 11.94 years, and mean presurgery BMI of 44.94 ± 6.88 kg/m2, with a median follow-up of 6 years (IQR=5-8). The prevalences of T2D and HTN were 36.0% and 46.7% respectively. WR rates over thresholds ranged from 25.4 to 68.1%, with significant differences between groups in the WR measured as the percentage of maximum weight loss (MWL) and the increase in excess weight loss (EWL). Presurgery BMI was a significant predictor in 3 models; restrictive techniques were associated with WR in all the models except for those considering WR over 10 kg and WR over 15% from nadir as dependent variables. CONCLUSIONS: In this long-term study, WR defined as percentage of MWL and increase in EWL from nadir had the greatest significance in logistic regression models with preoperative BMI and type of surgery as independent variables. These findings could serve to establish a standardized outcome reporting WR in other longitudinal studies. KEY POINTS: • Lack of standardized outcome to measure weight regain after bariatric surgery. • Lowest rates of weight regain in malabsorptive techniques in all definitions applied. • Weight regain measured as percentage of maximum weight lost.

Short- to medium-term results of single-anastomosis duodeno-ileal bypass compared with one-anastomosis gastric bypass for weight recidivism after laparoscopic sleeve gastrectomy.

BACKGROUND: Single-anastomosis duodeno-ileal bypass (SADI) and the one-anastomosis gastric bypass (OAGB) are 2 revisional procedures to address the problem of weight recidivism after laparoscopic sleeve gastrectomy (LSG). OBJECTIVES: To evaluate the efficacy and safety of SADI and OAGB as revisional bariatric surgery (RBS) in initially super-obese patients (body mass index [BMI] >50 kg/m2). SETTING: Academic hospital, bariatric center of excellence, Germany. METHODS: Observational study of outcomes in 84 initially super-obese patients who had undergone RBS after LSG (SADI n = 42, OAGB n = 42) between July 2013 and April 2018. Follow-up examinations were performed at 1, 6, 12, 24, and 36 months after RBS. The variables analyzed included time between LSG and RBS, BMI, excess weight loss, total weight loss, operation time, and complications. RESULTS: The time interval between LSG and RBS was 45.5 ± 22.8 and 43.5 ± 24.2 months for SADI and OAGB, respectively. At the time of RBS, the mean BMI was 42.8 ± 7.9 kg/m2 for SADI and 43.4 ± 9.2 kg/m2 for OAGB. The follow-up examinations rates (%) after SADI were 97.6, 92.8, 90.5, 78.6, 57.1, and 100, 97.6, 95.2, 85.7, and 59.5 after OAGB. The BMI at the follow-up examinations were 39.1 ± 7.2, 34.2 ± 6.9, 31.2 ± 5.8, 30.2 ± 5.3, 29.3 ± 5.1 for SADI, and 39.5 ± 8.1, 36.6 ± 7.4, 34.7 ± 7.9, 32.9 ± 6.3, and 31.6 ± 5.9 for OAGB. The mean operating times for SADI and OAGB were 138 ± 40 and 123 ± 39 minutes, respectively. Three patients in the SADI group and 1 patient in the OAGB group developed a major complication within the first 30 postoperative days. CONCLUSION: SADI and OAGB were effective second-step procedures for further weight reduction after LSG in initially super-obese patients after short to medium follow-up. There was a trend toward higher weight loss for SADI though this did not reach statistical significance. Substantial differences concerning surgery time and complications between the 2 procedures were not observed.

CD133 + cell infusion in patients with colorectal liver metastases going to be submitted to a major liver resection (CELLCOL): A randomized open label clinical trial.

