Are the standards of professionalism expected in dentistry justified? Views of dental professionals and the public.

Introduction In the UK, the General Dental Council specifies nine principles of professional standards that dental registrants must follow. There are views that such standards are high, patients' expectations are rising, and the professionalism of dental professionals is increasingly scrutinised. This paper explores whether the high standards expected in dentistry are justified.Methods We applied thematic analysis to 772 free-text responses from dental team members and the public to a modified Delphi survey. Respondents described their views of professional and unprofessional behaviours in dentistry. Data were obtained as part of a larger review of professionalism in dentistry.Results Two lines of argument were identified: professionalism standards are high, but justifiably so; and professionalism standards are too high. Within these, four broad themes emerged: patient trust; comparison with other professions; a culture of fear; and perfection.Conclusion High professionalism standards are justified in a profession where patient trust is paramount. However, a problem lies in the culture that surrounds professionalism in terms of litigation and dental professionals feel pressure to possess an unattainable, infallible nature. These negative impacts need minimising. We suggest that undergraduates and continuing professional development approach professionalism with care, to foster a supportive, positive and reflective culture of professionalism.

Completion Total Mesorectal Excision After Transanal Local Excision of Early Rectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Completion total mesorectal excision is recommended when local excision of early rectal cancers demonstrates high-risk histopathological features. Concerns regarding the quality of completion resections and the impact on oncological safety remain unanswered. OBJECTIVE: This study aims to summarize and analyze the outcomes associated with completion surgery and undertake a comparative analysis with primary rectal resections. DATA SOURCES: Data sources included PubMed, Cochrane library, MEDLINE, and Embase databases up to April 2021. STUDY SELECTION: All studies reporting any outcome of completion surgery after transanal local excision of an early rectal cancer were selected. Case reports, studies of benign lesions, and studies using flexible endoscopic techniques were not included. INTERVENTION: The intervention was completion total mesorectal excision after transanal local excision of early rectal cancers. MAIN OUTCOME MEASURES: Primary outcome measures included histopathological and long-term oncological outcomes of completion total mesorectal excision. Secondary outcome measures included short-term perioperative outcomes. RESULTS: Twenty-three studies including 646 patients met the eligibility criteria, and 8 studies were included in the meta-analyses. Patients undergoing completion surgery have longer operative times (standardized mean difference, 0.49; 95% CI, 0.23-0.75; p = 0.0002) and higher intraoperative blood loss (standardized mean difference, 0.25; 95% CI, 0.01-0.5; p = 0.04) compared with primary resections, but perioperative morbidity is comparable (risk ratio, 1.26; 95% CI, 0.98-1.62; p = 0.08). Completion surgery is associated with higher rates of incomplete mesorectal specimens (risk ratio, 3.06; 95% CI, 1.41-6.62; p = 0.005) and lower lymph node yields (standardized mean difference, -0.26; 95% CI, -0.47 to 0.06; p = 0.01). Comparative analysis on long-term outcomes is limited, but no evidence of inferior recurrence or survival rates is found. LIMITATIONS: Only small retrospective cohort and case-control studies are published on this topic, with considerable heterogeneity limiting the effectiveness of meta-analysis. CONCLUSIONS: This review provides the strongest evidence to date that completion surgery is associated with an inferior histopathological grade of the mesorectum and finds insufficient long-term results to satisfy concerns regarding oncological safety. International collaborative research is required to demonstrate noninferiority. REGISTRATION NO: CRD42021245101.

Laparoscopic Surgery Is Safe and Beneficial in True Functional High-Risk Patients with Colorectal Cancer: Utilization of Cardiopulmonary Exercise Test.

