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BACKGROUND The aim of this study was the analysis of the influence of prognostic factors on short- and long-term outcomes of gastric cancer resection. PATIENTS AND METHODS A database of 709 patients who had gastric cancer resection between 2007 and 2015 was compiled. RESULTS Total gastrectomy (TG) and subtotal proximal gastrectomy (SPG) significantly increased the risk of overall complications (p=0.0015 and 0.0173, respectively) and surgical complications (p=0.0141 and 0.0035, respectively). Moreover the resection of an additional organ was an independent prognostic factor of overall complications (p

For many years, intensive research has been carried out on the in-depth understanding of the pathogenesis of multiple myeloma (MM). Nevertheless, the multifactorial nature of the disease, the development of drug resistance, and the side effects of therapy, make it difficult to effectively treat patients. One of the many factors involved in the pathogenesis of MM is brain-derived neurotrophic factor (BDNF). This factor is widely described as a neuroregenerative and neuroprotective agent, but it also regulates non-neuronal cell functions, such as proliferation, apoptosis, and viability. Therefore, BDNF appears to be a good therapeutic target in MM. On the other hand, its decreased concentration during treatment closely correlates with the development of peripheral neuropathy (PN). BDNF dualism requires a detailed understanding of its action on individual molecular mechanisms. Perhaps the optimization of the BDNF level will contribute to the improvement of MM treatment and the reduction of chemotherapy side effects.

Bortezomib-induced peripheral neuropathy (BiPN) occurs in approximately 40% of patients with multiple myeloma. The induction of severe neuropathy entails the dose reduction or complete elimination of bortezomib (BTZ). Interestingly, discontinuation of BTZ mostly results in a reduction or complete resolution of peripheral neuropathy (PN) symptoms. Therefore, it is likely that the BiPN mechanisms are based on temporary/reversible changes such as epigenetic alterations. In this study, we examined the effect of treating nerve cells, differentiated from the Lund human mesencephalic (dLUHMES) cell line, with several low-dose BTZ (0.15 nM) applications. We showed a significant decrease in global histone H3 acetylation as well as histone H3 lysine 9 acetylation. Moreover, analysis of the genetic microarray showed changes mainly in epigenetic processes related to chromatin rearrangement, chromatin silencing, and gene silencing. GSEA analysis revealed three interesting signaling pathways (SIRT1, B-WICH and, b-Catenin) that may play a pivotal role in PN development. We also performed an analysis of the miRNA microarray which showed the interactions of miR-6810-5p with the genes MSN, FOXM1, TSPAN9, and SLC1A5, which are directly involved in neuroprotective processes, neuronal differentiation, and signal transduction. The study confirmed the existence of BTZ-induced complex epigenetic alterations in nerve cells. However, further studies are necessary to assess the reversibility of epigenetic changes and their potential impact on the induction/resolution of PN.

Background/Aim: The purpose of this study was to examine the impact of clinicopathological prognostic factors on tumor resectability, perioperative complications, and 5-year survival rates in patients with gastric cancer treated surgically. Patients and Methods: A cohort of 834 patients operated on for gastric cancer between 2007 and 2016 was analyzed. Results: Patients over 70 years of age manifested a significantly higher rate of overall complications, systemic complications, surgical complications, perioperative mortality, and a worse 5-year survival. The diffuse type according to the Lauren classification was an independent prognostic factor for perioperative mortality. TNM stage significantly influenced resectability and 5-year survival rates. Furthermore, the presence of distant metastases (M1 stage) significantly increased the rates of overall complications, systemic complications, and perioperative mortality. Conclusion: Although TNM stage was the most important prognostic factor for resectability, perioperative complications and 5-year survival, other clinicopathological prognostic factors, such as age, and Lauren type also significantly affected treatment outcomes in gastric cancer surgery.

