ABSTRACT
BACKGROUND: The early risk assessment of anastomotic leak (AL) after colorectal surgery is crucial. Several markers have been proposed, including peritoneal fluid's pH. Aim of the present study is to evaluate the role of drain fluid pH as predictor of AL. METHODS: All patients undergoing colorectal surgery from January 2015 to December 2017 were considered eligible. Hartmann procedures, procedures including temporary ileostomy and emergency surgery were excluded. Drain fluid was submitted for pH and chemical-physical assessment on postoperative day 1 (POD1) and postoperative day 3 (POD3). RESULTS: Out of 173 patients, those who developed AL showed a lower drain fluid's pH on POD1 and on POD3 compared to patients who did not (P<0.05). The plotted ROC curves identified 7.53 as pH cut-off on POD1 (AUC 0.80) and 7.21 on POD3 (AUC 0.86). With both the cut-offs, pH was an independent predictor of AL at multivariable analysis (P<0.001). pH<7.53 on POD1 and pH<7.21 on POD3 showed 93.75% sensitivity and 97% specificity respectively. CONCLUSIONS: Drain fluid's pH on POD1 is useful to select patients who will not develop AL while on POD3 it might identify those requiring a more careful management.
Subject(s)
Anastomotic Leak/diagnosis , Colectomy/adverse effects , Drainage , Elective Surgical Procedures/adverse effects , Adult , Aged , Aged, 80 and over , Analysis of Variance , Body Fluids/chemistry , Colectomy/methods , Female , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Postoperative Period , Prospective StudiesABSTRACT
BACKGROUND: INI1 (Integrase interactor 1), also known as SMARCB1, is the most studied subunit of chromatin remodelling complexes. Its role in colorectal tumorigenesis is not known. METHODS: We examined SMARCB1/INI1 protein expression in 134 cases of colorectal cancer (CRC) and 60 matched normal mucosa by using tissue microarrays and western blot and categorized the results according to mismatch repair status (MMR), CpG island methylator phenotype, biomarkers of tumor differentiation CDX2, CK20, vimentin and p53. We validated results in two independent data sets and in cultured CRC cell lines. RESULTS: Herein, we show that negative SMARCB1/INI1 expression (11% of CRCs) associates with loss of CDX2, poor differentiation, liver metastasis and shorter patients' survival regardless of the MMR status or tumor stage. Unexpectedly, even CRCs displaying diffuse nuclear INI1 staining (33%) show an adverse prognosis and vimentin over-expression, in comparison with the low expressing group (56%). The negative association of SMARCB1/INI1-lack of expression with a metastatic behavior is enhanced by the TP53 status. By interrogating global gene expression from two independent cohorts of 226 and 146 patients, we confirm the prognostic results and identify a gene signature characterized by SMARCB1/INI1 deregulation. Notably, the top genes of the signature (BCR, COMT, MIF) map on the long arm of chromosome 22 and are closely associated with SMARCB1/INI1. CONCLUSION: Our findings suggest that SMARCB1/INI1-dysregulation and genetic hot-spots on the long arm of chromosome 22 might play an important role in the CRC metastatic behavior and be clinically relevant as novel biomarkers.
Subject(s)
Chromatin Assembly and Disassembly/genetics , Chromosomal Proteins, Non-Histone/metabolism , Chromosomes, Human, Pair 22/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA-Binding Proteins/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Transcription Factors/metabolism , Aged , Biomarkers, Tumor/metabolism , Cell Differentiation , Chromosomal Proteins, Non-Histone/genetics , Cohort Studies , DNA-Binding Proteins/genetics , Female , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Male , Prognosis , SMARCB1 Protein , Survival Analysis , Tissue Array Analysis , Transcription Factors/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
Rhabdoid colon tumors (RCTs) are rare lesions whose existence as an independent distinct entity remains controversial. To date, 6 RCTs have been reported. This study reports a novel case associated with polyposis coli in a 73-year-old woman. Histologically, the neoplasia was heterogeneous consisting of an adenocarcinoma associated with rhabdoid features. In rhabdoid component, an intense expression of MSH2 was noted but MLH1 was negative. A BRAF V600E mutation and no KRAS mutations were identified. The promoter regions of subset of genes highly specific to characterize the CIMP status (NEUROG1, IGF2, RUNX3, SOCS1, including MLH1) were hypermethylated, suggesting the presence of CIMP+ and MSI high tumor. In conclusion, all RCTs have similar clinical features. The presence of polyposis and adenocarcinoma component as well as the expression of mesenchymal marker suggests a sarcomatous dedifferentiation. It is argued that RCT could be a very aggressive entity of colon, which could benefit from new biological colonic treatments.
