The Impact of Artificial Intelligence in the Endoscopic Assessment of Premalignant and Malignant Esophageal Lesions: Present and Future.

In the gastroenterology field, the impact of artificial intelligence was investigated for the purposes of diagnostics, risk stratification of patients, improvement in quality of endoscopic procedures and early detection of neoplastic diseases, implementation of the best treatment strategy, and optimization of patient prognosis. Computer-assisted diagnostic systems to evaluate upper endoscopy images have recently emerged as a supporting tool in endoscopy due to the risks of misdiagnosis related to standard endoscopy and different expertise levels of endoscopists, time-consuming procedures, lack of availability of advanced procedures, increasing workloads, and development of endoscopic mass screening programs. Recent research has tended toward computerized, automatic, and real-time detection of lesions, which are approaches that offer utility in daily practice. Despite promising results, certain studies might overexaggerate the diagnostic accuracy of artificial systems, and several limitations remain to be overcome in the future. Therefore, additional multicenter randomized trials and the development of existent database platforms are needed to certify clinical implementation. This paper presents an overview of the literature and the current knowledge of the usefulness of different types of machine learning systems in the assessment of premalignant and malignant esophageal lesions via conventional and advanced endoscopic procedures. This study makes a presentation of the artificial intelligence terminology and refers also to the most prominent recent research on computer-assisted diagnosis of neoplasia on Barrett's esophagus and early esophageal squamous cell carcinoma, and prediction of invasion depth in esophageal neoplasms. Furthermore, this review highlights the main directions of future doctor-computer collaborations in which machines are expected to improve the quality of medical action and routine clinical workflow, thus reducing the burden on physicians.

Mucin-Producing Lobular Breast Carcinoma Metastasis to an Ovarian Fibroma: Histopathological and Immunohistochemical Analysis of a Rare Case and Literature Review.

Breast cancer stands as the primary cause of cancer-related mortality among women worldwide, often presenting with distant metastases upon diagnosis. Ovarian metastases originating from breast cancer represent a range of 3-30% of all ovarian neoplasms. Case Report: Herein, we present the histopathological, histochemical, and immunohistochemical findings of a rare case involving mucin-producing lobular breast carcinoma metastasizing to an ovarian fibroma in an 82-year-old female previously diagnosed with lobular breast carcinoma. Histopathological examination of the excised tissues revealed a biphasic neoplasm characterized by tumor cells expressing AE-1/AE-3 cytokeratin, mammaglobin, GCDFP-15, inhibin, and calretinin. Positive mucin staining was observed using histochemical techniques, and reticulin fibers were demonstrated using the Gordon-Sweets technique. A final diagnosis of mucin-producing lobular breast carcinoma metastatic to a benign ovarian fibroma was rendered. Conclusion: The occurrence of metastatic breast carcinoma overlaid on an ovarian tumor represents a rare and diagnostically challenging scenario.

Artificial intelligence as a noninvasive tool for pancreatic cancer prediction and diagnosis.

Pancreatic cancer (PC) has a low incidence rate but a high mortality, with patients often in the advanced stage of the disease at the time of the first diagnosis. If detected, early neoplastic lesions are ideal for surgery, offering the best prognosis. Preneoplastic lesions of the pancreas include pancreatic intraepithelial neoplasia and mucinous cystic neoplasms, with intraductal papillary mucinous neoplasms being the most commonly diagnosed. Our study focused on predicting PC by identifying early signs using noninvasive techniques and artificial intelligence (AI). A systematic English literature search was conducted on the PubMed electronic database and other sources. We obtained a total of 97 studies on the subject of pancreatic neoplasms. The final number of articles included in our study was 44, 34 of which focused on the use of AI algorithms in the early diagnosis and prediction of pancreatic lesions. AI algorithms can facilitate diagnosis by analyzing massive amounts of data in a short period of time. Correlations can be made through AI algorithms by expanding image and electronic medical records databases, which can later be used as part of a screening program for the general population. AI-based screening models should involve a combination of biomarkers and medical and imaging data from different sources. This requires large numbers of resources, collaboration between medical practitioners, and investment in medical infrastructures.

Artificial intelligence in improving the outcome of surgical treatment in colorectal cancer.

