Stage-dependent Survival Research Articles

Comment on: "Stage-dependent survival in patients treated with neoadjuvant chemotherapy and radical cystectomy".

Comment on: "Stage-dependent survival in patients treated with neoadjuvant chemotherapy and radical cystectomy".

P153 - Stage dependent survival in patients treated with NAC and RC: Implications for patient selection and adjuvant therapy

P153 - Stage dependent survival in patients treated with NAC and RC: Implications for patient selection and adjuvant therapy

Effectiveness of population-based colorectal cancer screening programme in down-staging

BackgroundThis is the first evaluation study to assess the demographic characteristics of the colorectal cancer (CRC) cases detected in the prevalent round of the population-based Colorectal Cancer Screening Programme (CRCSP) in Hong Kong and to explore the effectiveness of the programme on the stage distribution of CRC. MethodsThis study covered the period between 28 September 2016 and 31 December 2018. Information on CRC diagnosis, age and stage at diagnosis were retrieved and reviewed by the Hong Kong Cancer Registry (HKCaR). The CRC detection rate among CRCSP-screened participants and incidence rate among the Hong Kong general population were calculated respectively. The odds ratio (OR) was calculated to measure the strength of association and quantify the effect of CRCSP on stage shift between CRCSP-detected CRC cases and an age-matched cohort of CRC cases diagnosed outside the programme. ResultsThe CRC detection rate among participants of the CRCSP during the study period was 736.0/100,000, whereas the overall CRC incidence rate among general population of similar age groups was 393.7/100,000. For all ages and both sexes, the OR of stage I CRCSP-detected CRC compared to the CRC from the age-matched cohort was 3.91 (95%CI=3.41–4.48) and the OR dropped to 0.54 (95%CI=0.41–0.70) at stage IV. Meanwhile, the overall OR of CRCSP-detected CRC compared to CRC from the age-matched cohort dropped from 2.24 (95%CI=1.97–2.56) to 1.62 (95%CI=1.40–1.87) with increasing age. ConclusionThe present study has demonstrated the initial impact of the CRCSP on shifting the stage at diagnosis towards earlier stage. The benefit of stage-shift was similar for all ages from 60 to 77 in both sexes and seems to increase with younger age. Given the stage-dependent survival outcomes, this stage-shift could lead to a reduction in CRC-associated mortality in Hong Kong in future.

Similar Stage-dependent Survival and Outcome in Sporadic and Hereditary Medullary Thyroid Carcinoma.

Long-term data are scarce on large cohorts with sporadic (sMTC) and hereditary medullary thyroid carcinoma (hMTC). To compare long-term disease-specific survival (DSS) and outcomes between sMTC and hMTC groups. Retrospective analysis. German tertiary referral center. A total of 673 patients with MTC that underwent surgery from January 1974 to July 2019. None (observational study). Differences between sMTC and hMTC in long-term, stage-dependent survival and outcomes. Surgery was performed at median ages of 49 years for sMTC (n = 477, 44% male) and 29 years for hMTC (n = 196, 43% male; P < 0.0001). The mean follow-up times were 9.2 ± 8.0 (sMTC) and 14.6 ± 10.3 years (hMTC). Age and tumor stage at diagnosis were significantly different between the 2 groups (P < 0.0001). The sMTC and hMTC groups had different overall DSS (log rank, P = 0.0183), but similar stage-dependent DSS (log rank, P = 0.1242-0.8981). In a multivariate analysis, sMTC and hMTC did not differ in DSS (hazard ratio [HR] = 1.56; 95% CI, 0.94-2.57), but in both groups, a worse DSS was significantly associated with age at diagnosis (HR = 1.04; 95% CI, 1.02-1.05), male sex (HR = 0.49; 95% CI, 0.32-0.76), and stages III and IV at diagnosis (HR = 20.00; 95% CI, 2.74-145.91 and HR = 97.47; 95% CI, 13.07-726.67, respectively). The groups had significantly different (P < 0.0001) outcomes (i.e., cured, minimal residual disease, structural detectable disease, and death), but similar stage-dependent outcomes (P = 0.9449-0.0511), except for stage III (P = 0.0489). Patients with sMTC and hMTC had different ages of onset, but similar stage-dependent DSS and outcomes after the MTC diagnosis. This finding suggested that tumor behavior was similar in sMTC and hMTC.

