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World Journal of Gastrointestinal... May 2024Treatment of ulcerative colitis (UC) and Crohn's disease (CD) represents, in the majority of cases, a real challenge to the gastroenterologist's abilities and skills as...
Treatment of ulcerative colitis (UC) and Crohn's disease (CD) represents, in the majority of cases, a real challenge to the gastroenterologist's abilities and skills as well as a clinical test concerning his/her levels of medical knowledge and experience. During the last two decades, our pharmaceutical arsenal was significantly strengthened, especially after the introduction of the so-called biological agents, drugs which to a large extent not only improved the results of conservative treatment but also changed the natural history of the disease. However, colectomy is still necessary for some patients with severe UC although smaller compared to the past, precisely because of the improvements achieved in the available conservative treatment. Nevertheless, surgeries to treat colon dysplasia and cancer are increasing to some extent. At the same time, satisfactory improvements in surgical techniques, the pre-and post-operative care of patients, as well as the selection of the appropriate time for performing the surgery have been noticed. Regarding patients with CD, the improvement of conservative treatment did not significantly change the need for surgical treatment since two-thirds of patients need to undergo surgery at some point in the course of their disease. On the other hand, the outcome of the operation has improved through good preoperative care as well as the wide application of more conservative surgical techniques aimed at keeping as much of the bowel as possible. This article discusses the indications for surgical management of UC patients from the gastroenterologist's point of view, the results of the emerging new techniques such as transanal surgery and robotics, as well as alternative operations to the classic ileo-anal-pouch anastomosis. The author also discusses the basic principles of surgical management of patients with CD based on the results of the relevant literature. The self-evident is emphasized, that is, to achieve an excellent therapeutic result in patients with severe inflammatory bowel disease in today's era; the close cooperation of gastroenterologists with surgeons, pathologists, imaging, and nutritionists is of paramount importance.
PubMed: 38817292
DOI: 10.4240/wjgs.v16.i5.1235 -
Endoscopy Dec 2024
Topics: Humans; Endoscopic Mucosal Resection; Male; Colonic Neoplasms; Aged; Female; Middle Aged; Wound Closure Techniques; Colonoscopy
PubMed: 38810977
DOI: 10.1055/a-2318-3282 -
BMC Medicine May 2024Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not...
BACKGROUND
Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood.
METHODS
This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period.
RESULTS
We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001).
CONCLUSIONS
This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops.
Topics: Humans; Female; Male; Neoplasms; Middle Aged; Retrospective Studies; Aged; Adult; Longitudinal Studies; Incidence; Diabetes Mellitus; Taiwan; Risk Factors; Young Adult; Diabetes Complications; Aged, 80 and over
PubMed: 38807177
DOI: 10.1186/s12916-024-03430-y -
Cell Reports. Medicine May 2024Primary colon cancers arising from the left and right sides exhibit distinct clinical and molecular characteristics. Sidedness-associated heterogeneity relies...
Primary colon cancers arising from the left and right sides exhibit distinct clinical and molecular characteristics. Sidedness-associated heterogeneity relies intricately on the oncogenic properties of cancer cells and multicellular interactions in tumor microenvironments. Here, combining transcriptomic profiling of 426,863 single cells from 105 colon cancer patients and validation with spatial transcriptomics and large-scale histological analysis, we capture common transcriptional heterogeneity patterns between left- and right-sided malignant epithelia through delineating two side-specific expression meta-programs. The proliferation stemness meta-program is notably enriched in left-sided malignant epithelia that colocalize with Mph-PLTP cells, activated regulatory T cells (Tregs), and exhausted CD8-LAYN cells, constituting the glucose metabolism reprogramming niche. The immune secretory (IS) meta-program exhibits specific enrichment in right-sided malignant epithelia, especially in smoking patients with right-sided colon cancer. The IS malignant epithelia spatially localize in hypoxic regions and facilitate immune evasion through attenuating Mph-SPP1 cell antigen presentation and recruiting innate-like cytotoxicity-reduced CD8-CD161 cells.
