Publications by authors named "Robert Sitarz"

24 Publications

  • Page 1 of 1

Status of CHEK2 and p53 in patients with early-onset and conventional gastric cancer.

Oncol Lett 2021 May 3;21(5):348. Epub 2021 Mar 3.

Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Gastric cancer (GC) is the fourth most common cause of cancer-associated death. Based on the age at diagnosis, GC is divided into early-onset GC (EOGC; ≤45 years) and conventional GC (CGC; >45 years). Mutations in the cell cycle checkpoint kinase 2 () and genes are associated with several types of cancer; however, their genetic defects in GC remain poorly understood. The aim of the present study was to determine the subcellular distribution of the CHEK2 protein and its redistribution following DNA damage, to improve the understanding of the DNA damage response. Genetic alterations and patterns of expression of CHEK2 and p53 proteins were investigated to identify potential biological markers and indicators of GC development. Additionally, the affected signaling pathways and their clinical importance in GC development and associated syndromes were investigated. A total of 196 GC samples (89 CGC and 107 EOGC samples) were used in the present study. DNA from 53 samples (18 CGC and 35 EOGC samples) was sequenced using targeted next-generation sequencing technology to identify and compare common and rare mutations associated with GC. Subsequently, the cytoplasmic and nuclear expression levels of CHEK2, phosphorylated (p)-CHEK2 at threonine 68 and p53 in GC tissues were determined via immunohistochemistry. Sequencing resulted in the identification of 63 single nucleotide polymorphisms (SNPs) in the gene amongst 5 different variants, and the intron variant c.319+379A>G was the most common SNP. In the gene, 57 different alterations were detected amongst 9 variant types, and the missense variant c.215C>G was the most common. Nuclear CHEK2 expression was high in both the EOGC and CGC subtypes. However, the prevalence of cytoplasmic CHEK2 expression (P<0.001) and nuclear p-CHEK2 expression (P=0.011) was significantly higher in CGC compared with in EOGC tissues. There was a statistically significant difference between high and low cytoplasmic CHEK2 expression in patients with p53-positive EOGC compared with in patients with p53-positive CGC (P=0.002). The present study was designed to determine the association between CHEK2 and p53 expression patterns in patients with EOGC and CGC, as well as genetic alterations in the and genes.
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http://dx.doi.org/10.3892/ol.2021.12609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967923PMC
May 2021

Giant Lipoma in the Fronto-Temporo-Parietal Region in an Adult Man: Case Report and Literature Review.

Clin Cosmet Investig Dermatol 2020 24;13:1015-1020. Epub 2020 Dec 24.

Department of Normal Anatomy, Medical University of Lublin, Lublin, Poland.

Lipoma belongs to a group of benign mesenchymal tumors. It is in the form of soft masses of adipose tissue encapsulated by a thin layer of fibrous tissue and usually localized subcutaneously. The tumor most often appears in the upper part of the body. Lipomas tend to grow slowly and are small (less than 5cm) lesions. Larger tumors are rare. In this article, we present the case of a patient with a giant head lipoma in the fronto-temporo-parietal region. Both tumor size and location are unique and no such case has been described in the literature so far.
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http://dx.doi.org/10.2147/CCID.S273189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769594PMC
December 2020

Awareness of gastrointestinal tract malignancies among the population of Lublin province (Eastern Poland) - A cross-sectional study.

Ann Agric Environ Med 2020 Sep 20;27(3):469-475. Epub 2019 Dec 20.

Medical University, Lublin, Poland.

Introduction: Currently, malignancies are the most severe medical problems worldwide. Numerous, already known risk factors in carcinogenesis could be potentially avoided. Some cancer risk factors have been recognized and have become the targets of primary prophylaxis.

Objective: The aim of the study was to ascertain the state of knowledge about risk factors, primary prevention and early detection of malignancies of gastrointestinal tract (GIT) in the urban and rural population of the Lublin province in Eastern Poland.

Material And Methods: The study was cross-sectional. The originally designed questionnaire was applied to the group of 1,352 patients, representatives of both the rural and urban environments of the Lublin province during random appointments with their general practitioner (GP).

Results: The study showed low awareness of the issues connected with GIT malignancies within the studied group. The problem was particulary apparent in the rural population.

