Pulmonary metastasectomy with therapeutic intent for soft-tissue sarcoma Chudgar, Neel P., MD; Brennan, Murray F., MD; Munhoz, Rodrigo R., MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
07/2017, Letnik:
154, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract Objective Soft-tissue sarcoma is a heterogeneous disease that frequently includes the development of pulmonary metastases. The purpose of this study is to determine factors associated with ...improved survival among patients with soft-tissue sarcoma to help guide selection for pulmonary metastasectomy. Methods We reviewed a prospectively maintained database and identified 803 patients who underwent pulmonary metastasectomy for metastatic soft-tissue sarcoma between September 1991 and June 2014; of these, 539 patients undergoing 760 therapeutic-intent pulmonary metastasectomies were included. Clinicopathologic variables and characteristics of treatment were examined. The outcomes of interest were overall survival and disease-free survival. Survival was estimated with the Kaplan-Meier method and compared between variables with the log-rank test. Factors associated with hazard of death and recurrence were identified via the use of univariable and multivariable Cox proportional hazards models. Results Median overall survival was 33.2 months (95% confidence interval, 29.9-37.1), and median disease-free survival was 6.8 months (95% confidence interval, 6.0-8.0). In multivariable analyses, leiomyosarcoma histologic subtype ( P = .007), primary tumor size ≤10 cm ( P = .006), increasing time from primary tumor resection to development of metastases ( P < .001), solitary lung metastasis ( P = .001), and minimally invasive resection ( P = .023) were associated with lower hazard of death. Disease-free interval ≥1 year ( P = .002), and 1 pulmonary metastasis ( P < .001) were associated with lower hazard of disease recurrence. Conclusions In a large single-institution study, primary tumor histologic subtype and size, numbers of pulmonary metastases, disease-free interval, and selection for minimally invasive resection are associated with increased survival in patients undergoing pulmonary metastasectomy for soft-tissue sarcoma.
Objective
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by variable motor and behavioral symptoms attributed to major neuropathology of mainly the basal ...ganglia and cerebral cortex. The role of the cerebellum, a brain region involved in the coordination of movements, in HD neuropathology has been controversial. This study utilizes postmortem human brain tissue to investigate whether Purkinje cell degeneration in the neocerebellum is present in HD, and how this relates to disease symptom profiles.
Methods
Unbiased stereological counting methods were used to quantify the total number of Purkinje cells in 15 HD cases and 8 neurologically normal control cases. Based on their predominant symptoms, the HD cases were categorized into 2 groups: “motor” or “mood.”
Results
The results demonstrated a significant 43% loss of Purkinje cells in HD cases with predominantly motor symptoms, and no cell loss in cases showing a major mood phenotype. There was no significant correlation between Purkinje cell loss and striatal neuropathological grade, postmortem delay, CAG repeat in the IT15 gene, or age at death.
Interpretation
This study shows a compelling relationship between Purkinje cell loss in the HD neocerebellum and the HD motor symptom phenotype, which, together with our previous human brain studies on the same HD cases, provides novel perspectives interrelating and correlating the variable cerebellar, basal ganglia, and neocortical neuropathology with the variability of motor/mood symptom profiles in the human HD brain. ANN NEUROL 2019;85:396–405.
Traditionally regarded to coordinate movement, the cerebellum also exerts non-motor functions including the regulation of cognitive and behavioral processing, suggesting a potential role in ...neurodegenerative conditions affecting cognition, such as Alzheimer's disease (AD). This study aims to investigate neuropathology and AD-related molecular changes within the neocerebellum using post-mortem human brain tissue microarrays (TMAs).
Immunohistochemistry was conducted on neocerebellar paraffin-embedded TMAs from 24 AD and 24 matched control cases, and free-floating neocerebellar sections from 6 AD and 6 controls. Immunoreactivity was compared between control and AD groups for neuropathological hallmarks (amyloid-β, tau, ubiquitin), Purkinje cells (calbindin), microglia (IBA1, HLA-DR), astrocytes (GFAP) basement-membrane associated molecules (fibronectin, collagen IV), endothelial cells (CD31/PECAM-1) and mural cells (PDGFRβ, αSMA).
Amyloid-β expression (total immunolabel intensity) and load (area of immunolabel) was increased by >4-fold within the AD cerebellum. Purkinje cell counts, ubiquitin and tau immunoreactivity were unchanged in AD. IBA1 expression and load was increased by 91% and 69%, respectively, in AD, with no change in IBA1-positive cell number. IBA1-positive cell process length and branching was reduced by 22% and 41%, respectively, in AD. HLA-DR and GFAP immunoreactivity was unchanged in AD. HLA-DR-positive cell process length and branching was reduced by 33% and 49%, respectively, in AD. Fibronectin expression was increased by 27% in AD. Collagen IV, PDGFRβ and αSMA immunoreactivity was unchanged in AD. The number of CD31-positive vessels was increased by 98% in AD, suggesting the increase in CD31 expression and load in AD is due to greater vessel number. The PDGFRβ/CD31 load ratio was reduced by 59% in AD.
