Renal cell carcinoma with renocolic fistula presenting as an emphysematous pyelonephritis in a non-functioning kidney: case report

Background The uniqueness of this case is in its rarity and divergent presentation. Case presentation Here, we report a case of 56-year-old male patient with pain in the left flank for 1 year. On evaluation, patient was diagnosed with multiple left renal calculi and emphysematous pyelonephritis with non-functioning kidney. Intraoperatively, dense perinephric adhesions, necrotic kidney and renocolic fistula were encountered. The patient underwent left nephrectomy with resection anastomosis of descending colon segment with loop ileostomy. Histopathological examination showed a poorly differentiated high-grade clear cell carcinoma with squamous metaplasia. Conclusion Renal cell carcinoma can present in unusual ways. Sometimes, it can mimic emphysematous pyelonephritis because of fistulous communication with gut. It is rare but challenging for urologists to diagnose and manage such cases.

The metabolome and lipidome of colorectal adenomas and cancers

Introduction: In-depth knowledge of metabolic dysregulations in colorectal cancer (CRC) (and other cancers as well) is essential for developing treatments that specifically kill neoplastic cells. It may also allow us to pinpoint metabolites or lipids with potential for development as tumor biomarkers for use in body-fluid or breath assays. CRC onset is preceded by an interval of about 10 years characterized by the presence of precancerous lesions, and our previous studies have revealed epigenomic, transcriptomic, and proteomic evidence in these lesions of certain metabolic changes typical of CRC. These findings prompted us to conduct untargeted metabolomic and lipidomic analyses of CRCs and colorectal adenomas (the most common precancerous lesions of the gut). Methods: We analyzed 29 endoscopically collected tumor tissue samples (29 adenomas [ADNs], 10 CRCs, each with a colon segment-matched sample of normal mucosa [i.e., 29 NM-ADN, 10 NM-CRC]). The freshly collected samples were promptly frozen in liquid nitrogen and later processed to obtain metabolite and lipid extracts. Each of the 78 samples was analyzed with nano-flow LC-MS/MS (liquid chromatography with mass spectrometry) to characterize its metabolome (using HILIC, Hydrophilic Interaction Liquid Chromatography) and lipidome (using RP, Reversed Phase chromatography). The data acquired were processed using Progenesis QI. For statistical and multivariate analysis of the resulting peak tables, we used basic R packages and the R package made4. Results: Unsupervised between-group analysis based on the full set of detected metabolites (n=1830) and lipids (n=2365) clearly discriminated ADNs and CRCs from their matched samples of normal mucosa at both the metabolome and lipidome levels. Compared with the NM-ADN, the ADNs contained significantly different levels of 14.6% of the metabolites and 10.8% of the lipids. Fewer compounds (9.1% of metabolites, 6.2% of lipids) displayed differential abundance in CRCs (vs. NM-CRC). The metabolome and lipidome of the NM-ADN also differed from those of the NM-CRC, probably reflecting the presence of a field cancerization effect exerted by the invasive tumors. A substantial number of metabolites (n=340) and lipids (n=201) also displayed abundance differentials across the sequential tumorigenic stages represented by the NM-ADN (considered more representative of NM from a lesion-free colon) → ADN → CRC. In most cases, the trend consisted of progressive increases or progressive decreases in abundance as the tumorigenesis advanced. Conclusions: Our findings provide a preliminary picture of the progressive metabolomic and lipidomic changes occurring during the adenomatous phase of colorectal tumorigenesis. Once definitively annotated, the numerous differentially abundant compounds detected in this study may well shed valuable light on the metabolic dysregulations occurring during this process and provide useful clues for the development of novel tools for the diagnosis and treatment of colorectal tumors.