Background: A considerable number of recent research have used artificial intelligence (AI) in the area of colorectal cancer (CRC). Surgical treatment of CRC still remains the most important curative component. Artificial intelligence in CRC surgery is not nearly as advanced as it is in screening (colonoscopy), diagnosis and prognosis, especially due to the increased complexity and variability of structures and elements in all fields of view, as well as a general shortage of annotated video banks for utilization. Methods: A literature search was made and relevant studies were included in the minireview. Results: The intraoperative steps which, at this moment, can benefit from AI in CRC are: phase and action recognition, excision plane navigation, endoscopy control, real-time circulation analysis, knot tying, automatic optical biopsy and hyperspectral imaging. This minireview also analyses the current advances in robotic treatment of CRC as well as the present possibility of automated CRC robotic surgery. Conclusions: The use of AI in CRC surgery is still at its beginnings. The development of AI models capable of reproducing a colorectal expert surgeon's skill, the creation of large and complex datasets and the standardization of surgical colorectal procedures will contribute to the widespread use of AI in CRC surgical treatment.

Etiology Study of Acquired Developmental Defects of Enamel and Their Association with Dental Caries in Children between 3 and 19 Years Old from Dolj County, Romania.

Background: Developmental defects of enamel (DDE) are frequently encountered in primary and permanent teeth, yet their etiology is not completely known. Enamel hypoplasia is considered a predisposing factor for early caries. The objective of this study was the evaluation of several risk factors potentially causing DDE and the possible association between DDE and dental caries. Methods: This study was performed on a group of 213 rural children from Romania. It combined a thorough dental examination for all children, and a questionnaire filled in by their mothers, regarding the evolution of their pregnancy and the child's health status in the first years of life. Results: There was no statistically significant association between DDE presence and data regarding the evolution of pregnancy, mothers' health status or children's conditions during early childhood. There was a significant association between the use of amoxicillin, ibuprofen, and cephalosporin during the period of formation of permanent teeth, and one environmental factor (water source), and the presence of DDE (Chi Square, p < 0.05). Also, DDEs were associated with the presence of caries (Fisher, p = 0.001). Conclusions: Children who consumed water from private wells and children who received medication during early childhood developed more enamel defects, presenting a higher risk of caries development.

Biologic Impact of Green Synthetized Magnetic Iron Oxide Nanoparticles on Two Different Lung Tumorigenic Monolayers and a 3D Normal Bronchial Model-EpiAirwayTM Microtissue.

The present study reports the successful synthesis of biocompatible magnetic iron oxide nanoparticles (MNPs) by an ecofriendly single step method, using two ethanolic extracts based on leaves of Camellia sinensis L. and Ocimum basilicum L. The effect of both green raw materials as reducing and capping agents was taken into account for the development of MNPs, as well as the reaction synthesis temperature (25 °C and 80 °C). The biological effect of the MNPs obtained from Camellia sinensis L. ethanolic extract (Cs 25, Cs 80) was compared with that of the MNPs obtained from Ocimum basilicum L. ethanolic extract (Ob 25, Ob 80), by using two morphologically different lung cancer cell lines (A549 and NCI-H460); the results showed that the higher cell viability impairment was manifested by A549 cells after exposure to MNPs obtained from Ocimum basilicum L. ethanolic extract (Ob 25, Ob 80). Regarding the biosafety profile of the MNPs, it was shown that the EpiAirwayTM models did not elicit important viability decrease or significant histopathological changes after treatment with none of the MNPs (Cs 25, Cs 80 and Ob 25, Ob 80), at concentrations up to 500 µg/mL.

The role of computer-assisted systems for upper-endoscopy quality monitoring and assessment of gastric lesions.

This article analyses the literature regarding the value of computer-assisted systems in esogastroduodenoscopy-quality monitoring and the assessment of gastric lesions. Current data show promising results in upper-endoscopy quality control and a satisfactory detection accuracy of gastric premalignant and malignant lesions, similar or even exceeding that of experienced endoscopists. Moreover, artificial systems enable the decision for the best treatment strategies in gastric-cancer patient care, namely endoscopic vs surgical resection according to tumor depth. In so doing, unnecessary surgical interventions would be avoided whilst providing a better quality of life and prognosis for these patients. All these performance data have been revealed by numerous studies using different artificial intelligence (AI) algorithms in addition to white-light endoscopy or novel endoscopic techniques that are available in expert endoscopy centers. It is expected that ongoing clinical trials involving AI and the embedding of computer-assisted diagnosis systems into endoscopic devices will enable real-life implementation of AI endoscopic systems in the near future and at the same time will help to overcome the current limits of the computer-assisted systems leading to an improvement in performance. These benefits should lead to better diagnostic and treatment strategies for gastric-cancer patients. Furthermore, the incorporation of AI algorithms in endoscopic tools along with the development of large electronic databases containing endoscopic images might help in upper-endoscopy assistance and could be used for telemedicine purposes and second opinion for difficult cases.

