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.

Is prophylactic mesh closure effective to decrease the incidence of incisional hernia after laparotomy in colorectal surgery?

BACKGROUND: few studies have studied prophylactic mesh closure after laparotomy for colorectal surgery. METHODS: a retrospective cohort study was performed to compare patients with and without prophylactic mesh closure after open colorectal surgery. RESULTS: 309 patients were included from January 2014 to December 2016. Prophylactic mesh closure was performed in 98 patients (31.7%). After a mean follow-up of 21.7 months, incisional hernia was developed in 9 and 54 patients in the group with and without mesh respectively (9.2% vs. 25.7%, OR = 0.3, p = 0.001). In the multivariate Cox model prophylactic mesh closure was associated with a protective effect on incisional hernia development with a Hazard Ratio of 0.46 (p = 0.033). Surgical site infection was more frequent in the mesh group (19.4% vs. 9.5%, OR = 2.3, p = 0.015). CONCLUSIONS: prophylactic mesh closure is effective to decrease the incidence of incisional hernia after colorectal surgery.

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.

Extraction-site incisional hernia after laparoscopic colorectal surgery: should we carry out a study about prophylactic mesh closure?

BACKGROUND: Prophylactic mesh closure has only scarcely been studied to avoid extraction-site incisional hernia after laparoscopic colorectal surgery. The aim was to analyze extraction-site incisional hernia incidence after laparoscopic colorectal surgery to assess if prophylactic mesh closure should be studied. METHODS: A retrospective analytic cohort study was conducted in patients who had undergone laparoscopic colorectal surgery with an extraction-site incision. Extraction-site incisional hernia was diagnosed during clinical examination or imaging. Risk factors for extraction-site incisional hernia were analyzed. RESULTS: Two hundred and twenty-five patients were included. More than 80% of the patients had a malignant disease. Ninety-two patients (40.9%) underwent right colectomy. Midline extraction-site incision was used in 86 (38.2%) patients. After a mean follow-up of 2.4 years, 39 (17.3%) patients developed an extraction-site incisional hernia. Midline extraction-site incision was associated with incisional hernia when compared to transverse and Pfannenstiel incision (39.5% vs. 3.6%, OR 17.5, p < 0.001). Surgery to repair an extraction-site incisional hernia was also more frequent in the group of patients with a midline incision (10.5% vs. 1.4%, OR 8.0, p = 0.002). In the multivariate analysis, incisional hernia was associated with body mass index, high blood pressure, and midline incision. CONCLUSIONS: Extraction-site incisional hernia was mainly related to midline incisions; therefore, midline incision should be avoided whenever possible. Studying prophylactic mesh closure for Pfannesnstiel or transverse incisions is needless, as these incisions have a low incisional hernia risk.

Long-Term Food Tolerance After Bariatric Surgery: Comparison of Three Different Surgical Techniques.

BACKGROUND: Food tolerance has been related to quality of life after bariatric surgery. However, long-term results about this issue are quite limited. The aim of this study was to evaluate the long-term food tolerance in obese patients submitted to surgery, comparing the results between gastric bypass (GBP), long alimentary modified biliopancreatic diversion (MBPD), and long alimentary modified duodenal switch (MDS). METHODS: A cross-sectional analytic study was performed. Food tolerance was studied with a questionnaire based on subjective alimentary satisfaction, tolerance to different foods, and frequency of vomiting and regurgitation. A food tolerance score was obtained (1 point being the worst possible tolerance and 27 points being a perfect one). Information was obtained with a telephone interview. RESULTS: One hundred ninety-six patients submitted to bariatric surgery were included. Ninety-nine patients were submitted to GBP, 54 to MBPD, and 43 to MDS. One hundred and sixty-one patients (82.1%) were not lost during a mean follow-up time of 87.9 months. Mean food tolerance score was 24.2. Tolerance satisfaction was good or excellent in 73.3% of the patients. Red meat was the worst tolerated food, but nearly 80% of the patients could tolerate it without any problem. Mean food tolerance score was 24.6, 24.0, and 23.7 for GBP, MBPD, and MDS, respectively. There were no significant differences between these procedures in food tolerance score, alimentary satisfaction, or frequency of vomiting. CONCLUSIONS: Long-term food tolerance after bariatric surgery is good. No differences between GBP, MBPD, and MDS were found.

Technique of Hill's Gastropexy Combined with Sleeve Gastrectomy for Patients with Morbid Obesity and Gastroesophageal Reflux Disease or Hiatal Hernia.

BACKGROUND: Observational studies based on quality-of-life and endoscopy relate sleeve gastrectomy (SG) to gastroesophageal reflux disease (GERD), while some functional studies have demonstrated a decrease in esophageal exposure to gastric acid after SG. Currently, it is recommended to treat hiatal hernia along with the SG. However, as the sleeve gastrectomy involves the resection of the fundus, it is not possible to add a traditional fundoplication to the closure of the hiatus. METHODS: Based on the classic works of Hill et al., and more recent studies by Swänstrom and Aye, our group has incorporated a modified Hill's gastropexy to the sleeve gastrectomy for patients with pathologic GERD and/or huge hiatal hernia submitted to weight loss surgery. RESULTS: A 28-year-old male patient, 43 kg/m(2) BMI, with a small hiatal hernia and pathologic GERD was scheduled for sleeve gastrectomy. After complete fundus and left crus dissection, the phrenoesophageal membrane was opened and the distal esophagus dissected. The hiatus was closed with interrupted sutures. The sleeve was completed over a 42-French bougie. The preaortic fascia was dissected at the root of the crura and three interrupted sutures placed approximating the gastroesophageal junction to the aforementioned fascia. At 6 months from the operation, weight loss has been satisfactory and the patient does not complaint GERD. Barium swallow demonstrates absence of gastroesophageal reflux, pHmetry and manometry have normalized, and endoscopy shows no esophagitis. CONCLUSIONS: Gastropexy to the preaortic fascia is a possible antireflux technique to combine with SG.

Aortic injury during laparoscopic esophageal hiatoplasty.

A 75-year-old female patient with a type III hiatal hernia was submitted to laparoscopic mesh hiatoplasty. Soon after the last suture fixed the mesh to the left crura, a hemorrhage was observed. Conversion to open surgery was not performed. The most common sources of bleeding (liver, phrenic arteries, crura, spleen, and short gastric vessels) were discarded as the cause of the hemorrhage. The mesh was set free in order to explore the lower mediastinum. The source of the hemorrhage was identified: it was the last suture fixing the mesh to the left crura, which was found passing through the aortic wall. The hemorrhage stopped as soon as the suture was removed. When facing a hemorrhage during this kind of surgery, it is essential to be methodical to discover the source of the bleeding. First of all, the most common sources of bleeding must be checked out. Injury of the inferior vena cava must also be ruled out, because it is an uncommon but potentially lethal complication. Afterwards, the lower mediastinum must be explored. Conversion to an open approach is needed if the patient becomes unstable or the surgeon does not have enough laparoscopic skills to find and solve the bleeding. Most of the reported cases of aortic injury during laparoscopic hiatoplasty are secondary to vascular injuries during port insertion. When a suture is the cause of bleeding, the removal of the stitch should be enough to stop the bleeding. If there is a tear of the aortic wall, a patch should be employed for the repair. In conclusion, left crura and thoracic aorta are very close to one another. The surgeon must be very careful when working near the left crura, mostly in old patients with a dilated and aneurysmatic aorta.