P024 Development of a treatment for short bowel syndrome using small intestinal organoids

Background Massive small intestinal resection leads to short bowel syndrome (SBS), which is a severe malabsorption disorder. Crohn’s disease is one of the most frequent cause of surgical removal of the small intestine in adults. Severe SBS patients need to receive permanent parenteral nutrition, which can cause serious complications. Intestinal transplantation currently remains the only curative option for such patients but has not widespread due to its high mortality/rejection rates. Here, we propose a concept to generate a rejection-free small intestinalized colon (SIC) by replacing the native colonic epithelium with small intestinal organoids. Methods Human normal intestinal organoids and rat intestinal organoids derived from luciferase-expressing LEW transgenic rats were established and cultured as previously described (Fujii et al. Cell Stem Cell 2018). Human colon or ileum organoids were xenotransplanted onto the EDTA-injured colon of immunodeficient mice via transanal infusion as previously described (Sugimoto et al. Cell Stem Cell 2018). In LEW rats, a 4-cm segment of the ascending and proximal transverse colon was dissected with the preservation of the vasculature. After EDTA-based removal of the colon epithelium, rat colon or ileum organoids were transplanted in a blinded manner. Following organoid transplantation, the colon segment was fixed to the abdominal walls as stoma outlets for a week. Afterwards, organoid-transplanted colon segment was trimmed and interposed between the jejunum beginning and the ileocolic valve following total jejunoileum resection. Overall survival and detailed histological analyses were performed. Results Xenotransplanted human ileum organoids reconstituted nascent villus structures reminiscent of the ileum epithelium in mouse colon. Furthermore, ileum xenografts exhibited a formation of Lyve-1+ lacteal-like structure equipped with the absorption-related machinery, but not colon xenografts. In rats, engrafted ileum organoids initially formed crypt-like structures in the colostomy and, after interposition, they developed mature villus structures. The villus formation was small intestine-specific and flow-dependent. The SIC gained small intestinal function along with the remodelling of the underlying lymphovascular networks. Ileum organoid-transplanted rats exhibited milder body weight loss and significantly higher survival rate compared to colon organoid-transplanted rats. Conclusion The SIC with villus structure, intact vasculature and innervation, and the lacteal, had absorptive and peristalsis functions. Small intestinal organoid transplantation as cell source of the SIC ameliorated intestinal failure in a rat SBS model.

Growth Performance, Gut Environment and Physiology of the Gastrointestinal Tract in Weaned Piglets Fed a Diet Supplemented with Raw and Fermented Narrow-Leafed Lupine Seeds

The aim of this study was to: (1) provide controlled fermentation of narrow-leafed lupine seeds; (2) monitor seed composition, and (3) determine the influence of fermentation on the performance, gut environment and physiology, and selected blood metabolic parameters, in young pigs. Firstly, the effect of 24 h lupine seed fermentation by bacteria and yeast on seed chemical composition was determined. It increased contents of crude protein, crude fiber and ash, but reduced nitrogen-free extractive levels. The amino acid profile of fermented lupine (FL) was similar to that of raw lupine (RL) seeds, whereas the contents of oligosaccharides and P-phytate decreased significantly, in contrast to alkaloids. In fermented feed, pH dropped from 5.5 to 3.9. In the 28-day experiment, 24 male pigs were divided into three groups. The control group was fed a soybean meal diet (SBM), whereas in the experimental diets, 50% of SBM protein was replaced by RL or FL. Afterwards, eight pigs from each group were euthanized and their digesta and blood samples were collected. The FL use did not affect pigs’ performance, nor their metabolic, microbial and most gastrointestinal tract parameters, but influenced crypt depth. Fermentation affected concentrations of short chain fatty acids and p-cresole in the proximal colon segment. In the small intestine, the levels of acetate and butyrate decreased, and, in the caecum, the propionate level decreased. Fermentation significantly lowered the pH of the middle colon digesta and ammonia contents compared to RL. A part of SBM may be successfully replaced by RL and FL in young pigs’ diets.