PubMed: 38806057
DOI: 10.1016/j.xcrm.2024.101589 -
Journal of Translational Medicine May 2024Several studies have suggested secreted frizzled-related protein 2 (SFRP2) gene as a potential clinical biomarker in colorectal cancer (CRC). However, its diagnostic...
BACKGROUND
Several studies have suggested secreted frizzled-related protein 2 (SFRP2) gene as a potential clinical biomarker in colorectal cancer (CRC). However, its diagnostic role remains unclear. In this study, we aimed to investigate the significance of SFRP2 methylation levels in a large cohort of biological specimens (including blood, adipose and colonic tissues) from patients with CRC, thereby potentially identifying new biomarker utility.
METHODS
We examined the expression (by qPCR) and methylation status (by 450 K DNA array and DNA pyrosequencing) of the SFRP2 gene in healthy participants (N = 110, aged as 53.7 (14.2), 48/62 males/females) and patients with CRC (N = 85, aged 67.7 (10.5), 61/24 males/females), across different biological tissues, and assessing its potential as a biomarker for CRC. Additionally, we investigated the effect of recombinant human SFRP2 (rhSFRP2) as a therapeutic target, on cell proliferation, migration, and the expression of key genes related to carcinogenesis and the Wnt pathway.
RESULTS
Our findings revealed that SFRP2 promoter methylation in whole blood could predict cancer stage (I + II vs. III + IV) (AUC = 0.653), lymph node invasion (AUC = 0.692), and CRC recurrence (AUC = 0.699) in patients with CRC (all with p < 0.05). Furthermore, we observed a global hypomethylation of SFRP2 in tumors compared to the adjacent area (p < 0.001). This observation was validated in the TCGA-COAD and TCGA-READ cohorts, demonstrating overall hypermethylation (both with p < 0.001) and low expression (p < 0.001), as shown in publicly available scRNA-Seq data. Notably, neoadjuvant-treated CRC patients exhibited lower SFRP2 methylation levels compared to untreated patients (p < 0.05) and low promoter SFRP2 methylation in untreated patients was associated with poor overall survival (p < 0.05), when compared to high methylation. Finally, treatment with 5 µg of rhSFRP2 treatment in CRC cells (HCT116 cells) inhibited cell proliferation (p < 0.001) and migration (p < 0.05), and downregulated the expression of AXIN2 (p < 0.01), a gene involved in Wnt signaling pathway.
CONCLUSIONS
These findings establish promoter methylation of the SFRP2 gene as a prognostic candidate in CRC when assessed in blood, and as a therapeutic prognostic candidate in tumors, potentially valuable in clinical practice. SFRP2 also emerges as a therapeutic option, providing new clinical and therapeutical avenues.
Topics: Humans; Colorectal Neoplasms; Male; DNA Methylation; Membrane Proteins; Female; Middle Aged; Biomarkers, Tumor; Aged; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Promoter Regions, Genetic; Gene Silencing; Cell Proliferation; Cell Movement; Wnt Signaling Pathway; Cell Line, Tumor
PubMed: 38802858
DOI: 10.1186/s12967-024-05329-x -
Frontiers in Oncology 2024Bone metastases are associated with increased morbidity and decreased quality of life in patients with solid tumors. Identifying patients at increased risk of bone...
INTRODUCTION
Bone metastases are associated with increased morbidity and decreased quality of life in patients with solid tumors. Identifying patients at increased risk of bone metastases at diagnosis could lead to earlier interventions. We sought to retrospectively identify the incidence and predictive factors for bone metastases at initial diagnosis in a large population-based dataset.
METHODS
The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients 18 years-old or older diagnosed with solid cancers from 2010 to 2019. Patients with hematologic malignancies and primary tumors of the bone were excluded. We calculated the incidence and predictive factors for bone metastases according to demographic and tumor characteristics.
