Clinical Review and Management of Oral Potentially Malignant Disorders with Epithelial Dysplasia

Background: Oral potentially malignant disorders (OPMDs) comprise any disorders, tumors, in addition to any microscopic alterations that have a risk of malignant development of cancers of the mouth. When epithelial dysplasia is detected in an oral lesion, it is termed as a precancerous lesion. Finding: Several changes in the color or thickness of normal oral mucosa might be detected during the clinical diagnosis of the oral lesions. Leukoplakia of the oral cavity is a clinical name for one of the most predominant OPMDs of the oral mucosa. When comparing oral examination with naked eyes to planning to apply staining with special stain or using an image of optical fluorescence, the incidence of patients with oral epithelial dysplasia may rise, as well as the clearing of the lesion boundary. Increased size of more than 2cm2, the presence of colored regions with a red hue, the presence of lichenoid process characteristics, and severe epithelial dysplasia are all considered risk factors. One-third of premalignant lesions may progress to cancer, whereas the other two-thirds may stay stable or regress without progressing to malignancy. Conclusion: It is critical to research the patients' unique characteristics, which include psychological, genetic, dietary, and dental problems. When epithelial dysplasia is present in an oral lesion, it is termed a precancerous lesion. Oral potential malignant diseases with epithelial dysplasia may or may not develop into carcinoma and may or may not be recurrent.

Accuracy of Store-and-Forward Teledermatology for the Diagnosis of Skin Cancer: The Nouvelle-Aquitaine Experience

Background In Nouvelle-Aquitaine (a French region with a population of almost 6 million), the density of dermatologists is less than 3.8/100,000 inhabitants. This lack of dermatological care is delaying diagnosis and management, especially for skin cancer. The SmartDerm Project is a store-and-forward (SAF) teledermatology platform for primary care in Nouvelle-Aquitaine providing dermatological counselling to general practitioners (GPs). Objective The main objective was to determine the concordance between the diagnosis of skin cancer made by dermatologists and the pathologists’ diagnosis. Methods GPs in 3 pilot departments of Nouvelle-Aquitaine (Lot-Et-Garonne, Deux-Sèvres, Creuse) sent their dermatology requests using their smartphone, via an app called PAACO/Globule; dermatologists at the University Hospital of Bordeaux answered within 48-72 hours. Consecutive cases of skin cancer suspected by the referent dermatologists during the intervention were included, if the result of biopsy interpreted by a certified pathologist was available at the time of the study. Results Among the 1727 requests, 163 (9%) concerned a possible diagnosis of skin cancer and were eligible. For 61 cases, the histopathological findings were not available. Eventually, 93 patients with a total of 102 skin lesions were included. Median age was 75 years (range 26-97 years), with 53% women. The skin lesions had progressed for 8 months on average (range 0.5-36 months). The median response time was 1 day (range 0-61 days); 65 days (range 1-667 days) elapsed on average between the SAF opinion and the histological sample. Histopathology diagnosed 83 malignant lesions (57 basal cell carcinomas, 69%; 18 squamous cell carcinomas, 22%; 6 melanomas, 7%; 1 cutaneous lymphoma, 1%; 1 secondary location of a primary cancer, 1%), 1 precancerous lesion, and 18 benign lesions. The concordance between the opinion of the referent dermatologist and the final pathological finding was 83% for nonmelanocytic lesions and 67% for melanocytic lesions. Conclusions This study showed the reliability of SAF teledermatology in the diagnosis of skin cancer, comparable to literature data in the absence of dermatoscopy. The median delay of about two months between request and histology was an improvement compared to the delay of usual appointments in the intervention area. The lack of data for 61 patients showed that SAF telemedicine requires better coordination and follow-up, especially for the management of skin cancer. With this reservation in mind, teledermatology offers an alternative answer for the triage of patients with skin cancer residing in areas with low medical density. Conflicts of Interest None declared.

FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer

Human papillomavirus (HPV)-mediated cervical carcinogenesis is a multistep progressing from persistent infection, precancerous lesion to cervical cancer (CCa). Although molecular alterations driven by viral oncoproteins are necessary in cervical carcinogenesis, the key regulators behind the multistep process remain not well understood. It is pivotal to identify the key genes involved in the process for early diagnosis and treatment of this disease. Here we analyzed the mRNA expression profiles in cervical samples including normal, cervical intraepithelial neoplasia (CIN), and CCa. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to reveal the crucial modules in the dynamic process from HPV infection to CCa development. Furthermore, the differentially expressed genes (DEGs) that could distinguish all stages of progression of CCa were screened. The key genes involved in HPV-CCa were identified. It was found that the genes involved in DNA replication/repair and cell cycle were upregulated in CIN compared with normal control, and sustained in CCa, accompanied by substantial metabolic shifts. We found that upregulated fibronectin type III domain-containing 3B (FNDC3B) and downregulated bisphosphoglycerate mutase (BPGM) could differentiate all stages of CCa progression. In patients with CCa, a higher expression of FNDC3B or lower expression of BPGM was closely correlated with a shorter overall survival (OS) and disease-free survival (DFS). A receiver operating characteristic (ROC) analysis of CIN and CCa showed that FNDC3B had the highest sensitivity and specificity for predicting CCa development. Taken together, the current data showed that FNDC3B and BPGM were key genes involved in HPV-mediated transformation from normal epithelium to precancerous lesions and CCa.