The immunohistochemical expression of the p53-protein in gastric carcinomas. Correlation with clinicopathological factors and survival of patients.

BACKGROUND: P53-tumor suppressor gene has an essential role in controlling cell cycle and initiating carcinogenesis. In the case of gastric cancer, the role of p53-protein accumulation as prognostic factor is controversy. Various results are due to the different methods of study regarding patients' selection, immunohistochemical techniques used and the quantifying systems for immunoreactions. AIM: Assessment of p53-immunohistochemical expression in 61 patients with gastric carcinomas and the correlation with clinicopathological factors (gender, age, location, macroscopic, and histological type, degree of tumor differentiation and TNM-stage) and patients' survival. MATERIAL AND METHODS: From the total number of 265 patients (186 males and 79 females) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of five years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). We used the monoclonal antibody DO7 that detects the wild and mutant form of p53-protein, by EnVision technique and DAB-visualization. We considered positive reaction only in the presence of brown staining of the nuclei. RESULTS: P53-immunoreactions were positive in 25 gastric cancers (41%). We obtained positive stainings in 41.9% cases in men and 38.9% women. We found positive p53-immunoreactions in all the carcinomas developed in the upper third of the stomach (100%), in 53.3% of the corporeal tumors, 50% of the pangastric tumors; according to Lauren's classification, we noticed a significantly increased immunoreaction of p53 in the intestinal-type carcinomas. Among histological types, papillary, mucinous, anaplastic and tubular adenocarcinomas presented a relatively increased percentage of p53-positive immunoreactions. P53-positive stainings are more frequently encountered in moderate/poor differentiated carcinomas and those associated with lymphovascular invasion; according to pT- and pN-stage, we remarked a significantly increase of the number of p53-positive cases (p=0.02291 and p=0.038264). Five-year survival rate for patients with p53-positive carcinomas was significantly lower in comparison to the patients p53-negative (8% vs. 22.2%, p=0.0326). CONCLUSIONS: Immunohistochemical evaluation of p53-protein represents in our study an important prognostic factor, allowing the selection of a group of patients with an aggressive therapeutic indication, such as extensive lymphadenectomy and adjuvant chemotherapy.

Ki-67 expression in gastric cancer. Results from a prospective study with long-term follow-up.

BACKGROUND: The characteristics of the cellular kinetic reflect the aggressiveness of the tumors and even their prognosis, many studies proving the correlation between the increased proliferation activity and a poor prognosis in a variety of neoplasms. AIM: The analysis of immunohistochemical expression of the Ki-67 antigen using the monoclonal antibody MIB1 in 61 patients with gastric cancer, the correlation with clinicopathological factors and the prognosis of the patients. MATERIAL AND METHODS: We used the primary MIB1 antibody pre-diluted, using the LSAB technique, DAB visualization. The quantification of the reaction was performed by appreciating the marking index Ki-67 (MI Ki-67). Although all the lesions were positive, we noticed a marked intratumoral heterogeneity regarding the distribution of the Ki-67 score. The tumor cells were considered Ki-67 positive in the presence of brown nuclear staining of granular or diffuse type. The tumor invasion front has shown the most numerous Ki-67 positive cells. RESULTS: In the gastric carcinomas, we remarked various Ki-67 scores. For a proper grouping of the results, we classified gastric carcinomas into two categories: carcinomas with high MI Ki-67 (≥45%) and carcinomas with low MI Ki-67 (≤45%). We noticed an increased frequency of high MI Ki-67 carcinomas in elderly patients (p=0.03) and also in the tumors developed at cardia level and those extended in the entire stomach in the moment of diagnosis (p<0.001). The histological forms associated to high Ki-67 values are represented by the anaplastic carcinoma (100% of cases) and papillary adenocarcinoma (60% of cases).We observed a close correlation between the degree of tumor differentiation and the Ki-67 score (p<0.001). The results of our study do not reveal any correlation between the Lauren's Classification of gastric carcinomas, the lymphovascular invasion, the depth of tumor invasion, the TNM stage and the Ki-67 score (p>0.05). CONCLUSIONS: In our study, immunohistochemical assessment of the tumor proliferation does not represent a prognostic factor, but seems to be useful in identifying of a group of patients with aggressive tumors, needing adjuvant postoperatory chemotherapy.