RESULTS
Among 1,132,154 patients identified, 1,075,070 (95.0%) had known bone metastasis status and were eligible for the study. Bone metastases were detected in 55,903 patients (5.2% of those with known bone metastases status). Among patients with bone metastases, the most common primary tumors arose from lung (44.4%), prostate (19.3%), breast (12.3%), kidney (4.0%), and colon (2.2%). Bone metastases at presentation were most common in small cell lung cancer (25.2%), non-small cell lung cancer (18.0%), and esophageal adenocarcinoma (9.4%). In addition to stage classification, predictors for bone metastases included Gleason score (OR 95.7 (95% CI 73.1 - 125.4) for Grade Group 5 vs 1 and OR 42.6 (95% CI 32.3 - 55.9) for Group 4 vs 1) and PSA (OR 14.2 (95% CI 12.6 - 16.0) for PSA > 97 vs 0 - 9.9) for prostate cancer, HER2 and hormonal receptor (HR) status (OR 2.2 (95% CI 1.9 - 2.6) for HR+/HER2+ vs HR-/HER2-) for breast cancer, histology (OR 2.5 (95% CI 2.3 - 2.6) for adenocarcinoma vs squamous) for lung cancer, and rectal primary (OR 1.2 (95% 1.1 - 1.4) vs colon primary) and liver metastases (OR 8.6 (95% CI 7.3 - 10.0) vs no liver metastases) for colorectal tumors.
CONCLUSIONS
Bone metastases at presentation are commonly seen in solid tumors, particularly lung, prostate, breast, and kidney cancers. Clinical and pathologic factors are associated with a significantly increased risk for bone metastases.
PubMed: 38800383
DOI: 10.3389/fonc.2024.1392667 -
IScience Jun 2024Water is the most abundant substance in the human body and plays a pivotal role in various bodily functions. While underhydration is associated with the incidence of...
Water is the most abundant substance in the human body and plays a pivotal role in various bodily functions. While underhydration is associated with the incidence of certain diseases, the specific role of water in gut function remains largely unexplored. Here, we show that water restriction disrupts gut homeostasis, which is accompanied by a bloom of gut microbes and decreased numbers of immune cells, especially T17 cells, within the colon. These microbial and immunological changes in the gut are associated with an impaired ability to eliminate the enteric pathogen . Moreover, aquaporin 3, a water channel protein, is required for the maintenance of T17 cell function and differentiation. Taken together, adequate water intake is critical for maintaining bacterial and immunological homeostasis in the gut, thereby enhancing host defenses against enteric pathogens.
PubMed: 38799550
DOI: 10.1016/j.isci.2024.109903 -
International Journal of Surgery Case... May 2024Ingested foreign bodies fail to pass spontaneously through the gastrointestinal tract in about 20 % of the cases and result in complications in about 1 % of the cases....
INTRODUCTION
Ingested foreign bodies fail to pass spontaneously through the gastrointestinal tract in about 20 % of the cases and result in complications in about 1 % of the cases. One of the complications is the migration of the foreign body to the adjacent structure.
CASE PRESENTATION
A 25-year-old female lady presented to our hospital with a 15-cm-long coilable and insulated electrical wire foreign body in her abdomen, which extended from the descending colon to the right upper quadrant abdominal wall. Intra-abdominally, the object was located in the general peritoneum without penetrating the bowel or vascular structure. It was complicated by an abdominal wall abscess without any collection in the general peritoneum. The foreign body was then successfully retracted from the abdomen through a right upper quadrant incision without any complications thereafter.
CLINICAL DISCUSSION
The uncomplicated passage of foreign bodies through the gastrointestinal tract largely depends on the types of objects. Sharp, elongated objects are more likely to be arrested in the bowel commonly at the point of acute angulation and narrowing. The stacked foreign body may then result in different complications, including penetration and migration of the object. Migration of an insulated electrical wire to the anterior abdominal wall, which we encountered, is extremely rare and can pose a difficulty and dilemma in deciding on management options.
