Antoni M. Szczepanik

The impact of immunostimulating nutrition on infectious complications after upper gastrointestinal surgery: a prospective, randomized, clinical trial.

Background and Aim:Immunomodulating nutrition is supposed to reduce the number of complications and lengthen of hospital stay during the postoperative period in patients after major gastrointestinal surgery. The aim of the study was to assess the clinical effect of immunostimulatory enteral and parenteral nutrition in patients undergoing resection for gastrointestinal cancer in the group of well-nourished patients. Material and Methods:Between June 1, 2001, and December 31, 2005, a group of 214 well-nourished patients was initially assessed (150 men, 64 women, mean age 61.2 years) to participate in the study. Nine patients were subsequently excluded and the remaining 205 subjects were randomly assigned in a 2 × 2 factorial design into 4 study groups, ie, standard enteral nutrition (n = 53), immunomodulating enteral nutrition (n = 52), standard parenteral nutrition (n = 49), and immunomodulating enteral nutrition (n = 51). The study was designed to test the hypothesis that immunonutrition and enteral nutrition would reduce the incidence of infectious complications after upper gastrointestinal surgery; the secondary objective of the study was to evaluate the effect of nutritional intervention on overall morbidity and mortality rates, and hospital stay. The study was registered in the Clinical Trials Database–number NCT 00558155. Results:The overall morbidity rate was 33% and the incidence of individual complications was comparable between all groups. Infectious complications occurred in 26 of 102 patients given standard diets and in 22 of 103 patients receiving immunomodulatory formulas (odds ratio 0.81; 95% CI, 0.43–1.50). There were no significant differences between infectious complications in patients using parenteral nutrition (22 of 100 patients) and parenteral formulas (26 of 105, odds ratio 1.14; 95% CI, 0.61–2.14). Neither immunostimulating formulas nor enteral feeding significantly affected secondary outcome measures, including overall morbidity and mortality rates, and hospital stay. Conclusions:Our study failed to demonstrate any clear advantage of routine postoperative immunonutrition in patients undergoing elective upper gastrointestinal surgery. Both enteral and parenteral treatment options showed similar efficacy, tolerance, and effects on protein synthesis. Parenteral nutrition composed according to contemporary rules showed similar efficiency to enteral nutrition. However, because of its cost-efficiency, enteral therapy should be considered as the treatment of choice in all patients requiring nutritional therapy.

Standard and immunomodulating enteral nutrition in patients after extended gastrointestinal surgery – A prospective, randomized, controlled clinical trial

BACKGROUND & AIM The immunomodulating enteral diets are intended to reduce the incidence of postoperative complications in surgical patients. The aim of the study was to assess the clinical effect of such nutrition. MATERIALS AND METHODS Between June 2004 and September 2007 196 well-nourished patients undergoing resection for pancreatic and gastric cancer were randomized in double-blind manner to receive postoperative enteral nutrition with immunostimulating diet (IMEN group) or standard oligopeptic diet (SEN group). Outcome measures were: number and type of complications, length of hospital stay, mortality, treatment tolerance, liver and kidney function. RESULTS One hundred and ninety six patients were initially enrolled, finally 183 patients (91 SEN, 92 IMEN group; 69 F, 114 M, median age 61.2) were analyzed. Median postoperative hospital stay was 12.4 days (SD 5.9) in SEN and 12.9 days (SD 8.0) in IMEN group (p=0.42). Complications were observed in 21 patients (23.1%) in SEN and 23 (25.2%) in IMEN group (p>0.05). Four (4.4%) patients in SEN group and 4 (4.4%) in IMEN had surgical complications (p>0.05). There were no differences in liver and kidney function, visceral protein turnover and treatment tolerance. CONCLUSION Results of our study showed no benefit of immunomodulating enteral nutrition over standard enteral nutrition in patients after major gastrointestinal surgery. The Trial was registered in Clinical Trials Database--number: NCT00576940.

Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer

BackgroundDespite curative resection, 50%–90% of gastric cancer patients die of disease relapse. Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities, more recent studies have not been able to define the standard treatment for advanced gastric cancer. The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG (bacille Calmette-Guérin) and FAM (5-fluorouracil, adriamycin, mitomycin C) chemotherapy on the survival of patients with locally advanced resectable gastric cancer.MethodsA total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were randomly assigned to three treatment groups: BCG + FAM (immunochemotherapy), FAM (chemotherapy), and control (surgery only). Treatment was continued for 2 years or until death. Further postsurgical follow up was carried on for up to 10 years.ResultsOverall 10-year survival was 47.1% for the immunochemotherapy group (P < 0.037 vs FAM and P < 0.0006 vs control), 30% for the chemotherapy group (vs control, NS), and 15.2% for the control group. In patients with pT2/T3 primary tumors, 10-year survival was 55.3% for BCG + FAM vs 28.2% for FAM (P < 0.01) and 14.6% for the control group (P < 0.00018). BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer. Immunochemotherapy was well tolerated.ConclusionThis study, based on a limited number of patients, indicates that adjuvant immunochemotherapy (BCG + FAM) may prolong the survival of gastric cancer patients after curative gastrectomy; in particular, in patients with pT2/T3 tumors and intestinal-type primary tumors. There was no survival benefit from FAM adjuvant chemotherapy.