Gastric cancer: the correlation between the clinicopathological factors and patients' survival (I).

INTRODUCTION: The prognosis of the gastric cancer is generally reserved. The purpose of this study consists in the identification of the clinicopathological parameters that influence the prognosis of the patients that underwent surgery for gastric cancer. MATERIAL AND METHODS: Out of a total amount of 265 patients (186 males and 79 females) clinically and histopathologically diagnosed with gastric cancer, 61 patients operated for this disease have been selected from the Surgical Departments of the Emergency County Hospital in Timisoara. A prospective study was conducted on this group, regarding the gastric cancer's evolution and aggressiveness, for a period of 5 years. The survival time was calculated starting with the month when the surgery took place, and up to the month of death or that of the survival confirmation, and the survival rate was represented by the percentage of survivals at the end of the tracked period (in years and months). RESULTS: The study group was formed of 61 patients (43 males and 18 females) of ages between 30 and 80 years (mean age = 59.34 years). Gastric cancer was encountered more frequently in males (70.5%) than in females (29.5%) (p<0.001 ES). The amount of gastric cancer cases grows with age, the highest percent being observed in patients from the 51-70 years age group. However, the incidence is significantly lower after the age of 71 - 8.2% (p<0.001 ES). Antral localization of the gastric cancer predominates in both males and females, for all the age groups (50.8%). The average 5 years survival rate, for the whole group has been of 16.4%. We remark the extremely low survival rate for the older patients. In our study, we have identified five early gastric carcinomas (8.2%), classified as being type I protrusive tumors of intestinal type and 56 advanced gastric carcinomas, 16 cases in females (28.6%) and 40 cases in males (71.4%). The average survival for the patients with advanced gastric cancers was of 13.9 months, significantly lower than the average survival value of the patients with early gastric cancers (57.2 months). According to Borrmann's classification, we have identified five type I carcinomas (8.9%), 20 type II carcinomas (35.7%), 22 type III carcinomas (39.3%), and nine type IV carcinomas (16.1%). We did not notice any significant differences between the survival values of the patients with tumors of types I, II and III (p>0.05 NS), but the patients with diffuse infiltrative gastric cancers had an average survival of only 4.9 months after the surgery. CONCLUSIONS: The prognosis for gastric cancer is reserved, the 5 years average survival rate is of 16.4%. We have noticed a significantly decrease of survival rate with age (p = 0.024688 S). The 5 years survival is of 10.7% for patients with advanced cancers, significantly lower than the 5 years survival of 80% for patients with early gastric cancers (p<0.001 ES).The ulcerative-infiltrative type of cancer is predominant (39.3%). The patients with diffuse infiltrative forms of gastric cancers survived for an average period of only 4.9 months after surgical intervention.

Gastric cancer: correlation between clinicopathological factors and survival of patients. II.

PURPOSE: The purpose of this study was to identify the clinicopathological factors that influence the prognosis of patients having undergone surgery for gastric cancer. The analysis of the potential prognosis factors has included in this study parameters concerning the patient (sex, age), as well as parameters related with the tumor (macroscopic aspect of the tumor according to the Borrman's classification, histological type according to the WHO and Lauren's classifications, degree of tumor differentiation, tumor location, stage of disease, pT and pM parameters according to the TNM classification of AJCC/UICC). MATERIAL AND METHODS: From the total number of 265 patients (186 men and 79 women) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of 5 years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). RESULTS: The studied group consisted of 61 patients (43 men and 18 women), with ages between 30 and 80 (average age = 59.34 years). We have identified five papillary adenocarcinomas (8.2%), 28 tubular adenocarcinomas (46%), 17 "signet-ring" cell carcinomas (27.8%), eight mucinous adenocarcinomas (13.1%), and three undifferentiated or anaplastic carcinomas. Most gastric carcinomas examined were included in the category of poorly differentiated carcinomas (63.9%). According to the Lauren's classification, we have identified 38 intestinal type gastric carcinomas (62.3%), 17 diffuse type carcinomas (27.9%), and six mixed carcinomas (9.8%). We have identified aspects of lymphovascular invasion in 38 cases (62.3%). CONCLUSIONS: "Signet-ring" cells carcinomas, and the anaplastic ones, prove in our study to be extremely aggressive histological forms, characterized through low rates of survival. We remarked a significant correlation between the degree of tumor differentiation and survival of patients, the values recorded being significantly lower in medium and poorly differentiated carcinomas (p = 0.00871194 FS). Average survival, calculated in months, is significantly lower in patients with diffuse type carcinomas (11.3 months), in comparison with patients presenting intestinal type carcinomas (20.4 months) (p = 0.0415 S). There is a direct proportional relationship between the lymphovascular invasion and the number of positive lymph nodes. Survival after 5 years decreases significantly in the presence of lymphovascular invasion.

