Surgical treatment outcomes of patients with T1-T2 gastric cancer: does the age matter when excellent treatment results are expected?

Abstract Background The proportion of early gastric cancer stages is increasing, as is the incidence of gastric cancer among the elderly population. Therefore, this study was designed to analyze surgical treatment outcomes of T1-T2 gastric cancer in elderly patients. Methods A total of 457 patients with T1-T2 gastric cancer who underwent gastrectomy between 2005 and 2015 were enrolled in this retrospective study. Patients were classified into two groups according to age (< 70 years versus ≥ 70 years). Clinicopathological features, surgical treatment results, and clinical outcomes were compared between the groups. Results Higher ASA score (ASA 3/4), differentiated cancer, and intestinal-type tumors were more common in elderly patients. Postoperative complication rates were similar between the two groups; however, postoperative mortality rates were significantly higher in the elderly group. Higher ASA score was independently associated with postoperative complications in the elderly group. Furthermore, severe postoperative complications were found as an independent factor associated with higher 90-day mortality rate. Elderly patients had a significantly poorer 5-year overall survival rate. Two surgery-related factors—total gastrectomy and complicated postoperative course—were revealed as independent prognostic factors for poor overall survival in the elderly group. Conclusions Despite higher postoperative mortality rate and poorer overall survival results, elderly patients with gastric cancer should be considered for radical surgery. ASA score may be useful for predicting surgical treatment outcomes in elderly patients undergoing surgery for GC and hence assists clinicians in planning treatment strategies for each individual patient

Risk factors for lymph node metastasis in early gastric cancer patients: Report from Eastern Europe country– Lithuania

Abstract Background Current risk factors for lymph node metastasis in early gastric cancer have been primarily determined in Asian countries; however their applicability to Western nations is under discussion. The aim of our study was to identify risk factors associated with lymph node metastasis in Western cohort patients from the Eastern European country - Lithuania. Methods A total of 218 patients who underwent open gastrectomy for early gastric cancer were included in this retrospective study. After histolopathological examination, risk factors for lymph node metastasis were evaluated. Overall survival was evaluated and factors associated with long-term outcomes were analyzed. Results Lymph node metastases were present in 19.7% of early gastric cancer cases. The rates were 5/99 (4.95%) for pT1a tumors and 38/119 (31.9%) for pT1b tumors. Submucosal tumor invasion, lymphovascular invasion, and high grade tumor differentiation were identified as independent risk factors for lymph node metastasis. Submucosal tumor invasion and lymphovascular invasion were also associated with worse 5-year survival results. Conclusion Our study established submucosal tumor invasion, lymphovascular invasion, and high grade tumor differentiation as risk factors for lymph node metastasis

DDR increases with past reproductive activity and curtails reproductive capacity.

<p>(A) Average number of RPA-1::YFP foci per nucleus in late pachytene. Image panels show example RPA-1 foci (arrows; YFP: green; DNA: red). Scale bars: 2.5 μm. For statistical tests see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s010" target="_blank">S4A Table</a>. (B) Total brood size is larger for mated hus-1(op241) (red bar) than for mated wild-type (blue bar). For statistical tests see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s010" target="_blank">S4B Table</a>. Error bars represent 83% confidence intervals; asterisks indicate significance of Wilcoxon rank sum test p‑value. To test whether the DDR curtails reproductive activity, we utilized the <i>hus-1</i> reduction of function allele <i>op241</i>. This mutation abrogates multiple forms of DDR [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.ref030" target="_blank">30</a>] but preserves normal reproductive activity in selfed worms [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.ref031" target="_blank">31</a>]. Mated <i>hus-1(op241)</i> hermaphrodites had a significantly larger brood size than wild-type controls (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s010" target="_blank">S4B Table</a> and Fig 4B); the reproductive schedule was almost identical between days 1 and 3, but from day 4 onward <i>op241</i> had a ~1.5-fold greater number of progeny. This shows that the DDR hastens reproductive senescence, by a mechanism that remains to be identified.</p

Starvation delays reproductive senescence.