Background: Patients with colorectal cancer deemed to be high-risk may be denied an elective laparoscopic resection due to subjective reasons. A comparison of the 30-day outcomes in true functional high-risk patients who underwent either open or laparoscopic colorectal resection was undertaken. Materials and Methods: A retrospective cohort of all functional high-risk patients as assessed by cardiopulmonary exercise test between July 2015 and April 2018 were identified. Anaerobic threshold of <11 mL/kg/minute was used as a physiologic indicator to determine a high-risk patient. Adherence to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) was ensured. P values were computed via two-sided Fisher's exact test, and the exact Mann-Whitney U-test. Forest plots for relative risks with 95% confidence intervals were displayed on a log scale. Results: One hundred forty-six patients were identified as high-risk. Outcomes demonstrated a trend to laparoscopic benefit in all Clavien-Dindo grades of postoperative complications, but especially in severe complications of grades 3-4 (3.5% versus 10.2%). Readmissions demonstrated a trend to laparoscopic surgery benefit (7% versus 11.8%), as did mortality (1.7% versus 3.4%). The rate of surgery-site complications was higher after open surgery (42.1% versus 22.4%, P = .0201). Wound infections were observed more frequently after open surgery (12.5% versus 1.72%, P = .0280). The estimated risk of all-grade complications was significantly higher after open anterior rectal resection (63.0% versus 29.6%, P = .0281) and there was significantly shorter stay after laparoscopic right colectomy (5 v. 7 days, P = .0490). Conclusions: Laparoscopic approach for colorectal resections in high-risk patients is safe and beneficial compared to open surgery, especially in patients undergoing laparoscopic resection of the rectum and right colon.

Peanut agglutinin appearance in the blood circulation after peanut ingestion mimics the action of endogenous galectin-3 to promote metastasis by interaction with cancer-associated MUC1.

Peanut agglutinin (PNA), which accounts for ~0.15% of the weight of the common peanut, is a carbohydrate-binding protein that binds the oncofoetal Thomsen-Friedenreich (TF) disaccharide (galactoseß1,3N-acetylgalactosamineα-) that is overexpressed by ~90% of human cancers. Previous studies have shown that PNA is highly resistant to cooking and digestion and rapidly enters the human blood circulation after peanut ingestion. This study investigates the hypothesis that PNA appearance in the circulation after peanut ingestion may mimic the actions of endogenous TF-binding human galectin-3 in metastasis promotion. It shows that PNA at concentrations similar to those found in blood circulation after peanut ingestion increases cancer cell heterotypic adhesion to the blood vascular endothelium and enhances the formation of tumour cell homotypic aggregates, two important steps in the metastasis cascade, and enhances metastasis in a mouse metastasis model. These effects of PNA are shown to result from its interaction with the cancer-associated TF disaccharide on the transmembrane mucin protein MUC1, causing MUC1 cell surface polarization that reveals underlying cell surface adhesion molecules. Thus, PNA appearance in the blood circulation after peanut ingestion mimics the actions of endogenous galectin-3 and promotes cancer cell metastatic spread by interaction with cancer-associated TF/MUC1. As metastasis accounts for the majority of cancer-associated fatality, regular consumption of peanuts by cancer patients would therefore be expected to have an adverse effect on cancer survival.

Suppression of core 1 Gal-transferase is associated with reduction of TF and reciprocal increase of Tn, sialyl-Tn and Core 3 glycans in human colon cancer cells.

It has long been presumed, though with surprisingly little evidence, a competition between Core 1 Gal-transferase (C1GalT), Core 3 GlcNAc-transferase (C3GnT) and sialyl-transferase (ST6GalNAc-T) for elongation of O-linked mucin-type glycans initiated with GalNAcα-Ser/Thr. This study tested this presumption by selective suppression of one of these glycosyltransferases and then analysed the expressions of the enzymatic products of the other three glycosyltransferases. It was found that siRNA suppression of C1GalT markedly reduced the expression of Galß1,3GalNAcα- (Core 1) and in the meantime increased the expressions of sialyl-GalNAcα- (sialyl-Tn), GalNAcα- (Tn) and GlcNAcß1,3GalNAcα- (Core 3)-associated glycans in human colon cancer HT29 and SW620 cells. This supports a competitive modification of the GalNAcα-Ser/Thr between C1GalT, C3GnT and ST6GalNAc-T in O-glycan biosynthesis. As Tn, TF and sialyl-Tn are oncofetal antigens and are over-expressed in most human cancers, this information is useful for the development of glycosyltransferase-targeted therapeutic strategies for cancer treatment.

Simultaneous determination of serum galectin-3 and -4 levels detects metastases in colorectal cancer patients.

