Hepatic micrometastases outside macrometastases are present in all patients with ileal neuroendocrine primary tumour at the time of liver resection.

Background: Neuroendocrine tumours (NETs) in the ileum grow slowly but metastasise to the liver at an early stage. After resection of the primary tumour and mesenteric lymph nodes, selected patients with liver metastases have been operated with curative intention. Recurrence-free survival seems low, suggesting that micrometastases are present in the liver at the time of surgery. We have therefore examined whether NET metastases could be detected in perceived normal liver tissue at the time of liver resection. Material and methods: Liver tissue outside the macrometastases from patients (n = 10) operated by liver resection due to metastases from ileal NETs G1/2, were examined for NE cells by immunohistochemistry. Liver tissue from patients operated for metastatic colon cancer was used as control (n = 6). Groups of ≥3 NE cells ≥3 mm from macrometastases were considered micrometastases. Clinical course was recorded retrospectively. Results: Ten of 10 patients had micrometastases, consisting of multiple groups of NE cells. None of the control patients had NE cells in the liver tissue. After median follow-up time of 5.5 (0.8-18.7) years 6 of 10 patients had developed recurrent NET metastases detected by cross-sectional imaging. The follow-up time of the four patients without detectable metastases was 4.8 (0.8-7.5) years vs. with detectable metastases 7.9 (3.2-18.7) years. Conclusions: All patient had micrometastases outside macrometastases at the time of liver resection, suggesting that subsequently recurrent liver metastases develop from NET depositions in the liver already present at the time of surgery. The likelihood of curation by hepatic resection appears very low.

Perioperative chemotherapy for resectable gastric cancer - what is the evidence?

The UK MAGIC trial published in 2006 was the first RCT to identify improved long-term survival rates using preoperative chemotherapy for resectable gastric or gastroesophageal cancer. Overnight, the treatment regimen impacted European guidelines. However, the majority of patients underwent limited lymph node dissection, and analyses of the rates of curative resection, downsizing and downstaging were not by intention to treat, rightfully raising concerns about their validity. For the subset of true gastric cancers, meta-analyses may even question the claims of improved long-term survival rates by present-day regimens. A rhetorical question can be posed as to whether downstaging and improved survival rates by preoperative (radio)-chemotherapy for cancers of the distal esophagus or gastric cardia, has confounded our conclusions on the (lack of) effect of present-day regimens of perioperative chemotherapy for true gastric cancers, let alone in a situation with proper lymph node dissection. At present, a plea can be made to move one step back and revert to an RCT with a surgery alone arm. Inclusion criteria and analyses of future RCTs must stratify on tumor location and the Lauren type and embrace the newly developed scheme of sub-classification of gastric cancers based on extensive molecular profiling as reported in the seminal Cancer Genome Atlas Study.

A population-based study on incidence rates, Lauren distribution, stage distribution, treatment, and long-term outcomes for gastric adenocarcinoma in Central Norway 2001-2011.

BACKGROUND: Population-based studies for gastric adenocarcinoma are scarce, particularly studies conducted within a defined geographical area with publicly available censuses that allow incidence rates to be calculated. MATERIAL AND METHODS: Population-based study in Central Norway from 2001 to 2011, covering a population of 636 000-680 000, respectively. Patients were identified through the Cancer Registry of Norway and the Norwegian Patient Register, and were characterized by data from individual electronic patient records. Outcomes were compared across the early and the late half of the study period. RESULTS: A total of 878 patients were identified with a median age of 76.2 years. The male to female ratio was 1.72. Annual world age-standardized incidence was 8.0/105 and 3.6/105, respectively. The Lauren diffuse type was significantly more frequent among patients below 60 years, among females and for non-cardia cancers, compared to their counterparts (p < .001). The Lauren mixed type had a stable proportion of around 13% irrespective of age, sex or tumor location. Early gastric cancers (EGC) represented 8.3% of the cases, whereas 44% of all patients were diagnosed with metastatic disease. In males, the proportion of cardia cancers increased from 29.7% to 39.1% during the study period (p = .005). The five-year overall survival was 16%, and was substantially better for the Lauren intestinal type compared to the diffuse type, log-rank p = .003. The R0-R1 resection rate was 39%, with a corresponding five-year survival of 40.9%. CONCLUSIONS: This study provides population-derived data lacking in hospital-based studies. Lauren categories with epidemiological aspects and clinical outcomes are displayed. Gastric cancer was associated with a dismal prognosis. Few patients had EGC and close to 50% had metastatic disease. Many were too old or frail to be considered for surgery.

Bronchial microdialysis of cytokines in the epithelial lining fluid in experimental intestinal ischemia and reperfusion before onset of manifest lung injury.

Today, there is no continuous monitoring of the bronchial epithelial lining fluid. This study used microdialysis as a method of continuous monitoring of early lung cytokine response secondary to intestinal ischemia-reperfusion in pigs. The authors aimed to examine bronchial microdialysis for continuous monitoring of IL-1ß, TNF-α, IL-8, and fluorescein isothiocyanate Dextran 4,000 Da (FD-4). The superior mesenteric artery was cross-clamped for 120 min followed by 240 min of reperfusion (ischemia group, n = 8). Four sham-operated pigs served as controls. The pigs were anesthetized and normoventilated (peak inspiratory pressure, <20 cm H2O; positive end-expiratory pressure, 7 cm H2O). Samples from bronchial and luminal intestinal and arterial microdialysis catheters (flow-rate of 1 µL/min) were collected during reperfusion in 60-min fractions. Samples were analyzed for TNF-α, IL-1ß, IL-8, and FD-4. Data are presented as median (interquartile range). A lung biopsy was collected at the end of the experiment. During reperfusion, there was an increase in bronchial concentrations of both IL-8 (3.70 [1.47-8.93] ng/mL per h vs. controls, 0.61 [0.47-0.91] ng/mL per h; P < 0.001) and IL-1ß (0.32 [0.05-0.56] ng/mL per h vs. controls, 0.07 [0.04-0.10] ng/mL per h; P = 0.008). In the intestinal lumen, IL-8 was increased in the ischemia group (6.33 [3.13-9.23] ng/mL per h vs. controls, 0.89 [0.21-1.86] ng/mL per h; P < 0.001). The FD-4 did not differ between groups. Pulmonary vascular resistance and pulmonary shunt increased versus controls. During reperfusion, PaO2/FiO2 ratio decreased in the ischemia group. Histology was normal in both groups. Bronchial microdialysis detects altered levels of cytokines in the epithelial lining fluid and can be used for continuous monitoring of the immediate local lung cytokine response secondary to intestinal ischemia-reperfusion.

Gene expression based classification of gastric carcinoma.

The aim of the present work is to identify molecular markers that allow classification of gastric carcinoma with respect to important clinicopathological parameters. Gastric adenocarcinomas were subjected to cDNA microarray analysis with a 2.504 gene probe set. Using the Rosetta rough-set based learning system, good classifiers were generated for gene-expression based prediction of intestinal or diffuse growth pattern according to Laurén's classification and presence of lymph node metastases. To our knowledge, this is the first study on gastric carcinoma in which molecular classification has been achieved for more than one clinicopathological parameter based on microarray gene expression profiles.