Short-Term Outcomes in Patients Undergoing Paraesophageal Hiatal Hernia Repair.

Many patients with hiatal hernias (HH) are asymptomatic; however, symptoms may include heartburn, regurgitation, dysphagia, nausea, or vague epigastric pain depending on the hernia type and severity. The ideal technique and timing of repair remains controversial. This report describes short-term outcomes and readmissions of patients undergoing HH repair at our institution. All patients who underwent HH repair from January 2012 through April 2017 were reviewed. Patients undergoing concomitant bariatric surgery were excluded. 239 patients were identified and 128 were included. Eighty-eight were female (69%) and 40 were male (31%) with a mean age of 59 years (range 20-91 years) and a mean BMI of 29.2 kg/m2 (17-42). Worsening GERD was the most common presenting symptom in 79 (61.7%) patients. Eighty-four laparoscopic cases (65.6%) and 44 robotic assisted (34.4%) procedures were performed. Mesh was used in 59 operations (3 polytetrafluoroethylene; 56 biologic). All hiatal hernia types (I-IV) were collected. Majority were initial operations (89%). Techniques included: Toupet fundoplication in 68 cases (63.0%), Nissen fundoplication in 36 (33.3%), Dor fundoplication in 4 (3.7%), concomitant Collis gastroplasty in 4 (3.1%), and primary suture repair in 20 (15.6%). Outcomes between robotic and laparoscopic procedures were compared. Length of stay was reported as median and interquartile range for laparoscopic and robotic: 1.0 day (1.0-3.0) and 2.0 days (1.0-2.5); p = 0.483. Thirty-day readmission occurred in 9 patients, 7 (8.3%) laparoscopic and 2 (4.6%) robotic; p = 0.718. Two 30-day reoperations occurred, both laparoscopic; p = 0.545. Total of 16 complications occurred; 18.6% had a complication with the use of mesh compared to 8.7% without the use of mesh, p = 0.063. There were no conversion to open modality and no mortalities were reported. Hiatal hernia repair can be performed safely with a low incidence of complications.

Spatio-temporal tumor heterogeneity in metastatic CRC tumors: a mutational-based approach.

It is well known that activating mutations in the KRAS and NRAS genes are associated with poor response to anti-EGFR therapies in patients with metastatic colorectal cancer (mCRC). Approximately half of the patients with wild-type (WT) KRAS colorectal carcinoma do not respond to these therapies. This could be because the treatment decision is determined by the mutational profile of the primary tumor, regardless of the presence of small tumor subclones harboring RAS mutations in lymph nodes or liver metastases. We analyzed the mutational profile of the KRAS, NRAS, BRAF and PI3KCA genes using low-density microarray technology in samples of 26 paired primary tumors, 16 lymph nodes and 34 liver metastases from 26 untreated mCRC patients (n=76 samples). The most frequent mutations found in primary tumors were KRAS (15%) and PI3KCA (15%), followed by NRAS (8%) and BRAF (4%). The distribution of the mutations in the 16 lymph node metastases analyzed was as follows: 4 (25%) in KRAS gene, 3 (19%) in NRAS gene and 1 mutation each in PI3KCA and BRAF genes (6%). As expected, the most prevalent mutation in liver metastasis was in the KRAS gene (35%), followed by PI3KCA (9%) and BRAF (6%). Of the 26 cases studied, 15 (58%) displayed an overall concordance in the mutation status detected in the lymph node metastases and liver metastases compared with primary tumor, suggesting no clonal evolution. In contrast, the mutation profiles differed in the primary tumor and lymph node/metastases samples of the remaining 11 patients (48%), suggesting a spatial and temporal clonal evolution. We confirm the presence of different mutational profiles among primary tumors, lymph node metastases and liver metastases. Our results suggest the need to perform mutational analysis in all available tumor samples of patients before deciding to commence anti-EGFR treatment.

Paraesophageal Hiatal Hernia Repair With Urinary Bladder Matrix Graft.

BACKGROUND AND OBJECTIVES: Paraesophageal hiatal hernia repair can be performed with or without mesh reinforcement. The use, technique, and mesh type remain controversial because of mixed reports on mesh-related complications. Short-term outcomes have become important in all forms of surgery. METHODS: From January 2012 through April 2017, all patients who underwent isolated hiatal hernia repair in our center were reviewed. Concomitant bariatric surgery cases were excluded. Repairs reinforced by porcine urinary bladder matrix (UBM) graft were compared to non-UBM repairs. Statistical comparison was based on a Wilcoxon 2-sample test or Fisher's exact test. RESULTS: We reviewed 239 charts; 110 bariatric cases and 8 cases with non-UBM reinforcement were excluded. We identified 121 patients: 56 UBM-reinforced (46.3%) versus 65 non-UBM (53.7%). Sixteen (28.6%) UBM cases were male versus 23 (35.4%) non-UBM cases. The UBM patients were significantly older (63.9 versus 54.3; P = .001). There was no difference in mean BMI (29.6 vs 28.5; P = .28). Cases were performed laparoscopically (60.7% vs 67.7%; P = .45) or robotically (39.3% vs 32.3%; P = .45), with no conversions to open. The UBM group had a longer mean operative time (183 minutes vs 139 minutes; P = .001).There was no difference in median length of stay (2 days vs 2 days; P = .09) or 30-day readmission rate (7.1% vs 7.5%; P =.99). Postoperative complications were graded according to the Clavien-Dindo classification, and there was no difference (19.6% vs 9.2%; P = .12). CONCLUSIONS: Hiatal hernia repair with UBM reinforcement can be performed safely with no increase in postoperative complications.