Haploid females in the isomorphic biphasic life-cycle of Gracilaria chilensis excel in survival

BackgroundConditional differentiation is one of the most fundamental drivers of biodiversity. Competitive entities (usually species) differ in environmental or ecological niche enabling them to co-exist. Conditional differentiation of haploid and diploid generations is considered to be a requirement for the evolutionary stability of isomorphic biphasic life-cycles and the cause for the natural occurrence of both phases at uneven abundances. Theoretically, stage dependent survival rates are the most efficient way to explain conditional differentiation.ResultsWe tested for conditional differentiation in survival rates among life stages (haploid males, haploid females, and diploids) of Gracilaria chilensis, an intertidal red alga occurring along the Chilean shores. Therefore, the fate of individuals was followed periodically for 3 years in five intertidal pools and, for the first time in isomorphic red algae, a composite model of the instantaneous survival rates was applied. The results showed the survival dependency on density (both competition and Allee effects), fertility, age, size, season and location, as well as the differentiation among stages for the survival dependencies of these factors. The young haploid females survived more than the young of the other stages under Allee effects during the environmentally stressful season at the more exposed locations, and under self-thinning during the active growth season. Furthermore, fertile haploid females had a higher survival than fertile haploid males or fertile diploids.ConclusionsHere, we show a survival advantage of haploids over diploids. The haploid females probably optimize their resource management targeting structural and physiological adaptations that significantly enhance survival under harsher conditions. In a companion paper we demonstrate a fertility advantage of diploids over haploids. Together, the survival and fertility differentiation support the evolution and prevalence of biphasic life-cycles.

The Updated AJCC/TNM Staging System for Papillary Thyroid Cancer (8th Edition): From the Perspective of Genomic Analysis.

Recently, the American Joint Committee on Cancer published the 8th edition of its Cancer Staging Manual with major changes regarding the staging of thyroid cancer, including the raising of the age cutoff from 45 to 55years. Using the clinical and genetic data of 505 papillary thyroid cancer (PTC) cases, we aimed to compare overall survival (OS) and recurrence-free survival (RFS) with different age cutoff values, and also investigate the efficacy of the new staging system on a genomic level. We downloaded gene expression data, somatic mutation profile, copy number alteration data and clinical data of 505 PTC patients from The Cancer Genome Atlas data portal. We used multiple statistical analysis and multiplatform genomic analysis to evaluate the efficacy of the 8th edition. When using 55years as the cutoff value for analyzing RFS, the Kaplan-Meier plot showed a significant p value but not when using 45years (p = 0.006 vs. p = 0.493), but both cutoff values were significant when analyzing OS (p = 1.1 × 10-9 with age 55 vs. p = 4.4 × 10-5 with age 45). When looking at stage-dependent survival, both the 7th and 8th edition had significant p values (p = 0.048 vs. p = 3.1 × 10-9 in RFS and p = 5.9 × 10-10 vs. p = 2.2 × 10-10 in OS). Multiplatform genomic analysis showed patients ≥55years had 103 differently expressed genes when compared with other age groups. Signaling pathway analysis revealed that patients ≥55years had altered pathways associated with aggressiveness of thyroid cancer. In conclusion, this is the first study to show clinical and genetic evidence supporting the altered age cutoff point of 55years in the AJCC 8th edition for PTC patients.