The exact pathophysiology of severe COVID-19 is not entirely elucidated, but it has been established that hyperinflammatory responses and cytokine storms play important roles. The aim of this study was to examine CMV status, select chemokines, and complement components in COVID-19, and how concentrations of given molecules differ over time at both molecular and proteomic levels. A total of 210 COVID-19 patients (50 ICU and 160 non-ICU patients) and 80 healthy controls were enrolled in this study. Concentrations of select chemokines (CXCL8, CXCL10, CCL2, CCL3, CCR1) and complement factors (C2, C9, CFD, C4BPA, C5AR1, CR1) were examined at mRNA and protein levels with regard to a COVID-19 course (ICU vs. non-ICU group) and CMV status at different time intervals. We detected several significant differences in chemokines and complement profiles between ICU and non-ICU groups. Pro-inflammatory chemokines and the complement system appeared to greatly contribute to the pathogenesis and development of severe COVID-19. Higher concentrations of CXCL8 and CCL2 in the plasma, with reduced mRNA expression presumably through negative feedback mechanisms, as well as CMV-positive status, correlated with more severe courses of COVID-19. Therefore, CXCL8, CCL2, and CMV seropositivity should be considered as new prognostic factors for severe COVID-19 courses. However, more in-depth research is needed.

Multiple myeloma (MM) is a plasma cell malignancy with multifactorial etiology. One of the underlying mechanisms is immune system dysregulation. Immunotherapy is being widely introduced into various MM treatment protocols. Nevertheless, little is known about boosting the immune system with supportive treatment. Although classical actions of vitamin D (VD) are very well established, their non-classical actions related to the modulation of the immune system in MM are still a subject of ongoing research. In this literature review, we intend to summarize research conducted on VD and MM, both in vitro and in vivo, with particular emphasis on immune system modulation, the induction of the differentiation of malignant MM cells, synergic activity with anti-MM drugs, and MM-associated peripheral neuropathy.

Background: Little data are available for abscess and non-abscess abdominal fluid collections (AFCs) after gastric cancer surgery and their clinical implications. We sought to analyse the natural history of such collections in a population of patients subject to routine postoperative imaging.Methods: From 1996 to 2012, 1381 patients underwent gastric resections and routine postoperative monitoring with abdominal ultrasound. As a unit protocol, examinations were carried out in all patients prior to drain removal, immediately before discharge, and at follow-up visits.Results: AFCs were diagnosed in 134 (9.7%) patients after a median time from surgery of seven days (interquartile range (IQR) 5-11 days). Sixty-four of the 134 AFCs (48%) were asymptomatic and resolved spontaneously after a median follow-up of 26.5 days (IQR 14-91 days). Seventy (52%) AFCs required interventional drainage. A stepwise logistic regression model demonstrated that interventional treatment was much more likely among patients with enteric fistula (odds ratio (OR) 9.542, 95% CI 1.418-46.224, p=.003) and pancreatic fistula (OR 7.157, 95% CI 1.340-39.992, p=.012).Conclusions: About one half of AFCs after gastric surgery were asymptomatic and eventually resolved spontaneously without any intervention. However, the need for interventional drainage was significantly increased by coexisting pancreatic or enteric fistula.

Background Little data are available supporting the feasibility and safety of early oral feeding in patients after total gastrectomy. The aim of this study was to analyze the potential applicability of early provision of oral diet in these settings. Methods Medical records of 353 patients who underwent total gastrectomy for gastric cancer between 2006 and 2012 were retrospectively analyzed. Early oral feeding was defined as clear liquid diet on postoperative day (POD) 1 followed by gradual introduction of solid diet on POD 2 to 3. Late oral feeding was defined as initiation of liquid diet from POD 4 to 6 and gradually advancing to solid diets. Results Early oral feeding was implemented in 185 of 353 (52 %) patients. Prompt provision of food did not increase the risk of anastomotic failure (odds ratio 0.924, 95 % confidence interval 0.609–1.402, P = 0.709). The number of reoperations and in-hospital mortality rates was unaffected by the timing of nutritional intervention. Early feeding tended to be associated with fewer surgical (15 vs 24 %, P = 0.027) and general (8 vs 23 %, P

