Ileal Lactase Expression Associates with Lactase Persistence Genotypes

(1) Background: Lactose digestion depends on persistence genotypes (including rs4988235), the frequency of which exhibits broad geographical variability. However, little is known about the relationship between lactase (LCT) genotypes and intestinal expression of LCT. We aimed to investigate ileal expression of LCT depending on main genetic polymorphisms (rs4988235, rs3754689, rs3739022), age, sex, smoking status, body mass index (BMI), and the expression of other genes; (2) Methods: phenotype, array-based genotype, and ileal mucosal biopsy expression data were obtained from the CEDAR study; (3) Results: analyses included 196 healthy Europeans (53.6% women) aged 53.0 ± 13.6 years with a mean BMI of 25.6 ± 4.2 kg/m2, of whom 17.4% were smoking. Ileal LCT expression was mostly independent of age, sex, BMI, or smoking. Rs4988235 homozygous minor allele (GG) associated with lower LCT expression (vs. AG p = 2.2 × 10−6, vs. AA p = 1.1 × 10−7). Homozygous major allele of rs3754689 (GG) was related to higher LCT expression (vs. AG p = 1.7 × 10−5, vs. AA p = 0.0074). Rs3754689 genotype did not modify LCT expression (GG vs. AG p = 0.051) in rs4988235-heterozygous subgroup. Interestingly, CD14, which is a marker of monocytes and macrophages, was the strongest negative transcriptomic correlate of LCT expression (r = −0.57, pFDR = 1.1 × 10−14); (4) Conclusions: both rs4988235 and rs3754689 associated with ileal LCT expression, which did not seem related to age, sex, smoking, or BMI. The inverse correlation between LCT and CD14 expression in the ileum is striking and requires further investigation.

High Concordance of HER2 Overexpression by Immunohistochemistry on Mucosal Biopsies and Resection in Gastric Adenocarcinoma

Introduction: High expression of Human Epidermal growth factor Receptor 2 (HER2) is a predictive biomarker for the treatment of gastric carcinomas with targeted agents. Targeted therapy could improve the outcome of patients with gastric carcinoma overexpressing HER2. There is limited information on mucosal biopsies to characterise the HER2 expression status of a tumour. Aim: To study HER2 expression by Immunohistochemistry (IHC) in matched mucosal biopsies and surgical specimens in patients with gastric adenocarcinoma and to discover the level of concordance. Materials and Methods: This was a prospective observational study conducted in the Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India, for one year (1st July 2016 to 30th June 2017). The IHC for HER2 was performed on matched mucosal biopsies and corresponding gastrectomy specimens of 72 patients. The HER2 overexpression (HER2+) was defined by a score 3+ on IHC. The results were analysed using Statistical Package for the Social Sciences (SPSS) software and Chi-square test was done for statistical significance. Results: The overall HER2 positivity rate was 11.11% (8/72). The HER2 positive rates (score 3+) were 9.72% on biopsy (7/72) and 8.33% on resection (6/72). Five cases showed concordance of HER2 between mucosal biopsies and resection specimens, however the other three cases showed a discordance i.e., two mucosal biopsies showed HER2 positivity and one resection showed HER2 positivity. The concordance rate in this study was 95.83% between resection and mucosal biopsies. Among the eight HER2 positive cases, five cases showed good concordance. One case showed positive shift: HER2 score was 0 on the mucosal biopsy and HER2 score was 3+ on the resection. Two cases showed a negative shift: mucosal biopsy showed HER2 score 3+ and the resection HER2 score 0. All the three discordant cases had received Neoadjuvant Chemotherapy (NACT) and showed heterogeneous staining on the resection specimen. None of the five concordant cases had received NACT and three of the five resections showed heterogeneous staining pattern. Conclusion: To the best of the authors’ knowledge, this was the first study to compare HER2 expression in gastric adenocarcinoma in matched biopsies and the corresponding resections in India. There was concordance of HER2 expression in 69 cases and discordance in three. Differences between biopsy and resection HER2 expression could be explained by intra-tumoural heterogeneity and possibly by decreased HER2 expression after NACT. The HER2 analysis by IHC on both mucosal biopsy and resections could optimise the selection of trastuzumab-eligible patients in case of gastric adenocarcinoma.