Gastric cancer: correlation between clinicopathological factors and survival of patients (III).

PURPOSE: The purpose of this study was to identify the clinicopathological factors that influence the prognosis of patients having undergone surgery for gastric cancer. The analysis of the potential prognosis factors has included in this study parameters concerning the patient (sex, age), as well as parameters related with the tumor (histological type according to the WHO classification; degree of tumor differentiation; tumor location; stage of disease; pT and pM parameters according to the TNM classification of AJCC/UICC). MATERIAL AND METHODS: From the total number of 265 patients (186 men and 79 women) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of 5 years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). RESULTS: The studied group consisted of 61 patients (43 men and 18 women), with ages between 30 and 80 (average age = 59.34 years). According to the maximum level of tumor invasion we identified: pTis - one case (1.6%); pT1 - four cases (6.6%); pT2 - nine cases (14.7%); pT3 - 17 cases (27.9%); most gastric cancers were included in the pT4 category (49.2%). We identified 43 gastric carcinomas with metastases in regional lymph nodes (70.5% of the cases). According to the number of lymph nodes involved: pN0 - 18 cases (29.5%); pN1 - 16 cases (26.2%); pN2 - 23 cases (37.7%); pN3 - four cases (6.6%). Distance synchronous metastases were present in 14 gastric carcinomas (pM1 - 23% of the cases), nine cases with hepatic metastases and five cases with distance peritoneal disseminations. Classification of gastric carcinomas: we identified one single case listed in the 0 stage, three cases in the IA stage, five cases in the IB stage, seven cases in the II stage, 11 cases in the IIIA stage, eight cases in the IIIB stage, and 26 cases in the IV stage. From the total of carcinomas, stage IV consisted of the greatest number of tumors, representing 42.6%. We generally remarked the increase of the number of cases in advanced stages. CONCLUSIONS: In the studied group, we noted a great number of gastric carcinomas diagnosed in stages T3 and T4 (77.1% of cases). Cardial tumor locations and gastric stump locations, as well as "signet-ring" cell and undifferentiated carcinomas prove to be aggressive, being diagnosed in advanced stages. 70.5% of gastric neoplasms presented lymph node metastases, most cases representing pN2 tumors (37.7%). 23% of neoplasms studied presented distance metastases at the time of diagnosis. We noted a significant correlation between the degree of tumor differentiation and the level of invasion, as well as the presence of distance and lymph node metastases. Survival at 5 years of patients included in the study was correlated significantly with the level of tumor invasion, the presence of lymph node and distance metastases, and the TNM stage.

Predictors of rebleeding and in-hospital mortality in patients with nonvariceal upper digestive bleeding.

BACKGROUND: Nonvariceal upper digestive bleeding (NVUDB) represents a severe emergency condition and is associated with significant morbidity and mortality. Despite a decrease in the incidence due to the widespread use of potent therapy with proton pump inhibitors as well as the implementation of modern endoscopic techniques, the mortality rate associated with NVUDB is still high. AIM: To identify the clinical, biological, and endoscopic parameters associated with a poor outcome in patients with NVUDB to allow the stratification of risk, which will lead to the implementation of the most accurate management. METHODS: We performed a retrospective study including patients who were admitted to the Gastroenterology Department of Clinical Emergency County Hospital Timisoara, Romania, with a diagnosis of NVUDB between 1 January 2008 and 31 December 2016. All the data were collected from the patient's records, including demographic data, medication history, hemodynamic status, paraclinical tests, and endoscopic features as well as the methods of hemostasis, rate of rebleeding, need for surgery and death; we also assessed the Rockall score of the patients, length of hospitalization and associated comorbidities. All these parameters were evaluated as potential risk factors associated with rebleeding and death in patients with NVUDB. RESULTS: We included a batch of 1581 patients with NVUDB, including 523 (33%) females and 1058 (67%) males with a median age of 66 years. The main cause of NVUDB was peptic ulcer (73% of patients). More than one-third of the patients needed endoscopic treatment. Rebleeding rate was 7.72%; surgery due to failure of endoscopic hemostasis was needed in 3.22% of cases; the in-hospital mortality rate was 8.09%, and the bleeding-episode-related mortality rate was 2.97%. Although our predictive models for rebleeding and death had a low sensitivity, the specificity was very high, suggesting a better discriminative capacity for identifying patients with better outcomes. Our results showed that the Rockall score was associated with both rebleeding and death; comorbidities such as respiratory conditions, liver cirrhosis and sepsis increased significantly the risk of in-hospital mortality (OR of 3.29, 2.91 and 8.03). CONCLUSION: Our study revealed that the Rockall score, need for endoscopic therapy, necessity of transfusion and sepsis were risk factors for rebleeding. Moreover, an increased Rockall score and the presence of comorbidities were predictive factors for in-hospital mortality.

