Robert Sitarz

Early Onset Gastric Cancer: On the road to unraveling gastric carcinogenesis

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.

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

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.

Gastroenterostoma after Billroth antrectomy as a premalignant condition

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.

Gastric cancer : Epidemiology, prevention, classification, and treatment

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 Helicobacter pylori 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.

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

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.

The Pattern of Signatures in Gastric Cancer Prognosis

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.

Effective Cancer Treatment by Multidisciplinary Teams

Neoplastic diseases are second, in terms of frequency, cause of death. There are 140 thousand new neoplasm cases and 90 thousand of deaths due to cancer recorded in Poland annually (1). Over 400 thousand people suffer from cancer in Poland and often they remain socially active. The natural neoplasm development is usually unfavourable and active oncological treatment is necessary, with the primary method being surgery, although collaboration of many specialists is increasingly more often required. The developments in surgical techniques influence the improvement in treatment results, yet still the majority of patients reporting to a physician suffer from advanced neoplastic process requiring combination therapy. Combination therapy leads to an improvement in treatment results in approx. 1/3 of patients with neoplasm, most commonly a locally/regionally advanced one. In Poland, the above therapy is used in only half of the patients having indications for such treatment (2). For years, the role of multidisciplinary teams (MTs), the diagnostic and therapeutic activity of which clearly improves the treatment results in neoplasms, has been growing (3, 4).

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

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.

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

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, Helicobacter pylori, has been particularly associated with intestinal subtype of gastric cancers. The significant association of Helicobacter pylori infection in young patients with gastric cancers suggests that the bacterium 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 Helicobacter pylori infection in the development of gastric carcinoma in young patients. The review summarizes recent literature on early-onset gastric cancers with special reference to Helicobacter pylori infection.

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

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 patients 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.