Combined treatment of pancreatic cancer - current strategies

Wśród chorób nowotworowych jedną z najczęstszych przyczyn zgonów jest rak trzustki. Współczynniki zachorowalności na raka trzustki są właściwie równe współczynnikom umieralności, co świadczy o szczególnie niekorzystnym rokowaniu. Obecnie jedyną szansą wyleczenia jest zabieg resekcyjny, jednak usunięcie nowotworu jest możliwe tylko u około 20-30% chorych. W ciągu ostatnich dziesięcioleci odsetki przeżyć 5-letnich po zabiegach resekcyjnych wykazywały tendencję wzrostową, ale nadal wynoszą jedynie około 10-30% z medianą przeżycia sięgającą 15-20 miesięcy. Poza wzrastającą liczbą zabiegów resekcyjnych, centralizacja leczenia operacyjnego chorych na raka trzustki w ośrodkach dysponujących odpowiednim doświadczonym personelem pozwoliła zmniejszyć ryzyko powikłań i współczynnik śmiertelności pooperacyjnej. W świetle wyników dotychczasowych badań klinicznych konieczne jest wdrożenie programu kompleksowego leczenia skojarzonego, w którym chemioterapia lub chemioradioterapia są nierozłącznym uzupełnieniem zabiegów chirurgicznych. Mimo wielu entuzjastycznych doniesień nadal nie opracowano optymalnego modelu leczenia skojarzonego chorych z rakiem trzustki, a różnice obserwowane między wynikami poszczególnych badań wskazują na konieczność przeprowadzenia dalszych, odpowiednio zaprojektowanych badań klinicznych z udziałem dużych populacji chorych.Pancreatic cancer is one of the most common causes of cancer-related death. The prognosis, as indicated by nearly equal incidence and mortality rates, is very poor. Although the only chance for cure is currently pancreatic resection, the tumour can be removed only in about 20-30% of patients. Five-year survival rates reported in recent decades have demonstrated an increasing trend, but the 5-year survival is still only about 10-30% with the median survival of 15-20 months. A rising number of pancreatic resections along with centralisation of pancreatic cancer surgery in hospitals with adequately trained personnel resulted in reduced rates of morbidity and postoperative mortality. Previous clinical trials have emphasised the need for a combined treatment where chemotherapy or chemoradiotherapy are inseparably associated with surgical interventions. Though many enthusiastic studies have been reported, the optimal regimen of the combined therapy has not been agreed. Moreover, the differences observed between individual studies suggest that further well-designed clinical trials involving large patient populations are necessary

Natural history of intra-abdominal fluid collections following pancreatic surgery

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

Factors predicting adequate lymph node yield in patients undergoing pancreatoduodenectomy for malignancy

BACKGROUND: Most pancreatoduodenectomy resections do not meet the minimum of 12 lymph nodes recommended by the American Joint Committee on Cancer for accurate staging of periampullary malignancies. The purpose of this study was to investigate factors affecting the likelihood of adequate nodal yield in pancreatoduodenectomy specimens subject to routine pathological assessment. METHODS: Six hundred sixty-two patients subject to pancreatoduodenectomy between 1990 and 2013 for pancreatic, ampullary, and common bile duct cancers were reviewed. Predictors of yielding at least 12 lymph nodes were evaluated with a logistic regression model, and a survival analysis was carried out to verify the prognostic implications of nodal counts. RESULTS: The median number of evaluated nodes was 17 (interquartile range 11 to 25), and less than 12 lymph nodes were reported in surgical specimens of 179 (27 %) patients. Tumor diameter ≥20 mm (odds ratio [OR] 2.547, 95 % confidence interval [CI] 1.225 to 5.329, P = 0.013), lymph node metastases (OR 2.642, 95 % CI 1.378 to 5.061, P = 0.004), and radical lymphadenectomy (OR 5.566, 95 % CI 2.041 to 15.148, P = 0.01) were significant predictors of retrieving 12 or more lymph nodes. Lymph node counts did not influence the overall prognosis of the patients. However, a subgroup analysis carried out for individual cancer sites demonstrated that removing at least 12 lymph nodes is associated with better prognosis for pancreatic cancer. CONCLUSIONS: Few variables affect adequate nodal yield in pancreatoduodenectomy specimens subject to routine pathological assessment. Considering the ambiguities related to the only modifiable factor identified, appropriate pathology training should be considered to increase nodal yield rather than more aggressive lymphatic dissection

CD44+ cytokeratin-positive tumor cells in blood and bone marrow are associated with poor prognosis of patients with gastric cancer

Background The phenotypic heterogeneity of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells (DTC) in bone marrow is an important constraint for clinical decision making. Here, we investigated the implications of two different subpopulations of these cells in gastric cancer (GC). Methods GC patients (n=228) who underwent elective gastric resections were prospectively examined for CTC/DTC. The cells obtained from peripheral blood and bone marrow aspirates were sorted by flow cytometry and CD45- cells expressing cytokeratins (8, 18, and 19) and CD44 were identified by immunofluorescent double staining. Results Ninety-three (41%) patients had cytokeratin-positive tumor cells in either blood or bone marrow, while cells expressing CD44 were found in 22 (10%) cases. CK+CD44+ cells were significantly more common among patients with distant metastases (50 vs 19%, P=0.001), while no such correlations were demonstrated for CK+CD44- cells. Detection of CK+CD44+ cells, but not CK+CD44-, was associated with significantly shortened survival. Moreover, the Cox proportional hazards model identified CK+CD44+ cells as a negative prognostic factor with an odds ratio of 2.38 (95% CI 1.28-4.41, P=0.006). Conclusion CD44+ phenotype of cytokeratin-positive cells in blood and bone marrow is an independent prognostic factor in patients with gastric cancer