Malignant hepatic vascular tumors in adults: Characteristics, diagnostic difficulties and current management.

Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation (LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma (HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation Association-European Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma (HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient. Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches, alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.

Prognostic significance of E-cadherin expression in hepatocellular carcinoma: correlations with clinical features.

BACKGROUND: Hepatocellular carcinoma (HCC) represents a major public health issue, being associated with high morbidity and mortality rates. Previous studies have demonstrated that reduction and∕or absence of E-cadherin expression is correlated with a potential for invasion and low survival rate in patients with HCC. PATIENTS, MATERIALS AND METHODS: We assessed the immunohistochemical expression of E-cadherin in 32 HCCs and peritumoral hepatic tissues using monoclonal anti-E-cadherin antibody (clone EP700Y), at 1:50 dilution, followed by incubation with Labeled Streptavidin-Biotin 2 (LSAB2) for 20 minutes, visualization of the reaction with 3,3'-Diaminobenzidine (DAB) and counterstaining with Mayer's Hematoxylin. RESULTS: The results we obtained show: an aberrant E-cadherin expression more frequent in dysplastic nodules (p=0.285) and in 81.25% of HCC cases, as compared to normal hepatic tissue (p<0.001); the absence of a statistically significant relationship between E-cadherin expression and patients' gender (p=0.854), tumor localization (p=0.429), associated viral infection [hepatitis B virus (HBV) or hepatitis C virus (HCV)] (p=0.513) or tumor size (p=0.788); the rate of positive E-cadherin expression was significantly higher in tumors with capsular infiltration (75%) (p=0.017) and does not appear to be influenced by vascular invasion (62.5%) (p=0.411), the presence of satellite nodules (p=0.285) or the serum level of alpha-fetoprotein (α-FP) (p=0.787). CONCLUSIONS: Reduced E-cadherin expression indicates a poor prognosis for patients with HCC and can be considered a potential predictive marker for the prognosis of these patients.

Comparison of the liver stiffness measurement by transient elastography with the liver biopsy.

AIM: To compare the liver stiffness (LS) measurement by transient elastography (TE) to the liver biopsy (LB)-considered the "gold standard" in the evaluation of patients with chronic hepatitis C. METHODS: During a period of 12 mo, we evaluated 199 consecutive patients with chronic hepatitis due to hepatitis C virus (HCV), in which LB and LS assessments (by means of TE) were performed during the same session. RESULTS: Out of 199 patients, a valid measurement of the LS could not be obtained in 8. The mean value of LS in the cohort of 191 valid measurements was 8.45 +/- 4.96 kPa, ranging from 2.3 to 38 kPa. The mean value of LS in patients with significant fibrosis at biopsy (161 patients with F >= 2 according to Metavir) was 9.02 +/- 5.15 kPa, significantly higher than in patients with no or mild fibrosis (30 patients with F < 2 Metavir): 5.39 +/- 1.81 kPa (P < 0.0001). For a cut-off value of 6.8 kPa, the LS had a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6% and a specificity of 93.3% for the presence of significant fibrosis (at least F2 Metavir), with a diagnostic performance of 77.3% (AUROC 0.773). Using this cut-off value, we reached the best discrimination between absence of fibrosis/mild fibrosis (F < 2 Metavir) and the presence of moderate to severe fibrosis (F >= 2 Metavir). CONCLUSION: In patients with chronic hepatitis due to HCV, a cut-off value of 6.8 kPa measured by TE can differentiate between significant fibrosis and absent or mild fibrosis, with a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6%, a specificity of 93.3%, and a diagnostic performance of 77.3%.