T-regulatory lymphocytes in peripheral blood of gastric and colorectal cancer patients.

AIM To assess the absolute number of T-regulatory cells (Tregs; CD4+CD25+Foxp3+) in the peripheral blood of gastric and colorectal cancer patients. METHODS We enrolled 70 cancer patients (33 gastric cancer, 37 colorectal cancer) and 17 healthy volunteers. The CD3+CD4+ lymphocytes and CD4+CD25+Foxp3+ Tregs in the peripheral blood were analyzed with flow cytometry. The absolute numbers of Tregs were calculated based on the CD4+CD25+Foxp3+ cells percentage of CD3+CD4+ cells and the absolute numbers of CD3+CD4+ cells per microliter. RESULTS The mean number of CD4+CD25+Foxp3+ cells per microliter in colorectal cancer patients was 15.7 (SD: 21.8), for gastric cancer patients 12.2 (SD: 14.3), and for controls 17.5 (SD: 11.4). The absolute number of Tregs was significantly lower in gastric cancer patients than in controls (P = 0.026). There was no statistically significant difference for gastric vs colorectal cancer or colorectal cancer vs controls. The absolute number of Tregs was also significantly depressed in N+ vs N⁻ cancer patients [22.0 (27.7) vs 10.1 (9.0), P = 0.013], and in the subgroup of gastric cancer patients [30.3 (27.6) vs 9.6 (8.0), P = 0.003]. No statistical difference was observed in the proportion of Tregs in the CD4+ population between the groups. CONCLUSION The absolute number of Tregs in peripheral blood of gastric cancer but not colorectal cancer patients was significantly decreased in comparison with that in healthy controls.

Depressed tumor necrosis factor alpha and interleukin-12p40 production by peripheral blood mononuclear cells of gastric cancer patients: Association with IL-1R-associated kinase-1 protein expression and disease stage

Our study investigated the ability of peripheral blood mononuclear cells (PBMCs) isolated from patients with different clinical stages of gastric cancer to produce proinflammatory (tumor necrosis factor alpha [TNFα], interleukin 12p40 [IL‐12p40] and interleukin 6 [IL‐6]) and antiinflammatory (interleukin‐10 [IL‐10]) cytokines after stimulation with lipopolysaccharide (LPS) or tumor cells, and its correlation with IL‐1R‐associated kinase‐1 (IRAK‐1) protein expression. The data showed that TNF production by tumor cell–stimulated PBMCs obtained from patients with advanced gastric cancer was significantly depressed in comparison to the control group. The response to LPS was less affected. IL‐12p40 production was depressed in all stages of disease, while the release of IL‐10 and IL‐6 remained unchanged. Depressed tumor cell–induced TNF and IL‐12p40 production was associated with diminished IRAK‐1 protein expression in PBMC. These findings may suggest that in advanced gastric cancer (at least in some cancer patients) diminished IRAK‐1 protein expression may be a novel mechanism responsible for or facilitating downregulation of innate immune response to tumor cells.

Ultrasound-guided vacuum-assisted core biopsy in the diagnosis and treatment of focal lesions of the breast – own experience

INTRODUCTION Vacuum-assisted core biopsy (VACB) guided by ultrasound is a minimally invasive method used in diagnosis and treatment of breast focal lesions. Vacuum-assisted core biopsy is an interesting minimally invasive alternative to open surgical biopsy. AIM To assess the value of ultrasound-guided vacuum-assisted core biopsy in the diagnosis and treatment of breast focal lesions. MATERIAL AND METHODS In the period 2009-2010, 397 ultrasound-guided vacuum-assisted core biopsies were performed. Mean age of the patients was 41.7 years (18-92 years), and size of the lesions ranged from 3 mm to 65 mm, mean size being 12 mm. All women with diagnosed atypical ductal hyperplasia or cancer were qualified for surgery. The patients with histopathologically benign lesions were under follow-up. RESULTS Samples sufficient for histopathological examination were obtained from 394 cases (99.2%). Of all 397 lesions, 293 (73.7%) were diagnosed as benign, there were 6 (1.6%) cases of atypical ductal hyperplasia and 98 (24.7%) malignant lesions. Three hundred and sixty-nine lesions were below 15 mm in diameter, of which 339 (91.9%) were totally removed during the VACB. CONCLUSIONS The results obtained confirm high efficiency of ultrasound-guided VACB in the differential diagnosis of breast focal lesions, including impalpable ones. It is a safe method with a low complication rate. In the case of benign lesions with a diameter not exceeding 15 mm, it allows one to excise the whole lesion and is a very good alternative to an open surgical biopsy. Vacuum-assisted core biopsy should be a standard and the method of choice in diagnosing breast lesions.