CONCLUSION
For an externally accessible, migrated intra-abdominal foreign body that does not result in peritonitis and is confirmed to be located out of the bowel, an exploratory laparotomy could be avoided.
PubMed: 38796941
DOI: 10.1016/j.ijscr.2024.109794 -
Cancers May 2024The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing;...
The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing; however, ROR1 tissue expression remains understudied. We performed an immunohistochemistry analysis of ROR1 protein expression in a large cohort of multiple tumor and histologic types. We analyzed 12 anonymized multi-tumor tissue microarrays (TMAs), including mesothelioma, esophageal and upper gastrointestinal carcinomas, and uterine endometrioid carcinoma, among other tumor types. Additionally, we studied 5 different sarcoma types of TMAs and 6 patient-derived xenografts (PDX) TMAs developed from 19 different anatomic sites and tumor histologic types. A total of 1142 patient cases from different histologic types and 140 PDXs placed in TMAs were evaluated. Pathologists assessed the percentage of tumor cells in each case that were positive for ROR1 and the intensity of staining. For determining the prevalence of staining for each tumor type, a case was considered positive if >1% of its tumor cells showed ROR1 staining. Our immunohistochemistry assays revealed a heterogeneous ROR1 expression profile. A high prevalence of ROR1 expression was found in mesothelioma (84.6%), liposarcoma (36.1%), gastrointestinal stromal tumors (33.3%), and uterine endometrioid carcinoma (28.9%). Other histologic types such as breast, lung, renal cell, hepatocellular, urothelial carcinoma, and colon carcinomas; glioblastoma; cholangiocarcinoma; and leiomyosarcoma showed less ROR1 overall expression, ranging between 0.9 and 13%. No ROR1 expression was seen in mesenchymal chondrosarcoma, rhabdomyosarcoma, or gastric adenocarcinoma cases. Overall, ROR1 expression was relatively infrequent and low in most tumor types investigated; however, ROR1 expression was infrequent but high in selected tumor types, such as gastroesophageal GIST, suggesting that ROR1 prescreening may be preferable for those indications. Further, mesothelioma exhibited frequent and high levels of ROR1 expression, which represents a previously unrecognized therapeutic opportunity. These findings can contribute to the development of ROR1-targeted therapies.
PubMed: 38791952
DOI: 10.3390/cancers16101874 -
Children (Basel, Switzerland) Apr 2024Despite limited research, existing studies using generic quality of life (QOL) tools indicate decreased physical health and compromised emotional functioning in children...
Despite limited research, existing studies using generic quality of life (QOL) tools indicate decreased physical health and compromised emotional functioning in children with IF. This study investigates QOL in children with short bowel syndrome (SBS) and its determinants. The study included 57 pediatric patients with SBS treated at Mannheim's University Hospital between 1998 and 2014. To evaluate QOL, the KINDL questionnaire was used. Three age-specific questionnaire variants were employed, and parental proxy reports were collected. Most patients underwent intestinal lengthening procedures, with varying primary diagnoses. A comparison with healthy children from the patient's perspective revealed no difference but from the parent's perspective showed lower QOL in SBS patients, especially regarding physical and mental well-being. QOL varied with age, with 7-10-year-olds reporting the lowest scores. Several factors, including independence from parenteral nutrition and the presence of a complete colon, positively influenced QOL. The independence of parenteral nutrition and the presence of a complete colon positively influenced QOL. The Bianchi technique for intestinal lengthening has also shown promise but needs further research. The observation sample in this study is too small to generalize about the whole population of SBS patients. However, this study shows that many health and treatment factors affect QOL, and a large multicenter study is necessary. Our findings underline the importance of appropriate psychological support for children with SBS and their families.
PubMed: 38790531
DOI: 10.3390/children11050536