Immunohistochemical evaluation of the tumor neoangiogenesis as a prognostic factor for gastric cancers.

INTRODUCTION: The angiogenesis, the process by which new blood vessels are formed, plays an essential role in the survival of the malignant cells, in the local expansion and tumor invasion, as well as in the appearance of distant metastases. MATERIAL AND METHODS: We evaluated the relation between MVD, the VEGF expression, the clinicopathologic factors and the survival in patients with gastric cancer. A prospective study has been carried out, regarding the evolution and aggressiveness of the gastric cancer, with a duration of 5 years, 61 patients that underwent a surgery for gastric cancer being included in the study. The immunohistochemical reactions for CD34 and VEGF were performed for all gastric cancers cases included in the study group. RESULTS: MVD has shown in the gastric carcinomas an average value significantly higher in comparison to the normal mucosa (38.7 vs. 12.5, p<0.001 ES). In the intestinal type we have noticed a much lower average MVD than the average MVD in the diffuse type of gastric carcinomas (36.8 vs. 41.6) (p=0.02478 S). The anaplastic carcinoma and the signet ring cell carcinoma are detaching themselves as histological forms associated to an intense neoangiogenesis activity. The neoangiogenesis activity is correlated with: the histologic grade, the lymphovascular invasion, the level of extend, the lymph node metastasizing, the distant metastasizing and the TNM stage. The positive immunoreactions for VEGF are significantly more frequent in the gastric carcinomas, in comparison to the normal gastric mucosa (65.6% vs. 6.5%, p<0.001 ES). The immunoreactions to the VEGF protein were positive in 71.1% of the intestinal carcinomas, significantly more frequent in comparison to the diffuse type carcinomas (52.9%) (p=0.018178 S). Our results show a tight correlation between the histologic grade, the level of the tumor invasion and the VEGF expression. CONCLUSIONS: Our results prove the major correlation between the VEGF expression and the 5-year survival rate of the patients with gastric cancer, the survival rate for the carcinomas with VEGF +~++ being significantly lower than for the VEGF negative ones (12.5% vs. 23.8%) (p=0.027983 S). Our study proves a tight correlation between the VEGF expression and the MVD (p=0.03986 S), these factors playing an important role in the tumoral biologic conduct, in the progression and the prognostic.

The immunohistochemical expression of E-cadherin in gastric cancer; correlations with clinicopathological factors and patients' survival.

BACKGROUND: The aim of our study is to investigate the immunohistochemical expression of E-cadherin in gastric carcinomas and in surrounding mucosa (normal or with lesions of chronic atrophic gastritis, intestinal metaplasia or dysplasia). MATERIAL AND METHODS: We included 61 patients with gastric cancers operated in Emergency County Hospital Timisoara. We analyzed the E-cadherin immunohistochemical expression, the correlation with clinical and pathological factors and the outcome of the patients. The positive homogeneous pattern of staining for the cellular membranes is considered normal. The negative homogeneous or the heterogeneous pattern (of the cytoplasm and membrane) represented aberrant E-cadherin expression. RESULTS: Areas of chronic atrophic gastritis and intestinal metaplasia presented a normal pattern of immunostaining for the membranes. Aberrant E-cadherin expression was noticed in 30 cases of gastric carcinomas (49.2%) and in 11 cases (35.5%) of epithelial dysplasia in the surrounding tissue. Our results showed no correlation between E-cadherin expression and gender, age, tumor location, pT, pN, pTNM and lympho-vascular invasion. Aberrant E-cadherin immunostainings were significantly more frequent in diffuse-type carcinomas in comparison with the intestinal-type carcinomas (82.4% vs. 31.6%) (p = 0.000491 ES). Signet-ring carcinomas and anaplastic carcinomas presented a high-proportion of aberrant immunostainings (82.4% and 100%), as well as poor differentiated carcinomas (61.5%). Carcinomas with distant metastasis presented significantly more aberrant immunostainings than those without metastasis (71.4% vs. 42.6%). Five-year survival rate was significantly lower in patients with aberrant E-cadherin expression in comparison with the patients presenting normal staining (10% vs. 22.6%). CONCLUSIONS: In gastric carcinomas and areas of epithelial dysplasia, aberrant E-cadherin expression was significantly more frequent in comparison with the surrounding normal mucosa (p<0.001 ES). Our data suggest a strong correlation between Lauren's classification of gastric carcinomas and E-cadherin immunohistochemical expression. Assessment of the survival curve of the patients highlighted the role of prognostic factor for the aberrant immunohistochemical E-cadherin expression.