BACKGROUND: Development of effective ways to detect metastases is highly desirable for improving the therapeutic strategies and survival of cancer patients. Serum levels of galectin-3 and -4, two members of the galactoside-binding galectin family, have recently been reported to be markedly increased up to 31-fold in the bloodstream of colorectal cancer patients and in particular those with metastases. RESULTS: We found that simultaneous determination of serum galectin-3 and -4 levels in a single assay provides a high specificity and sensitivity in distinguishing colorectal cancer patients without metastases from those with liver metastases. This result was partly attributed by a reciprocal relationship of serum galectin-3 and -4 levels in patients with metastases. Higher serum galectin-3/-4 levels at the time of primary tumour removal in patients who did not exhibit clinically detectable metastases were associated with a trend of a poorer patients' survival in the next 10 years. CONCLUSION: Simultaneous determination of serum galectin-3 and -4 levels can potentially be used alone or in combination with other assessments to detect colorectal cancer metastases.

Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium.

PURPOSE: Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion. EXPERIMENTAL DESIGN: Serum galectins and auto-anti-MUC1 antibodies were assessed using ELISA and mucin protein (MUC1) glycan microarrays, and cancer-endothelium adhesion was determined using monolayers of human microvascular lung endothelial cells. RESULTS: The levels of serum galectin-2, -3, -4, and -8 were significantly increased up to 31-fold in patients with cancer and, in particular, those with metastases. As previously shown for galectin-3, the presence of these galectins enhances cancer-endothelium adhesion by interaction with the Thomsen-Friedenreich (TF; Galß1,3GalNAcα-) disaccharide on cancer-associated MUC1. This causes MUC1 cell surface polarization, thus exposing underlying adhesion molecules that promote cancer-endothelium adhesion. Elevated circulating galectin-2 levels were associated with increased mortality in patients with colorectal cancer, but this association was suppressed when anti-MUC1 antibodies with specificity for the TF epitope of MUC1 were also present in the circulation. CONCLUSIONS: Increased circulation of several members of the galectin family is common in patients with cancer and these may, like circulating galectin-3, also be involved in metastasis promotion.

The role of galectins in colorectal cancer progression.

Galectins constitute a family of 15 mammalian galactoside-binding proteins that share a consensus amino acid sequence in their carbohydrate binding sites. They are multi-functional molecules and are expressed widely in human tissues. Four galectins: galectin -1, -3, -4 and -8 are expressed in the human colon and rectum and their expressions show significant changes during colorectal cancer development and metastasis. These changes in galectin expression correlate with alterations in cancer cell growth, apoptosis, cell-cell and cell-matrix interactions and angiogenesis. This review summaries current knowledge of the expression and roles of these galectins in the progression of human colorectal cancer and discusses the relevance of galectins and their ligands as potential therapeutic targets for cancer treatment.

Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis.

BACKGROUND: Formation of tumour cell aggregation/emboli prolongs the survival of circulating tumour cells in the circulation, enhances their physical trapping in the micro-vasculature and thus increases metastatic spread of the cancer cells to remote sites. RESULTS: It shows here that the presence of the galactoside-binding galectin-3, whose concentration is markedly increased in the blood circulation of cancer patients, increases cancer cell homotypic aggregation under anchorage-independent conditions by interaction with the oncofetal Thomsen-Friedenreich carbohydrate (Galbeta1,3GalNAcalpha-, TF) antigen on the cancer-associated transmembrane mucin protein MUC1. The galectin-3-MUC1 interaction induces MUC1 cell surface polarization and exposure of the cell surface adhesion molecules including E-cadherin. The enhanced cancer cell homotypic aggregation by galectin-MUC1 interaction increases the survival of the tumour cells under anchorage-independent conditions by allowing them to avoid initiation of anoikis (suspension-induced apoptosis). CONCLUSION: These results suggest that the interaction between free circulating galectin-3 and cancer-associated MUC1 promotes embolus formation and survival of disseminating tumour cells in the circulation. This provides new information into our understanding of the molecular mechanisms of cancer cell haematogenous dissemination and suggests that targeting the interaction of circulating galectin-3 with MUC1 in the circulation may represent an effective therapeutic approach for preventing metastasis.