Piotr Kolodziejczyk

Impact of anastomotic leakage on long‐term survival after total gastrectomy for carcinoma of the stomach

Recent studies suggest that anastomotic leak may adversely affect long‐term survival in patients undergoing surgery for gastrointestinal malignancies. Data relating to total gastrectomy for gastric cancer are scarce.

Ratio of metastatic to resected lymph nodes for prediction of survival in patients with inadequately staged gastric cancer

Staging is inadequate in up to 70 per cent of patients with gastric cancer in Western countries owing to the small number of lymph nodes dissected during surgery. The aim was to determine whether using the ratio of metastatic to resected lymph nodes (LNR) might improve accuracy.

Adjuvant Chemotherapy with Etoposide, Adriamycin and Cisplatin Compared with Surgery Alone in the Treatment of Gastric Cancer: A Phase III Randomized, Multicenter, Clinical Trial

Objective: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy with etoposide, Adriamycin and cisplatin (EAP) after potentially curative resections for gastric cancer. Methods: After surgery, patients were randomly assigned to the EAP or control arm. Chemotherapy included 3 courses, administered every 28 days. Each cycle consisted of doxorubicin (20 mg/m2) on days 1 and 7, cisplatin (40 mg/m2) on days 2 and 8, and etoposide (120 mg/m2) on days 4, 5, and 6. Results: Of 309 eligible patients, 141 were allocated to chemotherapy and 154 to the supportive care group. Four (2.8%) treatment-related deaths were recorded, including 3 due to septic complications of myelosuppression and 1 due to cardiocirculatory failure. Grade 3 or 4 toxicities were found in 17 (22%) patients. According to the intention-to-treat analysis, the median survival was 41.3 months (95% confidence interval, 24.5–58.2) and 35.9 months (95% confidence interval, 25.5–46.3) in the chemotherapy and control group, respectively (p = 0.398). Subgroup analysis revealed survival benefit from chemotherapy in patients with tumors infiltrating the serosa and in those with 7–15 metastatic lymph nodes. Conclusion: Three cycles of EAP regimen postoperatively offer no survival advantage in gastric cancer patients.

CDH1 gene promoter hypermethylation in gastric cancer - Relationship to Goseki grading, microsatellite instability status, and EBV invasion

Hypermethylation of the CDH1 promoter region seems to be the most common epigenetic mechanism in this gene silencing in gastric cancer. In this study, CDH1 promoter hypermethylation was observed in 54.8% (46/84) of the analyzed sporadic gastric carcinomas. We introduce a new relation: clustering of Goseki grading into 3 grade was determined by CDH1 promoter hypermethylation. The percentage of methylation in Goseki III cancers was significantly higher (83%) when compared with other grades; the lowest proportion was detected in IV (36%) and II (38%) groups, whereas grade I demonstrated typical percentage of promoter hypermethylation. A novel polymorphism R732R in exon 14 of the CDH1 gene was detected by mutational analysis. Additionally, all cases with the MSI-high phenotype revealed CDH1 promoter hypermethylation. In MSI-low and MSS gastric cancers, this percentage was lower, reaching 71% and 41%, respectively. Moreover, the methylation status was correlated with the LOH phenotype. We detected CDH1 promoter hypermethylation in all EBV-positive gastric cancers (5/5), whereas methylation in the EBV-negative group occurred in 58% of cases. We also report that “methylated” tumors were slightly larger than “nonmethylated,” whereas the second group revealed a higher probability of longer patient survival, though these relationships were not statistically significant. These results suggest that downregulation of E-cadherin, caused by promoter hypermethylation, in sporadic gastric carcinomas may be associated with a worse prognosis and specific tumor phenotype.

Non-curative gastrectomy for metastatic gastric cancer: Rationale and long-term outcome in multicenter settings

BACKGROUND Metastatic gastric cancer remains a significant problem as the majority of Western patients are diagnosed with disseminated disease and no routine therapeutic regimen is accepted in such cases. METHODS A cohort of 3141 patients with gastric cancer operated between 1990 and 2005 was evaluated using a multicenter data set held by the Polish Gastric Cancer Study Group to determine potential risks and benefits of non-curative gastrectomy for metastatic disease. Additionally, parameters of Quality of Life (QoL) were evaluated prospectively in 140 patients undergoing gastrectomy using the QLQ-C30 questionnaire. RESULTS Gastrectomy was carried out in 2258 patients. Distant organ metastases were diagnosed in 951 patients, 415 of which underwent non-curative gastrectomy. The overall mortality rates were significantly higher in patients undergoing non-resectional surgery (10%) than either curative (3%, P < 0.001) or non-curative (4%, P = 0.002) gastrectomy. The overall median survival in patients with metastatic disease was significantly higher for non-curative gastrectomy (10.6 months, 95% confidence interval (CI) 9.3-11.9) than for non-resective operations (4.4 months, 95% CI 4.0 to 4.8, P < 0.001). The hazard ratio of death in patients subject to non-resectional surgery compared to those treated by gastrectomy was 2.923 (95% CI 2.473 to 3.454, P < 0.001). A gradual impairment in QoL parameters was found over 12 months after non-curative resections but changes did not reach statistical significance and individual parameters were similar to gastrectomy without distant metastases. CONCLUSION Non-curative gastrectomy for metastatic gastric cancer is associated with significantly better survival compared to non-resective surgery and does not impair quality of life.

Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331.

Background:High stability and disease-specific disarrangements suggest that microRNA molecules (miRNAs) present in body fluids are ideally suited for diagnostic applications, including gastric cancer (GC). However, the actual source of circulating miRNA biomarkers in GC has not been adequately evaluated, particularly in the Western populations that have some distinct characteristics compared with Asian patients.Methods:Twenty treatment-naive patients with GC along with 20 cancer-free controls were recruited. miRCURY LNA miRNA microarrays were used for miRNA expression profiling in primary tumours and adjacent healthy mucosa. Differentially expressed serum miRNAs were identified with a high throughput TaqMan OpenArray technology in tumour-draining veins of the portal system, as well as peripheral blood of the patients and controls.Results:Tissue profiling identified 108 sequences differentially expressed between primary tumours and adjacent mucosa (87 upregulated and 21 downregulated). Twenty miRNAs found in serum of GC patients showed expression levels higher than in controls. However, only seven of these molecules were overexpressed in primary tumours (miR-130a, miR-331, miR-19a, miR-223, miR-106a, miR-21, and miR-374). Moreover, expression of miR-331 and miR-21 was significantly higher in the peripheral circulation compared to tumour-draining veins of the portal system.Conclusions:The results indicate that the majority of potential serum miRNA biomarkers may originate from tissues other than the primary tumour.

The effects of preoperative chemotherapy on isolated tumour cells in the blood and bone marrow of gastric cancer patients

Recent studies in breast cancer suggest that monitoring the isolated tumour cells (ITC) may be used as a surrogate marker to evaluate the efficacy of systemic chemotherapy. In the present study, we have investigated the effects of preoperative chemotherapy on ITC in the blood and bone marrow of patients with potentially resectable gastric cancer. After sorting out the CD45-positive cells, the presence of ITC defined as cytokeratin-positive cells was examined before and after preoperative chemotherapy. The patients received two courses of preoperative chemotherapy with cisplatin (100 mg m−2, day 1) and 5-fluorouracil (1000 mg m−2, days 1–5), administered every 28 days. Fourteen of 32 (44%) patients initially diagnosed with ITC in blood and/or bone marrow were found to be negative (responders) after preoperative chemotherapy (P<0.01). The incidence of ITC in bone marrow was also significantly (P<0.01) reduced from 97 (31 of 32) to 53% (17 of 32). The difference between patients positive for ITC in the blood before (n=7, 22%) and after (n=5, 16%) chemotherapy was statistically insignificant. The overall 3-year survival rates were 32 and 49% in the responders and non-responders, respectively (P=0.683). These data indicate that preoperative chemotherapy can reduce the incidence of ITC in patients with gastric cancer.

Targeted therapy for gastric cancer—current status

In patients with metastatic gastric cancer, median overall survival remains under 1 year and standard chemotherapy regimens are not able to substantially improve the prognosis of the patients. Amplification and over-expression of HER2 is reported in approximately 20% of gastric tumours, challenging the use of targeted therapies. There are several targeted therapies in different stages of clinical development with trastuzumab being the first overcoming the regulatory hurdle and getting European Medicines Agency approval. In patients with advanced gastric or gastro-oesophageal junction cancer, addition of trastuzumab to chemotherapy significantly improved overall survival compared with chemotherapy alone. Addition of trastuzumab to chemotherapy did not increase the incidence of adverse events. Other agents targeting the HER2 pathway (lapatinib) or other domains of epidermal growth factor receptor family (cetuximab) are currently being investigated for the treatment of an advanced gastric cancer.

The relationship between gastric cancer cells circulating in the blood and microsatellite instability positive gastric carcinomas.

Cancers characterized by microsatellite instability may be biologically different from their counterparts with stable microsatellite sequences. Circulating cancers cell present in blood prior to surgery may constitute an adverse prognostic finding.

Abdominal Ultrasonography in Detecting and Surgical Treatment of Pancreatic Carcinoma

THE AIM OF THE STUDY was to asses the clinical value of percutaneous abdominal ultrasonography in diagnosis, staging and surgical treatment of patients with pancreatic carcinoma. MATERIAL AND METHODS Prospective clinical trial on diagnostic accuracy of percutaneous abdominal ultrasonography was conducted in 409 consecutive patients with pancreatic cancer which were operated on at the I Dept. of General Surgery in Cracow between 2000 and 2010. RESULTS Diagnostic accuracy of percutaneous abdominal ultrasonography in pancreatic cancer was 91,1%. The accuracy in detecting different stages of local advancement according to TNM classification was assessed respectively 92.3%-T1, 91.3%-T2, 89.4%-T3, 92.1%-T4, a whole T1-T4 on 91.3%. Diagnostic accuracy of percutaneous abdominal ultrasonography in diagnosis of metastasis to lymph nodes, vascular infiltration, and resectability was respectively 80.7%, 86%, 91.4%. CONCLUSIONS Percutaneous abdominal ultrasonography has high diagnostic accuracy in diagnosis, staging and predicting surgical treatment of patients with pancreatic carcinoma.