Combined assessment of the TNM stage and BRAF mutational status at diagnosis in sporadic colorectal cancer patients.

The prognostic impact of KRAS mutations and other KRAS-related and non-related genes such as BRAF, NRAS and TP53, on sporadic colorectal cancer (sCRC) remain controversial and/or have not been fully established. Here we investigated the frequency of such mutations in primary sCRC tumors and their impact on patient progression-free survival (PFS) and overall survival (OS). Primary tumor tissues from 87 sCRC patients were analysed using a custom-built next generation sequencing (NGS) panel to assess the hotspot mutated regions of KRAS/NRAS (exons 2, 3 and 4), BRAF (exon 15) and TP53 (all exons). Overall, mutations in these genes were detected in 46/87 sCRC tumors analyzed (53%) with the following frequencies per gene: TP53, 33%; KRAS, 28%; BRAF, 7%; and NRAS, 1%. A significant association was found between KRAS mutations and right side colon tumor location (p=0.05), well-differentiated tumors (p=0.04) and absence of lymphovascular invasion (p=0.05). In turn, BRAF-mutated tumors frequently corresponded to poorly- or moderately-differentiated sCRC (p=0.02) and showed a higher frequency of peritoneal carcinomatosis (p=0.006) and microsatellite instability (p=0.007). From the prognostic point of view, the BRAF mutational status together with the TNM stage were the only variables that showed an independent adverse impact on patient outcome in the multivariate analyses for both PFS and OS. Based on these results a scoring system was built and patients were classified into three prognostic subgroups with different PFS rates at 2 years: 91% vs. 77% vs. 0%, respectively (p<0.0001). Additional prospective studies in larger series of sCRC patients where mutations in genes other than those investigated here are required to validate the utility of the proposed predictive model.

Prognostic impact of a novel gene expression profile classifier for the discrimination between metastatic and non-metastatic primary colorectal cancer tumors.

Despite significant advances have been achieved in the genetic characterization of sporadic colorectal cancer (sCRC), the precise genetic events leading to the development of distant metastasis remain poorly understood. Thus, accurate prediction of metastatic disease in newly-diagnosed sCRC patients remains a challenge. Here, we evaluated the specific genes and molecular pathways associated with the invasive potential of colorectal tumor cells, through the assessment of the gene expression profile (GEP) of coding and non-coding genes in metastatic (MTX) vs. non-metastatic (non-MTX) primary sCRC tumors followed for >5 years. Overall, MTX tumors showed up-regulation of genes associated with tumor progression and metastatic potential while non-MTX cases displayed GEP associated with higher cell proliferation, activation of DNA repair and anti-tumoral immune/inflammatory responses. Based on only 19 genes a specific GEP that classifies sCRC tumors into two MTX-like and non-MTX-like molecular subgroups was defined which shows an independent prognostic impact on patient overall survival, particularly when it is combined with the lymph node status at diagnosis. In summary, we show an association between the global GEP of primary sCRC cells and their metastatic potential and defined a GEP-based classifier that provides the basis for further prognostic stratification of sCRC patients who are at risk of distant metastases.

Genomic characterization of liver metastases from colorectal cancer patients.

Metastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases. Liver metastases from the sCRC patients analyzed, systematically showed deregulated transcripts of those genes identified as also deregulated in their paired primary colorectal carcinomas. However, some transcripts were found to be specifically deregulated in liver metastases (vs. non-tumoral colorectal tissues) while expressed at normal levels in their primary tumors, reflecting either an increased genomic instability of metastatic cells or theiradaption to the liver microenvironment. Newly deregulated metastatic transcripts included overexpression of APOA1, HRG, UGT2B4, RBP4 and ADH4 mRNAS and the miR-3180-3p, miR-3197, miR-3178, miR-4793 and miR-4440 miRNAs, together with decreased expression of the IGKV1-39, IGKC, IGKV1-27, FABP4 and MYLK mRNAS and the miR-363, miR-1, miR-143, miR-27b and miR-28-5p miRNAs. Canonical pathways found to be specifically deregulated in liver metastatic samples included multiple genes related with intercellular adhesion and the metastatic processes (e.g., IGF1R, PIK3CA, PTEN and EGFR), endocytosis (e.g., the PDGFRA, SMAD2, ERBB3, PML and FGFR2), and the cell cycle (e.g., SMAD2, CCND2, E2F5 and MYC). Our results also highlighted the activation of genes associated with the TGFß signaling pathway, -e.g. RHOA, SMAD2, SMAD4, SMAD5, SMAD6, BMPR1A, SMAD7 and MYC-, which thereby emerge as candidate genes to play an important role in CRC tumor metastasis.