Alternative staging of regional lymph nodes in gastric cancer

The TNM pN stage based on the number of metastatic lymph nodes is an independent prognostic factor in gastric cancer. Many studies have highlighted the phenomenon of stage migration and problems in comparing groups of patients with different numbers of total lymph nodes harvested within TNM staging. The current version of UICC/AJCC and JGCA TNM classifications postulates a minimal number of 16 lymph nodes as the base for N stage determination. Alternative systems such as lymph node ratio (LNR), positive to negative lymph node ratio (PNLNR), and LOGODDS (or LODDS), were implemented to increase the quality of LN assessment. These methods have reached the background in the literature, but to date no standard approach according to the cut-offs for the stages has been implemented. LOGODDS is the method that most reflects the number of harvested lymph nodes. The rationale for alternative staging methods, their correlations, and limitations are presented.

Elevated level of some chemokines in plasma of gastric cancer patients

Introduction Gastric cancer is one of the most common cancer-related causes of death. This is mainly due to the lack of good noninvasive method/biomarkers suitable for early-tumour diagnosis and planning of further therapy modalities. Chemokines play an important role in cancer progression and metastasis formation. In gastric cancer patients, clinical relevance of CXCL12 and CCL5 level has been postulated. Aim of the study Efforts were undertaken to examine whether expanded chemokine range may be relevant for evaluation of preoperative staging of gastric cancer patients. Material and methods Plasma from 66 gastric cancer patients and 11 healthy controls was obtained, and CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL9, and CXCL10 levels were determined by flow cytometry FlexSet system. Results In gastric cancer patients’ plasma an increased level of CCL2, CCL4, CCL5, CXCL8, CXCL9, and CXCL10 was observed. In the case of CCL2, CXCL9, and CXCL10, the chemokine levels correlated with advanced (III and IV in TNM classification) disease stage. In the case of CCL4, CCL5, and CXCL8, elevated levels were observed in all cancer patients in comparison to healthy donors. Conclusions The accuracy of preoperative diagnosis in gastric cancer may include the monitoring of a wide range of chemokines in patients’ plasma. Increased levels of chemokines may warn that the disease is more advanced than conventional diagnostic procedures suggest.

Clinical predictors of malignancy in patients diagnosed with atypical ductal hyperplasia on vacuum-assisted core needle biopsy

Introduction Atypical ductal hyperplasia (ADH) is a benign lesion, which due to the risk of coexisting cancer is classified as a lesion of uncertain malignant potential. Aim To identify clinical predictors of cancer underestimation in patients with ADH diagnosed after vacuum-assisted breast biopsy (VABB). Material and methods Between 2001 and 2016, a total of 3804 vacuum-assisted core needle biopsies were performed at the First Chair of General Surgery of the Jagiellonian University Medical College in Krakow, including 2907 ultrasound (US)-guided biopsies and 897 digital stereotactic procedures. Seventy-six women were diagnosed with ADH and 72 of them underwent subsequent surgical excision. Demographic factors, medical history, family history, clinical symptoms, type and size of lesion determined in imaging scans, size of biopsy needle, and presence of coexisting lesions in VABB specimens were analysed as potential predictors of malignancy underestimation. Results Underestimation of breast carcinoma occurred in 21 (29.2%) patients. The upgrade rate was significantly higher only in patients with a lesion visible both in mammography (MMG) and US examinations and combined BIRADS-5. Conclusions Vacuum-assisted core needle biopsy is a minimally invasive technique used in diagnosing ADH. As the risk of breast malignancy underestimation is relatively high, open surgical biopsy remains the recommended procedure, especially in patients with lesions detected both in mammography and US examination. As we could not identify the factors that preclude cancer underestimation, all the women diagnosed with ADH should be informed about the risk of cancer underestimation.

Characterization of human gastric adenocarcinoma cell lines established from peritoneal ascites

The three cell lines, designated as gastric cancer (GC)1401, GC1415 and GC1436 were derived from peritoneal effusions from patients with gastric adenocarcinoma. Cell lines were established in tissue culture and in immunodeficient, non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. All cell lines were cultured in Dulbeccos modified Eagles medium supplemented with 5% fetal bovine serum. These cell lines were grown as an adherent monolayer with doubling time ranging between 25 h (GC1436 cell line) and 30–34 h (GC1401 and GC1415, respectively). All cells showed morphological features of epithelial-like cells, forming sheets of polygonal cells. Chromosomal analysis showed that the modal numbers ranged from 52 (GC1401), 51–56 (GC1415) and 106 (GC1436). High heterogeneity, resulting from several structural and numerical chromosomal abnormalities were evident in all cell lines. The surface marker expression suggested a tumor origin of the cells, and indicated the intestinal phenotype of a GC (CD10+, MUC1). All three cell lines were tumorigenic but not metastatic, in vivo, in NOD/SCID mice. The lack of metastatic potential was suggested by the lack of aldehyde dehydrogenase 1A1 activity. In conclusion, these newly established GC cell lines widen the feasibility of the functional studies on biology of GC as well as drug testing for potential therapeutic purposes.