Preoperative plasma level of IL-10 but not of proinflammatory cytokines is an independent prognostic factor in patients with gastric cancer

There have been many discrepant observations on the serum levels of cytokines in cancer patients and their prognostic value. The purpose of this study was to determine the plasma levels of pro- and anti-inflammatory cytokines and their clinical significance in a large group of patients with gastric carcinoma. The levels of tumour necrosis factor alpha (TNF α), interleukin-12p40 (IL-12p40), IL-12p70, IL-18, IL-10 and soluble TNF receptors I and II sTNF-Rs were investigated in the plasma of 136 consecutive patients with biopsy proven gastric cancer using specific enzymelinked immunoabsorbent assays (ELISA). Survival curves were estimated using the method of Kaplan and Meier and the differences in the survival rates were tested by the logrank test. For multivariate analysis of prognostic factors, the Cox proportional hazard model was used. Proinflammatory cytokines and sTNF-Rs were higher in the whole group of patients in comparison to healthy volunteers. IL-10 was elevated mostly in advanced disease. The increased levels of IL-10 (>10 pg/ml) were associated with significantly poorer survival of patients, while the levels of the other cytokines and sTNF-Rs showed no correlation with prognosis. The increased level of IL-10 is an independent unfavorable prognostic factor in patients with gastric cancer

Feasibility and outcomes of early oral feeding after total gastrectomy for cancer

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 inhospital 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<0.001) complications. However, subsequent multivariate regression models failed to confirm significant correlations between timing of oral meals and postoperative morbidity. Conclusion Our findings suggested that early oral feeding is feasible and safe after total gastrectomy for gastric cancer. However, benefits of such early nutritional interventions require further studies

Preoperative neutrophil-lymphocyte and lymphocyte-monocyte ratios reflect immune cell population rearrangement in resectable pancreatic cancer

BACKGROUND: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) may serve as a simple index of the immune function. The aim of this study was to investigate the prognostic significance of NLR, PLR, and LMR in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and to verify whether such biomarkers are associated with changes in populations of lymphoid cells. METHODS: The prognostic implications of blood count parameters were evaluated in a retrospective cohort of 442 subjects undergoing pancreatic resections for PDAC. Subpopulations of lymphocytes and monocytes in peripheral blood were identified by FACS in a prospective cohort of 54 patients. RESULTS: In the univariate analysis, NLR < 5 and LMR ≥ 3 were associated with significantly longer median survival of 25.7 vs 12.6 months and 29.2 vs 13.1 months, respectively. PLR did not influence survival. The Cox proportional hazards model showed that high NLR (HR 1.66, 95 % CI 1.12 to 2.46, P = 0.012) and low LMR (HR 1.65, 95 % CI 1.06 to 2.58, P = 0.026) were independent predictors of poor prognosis. NLR ≥ 5 and LMR < 3 correlated with an approximately twofold decrease in counts of helper and cytotoxic T cells, B cells, and NK cells. High NLR was also accompanied with increased neutrophil counts, while low LMR showed increased numbers of monocytes, mostly classical. CONCLUSIONS: NLR and LMR may carry important prognostic information for patients with resected PDAC. The unfavorable prognosis likely correlates with reduced numbers of immune cells effective against the tumor and increased populations of cells involved in immune suppression

Oprogramowanie do rekonstrukcji i analizy 3D obrazów diagnostycznych

Background: Recent advances in computer technologies have opened new frontiers in medical diagnostics. Interesting possibilities are the use of three-dimensional (3D) imaging and the combination of images from different modalities. Software prepared in our laboratories devoted to 3D image reconstruction and analysis from computed tomography and ultrasonography is presented. In developing our software it was assumed that it should be applicable in standard medical practice, i.e. it should work effectively with a PC. An additional feature is the possibility of combining 3D images from different modalities. Materials/Methods: The program was tested on a PC using DICOM data from computed tomography and TIFF files obtained from a 3D ultrasound system. The results of the anthropomorphic phantom and patient data were taken into consideration. A new approach was used to achieve spatial correlation of two independently obtained 3D images. The method relies on the use of four pairs of markers within the regions under consideration. The user selects the markers manually and the computer calculates the transformations necessary for coupling the images. Results: The main software feature is the possibility of 3D image reconstruction from a series of twodimensional (2D) images. The reconstructed 3D image can be: (1) viewed with the most popular methods of 3D image viewing, (2) filtered and processed to improve image quality, (3) analyzed quantitatively (geometrical measurements), and (4) coupled with another, independently acquired 3D image. The reconstructed and processed 3D image can be stored at every stage of image processing. The overall software performance was good considering the relatively low costs of the hardware used and the huge data sets processed. The program can be freely used and tested (source code and program available at http://www.biofizyka.cm-uj.krakow.pl). Improvements allowing the processing of new data types and new procedures can be implemented for specific demands. Conclusions: The reconstruction and data processing can be conducted using a standard PC, so low investment costs result in the introduction of advanced and useful diagnostic possibilities