The aim of this study was to assess the predictive value of blood flow velocity and vascular resistance measured by Doppler ultrasound in terms of pulsatility index (PI) and resistive index (RI) respectively, in the occurrence of delayed graft function (DGF) after kidney transplantation. This prospective study enrolled kidney transplant recipients operated from January 2005 to April 2009 in the 1st Department of General, Oncological and Gastroenterological Surgery, Jagiellonian University Medical College, Kraków, Poland. The medical records of 53 kidney transplant recipients from deceased donors were reviewed. PI and RI values of the graft arcuate artery were calculated immediately after blood flow restoration and on the 1st, 2nd, 4th and 8th post-operative day. DGF was observed in 20 patients (37.7%), while 33 patients (62.3%) had immediate restoration of the kidney function. The mean intraoperative values of RI and PI from patients with DGF were significantly higher in comparison to patients without DGF (0.9 vs. 0.74, p0.001; 1.76 vs. 1.54, p = 0.019, respectively). Post-operatively, the RI and PI values remained stable and significantly higher in DGF group. The highest sensitivity of RI to predict DGF occurrence was observed intraoperatively and on the first postoperative day, with values of 77.8% and 72.2%, respectively. The risk of DGF occurrence with intraoperative RI value ≥0.9 increased by 13-fold, and with intraoperative PI value ≥1.9 by 12-fold. This increase was even more prominent during the first post-operative day with RI value ≥0.9 or PI value ≥1.9 with 19-fold increase in the risk of DGF occurrence. According to our study, the utilization of Doppler ultrasound with measurement of hemodynamic parameters (PI, RI), play a crucial role in predicting the outcomes of kidney transplantation.

Objectives The aim of this study was to examine the relevance of expression profiling of 4 genes involved in the action of gemcitabine among patients with pancreatic ductal-cell adenocarcinoma (PDAC). Methods A group of 100 patients who underwent pancreatic resections for PDAC and received adjuvant chemotherapy with gemcitabine between 2007 and 2010 was identified. Expression of mRNAs for human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunits (RRM1, RRM2), and deoxycytidine kinase (dCK) was examined by quantitative real-time polymerase chain reaction, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and dichotomized into groups of low and moderate/high expression levels grouped by tertiles. Results Significantly better median survival times were found for high/moderate expression levels of hENT1 (27.9 vs 12.4 months, P = 0.001) and dCK (19.7 vs 10.5 months, P = 0.003), as well as low expression of RRM1 (23.4 vs 11.4 months, P = 0.027). A Cox proportional hazards model identified low expression of hENT1 (hazard ratio [HR], 3.38; 95% confidence intervals [CI], 2.28-10.50) and dCK (HR, 2.24; 95% CI, 1.63-3.39), and high/moderate levels of RRM1 (HR, 1.65; 95% CI, 1.23-2.45) as negative prognostic factors. Conclusions Expression of hENT, RRM1, and dCK genes provides important prognostic information for PDAC patients treated with adjuvant gemcitabine.

Background The anatomical Siewert classification for adenocarcinoma of the oesophagogastric junction (OGJ) was dictated by the potential differences in tumour epidemiology and pathology. However, there are some uncertainties whether the distinction of true carcinoma of the cardia (type II) and subcardial gastric cancer (type III) is of clinical value. Methods Using a multicentre data set, we studied 243 patients with OGJ adenocarcinomas who underwent gastric resections between 1998 and 2008. Postoperative complications and long-term survival were compared to evaluate the potential differences in clinically relevant outcomes. Results A group of 109 patients with Siewert type II and 134 with Siewert type III OGJ adenocarcinoma was identified. Both groups showed similar baseline characteristics, including clinical symptoms and duration of diagnostic delay. However, the prevalence of node-negative cancers and superficial (T1–T2) lesions was significantly higher among type II tumours, i.e. 42% vs 21% ( P = 0.003) and 43% vs 20% ( P = 0.045), respectively. Morbidity and mortality rates were 25% and 3.7%, respectively, but types and incidence of postoperative complications were not affected by the anatomical location of the tumour. The overall median survival was significantly longer for Siewert type II tumours (42 vs 16 months; P 70 years, depth of tumour infiltration, lymph node metastases, distant metastases, and radical resection were identified as independent prognostic factors using the Cox proportional hazards model. Conclusion The topographic-anatomic sub-classification of OGJ adenocarcinomas does not correspond to relevant differences in clinical parameters of safety and efficacy of surgical treatment.