Evaluation of Precancerous Breast Lesion Upgrade Rate

Background: Breast imaging guided core-needle biopsy enable the assessment of suspected precancerous lesions. In some precancerous lesion there is a risk of upgrading to cancer after surgical removal. This study was conducted to determine the upgrading rate of CNB-diagnosed precancerous breast lesions. Methods: A retrospective study was conducted to examine the data of patients who had undergone core needle biopsy from April 2016 to March 2019 at the Radiology Department of the Breast Clinic of Motamed Cancer Institute and whose pathological reports were indicative of a precancerous lesion such as atypical ductal hyperplasia, sclerosing adenosis, flat epithelial atypia or papillary lesion and had undergone surgery for this lesion. The upgrading rate and its related factors such as the size of the lesion, patient’s age, family history of breast cancer and method of core-needle biopsy were analyzed in SPSS software. Results: A total of 241 patients were recruited with a pathological report of pre-cancerous predisposing lesions. The mean age of the patients was 42.14 years and the highest upgrading rates in the analysis were observed for papillary lesion (19.3%) and atypical ductal hyperplasia, (21.4%), while the upgrading rates were (1.2% ) for sclerosing adenosis and (0%) for flat epithelial atypia. Data analysis showed that the lesions’ upgrading rate correlated with the lesion’s size (P=0.005).Conclusion: The findings of this study showed that size of the lesions increase the risk of upgrading to cancer, which is much higher in papillary lesion and atypical ductal hyperplasia compared to sclerosing adenosis and flat epithelial atypia. It seems that surgical excision of the entire lesion in patients with larger mass size may decrease the upgrading rate of cancer. Conducting specific studies on each distinct lesion can help yield more conclusive results.

Alterations of the Oral Microbiota Profiles in Chinese Patient With Oral Cancer

Oral cancer is the most common malignant tumor in the oral and maxillofacial region, of which more than 90% is squamous cell carcinoma. The incidence of oral cancer is on the rise worldwide. An imbalance between the microorganism composition and its host may lead to the occurrence of oral malignant tumors. Accumulating evidence suggests that the oral microbiota plays an important role in oral cancer; however, the association between oral microbiota and oral cancer has not yet been comprehensively studied. In this study, metagenomic sequencing was used to compare the microbial composition of three groups of samples from Chinese patients with oral cancer, patients with precancerous lesion, and normal individuals. In terms of microbiota richness, the oral microbiota of patients with precancerous lesions was richer than that of oral cancer patients and healthy controls, whereas in terms of microbiota diversity, there was little difference between the three groups. The three groups of samples exhibited statistically significant differences in microbiota composition and metabolic function at the family, genus, and species levels (P < 0.05). The differentially enriched phylum in oral cancer samples was Bacteroidetes (P < 0.05). At the genus level, the main differentially enriched taxa were Prevotella, Peptostreptococcus, Carnobacterium, and Diastella (P < 0.05). The species level was differentially enriched in Prevotella intermedia and Peptostreptococcus stomatis (p < 0.05). The prediction of microbiota function shows that oral cancer is mainly associated with coenzyme A biosynthesis, phosphopantothenic acid biosynthesis, inosine 5’-phosphate degradation, and riboflavin biosynthesis. Furthermore, the increase in C-reactive protein level in oral cancer patients was found to be closely related to P. intermedia. Overall, oral bacterial profiles showed significant differences between the oral cancer group and normal group. Hence, microbes can be employed as diagnostic markers and treatment targets for oral cancer.

Accuracy of Store-and-Forward Teledermatology for the Diagnosis of Skin Cancer: The Nouvelle-Aquitaine Experience (Preprint)