BACKGROUND: Treatment of liver metastases of colorectal carcinoma is surgical resection. However, only 10-15% of the patients in this context will be candidate for curative resection arising other 10-13% after response to neoadyuvant chemotherapy. In order to perform the liver metastases surgery, it is necessary to have a sufficient remnant liver volume (RLV) which allows maintaining an optimal liver function after resection. Studies on liver regeneration have determined that CD133 + stem cells are involved in liver hypertrophy developed after an hepatectomy with encouraging results. As presented in previous studies, CD133 + stem cells can be selected from peripheral blood after stimulation with G-CSF, being able to obtain a large number of them. We propose to treat patients who do not meet criteria for liver metastases surgery because of insufficient RLV (<40%) with CD133 + cells together with portal embolization, in order to achieve enough liver volume which avoids liver failure. METHODS: /Design: The aim of this study is to evaluate the effectiveness of preoperative PVE plus the administration of CD133 + mobilized from peripheral blood with G-CSF compared to PVE only. SECONDARY AIMS ARE: to compare the grade of hypertrophy, speed and changes in liver function, anatomopathological study of hypertrophied liver, to determine the safety of the treatment and analysis of postoperative morbidity and surveillance. STUDY DESIGN: Prospective randomized longitudinal phase IIb clinical trial, open, to evaluate the efficacy of portal embolization (PVE) together with the administration of CD133 + cells obtained from peripheral blood versus PVE alone, in patients with hepatic metastasis of colorectal carcinoma (CCRHM). DISCUSSION: The number of CD133 + obtained from peripheral blood after G -CSF stimulation will be far greater than the number obtained with direct puncture of bone marrow. This will allow a greater intrahepatic infusion, which could have a direct impact on achieving a larger and quicker hypertrophy. Consequently, it will permit the treatment of a larger number of patients with an increase on their survival. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT03803241.

Laparoscopic Conversion from Single Anastomosis Duodeno-Jejunal Bypass with Sleeve Gastrectomy (SADJ-S) to Roux-en-Y Gastric Bypass (GBP): Improving Unsatisfactory Outcomes.

Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) can be considered as either a primary procedure or second stage procedure. Malnutrition is rare but could lead to a reversal of the SADI-S. The aim of this manuscript is to present the management and technique of weight regain after proximalization of a SADI-S by converting it to a gastric bypass.

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.

Poly (ADP-ribose) polymerase 3 (PARP3), a potential repressor of telomerase activity.

BACKGROUND: Considering previous result in Non-Small Cell Lung Cancer (NSCLC), we investigated in human cancer cells the role of PARP3 in the regulation of telomerase activity. METHODS: We selected A549 (lung adenocarcinoma cell line) and Saos-2 (osteosarcoma cell line), with high and low telomerase activity levels, respectively. The first one was transfected using a plasmid construction containing a PARP3 sequence, whereas the Saos-2 cells were submitted to shRNA transfection to get PARP3 depletion. PARP3 expression on both cell systems was evaluated by real-time quantitative PCR and PARP3 protein levels, by Western-blot. Telomerase activity was determined by TRAP assay. RESULTS: In A549 cells, after PARP3 transient transfection, data obtained indicated that twenty-four hours after transfection, up to 100-fold increased gene expression levels were found in the transfected cells with pcDNA/GW-53/PARP3 in comparison to transfected cells with the empty vector. Moreover, 48 hours post-transfection, telomerase activity decreased around 33%, and around 27%, 96 hours post-transfection. Telomerase activity average ratio was 0.67 ± 0.05, and 0.73 ± 0.06, respectively, with significant differences. In Saos-2 cells, after shRNA-mediated PARP3 silencing, a 2.3-fold increase in telomerase activity was detected in relation to the control. CONCLUSION: Our data indicated that, at least in some cancer cells, repression of PARP3 could be responsible for an increased telomerase activity, this fact contributing to telomere maintenance and, therefore, avoiding genome instability.

Methylation profiling in non-small cell lung cancer: clinical implications.