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.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.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%, P0.001) 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, P0.001). 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, P0.001). 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.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.

INTRODUCTION Various imaging modalities are used for the diagnosis and staging of pancreatic cancer. Abdominal ultrasonography is the most widely available method and usually the first -line diagnostic tool used in patients with suspicion of pancreatic carcinoma. OBJECTIVES The aim of the study was to assess the clinical value of abdominal ultrasonography used in a tertiary center for staging of pancreatic carcinoma. PATIENTS AND METHODS This prospective clinical trial included 454 consecutive patients with pancreatic cancer, who underwent a surgery between 2000 and 2012. The diagnostic accuracy of ultrasonography was established for each T category and lymph node involvement. Computed tomography and intraoperative staging of the pancreatic cancer were used as reference methods. RESULTS The diagnostic accuracy of ultrasonography in cancer staging according to T categories was 94.1% for T1, 95.7% for T2, 85.4% for T3, and 81.7% for T4 tumors. The diagnostic accuracy of abdominal ultrasonography in the diagnosis of lymph node metastasis and assessment of tumor resectability was 66.1% and 74.8%, respectively. CONCLUSIONS The results of our study summarize 12 years of our experience with abdominal ultrasonography in patients with pancreatic cancer and confirm that ultrasonography remains a valuable diagnostic modality in this patient group.

Background/objectives: Inflammation is a central process responsible for health outcomes among surgical patients. Immunonutrition has been investigated as a promising modifying factor; however, inflammatory properties of habitual diet have not yet been investigated. The purpose of this study was to describe inflammatory properties of diet measured by the dietary inflammatory index (DII) among surgical patients treated for colorectal cancer and to link inflammatory properties of habitual diet with a duration of hospitalization. Subjects/methods: A follow-up study among colorectal cancer patients treated surgically was performed in Krakow, Poland. In total, 689 patients were recruited for the study. Habitual diet was assessed using a standardized semiquantitative food frequency questionnaire. Overall, 23 dietary items (including macro-and micronutrients) were used to calculate individuals' DII. Gender, age, marital status, body mass index, smoking status, lifetime physical activity, taking vitamin supplements, number of chronic diseases, cancer site, Duke's staging and surgery type were considered as potential covariates. Results: Participants were aged 58 years, with the average hospitalization time of 11 days. Higher DII (meaning diet with higher anti-inflammatory properties) was negatively associated with the duration of hospitalization (univariable linear regression: b=−0.59; P=0.005). Multivariable logistic regression has shown the decrease of the risk of longer stays (>7 days) among patients with the DII >−4.25, but only among younger (⩽60 years) patients, irrespective of Duke's staging. Conclusions: The DII might be used as a potential predictor of longer hospitalization among colorectal cancer patients treated surgically. The study provides evidence for the role of dietary-related low-grade inflammation among surgical patients.

Background Little data are available for non-abscess abdominal fluid collections (AFCs) after pancreatic surgery and their clinical implications. We sought to analyze the natural history of such collections in a population of patients subject to routine postoperative imaging. Methods From 1995 to 2011, 709 patients underwent pancreatic resections and routine postoperative monitoring with abdominal ultrasound according to a unit protocol. AFCs were classified as asymptomatic (no interventional treatment), symptomatic (need for percutaneous drainage of sterile, amylase-poor fluid), and pancreatic fistula (drainage of amylase-rich fluid). Results Ninety-seven of 149 AFCs (65 %) were asymptomatic and resolved spontaneously after a median follow-up of 22 days (interquartile range, 9–52 days). Among 52 (35 %) AFCs requiring percutaneous drainage, there were 20 pancreatic fistulas and 32 symptomatic collections. A stepwise logistic regression model identified three factors associated with the need for interventional treatment, i.e., body mass index ≥25 (odds ratio, 3.23; 95 % confidence interval (CI), 1.32 to 7.91), pancreatic fistula (odds ratio, 2.93; 95 % CI, 1.20 to 7.17), and biliary fistula (odds ratio, 3.92; 95 % CI, 1.35 to 11.31). Conclusions One fourth of patients develop various types of non-abscess AFCs after pancreatic surgery. Around half of them are asymptomatic and resolve spontaneously.

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.