BACKGROUND In Nouvelle-Aquitaine (a French region with a population of almost 6 million), the density of dermatologists is less than 3.8/100,000 inhabitants. This lack of dermatological care is delaying diagnosis and management, especially for skin cancer. The SmartDerm Project is a store-and-forward (SAF) teledermatology platform for primary care in Nouvelle-Aquitaine providing dermatological counselling to general practitioners (GPs). OBJECTIVE The main objective was to determine the concordance between the diagnosis of skin cancer made by dermatologists and the pathologists’ diagnosis. METHODS GPs in 3 pilot departments of Nouvelle-Aquitaine (Lot-Et-Garonne, Deux-Sèvres, Creuse) sent their dermatology requests using their smartphone, via an app called PAACO/Globule; dermatologists at the University Hospital of Bordeaux answered within 48-72 hours. Consecutive cases of skin cancer suspected by the referent dermatologists during the intervention were included, if the result of biopsy interpreted by a certified pathologist was available at the time of the study. RESULTS Among the 1727 requests, 163 (9%) concerned a possible diagnosis of skin cancer and were eligible. For 61 cases, the histopathological findings were not available. Eventually, 93 patients with a total of 102 skin lesions were included. Median age was 75 years (range 26-97 years), with 53% women. The skin lesions had progressed for 8 months on average (range 0.5-36 months). The median response time was 1 day (range 0-61 days); 65 days (range 1-667 days) elapsed on average between the SAF opinion and the histological sample. Histopathology diagnosed 83 malignant lesions (57 basal cell carcinomas, 69%; 18 squamous cell carcinomas, 22%; 6 melanomas, 7%; 1 cutaneous lymphoma, 1%; 1 secondary location of a primary cancer, 1%), 1 precancerous lesion, and 18 benign lesions. The concordance between the opinion of the referent dermatologist and the final pathological finding was 83% for nonmelanocytic lesions and 67% for melanocytic lesions. CONCLUSIONS This study showed the reliability of SAF teledermatology in the diagnosis of skin cancer, comparable to literature data in the absence of dermatoscopy. The median delay of about two months between request and histology was an improvement compared to the delay of usual appointments in the intervention area. The lack of data for 61 patients showed that SAF telemedicine requires better coordination and follow-up, especially for the management of skin cancer. With this reservation in mind, teledermatology offers an alternative answer for the triage of patients with skin cancer residing in areas with low medical density.

The Abnormal Metabolites in Tongue Coating of Chronic Gastritis Patients Reflect the Changes in Indexes of Gastroscopic Observation and Gastric Mucosal Pathology

ObjectiveIn this study, we analyzed the correlation between different metabolites in the tongue coating of patients with chronic gastritis, gastroscopy and pathological indexes, and discussed the metabolic mechanism at different pathological stages in the development of chronic gastritis.MethodsWe used GC-TOF-MS and UHPLC-QE-MS metabonomics to detect the distribution of metabolites in the tongue coating of patients with chronic gastritis, and analyzed the correlation between different metabolites in the tongue coating of patients with chronic gastritis and gastroscopy and pathological indexes.ResultsCompared with 50 healthy people, 54 metabolites were upregulated and 47 metabolites were downregulated in 350 patients with chronic gastritis. The main differential metabolites were Lipids and lipid-like molecules, which contain 47 metabolites. The best diagnostic model was composed of 5 metabolites, with an accuracy of 95.4%, a specificity of 87.4% and a sensitivity of 88.0%. These 5 metabolites were 1-methyladenosine, Sphinganine 1-phosphate, 3-Hydroxycapric acid, 4-Ipomeanol, and Nervonic acid. Compared with healthy people, Sphinganine 1-phosphate, 4-Ipomeanol, and Nervonic acid were significantly upregulated in chronic gastritis patients, and 1-methyladenosine and 3-Hydroxycapric acid were significantly downregulated in chronic gastritis patients. After correlation analysis between differential metabolites in tongue coatings and gastroscopic indexes, we found that Trimethylaminoacetone, Sphinganine1-phosphate, alpha-Carboxy-delta-decalactone, and 5,6-Dihydroxyindole were positively correlated with intestinal metaplasia. Conduritol-beta-expoxide, Tetracosanoic acid, Lactosylceramide(d18:1/26:0), Chondrillasterol 3-[glucosyl-(1->4)-glucoside], Azelaic acid, and 1-Methyladenosine were negatively correlated with intestinal metaplasia. Sphinganine1-phosphate, alpha-Carboxy-delta-decalactone, and 5,6-Dihydroxyindole were positively correlated with atrophic. Octadecanol, conduritol-beta-expoxide, Tetracosanoic acid, Smilanippin A, Lactosylceramide(d18:1/26:0), Chondrillasterol 3-[glucosyl-(1->4)-glucoside], and Azelaic acid were negatively correlated with atrophic. 6-deoxyglucitol was negatively correlated with bile reflux, methylmaleic acid, 4-methylcatechol, and 2,4-dichloro-1-(2-chloroethenyl)-benzene were negatively correlated with Hp, 3-benzoyloxy-11-oxo-12-ursen-28-oic acid was negatively correlated with gastric mucosal erosion. From the change trend of different metabolites in different pathological stages, we found that the content of conduritol-beta-expoxide decreased significantly in mild atrophic compared with moderate atrophic and the content of conduritol-beta-expoxide decreased significantly in mild intestinal metaplasia compared with moderate intestinal metaplasia.ConclusionsWe found that Lipids and lipid-like molecules were the main abnormal metabolites in patients with chronic gastritis. Among them, Sphinganine 1-phosphate, which was significantly positively correlated with the aggravation of atrophic and intestinal metaplasia, could be used as one of the diagnostic model markers for chronic gastritis. Additionally, the amount of conduritol-beta-expoxide significantly decreased with the aggravation of atrophic and intestinal metaplasia. We believe that these differential markers in tongue coating may help us to establish a noninvasive and convenient auxiliary detection method for gastritis and gastric precancerous lesion in the future.