<p>(A) Schematic of starvation experiment. (B) Phalloidin-stained fog-2 gonads before and after starvation. Scale bar: 25 μm. (C) Total brood size for <i>fog-2</i> females mated after 2 days of starvation or control treatment. For statistical tests see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s008" target="_blank">S2C Table</a>. (D) Reproductive capacity retained by <i>fog-2</i> females after 2-day starvation or control treatment (computed by dividing numbers used in C by reproductive capacity at day 0). Error bars represent 83% confidence intervals; asterisks indicate significance of Wilcoxon rank sum test p-value.</p

Stem cell cycling drives reproductive senescence.

<p>(A) Schematic of cell cycle inhibitor experiments. (B) Total number of oocytes produced by fog-2 or inx-22; fog-2 females during the HU treatment window. For statistical tests see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s009" target="_blank">S3A Table</a>. (C) Brood size for fog-2 or inx-22; fog-2 females mated after the HU treatment window. For statistical tests see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s009" target="_blank">S3B Table</a>. (D) Reproductive capacity retained by fog-2 or inx-22; fog-2 females after HU or control treatment (computed by dividing numbers used in C by reproductive capacity at day 0). (E) Incidence of cells in M-phase following 24 h treatment with CDK inhibitor Roscovitine or control treatment with DMSO only. For statistical tests see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s009" target="_blank">S3D Table</a>. (F) Brood size for fog-2 females mated after the Roscovitine treatment window. For statistical tests see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s009" target="_blank">S3E Table</a>. Error bars represent 83% confidence intervals; asterisks indicate significance of Wilcoxon rank sum test p-value.</p

Mitotic zones in gonads with reduced reproductive activity intermittently occupy a dormant state.

<p>(A) Representative z-projection images of continuous EdU labeling of wild-type and fog-1 (DNA: red; EdU: green). “Dormant” mitotic zones are defined by the absence of any EdU positive cell, and are marked with an asterisk. Almost all wild-type mitotic zones show activity within 1 h of continuous labeling, whereas fog-1 mitotic zones take in excess of 6 h to all have experienced activity. (B) Fractions of day 1 mitotic zones remaining unlabeled as a function of time on EdU-labeled food (n = 40–82 for each genotype and time point).</p

Slower average cell cycle progression and loss of synchrony in gonads with reduced reproductive activity.

<p>(A, B) Principle of EdU pulse chase analysis. Three fictitious mitotic zones cycle steadily (A) or stochastically enter a dormant state (B; play and pause symbols within the squares). The position of each square on the circle represents mitotic zone cell cycle progression (progression from time of labeling highlighted by a colored band). A full revolution on the circle corresponds to all cells in the mitotic zone having undergone a full cycle. The red wedge in the bottom row shows average cycle progression (angle shown by red arrows) and the amount of dispersion between mitotic zones (width of the wedge, set to the inverse of the magnitude of the resultant computed as the vector sum of individual gonad positions). (C) Analysis of cell cycle progression after EdU pulse-chase. Mitotic zones from virgin females or old wild-type hermaphrodites lose synchrony at later chase times, as shown e.g. by wider wedges (virgin fog-2 data is repeated in rows 2 and 3 to facilitate comparisons). See also <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s005" target="_blank">S5 Fig</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s011" target="_blank">S5 Table</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s016" target="_blank">S1 Movie</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s015" target="_blank">S1 Dataset</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s017" target="_blank">S1 Text</a>.</p

Suboptimal kinetics of response to mating in genotypes and environmental conditions with high gonad dormancy.

<p>Early female response to mating on day 3 of adulthood, as assayed by numbers of viable progeny laid per hour. Each point is computed from the number of progeny of one worm over a time window ending at corresponding position on x axis (n = 40 worms per genotype tracked over the time course; some points in the graph overlap). Red lines are moving averages. Error bars represent 83% confidence intervals; asterisks indicate significance of Wilcoxon rank sum test p-value.</p

Reproductive senescence rates correlate with gonad activity.

<p>(A) Schematic of reproductive senescence assay, and brood sizes of females of various genotypes mated at increasing ages (n = 15–40 mothers for each genotype and time point). (B) Schematic of late reproductive activity assay, and brood sizes from day 7 for females mated at the onset of adulthood (day 0), on day 5 of adulthood, or both. For statistical tests see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005985#pgen.1005985.s007" target="_blank">S1C Table</a>. Error bars represent 83% confidence intervals; asterisks indicate significance of Wilcoxon rank sum test p-value.</p