Conclusions: In order to raise general awareness of cancer, different means should be applied in urban and rural populations. GPs and the media were found to have the leading rols in the promotion of primary prevention.
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http://dx.doi.org/10.26444/aaem/113469DOI Listing
September 2020

Expression of cyclooxygenase-2 and mucin 1 in colorectal cancer.

Mol Clin Oncol 2020 Nov 20;13(5):52. Epub 2020 Aug 20.

Department of Surgical Oncology, Medical University of Lublin, Lublin 20-090, Poland.

In colorectal cancer (CRC), pathological factors that correlate with negative prognosis include, among others, overexpression of cyclooxygenase-2 (COX-2) and abundant expression of mucin 1 (MUC1). COX-2 overexpression may therefore be associated with MUC1 overexpression. The aim of the present study was to investigate the possible correlation between COX-2 and MUC1 expression and to assess the correlation between their individual expression and the clinicopathological features of patients, paying particular attention to survival. The following data was collected from the 170 patients with CRC included in the present study: Age, sex, tumour localization, disease stage and survival. Tumour samples were immunostained with antibodies against COX-2 and MUC1. Protein expression was scored, relative to reference staining, and correlated with the clinicopathological data of patients. The results revealed no correlation between the expressions of COX-2 and MUC1, or with any of the studied clinicopathological variables. In addition, the expression of the two proteins were not associated. Neither of the proteins demonstrated prognostic value for survival. The present study did not confirm a direct relationship between the expressions of COX-2 and MUC1, or between the expression of either protein and the clinicopathological features of patients, including survival.
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http://dx.doi.org/10.3892/mco.2020.2122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453394PMC
November 2020

High-Throughput Sequencing of Gastric Cancer Patients: Unravelling Genetic Predispositions Towards an Early-Onset Subtype.

Cancers (Basel) 2020 Jul 21;12(7). Epub 2020 Jul 21.

Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Background: Gastric cancer is the fourth most common cause of cancer-related death. Currently, it is broadly accepted that the molecular complexity and heterogeneity of gastric cancer, both inter- and intra-tumor, display important barriers for finding specific biomarkers for the early detection and diagnosis of this malignancy. Early-onset gastric cancer is not as prevalent as conventional gastric carcinoma, but it is a preferable model for studying the genetic background, as young patients are less exposed to environmental factors, which influence cancer development.

Aim: The main objective of this study was to reveal age-dependent genotypic characteristics of gastric cancer subtypes, as well as conduct mutation profiling for the most frequent alterations in gastric cancer development, using targeted next-generation sequencing technology.

Patients And Methods: The study group included 53 patients, consisting of 18 patients with conventional gastric cancer and 35 with an early-onset subtype. The DNA of all index cases was used for next-generation sequencing, employing a panel of 94 genes and 284 single nucleotide polymorphisms (SNPs) (TruSight Cancer Panel, Illumina), which is characteristic for common and rare types of cancer.

Results: From among the 53 samples processed for sequencing, we were able to identify seven candidate genes (, and ) and nine variants among them: one splice_acceptor, four synonymous, and four missense variants. These were selected for the age-dependent differentiation of gastric cancer subtypes. We found four variants with C-Score ≥ 10, as 10% of the most deleterious substitutions: rs1800862 (), rs10138997 (), rs2230009 (), and rs2959656 (). We identified 36 different variants, among 24 different genes, which were the most frequent genetic alterations among study subjects. We found 16 different variants among the genes that were present in 100% of the total cohort: (rs2746462), (rs1670283), (rs2958057), (rs4925828; rs11342077, rs398010167; rs2721190), (rs326212), (rs540012), (rs4930199), (rs659243), (rs1169305), (rs206075; rs169547), (rs9514066; rs9514067), and (rs7183618).

Conclusions: The technology of next-generation sequencing is a useful tool for studying the development and progression of gastric carcinoma in a high-throughput way. Our study revealed that early-onset gastric cancer has a different mutation frequency profile in certain genes compared to conventional subtype.
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http://dx.doi.org/10.3390/cancers12071981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409326PMC
July 2020

Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies.

Int J Mol Sci 2020 Jun 4;21(11). Epub 2020 Jun 4.

Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.
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http://dx.doi.org/10.3390/ijms21114012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312039PMC
June 2020

Preoperative and Intraoperative Methods of Parathyroid Gland Localization and the Diagnosis of Parathyroid Adenomas.

Molecules 2020 Apr 9;25(7). Epub 2020 Apr 9.