The Expression of YKL-40 in Peripheral Blood of Colorectal Cancer and Its Effect on the Proliferation and Angiogenesis of Colorectal Cancer Cells

Objective To observe the expression of YKL-40 in the serum of patients with colorectal cancer, and to study the effect of YKL-40 gene on the proliferation and angiogenesis of colon cancer cell lines. Methods The serum of patients with colorectal cancer, precancerous lesions, and healthy controls were collected, and the expression of YKL-40 was detected by enzyme-linked immunosorbent assay (ELISA) technology. Screened cell lines with high expression of YKL-40 from colon cancer cell lines HCT-15, HCT-116, SW480, interfered with YKL-40 gene expression through siRNA technology, and co-cultured with bevacizumab, and detected cells with CCK8 method Proliferation, cell formation test to detect blood vessel formation. Results The mean values of serum YKL-40 in the colorectal cancer group, precancerous lesion group and control group were (178.50±71.91) μg/L, (91.37±35.79) μg/L and (78.23±26.52) μg/L, respectively. The colorectal cancer group (preoperative) was significantly higher than the precancerous lesion group and the control group (P <0.01). The precancerous lesion group was higher than the control group, but the difference between the two was not statistically significant (P = 0.244). The expression of YKL-40 was positively correlated with the stage of colorectal cancer (P <0.05). There was no significant difference in the expression of serum YKL-40 before and after surgery (p=0.07). HCT-116 is a YKL-40 highly expressing cell line. After inhibiting the expression of this gene, the survival rate of the experimental group was 78.75%, which was significantly lower than that of the control group (p<0.05). The angiogenesis test is used to detect the angiogenesis ability. siRNA interference with YKL-40 gene and the addition of bevacizumab can inhibit the angiogenesis ability in vitro. Moreover,the vascular inhibitory effect of bevacizumab in the experimental group was stronger than that in the control group. Conclusion YKL-40 is highly expressed in the peripheral blood of patients with colorectal cancer and is related to the tumor stage. The HCT-116 colon cancer cell line has a high expression of YKL-40. Interfering with the expression of YKL-40 can inhibit cell proliferation and angiogenesis. It suggests that YKL-40 plays an important role in the occurrence and development of colorectal cancer.

Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid–induced hepatic pre-neoplastic lesions in rats

Hepatocellular carcinoma (HCC) accounts for more than 5% of all human cancers. Diacerein (DIA), an interleukin (IL)-1β inhibitor, is used for the treatment of osteoarthritis. DIA is a potential anticancer drug acting on several protein targets in the process of apoptosis. The present study aimed to explore the molecular mechanisms underlying the effect of DIA in the treatment of trichloroacetic acid (TCA)–induced pre-neoplastic changes in rats. Rats were allocated into 5 groups and treated for 4 weeks. Group 1: control; received vehicle, Group 2: TCA group; received TCA (1 g/kg, orally for 5 days). Group 3: DIA-treated group; received TCA +DIA (50 mg/kg/day, orally, for 4 weeks). Group 4: positive control group; received TCA (1 g/kg, orally, for 5 days) + 5-fluorouracil (5-FU) (75 mg/kg) intraperitoneally (i.p.), for 4 weeks as a standard anticancer drug. Group 5: received TCA (1 g/kg, orally for 5 days) + DIA (50 mg/kg/day, orally, for 4 weeks) + 5-FU (75 mg/kg, i.p., for 4 weeks). Serum liver enzymes, oxidative stress parameters, inflammatory parameter (IL-1β), and angiogenesis marker vascular endothelial growth factor (VEGF) were assessed along with histopathological evaluation. An apoptotic marker as caspase-3 expression was measured by western blot analysis. Immunoexpression of proliferating cell nuclear antigen (PCNA) and hypoxia-inducible factor-1α (HIF-1α) was evaluated. Results and conclusion: The outcomes proved that at histological level, DIA ameliorated hepatic precancerous lesion via modulation of IL-1β–HIF-1α–VEGF pathway. Conclusion IL-1β mediates angiogenesis indirectly, as it has been shown to induce hypoxia-inducible factor-1α (HIF-1α) which upregulates VEGF.