Endoscopic Biopsies and Histopathological Findings in Diagnosing Chronic Gastrointestinal Disorders in Dogs and Cats

Nowadays, endoscopic examination is a diagnostic tool gaining popularity in the management of gastrointestinal disorders in dogs and cats. Direct accessibility of the lumen of gastrointestinal tract combined with the mucosal biopsy provides a great diagnostic potential. Using endoscopy and endoscopically guided biopsy, one can conduct both macro- and microscopic assessment of lesions and perform many specialist adjunct examinations. Histopathological examination of mucosal biopsy specimens collected from the stomach and intestines allows us to distinguish between types of inflammations and to diagnose ulcerative, polypoid, and cancerous lesions.

Untangling Species-Level Composition of Complex Bacterial Communities through a Novel Metagenomic Approach

ABSTRACT 16S small-subunit (SSU) rRNA gene-based bacterial profiling is the gold standard for cost-effective taxonomic reconstruction of complex bacterial populations down to the genus level. However, it has been proven ineffective in clinical and research settings requiring higher taxonomic resolution. We therefore developed a bacterial profiling method based on the internal transcribed spacer (ITS) region employing optimized primers and a comprehensive ITS database for accurate cataloguing of bacterial communities at (sub)species resolution. Performance of the microbial ITS profiling pipeline was tested through analysis of host-associated, food, and environmental matrices, while its efficacy in clinical settings was assessed through analysis of mucosal biopsy specimens of colorectal cancer, leading to the identification of putative novel biomarkers. The data collected indicate that the proposed pipeline represents a major step forward in cost-effective identification and screening of microbial biomarkers at (sub)species level, with relevant impact in research, industrial, and clinical settings. IMPORTANCE We developed a novel method for accurate cataloguing of bacterial communities at (sub)species level involving amplification of the internal transcribed spacer (ITS) region through optimized primers, followed by next-generation sequencing and taxonomic classification of amplicons by means of a comprehensive database of bacterial ITS sequences. Host-associated, food, and environmental matrices were employed to test the performance of the microbial ITS profiling pipeline. Moreover, mucosal biopsy samples from colorectal cancer patients were analyzed to demonstrate the scientific relevance of this profiling approach in a clinical setting through identification of putative novel biomarkers. The results indicate that the ITS-based profiling pipeline proposed here represents a key metagenomic tool with major relevance for research, industrial, and clinical settings.

The role of intraoperative kidney mucosal biopsy on screening of squamous cell carcinoma of the kidney in nephrolithiasis patients with stones larger than 20 mm

Introduction: Renal pelvic squamous cell carcinoma is a very rare tumor, with a prevalence <1% of all urinary tract tumors, about 0.5–8% of all kidney tumors, and the average age is 50–70 years. Although the incidence of renal squamous cell carcinoma is less common than renal cell carcinoma and renal transitional cell carcinoma, due to its more aggressive nature renal squamous cell carcinoma is often found intraoperatively and is already in an advanced stage or metastasis. The relevant medical history of squamous cell carcinoma is pyelonephritis, chronic nephrolithiasis, and a history of kidney stone surgery. Data which was obtained from previous research at Hasan Sadikin Hospital, from January 2014–December 2017, found the incidence of renal squamous cell carcinoma from nephrectomy procedures was 6%. Methods: This study was a cross-sectional study with a correlative analytic study, samples were taken consecutively from biopsy of kidney mucosa intraoperatively in hospitalized patients with kidney stones with size larger than 20 mm at the Department of Urology, Hasan Sadikin Hospital Bandung, which performed open kidney surgery or percutaneous nephrolithotomy from January–May 2019. Results: The number of samples in this study were from 30 patients, consisting of 16 males and 14 females. Five patients underwent open kidney surgery and 25 patients underwent percutaneous nephrolithotomy surgery, with an average of age of 49.5±11.8 years and 63.3% of patients were aged from 40–60 years. In this study, one patient (3.3%) showed squamous cell carcinoma of the kidney, a 57-year-old male patient with a left staghorn kidney stone who underwent left percutaneous nephrolithotomy surgery. Conclusion: There is a benefit for intraoperative kidney mucosal biopsy as a screening for squamous cell carcinoma of the kidney in nephrolithiasis patients with stones larger than 20 mm. Level of evidence: 3