Section of Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantations, University of Bari "Aldo Moro" Medical School, 70124 Bari, Italy.

Accurate pre-operative determination of parathyroid glands localization is critical in the selection of minimally invasive parathyroidectomy as a surgical treatment approach in patients with primary hyperparathyroidism (PHPT). Its importance cannot be overemphasized as it helps to minimize the harmful side effects associated with damage to the parathyroid glands such as in hypocalcemia, severe hemorrhage or recurrent laryngeal nerve dysfunction. Preoperative and intraoperative methods decrease the incidence of mistakenly injuring the parathyroid glands and allow for the timely diagnosis of various abnormalities, including parathyroid adenomas. This article reviews 139 studies conducted between 1970 and 2020 (49 years). Studies that were reviewed focused on several techniques including application of carbon nanoparticles, carbon nanoparticles with technetium sestamibi (99m Tc-MIBI), Raman spectroscopy, near-infrared autofluorescence, dynamic optical contrast imaging, laser speckle contrast imaging, shear wave elastography, and indocyanine green to test their potential in providing proper parathyroid glands' localization. Apart from reviewing the aforementioned techniques, this study focused on the applications that helped in the detection of parathyroid adenomas. Results suggest that applying all the reviewed techniques significantly improves the possibility of providing proper localization of parathyroid glands, and the application of indocyanine green has proven to be the 'ideal' approach for the diagnosis of parathyroid adenomas.
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http://dx.doi.org/10.3390/molecules25071724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181220PMC
April 2020

Ethanol extracts of sp. regulate cyclooxygenase-2 and E-cadherin expression in gastric cancer MKN74 cell line and enhance doxorubicin toxicity.

Food Nutr Res 2019 25;63. Epub 2019 Jun 25.

Department of Anatomy, Medical University of Lublin, Lublin, Poland.

Background: Gastric cancer (GC) remains one of the leading causes of cancer-related death. Its aetiology is multifactorial, but the major risk factor is a high in salt diet. During gastric carcinogenesis, cadherin-1 (CDH1) down-expression and cyclooxygenase 2 (COX2) overexpression may be observed. The intensity of these alterations contributes to the GC invasion, its metastases and poor prognosis. As the diet plays a significant role in the aetiology of GC, it is reasonable to include the nutritional chemoprevention agents. One of the plant genus demonstrating chemoprotective properties is genus, which includes garlic. The relationship between CDH1 and COX2 in GC cells treated with species extract has never been evaluated.

Methods: In this study, the MKN28 and MKN74 GC cell lines were treated with ethanol extracts of L., Lam., L. (from Malaysia and Poland), Rendle and L. The cytotoxicity of the extracts and their influence on COX2 and CDH1 mRNA and protein expression were evaluated as well as their influence on doxorubicin's (DOX) efficacy - a drug that has been used in GC treatment.

Results: Among the tested species, ethanol extracts of L. (Poland and Malaysia), Rendle and L. influenced the levels of CDH1 and COX2, but only in the MKN74 cell line. Thus, it is possible that tumours with increased COX2 expression will be more susceptible to garlic treatment. Observed phenomenon was independent of extract's toxicity. In comparison to DOX, tested extracts were more toxic. Moreover, revealed synergistic effect with the drug.

Conclusion: In conclusion, the results indicate the potential application of genus to GC chemoprevention and treatment support through CDH restoration and COX2 downregulation. This issue needs further investigations as it might be used in clinics.
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http://dx.doi.org/10.29219/fnr.v63.3449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604903PMC
June 2019

State of the art for gastric signet ring cell carcinoma: from classification, prognosis, and genomic characteristics to specified treatments.

Cancer Manag Res 2019 15;11:2151-2161. Epub 2019 Mar 15.