Stage-dependent survival in relation to timing of fledging in a migratory passerine, the Northern Wheatear (Oenanthe oenanthe)

A better understanding of factors affecting population change is needed to explain declines of long-distance migrants. As juvenile survival is generally an important determinant of population dynamics, assessing whether juvenile survival is primarily affected either during the post-fledging stage on the natal site or during the migration and winter stages (migration-winter) is important for developing conservation strategies. Here, we assess variation in stage-dependent survival of juvenile Northern Wheatears (Oenanthe oenanthe), a threatened passerine in northwestern Europe. We estimate apparent survival in a Dutch coastal breeding population based on frequent resightings during the whole breeding season. We show that post-fledging survival on the natal grounds was not clearly different from survival during migration-winter and that late fledging reduces survival during both post-fledging and migration-winter. It is unknown which factors are causal to lower survival of late-fledged juveniles and this hampers effective conservation. Meanwhile, conservation measures focusing on nest protection should increase average juvenile survival in the remaining small populations in the short term because the number of successfully fledged early juveniles should increase.

Effect of Growth Phase on Survival of Bromegrass Suspension Cells Following Cryopreservation and Abiotic Stresses

Cryopreservation is a practical method of preserving plant cell cultures and their genetic integrity. It has long been believed that cryopreservation of plant cell cultures is best performed with cells at the late lag or early exponential growth phase. At these stages the cells are small and non-vacuolated. This belief was based on studies using conventional slow prefreezing protocols and survival determined with fluorescein diacetate staining or 2,3,5-triphenyltetrazolium chloride assays. This classical issue was revisited here to determine the optimum growth phase for cryopreserving a bromegrass (Bromus inermis) suspension culture using more recently developed protocols and regrowth assays for determination of survival. Cells at different growth phases were cryopreserved using three protocols: slow prefreezing, rapid prefreezing and vitrification. Stage-dependent trends in cell osmolarity, water content and tolerance to freezing, heat and salt stresses were also determined. In all cases survival was assayed by regrowth of cells following the treatments. Slow prefreezing and rapid prefreezing protocols resulted in higher cell survival compared with the vitrification method. For all the protocols used, the best regrowth was obtained using cells in the late exponential or early stationary phase, whereas lowest survival was obtained for cells in the late lag or early exponential phase. Cells at the late exponential phase were characterized by high water content and high osmolarity and were most tolerant to freezing, heat and salt stresses, whereas cells at the early exponential phase, characterized by low water content and low osmolarity, were least tolerant. The results are contrary to the classical concept which utilizes cells in the late lag or early exponential growth phase for cryopreservation. The optimal growth phase for cryopreservation may depend upon the species or cell culture being cryopreserved and requires re-investigation for each cell culture. Stage-dependent survival following cryopreservation was proportionally correlated with the levels of abiotic stress tolerance in bromegrass cells.

FSH immunoneutralization acutely impairs spermatogonial development in normal adult rats.

Follicle-stimulating hormone (FSH) plays an important part in testicular development. Its role in the regulation of spermatogenesis in the adult, however, remains controversial. This study aimed to explore the role of FSH in the maintenance of adult rat spermatogenesis by using immunoneutralization to selectively withdraw FSH action for periods of up to 8.5 days and then assessing the outcome by quantification of germ cell number. Adult rats received either an ovine polyclonal rat FSH antibody (FSHAb, 2 mg/kg subcutaneous daily-a dosage known to neutralize >90% of FSH in serum) for 2, 4, 7, or 8.5 days or a control sheep immunoglobulin (ConAb, 2 mg/kg) for 8.5 days. Testes were perfusion fixed, and germ cell numbers per testis were quantified using the optical disector (sic) stereological method. The percentage of seminiferous tubules displaying apoptotic cells was determined by the in situ end labeling method (TUNEL). FSHAb treatment for 4, 7, or 8.5 days significantly reduced the number of type A/intermediate spermatogonia (approximately 74% of control values) associated with stages I-IV. Similar reductions were seen in type B spermatogonial and preleptotene spermatocyte numbers after 8.5 days of FSHAb treatment (approximately 69% of control values; P < 0.05). Decreases (P < 0.05) in the numbers of pachytene spermatocytes in stages I-III and VIII, round spermatids in stages I-III, VII, and VIII (approximately 70% of control values), and step 19 elongated spermatids in stage VII (51% of control values) were achieved after 8.5 days of FSHAb treatment. Compared with control, FSHAb treatment increased the percentage of stage XIV-III tubules containing TUNEL-positive cells by about twofold after 7 days of FSHAb treatment (P < 0.05). This study supports a role for FSH in the maintenance of quantitatively normal adult rat spermatogenesis, specifically by regulating A3 and A4 spermatogonial subtypes. FSH may act on these spermatogonia by enhancing the stage-dependent survival of type A spermatogonia. Effects at other sites in spermatogenesis are suggested by the changes in spermatocyte and spermatid populations. However, to clarify these effects, selective FSH withdrawal would need to be prolonged until steady state had been achieved.