Inter-Observer Agreement of a New Endoscopic Score for Ulcerative Colitis Activity: Preliminary Experience

Ulcerative colitis (UC) endoscopic scores translate mucosal damage into values standardizing image analysis. Due to potential limits of current endoscopic activity indexes, we have elaborated on a new score, the “Extended Mayo Endoscopic Score (EMES),” and evaluated its inter-observer agreement in a multicenter endoscopy team, comparing concordance with the Mayo subscore. Sixteen UC consecutive patients underwent follow-up colonoscopy. Recorded videos were anonymously loaded on a web platform. Thirteen expert endoscopists evaluated UC activity using both Mayo and EMES. EMES was described in every colon segment: erythema (0: absent, 1: mild, 2: moderate, 3: severe), vascular pattern (0: normal, 1: reduction, 2: disappearance), erosions and ulcers (0: absent, 1: from 1 to 5, 2: 6 to 10, 3: >10). Weighted Fleiss’ kappa with 95% confidence interval (CI) and p-value defined inter-rater agreement. Global inter-observer agreement of EMES was moderate (kappa = 0.56, 95% CI = 0.46–0.67, p < 0.001). The evaluation of each colonic segment showed moderate agreement for all segments: ascending (kappa = 0.46, 95% CI = 0.32–0.60, p < 0.001), transverse (kappa = 0.48, 95% CI = 0.29–0.67, p < 0.001); descending (kappa = 0.49, 95% CI = 0.35–0.64, p < 0.001), sigmoid (kappa = 0.52, 95% CI = 0.39–0.65, p < 0.001) and rectum (kappa = 0.55, 95% CI = 0.42–0.69, p < 0.001). Mayo subscore agreement was similar to global EMES (kappa = 0.53, 95% CI = 0.39–0.66, p = 0.001). Therefore, our report emphasizes the importance of assessing inter-observer agreement for EMES, but also for other known scoring systems, including the Mayo subscore.

Effect of Huangqin Tang on Colonic Gene Expression in Rats with Ulcerative Colitis

In this study, we explored the pharmacological mechanisms of Huangqin Tang (HQT; a traditional Chinese medicine formula) in ulcerative colitis (UC) and provided evidence for potential roles HQT plays by gene expression profiling. The UC rat model was made via a compound method (trinitrobenzene sulfonic acid plus ethanol). After a ten-day treatment, microarray analysis was performed from the colon segment of the rats. Biological functions and specific signaling pathways were enriched based on differentially expressed genes (DEG), and corresponding gene networks were constructed via Ingenuity Pathway Analysis (IPA). Through the network, we screened the potential “candidate targets,” such as ITGB1, FN1, CASP3, and ITGA5 and FABP1, ABCB1, FABP2, and SLC51B. These potential candidate targets were functionally related to immune responses, inflammation, and metabolism. Moreover, HQT significantly decreased serum levels of proinflammatory factors nitrogen monoxide (NO), proinflammatory cytokines interleukin- (IL-) 17, and prostaglandin E2 (PGE2). The degree of HE staining of colonic tissue was severe in the model group but reduced significantly in the HQT group. HQT exhibited protective effects against colon damage by inhibiting the inflammatory response.

Neovagina creation using sigmoid colon in vaginal agenesis: a case report and review of literature

Mullerian duct anomalies are rare and can present with abnormalities in upper vagina, cervix, uterus, and fallopian tubes. The exact incidence of cervicovaginal agenesis is unknown and there are very few cases recorded in the literature. Authors report a 12-year-old girl referred from gynaecologist with chronic cyclical abdominal pain with underdeveloped, geniatilia and developed secondary sexual characters. Radiological investigations showed hypoplastic cervix with hematometra and left hemato salpinx. A definitive repair with creation of a neovagina using a sigmoid colon segment was performed in a single stage. Many techniques are described for reconstruction of cervicovaginal canal. Use of colon in creation of a neovagina is described by authors. Here we report a case of complete vaginal agenesis presenting with Hematometra-Hematosalpinx where a neovagina was created using a segment of sigmoid colon. Single staged surgery for neovagina creation using segment of sigmoid colon offers a promising and safe alternative for cervicovaginal agenesis.