Department of Human Anatomy, Medical University of Lublin, Lublin, Poland,

Gastric cancer (GC) is responsible for 9% of cancer deaths worldwide. Over 950,000 new cases are diagnosed each year, and about 90% of them are in advanced stage, requiring chemotherapy. In Europe there has been research based on pre- and postoperative chemotherapy treatment, using 5-fluorouracil, epirubicin, cisplatin, capecitabine, and docetaxel. Chemotherapy significantly impairs the quality of life of patients; however, the final effects are not always satisfactory. There is scientific evidence that gastric mucus tumors and signet ring cell carcinomas have a pattern of specific signatures, that distinguish them from other gastric cancer subtypes, and may be associated with a poor response to systematic treatment. Signet ring cell carcinoma is less chemosensitive than others, and the increase in the percentage of signet ring cells correlates with resistance to chemotherapy. Perioperative chemotherapy in advanced signet ring cell carcinomas is an independent factor of poor prognosis and survival, which is explained by the toxicity of neoadjuvant treatment. Therefore, curative surgical resection enhanced by standardized lymphadenectomy remains the recommended gold standard in GC therapy. According to presented studies, early detection and aggressive treatments for this subtype of GC is a reasonable approach. This review paper is mostly addressed to physicians who are interested in updating to the state of the art concerning different subtypes of gastric carcinoma.
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http://dx.doi.org/10.2147/CMAR.S188622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421895PMC
March 2019

Madelung's disease - progressive, excessive, and symmetrical deposition of adipose tissue in the subcutaneous layer: case report and literature review.

Diabetes Metab Syndr Obes 2018 26;11:819-825. Epub 2018 Nov 26.

Department of Surgery with Trauma, Orthopaedic and Urological Subunit, Independent Public Health Care Center of the Ministry of Interior and Administration in Lublin, Lublin, Poland,

Madelung's disease is a rare disorder described for the first time in the year 1846 by Brodie. It is characterized by the occurrence of progressive, excessive, and symmetrical deposits of adipose tissue in the subcutaneous layer. Most often, these changes concern the neck, the nape of the neck, arms, and upper back, giving the patients a specific, pseudoathletic appearance. Madelung's disease is also known as multiple symmetrical lipomatosis, benign symmetrical lipomatosis, and Launois-Bensaude syndrome. The most commonly affected ones are men who drink alcohol in excessive amounts. The fat masses emerging in the course of the disease are painless but can lead to adverse repercussions. Patients may experience dysphagia, dysphonia, difficulty in breathing, and limited mobility of the neck. The reasons for the willingness to take up treatment are also often esthetic reasons. The disease is usually accompanied by numerous metabolic disorders. The etiology of the disease has not been sufficiently explained so far, which creates diagnostic and therapeutic difficulties. Currently used treatment is limited to surgical resection of the resulting lesions or liposuction. Unfortunately, the effectiveness of these activities is limited. Most patients experience recurrence after treatment. This paper discusses the essence of Madelung's disease, numerous aspects of etiology, the manner of diagnosis, and treatment based on current literature data.
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http://dx.doi.org/10.2147/DMSO.S181154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263218PMC
November 2018

associated factors in the development of gastric cancer with special reference to the early-onset subtype.

Oncotarget 2018 Jul 24;9(57):31146-31162. Epub 2018 Jul 24.

Department of Human Anatomy, Medical University of Lublin, Poland.

Nowadays, gastric cancer is one of the most common neoplasms and the fourth cause of cancer-related death on the world. Regarding the age at the diagnosis it is divided into early-onset gastric carcinoma (45 years or younger) and conventional gastric cancer (older than 45). Gastric carcinomas are rarely observed in young population and rely mostly on genetic factors, therefore provide the unique model to study genetic and environmental alternations. The latest research on early-onset gastric cancer are trying to explain molecular and genetic basis, because young patients are less exposed to environmental factors predisposing to cancer. In the general population, , has been particularly associated with intestinal subtype of gastric cancers. The significant association of infection in young patients with gastric cancers suggests that the has an etiologic role in both diffuse and intestinal subtypes of early-onset gastric cancers. In this paper we would like to ascertain the possible role of infection in the development of gastric carcinoma in young patients. The review summarizes recent literature on early-onset gastric cancers with special reference to infection.
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http://dx.doi.org/10.18632/oncotarget.25757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089554PMC
July 2018

The Pattern of Signatures in Gastric Cancer Prognosis.

Int J Mol Sci 2018 Jun 4;19(6). Epub 2018 Jun 4.

Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Gastric cancer is one of the most common malignancies worldwide and it is a fourth leading cause of cancer-related death. Carcinogenesis is a multistage disease process specified by the gradual procurement of mutations and epigenetic alterations in the expression of different genes, which finally lead to the occurrence of a malignancy. These genes have diversified roles regarding cancer development. Intracellular pathways are assigned to the expression of different genes, signal transduction, cell-cycle supervision, genomic stability, DNA repair, and cell-fate destination, like apoptosis, senescence. Extracellular pathways embrace tumour invasion, metastasis, angiogenesis. Altered expression patterns, leading the different clinical responses. This review highlights the list of molecular biomarkers that can be used for prognostic purposes and provide information on the likely outcome of the cancer disease in an untreated individual.
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http://dx.doi.org/10.3390/ijms19061658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032410PMC
June 2018

Awareness of hepatic arterial variants is required in surgical oncology decision making strategy: Case report and review of literature.

Oncol Lett 2018 May 22;15(5):6251-6256. Epub 2018 Feb 22.

Department of Surgical Oncology, Medical University of Lublin, 20-081 Lublin, Poland.

Surgery for the treatment of pancreatic cancer remains the gold standard, however, the identification of the vascular supply of the pancreas and the nearby organs remains a crucial difficulties in a curative resection. During pancreatic head resection for carcinoma dissection of regional arterial vasculature is mandatory. Normal coeliac and hepatic arterial anatomy occurs in ~50-70% of patients and multiple variations have been described. Knowledge of multiple arterial anomalies is essential in hepato-pancreatico-billary surgery to avoid unnecessary complications. The present study presents coeliac trunk and common hepatic artery (CHA) anomalies along with their clinical importance, as reviewed according to the available literature. Patients diagnosed with cancer of the pancreatic head were hospitalized for staging and planning of radical surgical therapy. Computed tomography (CT) revealed a large tumour mass in the head of the pancreas and CHA, which branched directly from the superior mesenteric artery. A three-dimensional CT reconstruction revealed a demonstrative vascular anomaly, which was confirmed during an operation. Despite the anomalous origin of the CHA, pylorus preserving pancreatoduodenectomy and regional lymph node dissection without intraoperative complications was performed in each case. The patient's postoperative clinical course was uneventful and adjuvant chemotherapy could be administered without delay. In the multidisciplinary treatment of pancreatic carcinoma the surgeon and radiologist must be aware of the aberrant anatomy in order to avoid potential complications. As CT scans used for the preoperative staging are of diagnostic value for vascular anomaly, it is required for appropriate surgical decision making.
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http://dx.doi.org/10.3892/ol.2018.8106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876442PMC
May 2018

The use of rifaximin in pre-operative period of patients with tumors of the gastrointestinal tract - a retrospective study (2013-2016).

Pol Przegl Chir 2018 Feb;90(1):35-40

6Klinika Chirurgii Onkologicznej, SPSK Nr 1 w Lublinie, Polska.

ntroduction: One of the most important goals of preparing a patient for elective gastrointestinal cancer surgery is prevention of postoperative complications. The literature gives many ways to prepare for surgery, but only a few suggests that pre-operative use of rifaximin provides benefits in the form of fewer perioperative complications and reduces the severity of pain during this period. O bjective: The presented project is a retrospective analysis of the effectiveness of rifaximin in the prevention of perioperative complications in patients treated in the Unit of General Surgery with the Orthopedic and Urology in the Hospital of the Ministry of the Interior and Administration in Lublin, and a review of international literature in this subject.

Materials And Methods: A retrospective analysis of the results of pre-operative use of rifaximin was performed in 181 patients scheduled for rectal and colorectal cancer between 2013 and 2016 in the General Surgery Unit with the Orthopedic and Urology in the Hospital of the Ministry of Interior and Administration in Lublin. Patients undergoing urgent surgery were excluded from the study. Patients were divided into 2 groups. The first group of 139 patients - patients operated on for rectal and colorectal cancer in 2013 until 2015, in whom rifaximine was not used in the preoperative period. The second group is 42 patients, operated on in 2016, in which the rifaximin was used in the pre-operative period at a dose of 2x2 tablets (400 mg) per day, 12-hour interval, for 7 days before the planned operation. Additionally, a probiotic was administered for 7 days. Drugs were ordained at the Oncological Outpatient Clinic as part of the pre-hospitalization check. R esults: The use of rifaximin in the preoperative period in patients with colorectal cancer had an effect on shortening the time of post-operative hospitalization and reduced post-surgical pain in comparison with the control group. The analysis of the cynumber and intensity of surgical complications in both groups did not differ. C onclusions: Large studies on the influence of rifaximin on the development of colorectal cancer have not been published so far. Only single reports suggest that its use has a positive effect on the perioperative period of patients treated for colorectal cancer including rectum and our retrospective analysis confirms these observations.
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http://dx.doi.org/10.5604/01.3001.0011.5958DOI Listing
February 2018

Gastric cancer: epidemiology, prevention, classification, and treatment.