Immunohistochemical expression of the cyclooxygenase-2 (COX-2) in gastric cancer. The correlations with the tumor angiogenesis and patients' survival.

INTRODUCTION: The mechanisms by which COX-2 contributes to the carcinogenesis are not known until present. It seems that the COX-2 enzyme stimulates the cell proliferation, inhibits the apoptosis, increases the malignant cells' invasiveness and induces the angiogenesis by elaborating some angiogenic factors. MATERIAL AND METHODS: In the present study, we intend to evaluate the immunohistochemical expression of COX-2 in gastric carcinomas, keeping track of the correlations between the clinicopathologic factors, the tumor angiogenesis (evaluated by microvascular density--MVD--determination and by VEGF expression) and the patients' survival. In addition, we have tracked the immunoreactions' positivation in the peritumoral mucosa with various lesions, with the purpose to establish the contribution of COX-2 to the gastric carcinogenesis during the pre-invasive stages. A prospective study was realized, regarding the evolution and aggressiveness of the gastric cancer, with a duration of five years, 61 patients operated of gastric cancer being included. RESULTS: The COX-2 immunoreactions have been significantly more frequent noticed in the gastric carcinomas included in the study (57.4%) and in the epithelial dysplasia areas adjacent to the carcinomas of intestinal type (35.5% of the cases), than in the normal peritumoral mucosa (4.9%) (p<0.001 ES). The COX-2 immunoreactions have turned positive more frequently in gastric carcinomas of intestinal type (68.4%), in comparison to the carcinomas of diffuse type (29.4%) (p<0.001 ES). The COX-2 expression is significantly correlated with the invasion level, the presence of the metastases in the regional lymph nodes and the pTNM stage, but without influencing the prognosis of the gastric cancer patients. The negative VEGF carcinomas have turned positive for COX-2 only for 19% of the cases. Different from those, the positive VEGF carcinomas have associated COX-2 immunoreactivity in 77.5% of the cases. CONCLUSIONS: The results obtained are suggestive for the predominant expression of COX-2 in the carcinomas of intestinal type and its precursory lesions. Our results show a tight correlation between the immunohistochemical expressions of COX-2 and VEGF in gastric carcinomas (r = 0.562, p < 0.001 ES) and also a MVD average value significantly higher in the positive COX-2 carcinomas, suggesting an intense angiogenesis activity in that group of tumors (p < 0.001 ES).

Immunohistochemical expression of vascular endothelial growth factor (VEGF) in intestinal type gastric carcinoma.

BACKGROUND: Gastric cancer still represents a difficult problem in the field of oncology, in terms of morbidity and mortality. The local progression and systemic spread is significantly influenced by tumor angiogenesis and lymphangiogenesis. In spite of many studies on the topic, data about the significance of growth factors in gastric cancer is controversial. AIM: to investigate the immunohistochemical expression of VEGF and to evaluate the relationships with the tumors stage and grade. MATERIAL AND METHODS: The immunohistochemical expression of VEGF was investigated on 80 patients with intestinal type gastric carcinoma. Specimens were fixed in buffer formalin, embedded in paraffin, and sections were stained with Hematoxylin-Eosin and immunohistochemistry was performed for VEGF (clone VG-1). Evaluation was performed using the VEGF score, based on the intensity of reaction and percent of positive cells. RESULTS: The reaction for VEGF was positive in 52 from 80 cases (70%). The final product of reaction was found in the cytoplasm of tumor cells, with granular pattern. Positive reaction was also found in eight from 28 cases with associated intestinal metaplasia, and in six from nine cases with gastric dysplasia. In the adjacent apparently normal mucosa, the reaction was positive in hyperplastic gastric pits and parietal cells. A strong correlation was found between VEGF expression and lymph node status and grade of the primary, but not with the stage of the tumor. CONCLUSIONS: The investigation of the immunohistochemical expression of VEGF in the intestinal type of gastric carcinoma showed positive reaction in 70% of the cases. It was demonstrated the expression of VEGF in intestinal metaplasia and gastric dysplasia, which could signify an early angiogenic switch during tumorigenesis.