The aim of this study was to identify a panel of methylation markers that distinguish non-small cell lung cancers (NSCLCs) from normal lung tissues. We also studied the relation of the methylation profile to clinicopathological factors in NSCLC. We collected a series of 46 NSCLC samples and their corresponding control tissues and analyzed them to determine gene methylation status using the Illumina GoldenGate Methylation bead array, which screens up to 1505 CpG sites from 803 different genes. We found that 120 CpG sites, corresponding to 88 genes were hypermethylated in tumor samples and only 17 CpG sites (16 genes) were hypomethylated when compared with controls. Clustering analysis of these 104 genes discriminates almost perfectly between tumors and normal samples. Global hypermethylation was significantly associated with a worse prognosis in stage IIIA NSCLC patients (P=0.012). Moreover, hypermethylation of the CALCA and MMP-2 genes were statistically associated to a poor clinical evolution of patients, independently of TNM tumor stage (P=0.06, RR=2.64; P=0.04, RR=2.96, respectively). However, hypermethylation of RASSF1 turned out to be a protective variable (P=0.02; RR=0.53). In conclusion, our results could be useful for establishing a gene methylation pattern for the detection and prognosis of NSCLC.

Differential colorectal carcinogenesis: Molecular basis and clinical relevance.

Colorectal cancer (CCR) is one of the most frequent cancers in developed countries. It poses a major public health problem and there is renewed interest in understanding the basic principles of the molecular biology of colorectal cancer. It has been established that sporadic CCRs can arise from at least two different carcinogenic pathways. The traditional pathway, also called the suppressor or chromosomal instability pathway, follows the Fearon and Vogelstein model and shows mutation in classical oncogenes and tumour suppressor genes, such as K-ras, adenomatous polyposis coli, deleted in colorectal cancer, or p53. Alterations in the Wnt pathway are also very common in this type of tumour. The second main colorectal carcinogenesis pathway is the mutator pathway. This pathway is present in nearly 15% of all cases of sporadic colorectal cancer. It is characterized by the presence of mutations in the microsatellite sequences caused by a defect in the DNA mismatch repair genes, mostly in hMLH1 or hMSH2. These two pathways have clear molecular differences, which will be reviewed in this article, but they also present distinct histopathological features. More strikingly, their clinical behaviours are completely different, having the "mutator" tumours a better outcome than the "suppressor" tumours.

Telomere function in colorectal cancer.

Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world. Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process. Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length. It is achieved mainly, by telomerase activation. Thus, the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized. Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours. Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis. Taking into account all the results achieved by different groups, quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.

Telomere shortening is associated with poor prognosis and telomerase activity correlates with DNA repair impairment in non-small cell lung cancer.

BACKGROUND AND PURPOSE: Telomere function and DNA damage response pathways are frequently inactivated in cancer. Moreover, some telomere-binding proteins have been implicated in DNA repair. The purpose of this work consists of evaluating the prognostic impact of telomere dysfunction and its relationship with DNA repair systems in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We analysed 83 NSCLCs and their corresponding control samples obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. DNA repair expression assays were established by using cDNA arrays containing 96 DNA-repair genes and by Real Time Quantitative PCR. RESULTS: Our data indicated that telomere attrition was significantly associated with poor clinical outcome of patients (P=0.02), being this parameter a significant prognostic factor independent of tumour stage (P=0.012; relative risk=1.887; 95% CI: 1.147-3.102). DNA-repair gene expression studies showed down regulation of DCLRE1C and GTF2H1 and a clear FLJ10858 up regulation in tumour tissues, as compared to controls. In addition, a number of genes related to DNA-repair were significantly down regulated in tumours that reactivated telomerase (DCLRE1C, GTF2H1, PARP-3, MLH1, and TRF2). CONCLUSIONS: Telomere shortening emerged as a poor clinical evolution parameter in NSCLC. Moreover, results from this work suggest a relationship between the loss of several DNA repair genes and telomerase activity, which may be of relevance in the pathogenesis of non-small lung cancer.

Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma.

BACKGROUND: Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status. METHODS: Ninety-one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric-repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors. RESULTS: Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P=0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P=0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P=0.04; relative risk, 6.48). Among patients with tumors classified as telomerase-positive, telomere length ratios (the ratio of tumor tissues to normal tissues)