Cancer Manag Res 2018 7;10:239-248. Epub 2018 Feb 7.

Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland.

Gastric cancer is the second most common cause of cancer-related deaths in the world, the epidemiology of which has changed within last decades. A trend of steady decline in gastric cancer incidence rates is the effect of the increased standards of hygiene, conscious nutrition, and eradication, which together constitute primary prevention. Avoidance of gastric cancer remains a priority. However, patients with higher risk should be screened for early detection and chemoprevention. Surgical resection enhanced by standardized lymphadenectomy remains the gold standard in gastric cancer therapy. This review briefly summarizes the most important aspects of gastric cancers, which include epidemiology, risk factors, classification, diagnosis, prevention, and treatment. The paper is mostly addressed to physicians who are interested in updating the state of art concerning gastric carcinoma from easily accessible and credible source.
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http://dx.doi.org/10.2147/CMAR.S149619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808709PMC
February 2018

Liver metastases from gastric carcinoma: A Case report and review of the literature.

Curr Probl Cancer 2017 May - Jun;41(3):222-230. Epub 2017 Mar 24.

Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland. Electronic address:

Gastric carcinoma (GC) is the fifth most common malignancy worldwide but the third leading cause of cancer death, and surgery remains the only curative treatment option. Prognosis of patients with liver metastases from gastric carcinoma (LMGC) is poor, and the optimal treatment of metastatic gastric cancer remains a matter of debate. In 2002, a 53-year-old male patient with GC and synchronous oligometastatic lesion in liver VIII segment underwent a total gastrectomy combined with metastasectomy. The pathologic diagnosis was stage IV gastric adenocarcinoma (pT3N2M1), which was treated with adjuvant chemotherapy (cisplatin, epirubicin, leucovorin, and 5-fluorouracil). In 2012, abdominal ultrasound and percutaneous liver biopsy revealed recurrence of the metastasis in the right liver lobe. Progression of the disease was observed after palliative chemotherapy (epirubicin, oxaliplatin, and capecitabine). Nevertheless, an extended right hemihepatectomy, with excision of segments 1, 4A, 5, 6, 7, and 8, was still performed. Pathologic examination confirmed large KRAS- and HER2-negative LMGC. The patient is alive and free of disease 47 months after the repeated hepatectomy and 13 years after removal of the primary GC and synchronous liver metastasis. Based on review of 27 articles, 5-year overall survival rate following gastrectomy and liver metastasectomy may reach 60%, with median survival time up to 74 months. Although the combination of aggressive surgical approach with systemic therapy for LMGC is controversial, it may allow favorable outcome. Careful selection of patients based on evaluable predictive factors for R0 surgical resection of both primary tumor and liver metastases can lead to cure, as shown in our case presentation, where a 10-year relapse-free survival was observed, followed by successful repeated hepatectomy due to liver metastases.
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http://dx.doi.org/10.1016/j.currproblcancer.2017.03.003DOI Listing
March 2018

Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery.

Surgery 2017 02 28;161(2):365-372. Epub 2016 Sep 28.

Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Background: Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available.

Methods: The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation.

Results: Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality.

Conclusion: This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication.
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http://dx.doi.org/10.1016/j.surg.2016.06.058DOI Listing
February 2017

Molecular alterations in gastric cancer with special reference to the early-onset subtype.

World J Gastroenterol 2016 Feb;22(8):2460-74

Małgorzata Skierucha, Ryszard Maciejewski, Robert Sitarz, Department of Human Anatomy, Medical University of Lublin, 20-950 Lublin, Poland.

Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These factors include genetic susceptibility expressed in a single-nucleotide polymorphism, various acquired mutations (chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances (e.g., Helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma (EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesis are modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.
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http://dx.doi.org/10.3748/wjg.v22.i8.2460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768192PMC
February 2016

Effective cancer treatment by multidisciplinary teams.

Pol Przegl Chir 2012 Jul;84(7):371-6

Department of Surgical Oncology, Medical University in Lublin.

