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 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.

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.

Prognostic significance of tumor immune microenvironment and immunotherapy: Novel insights and future perspectives in gastric cancer.

Despite a decrease in gastric cancer incidence, the development of novel biologic agents and combined therapeutic strategies, the prognosis of gastric cancer remains poor. Recently, the introduction of modern immunotherapy, especially using immune checkpoint inhibitors, led to an improved prognosis in many cancers. The use of immunotherapy was also associated with manageable adverse event profiles and promising results in the treatment of patients with gastric cancer, especially in heavily pretreated patients. These data have led to an accelerated approval of some checkpoint inhibitors in this setting. Understanding the complex relationship between the host immune microenvironment and tumor and the immune escape phenomenon leading to cancer occurrence and progression will subsequently lead to the identification of prognostic immune markers. Furthermore, this understanding will result in the discovery of both new mechanisms for blocking tumor immunosuppressive signals and pathways to stimulate the local immune response by targeting and modulating different subsets of immune cells. Due to the molecular heterogeneity of gastric cancers associated with different clinico-biologic parameters, immune markers expression and prognosis, novel immunotherapy algorithms should be personalized and addressed to selected subsets of gastric tumors, which have been proven to elicit the best clinical responses. Future perspectives in the treatment of gastric cancer include tailored dual immunotherapies or a combination of immunotherapy with other targeted agents with synergistic antitumor effects.

Vitamin D deficiency in a European inflammatory bowel disease inception cohort: an Epi-IBD study.

BACKGROUND: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing. MATERIALS AND METHODS: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores. RESULTS: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053). CONCLUSION: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke.

Occurrence of Anaemia in the First Year of Inflammatory Bowel Disease in a European Population-based Inception Cohort-An ECCO-EpiCom Study.

BACKGROUND AND AIMS: Anaemia is an important complication of inflammatory bowel disease [IBD]. The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis, in a European prospective population-based inception cohort. METHODS: Newly diagnosed IBD patients were included and followed prospectively for 1 year in 29 European and one Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization criteria. RESULTS: A total of 1871 patients (Crohn's disease [CD]: 686, 88%; ulcerative colitis [UC]: 1,021, 87%; IBD unclassified [IBDU] 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and, overall, 49% of CD and 39% of UC patients experienced at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed. CONCLUSIONS: Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting.

New advances in targeted gastric cancer treatment.

Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.

Costs and resource utilization for diagnosis and treatment during the initial year in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom Study.

BACKGROUND: No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe. METHODS: The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (€) using the Danish Health Costs Register. RESULTS: One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was €5,408,174 (investigations: €2,042,990 [38%], surgery: €1,427,648 [26%], biologicals: €781,089 [14%], and standard treatment: €1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations €1803 (€2160) (P = 0.44), surgery €11,489 (€13,973) (P = 0.14), standard treatment €1027 (€824) (P = 0.51), and biologicals €7376 (€8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations €1189 ( €1518) (P < 0.01), surgery €18,414 ( €12,395) (P = 0.18), standard treatment €896 ( €798) (P < 0.05), and biologicals €5681 ( €72) (P = 0.51). CONCLUSIONS: In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.

Ki-67 and p53 immunostaining assessment of proliferative activity in salivary tumors.

Salivary gland tumors are rare neoplasias with approximately 34 different histological types. Because they have a considerably histological and biological behavior variability, salivary gland tumors represent a challenge both for the pathologist and the surgeon regarding their diagnosis, prognosis and treatment. Evaluation of mitotic index in case of Ki-67 and p53 expression has proved to be useful in predicting the biological aggressiveness in many tumors. In this study, we have analyzed the p53 and Ki-67 immunohistochemical expressions in 40 cases of salivary gland tumors, their correlations with clinicopathological factors and the prognostic relevance and diagnostic value of the results obtained. We analyzed eight pleomorphic adenomas (PA), seven Warthin tumors (WT), five basal cell adenomas (BA), four carcinomas ex pleomorphic adenoma (CEPA), four mucoepidermoid carcinomas (MEC), four acinic cell carcinomas (AC), four adenoid cystic carcinomas (ACC) and four adenocarcinomas not otherwise specified (ADK NOS). p53 positive staining was detected in 18 of the 40 cases studied, with higher expression in the malignant salivary tumors investigated. Ki-67 was expressed in 29 cases. High p53 and Ki-67 expression was noted in 3/4 CEPA, 3/4 ADK NOS and 2/4 MEC. Also, 2/8 PA, 3/7 WT and 2/5 BA were p53 positive and 2/7 WT and 2/5 BA had high Ki-67 mitotic index. The investigation of p53 and Ki-67 expression is useful in identifying highly proliferative forms of salivary tumors, with aggressive potential of evolution. The evaluation of these proliferative markers seems to have a prognostic value for CEPA, ADK NOS and MEC types of salivary tumors.

Initial disease course and treatment in an inflammatory bowel disease inception cohort in Europe: the ECCO-EpiCom cohort.

BACKGROUND: The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. METHODS: Patients were followed-up every third month during the first 12 (±3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu). RESULTS: In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn's disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe. DISCUSSION: In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.

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.

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.

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.