Gastric Cancer: A Prospective Randomized Trial of Surgical Treatment

Despite declining incidence and improved surgical care, gastric cancer remains associated with high mortality. Incidence and survival show remarkable geographic differences. Japanese patients have a much better chance of cure than Western patients. Whether biological differences between Japanese and Western patients are responsible for this remains unclear. Japanese surgeons, however, generally use a different surgical approach. The so-called R2 resection for gastric cancer has been investigated in a number of retrospective trials and, even in the West, evidence is accumulating that a more extensive resection of lymph nodes might positively influence stage dependent survival rates. Whether this approach indeed improves treatment and not just influences staging is currently being studied in a nation-wide, prospective randomized trial in the Netherlands. The design and the first results of this trial are presented here.

Human fetal spinal cord xenografts survive in the eye of athymic nude rat hosts.

Human fetal spinal cord tissue was recovered from elective abortions and grafted to the anterior chamber of the eye of adult athymic nude rats. The transplants slowly became vascularized from the host iris during the first months. There was a clear cut stage-dependent survival and growth along a more "human" time-table. Fetal spinal cord tissue from embryos younger than gestational week 8 showed a much better survival and growth than tissue from older stages. Using laminin immunohistochemistry blood vessels could be visualized in the grafts. The pattern of vascularization was, however, clearly abnormal; there were fewer vessels which had abnormally thick walls as compared to those in the normal spinal cord. Similar to rat spinal cord allografts the human spinal cord xenografts displayed a relative gliosis and were surrounded by a glial layer visualized with antibodies against glial fibrillary acidic protein. Neurofilament-immunoreactive fibres were found inside the glial layer. A variety of neurons were found including large polygonal motoneuron-shaped cells, albeit with CGRP and AChE negative cell bodies. Both Substance P and enkephalin-immunoreactive cells and fibres were found. It is concluded that xenografted fetal human spinal cord survives, grows and may provide a useful model for experimental studies of human spinal cord development and connectivity.

Chapter 23 Intraocular spinal cord grafts: A model system for morphological and functional studies of spinal regeneration

Publisher Summary The intraocular grafting model provides a system for studies of isolated areas of the nervous system, in a more controlled environment than at intracerebral or intraspinal transplantation sites. This chapter describes the intraocular model system to study spinal cord (SC) alone or in combination with other tissues. The chapter discusses the possibility of morphological and functional spinal regeneration, and also addresses certain issues, such as whether the fetal SC survive and mature in a normal manner after intraocular transplantation, and whether it is possible to construct an isolated intraocular spinal pathway by means of double-grafting SC with an appropriate central nervous system (CNS) tissue. The results show that fetal SC has a stage dependent survival and growth in oculo, and using optimal donor stages, SC grafts grow considerably and develop several organitypic morphological and functional characteristics. Cografts of monoamine containing brainstem neurons from locus coeruleus will innervate SC in oculo, but in a delayed manner, while double grafting may be used to create intraocular replicas of descending spinal pathways. The chapter concludes that intraocular single and double grafts are valuable tools for studying structural and functional connectivity in the SC.