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http://dx.doi.org/10.2478/v10035-012-0063-7DOI Listing
July 2012

Gastroenterostoma after Billroth antrectomy as a premalignant condition.

World J Gastroenterol 2012 Jul;18(25):3201-6

Department of Pathology, University Medical Centre, Utrecht, 3584 CX Utrecht, The Netherlands.

Gastric stump carcinoma (GSC) following remote gastric surgery is widely recognized as a separate entity within the group of various types of gastric cancer. Gastrectomy is a well established risk factor for the development of GSC at a long time after the initial surgery. Both exo- as well as endogenous factors appear to be involved in the etiopathogenesis of GSC, such as achlorhydria, hypergastrinemia and biliary reflux, Epstein-Barr virus and Helicobacter pylori infection, atrophic gastritis, and also some polymorphisms in interleukin-1β and maybe cyclo-oxygenase-2. This review summarizes the literature of GSC, with special reference to reliable early diagnostics. In particular, dysplasia can be considered as a dependable morphological marker. Therefore, close endoscopic surveillance with multiple biopsies of the gastroenterostomy is recommended. Screening starting at 15 years after the initial ulcer surgery can detect tumors at a curable stage. This approach can be of special interest in Eastern European countries, where surgery for benign gastroduodenal ulcers has remained a practice for a much longer time than in Western Europe, and therefore GSC is found with higher frequency.
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http://dx.doi.org/10.3748/wjg.v18.i25.3201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3391756PMC
July 2012

The COX-2 promoter polymorphism -765 G>C is associated with early-onset, conventional and stump gastric cancers.

Mod Pathol 2008 Jun 29;21(6):685-90. Epub 2008 Feb 29.

Department of Pathology, University Medical Centre, Utrecht, The Netherlands.

COX-2 overexpression is known to be an important mechanism in gastric carcinogenesis. Previously we have found that early-onset gastric cancer has a unique COX-2 low-expressing phenotype that differs significantly from that of the frequent overexpression seen in conventional gastric cancers. To investigate whether the COX-2 -765 G>C promoter polymorphism (known to lead to a reduction of COX-2 promoter activity in the colon) may explain this difference in expression, we carried out single-nucleotide polymorphism (SNP) analysis of 241 gastric cancers, including early-onset gastric cancer, conventional gastric cancers and gastric stump cancers, as well as in 100 control patients, using real-time PCR and sequence analysis, and correlated these findings with COX-2 expression using immunohistochemistry. We found that the C allele was present in 30% of early-onset gastric cancers, 24% of conventional gastric cancer, 23% of stump cancers, in contrast to 41% in the control group. There was a statistically significant difference in the presence of the C allele in patients with gastric cancer compared with the control group (P=0.007), with the C allele being associated with protection against gastric cancer. However, there was no significant difference between the early-onset, conventional and stump gastric cancer groups. Interestingly, there was no correlation between the presence of the C allele and a difference in COX-2 expression. In summary, we show that the COX-2 -765 G allele promoter polymorphism is significantly associated with gastric cancer when compared with the normal control group, but does not appear to be related directly to COX-2 expression pattern in gastric cancer. Although early-onset gastric cancers appear to have a unique COX-2 expression pattern when compared with conventional gastric cancer, the exact mechanism by which this occurs is yet to be elucidated.
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http://dx.doi.org/10.1038/modpathol.2008.36DOI Listing
June 2008

Molecular analysis of primary gastric cancer, corresponding xenografts, and 2 novel gastric carcinoma cell lines reveals novel alterations in gastric carcinogenesis.

Hum Pathol 2007 Jun 21;38(6):903-13. Epub 2007 Mar 21.

Department of Pathology, University Medical Centre, 3508 GA Utrecht, The Netherlands.

We report the molecular characterization of 8 primary gastric carcinomas, corresponding xenografts, and 2 novel gastric carcinoma cell lines. We compared the tumors and cell lines, with respect to histology, immunohistochemistry, copy number, and hypermethylation of up to 38 genes using methylation-specific multiplex ligation-dependent probe amplification, and TP53 and CDH1 mutation analysis where relevant. The primary tumors and xenografts were histologically comparable and shared expression of 11 of 14 immunohistochemical markers (E-cadherin, beta-catenin, COX-2, p53, p16, TFF1, cyclin E, MLH1, SMAD4, p27, KLK3, CASR, CHFR, and DAPK1). Gains of CASR, DAPK1, and KLK3--not yet described in gastric cancer--were present in the primary tumors, xenografts, and cell lines. The most prominent losses occurred at CDKN2A (p16), CDKN2B (p15), CDKN1B (p27/KIP1), and ATM. Except for ATM, these losses were found only in the cell line or xenograft, suggesting an association with tumor progression. However, examination of p16 and p27 in 174 gastric cancers using tissue microarrays revealed no significant correlation with tumor stage or lymph node status. Further losses and hypermethylation were detected for MLH1, CHFR, RASSF1, and ESR, and were also seen in primary tumors. Loss of CHFR expression correlated significantly with the diffuse phenotype. Interestingly, we found the highest rate of methylation in primary tumors which gave rise to cell lines. In addition, both cell lines harbored mutations in CDH1, encoding E-cadherin. Xenografts and gastric cancer cell lines remain an invaluable research tool in the uncovering of the multistep progression of cancer. The frequent gains, losses, and hypermethylation reported in this study indicate that the involved genes or chromosomal regions may be relevant to gastric carcinogenesis.
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http://dx.doi.org/10.1016/j.humpath.2006.12.010DOI Listing
June 2007

Early onset gastric cancer: on the road to unraveling gastric carcinogenesis.

Curr Mol Med 2007 Feb;7(1):15-28

Department of Pathology, H04-312, University Medical Centre Utrecht, Post box 85500, 3508 GA Utrecht, The Netherlands.

Gastric cancer is thought to result from a combination of environmental factors and the accumulation of specific genetic alterations due to increasing genetic instability, and consequently affects mainly older patients. Less than 10% of patients present with the disease before 45 years of age (early onset gastric carcinoma) and these patients are believed to develop gastric carcinomas with a molecular genetic profile differing from that of sporadic carcinomas occurring at a later age. In young patients, the role of genetics is presumably greater than in older patients, with less of an impact from environmental carcinogens. As a result, hereditary gastric cancers and early onset gastric cancers can provide vital information about molecular genetic pathways in sporadic cancers and may aid in the unraveling of gastric carcinogenesis. This review focuses on the molecular genetics of gastric cancer and also focuses on early onset gastric cancers as well as familial gastric cancers such as hereditary diffuse gastric cancer. An overview of the various pathways of importance in gastric cancer, as discovered through in-vitro, primary cancer and mouse model studies, is presented and the clinical importance of CDH1 mutations is discussed.
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http://dx.doi.org/10.2174/156652407779940503DOI Listing
February 2007

Vestibular rehabilitation using visual displays: preliminary study.

Laryngoscope 2002 Mar;112(3):500-3

Division of Otolaryngology--Head and Neck Surgery, University of California, San Diego, School of Medicine, 92037, USA.

Objectives/hypothesis: Interactive computer displays can alter vestibular function. We hypothesized that by placing a vestibulopathic subject with chronic vertigo in a computer scene, slowing the visual scene motion to a rate slightly higher than their vestibuloocular reflex (VOR) gain, and gradually speeding up the scene, we could cause VOR improvement and symptom reduction.

Study Design: Randomized, nonblinded treatment/control study.

Methods: Subjects were selected for VOR gain less than 0.5 at 0.16, 0.32, or 0.64 Hz. They wore a computer display that interacted with the movement of their head. The scene magnification controlling image motion was initially set approximately 5% higher than the VOR gain. Subjects had interaction tasks for 10 sessions of 30 minutes twice daily for 5 days. The scene magnification was gradually increased over the sessions. Control subjects had a similar procedure but were shown a normal, x 1.0 magnification for each interaction session.

Results: Nine subjects and six control subjects were tested. Test subjects showed an average increase in VOR gain of 0.05 at 0.16 Hz, 0.048 at 0.32 Hz, and 0.098 at 0.64 Hz. In contrast, control subjects showed a decrease of 0.008 at 0.16 Hz, an increase of 0.016 at 0.32 Hz, and a decrease of 0.058 at 0.64 Hz. Improvement remained after 1 week but at a lower level than immediately after testing. Subject Dizziness Handicap Inventory scores decreased by 2.8 from 38.5 in the first week. Control subjects reported no symptom improvement.

Conclusion: Immersive computer environments can improve VOR function and reduce vertigo.
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http://dx.doi.org/10.1097/00005537-200203000-00017DOI Listing
March 2002