These findings provide evidence of molecular changes affecting microglia and the neurovasculature within the AD neocerebellum. These changes, occurring without overt neuropathology, support the hypothesis of microglial and neurovascular dysfunction as drivers of AD, which has implications on the neocerebellar contribution to AD symptomatology and pathophysiology.
•AD-related molecular changes were assessed in human neocerebellum tissue microarray.•Upregulation of amyloid-β with no changes in tau, ubiquitin, or Purkinje cells.•Microglial morphology and protein expression changes, with no change in cell number.•Increased expression of fibronectin with greater number of CD31-positive vessels.•Microglial and neurovascular dysfunction drive neocerebellar AD pathogenesis.
Trials typically group cancers of the gastro-oesophageal junction (GOJ) with oesophageal or gastric cancer when studying neoadjuvant chemoradiation and perioperative chemotherapy, so the results may ...not be fully applicable to GOJ cancer. Because optimal neoadjuvant treatment for GOJ cancer remains controversial, outcomes with neoadjuvant chemoradiation versus chemotherapy for locally advanced GOJ adenocarcinoma were compared retrospectively.
Data were collected from all patients who underwent neoadjuvant treatment followed by surgery for adenocarcinoma located at the GOJ at a single high-volume institution between 2002 and 2017. Postoperative major complications and mortality were compared between groups using Fisher's exact test. Overall survival (OS) and disease-free survival (DFS) were assessed by log rank test and multivariable Cox regression analyses. Cumulative incidence functions were used to estimate recurrence, and groups were compared using Gray's test.
Of 775 patients, 650 had neoadjuvant chemoradiation and 125 had chemotherapy. These groups were comparable in terms of clinical tumour and lymph node categories, although the chemoradiation group had greater proportions of white men, complete pathological response to chemotherapy, and smaller proportions of diffuse cancer, poor differentiation, and neurovascular invasion. Postoperative major complications (20.0 versus 17.6 per cent) and 30-day mortality (1.7 versus 1.6 per cent) were not significantly different between the chemoradiation and chemotherapy groups. After adjustment, type of therapy (chemoradiation versus chemotherapy) was not significantly associated with OS (hazard ratio (HR) 1.26, 95 per cent c.i. 0.96 to 1.67) or DFS (HR 1.27, 0.98 to 1.64). Type of recurrence (local, regional, or distant) did not differ after neoadjuvant chemoradiation versus chemotherapy.
In patients undergoing surgical resection for locally advanced adenocarcinoma of the GOJ, OS and DFS did not differ significantly between patients who had neoadjuvant chemoradiation compared with chemotherapy.
At the time of writing, coronavirus disease-2019 (COVID-19) has affected 6.42 million people globally and over 380,000 deaths, with the United Kingdom now having the highest death rate in Europe. The ...plastic surgery department at Leeds Teaching Hospitals put necessary steps in place to maintain an excellent urgent elective and acute service whilst also managing COVID-positive medical patients in the ward. We describe the structures and pathways implemented together with complex decision-making, which has allowed us to respond early and effectively. We hope these lessons will prove a useful tool as we look to open conversations around the recovery of normal activity.
Highlights • Patients were willing to accept high levels of perioperative mortality risk. • Decisions seemed to be separate from understanding of risk estimates. • Many indicated a preference for ...clinicians to make the treatment decision for them. • There was desire to ‘get rid of cancer’ and perception of no alternative to surgery. • Patients did not believe that adverse outcomes would happen to them.
The established treatment of limited-stage follicular lymphoma is radiotherapy (RT). There is an inherent risk of transformation of follicular lymphoma to aggressive lymphoma; however, the frequency ...and impact on the outcome are unknown in limited-stage patients.
We identified 237 patients with limited-stage follicular lymphoma treated with curative intent RT. Cases were reviewed to determine the frequency of transformation and subsequent survival.
With a median follow-up of 7.4 years, the 10-year risk of transformation was 18.5%. With a median follow-up after transformation of 4.7 years, the 3-year post-transformation progression-free survival (PFS) and overall survival (OS) were 42% and 44%, respectively. The addition of rituximab improved the 3-year post-transformation PFS and OS compared with combination chemotherapy alone (78% versus 15%, P < 0.00001) and (87% versus 38.5%, P < 0.00001), respectively. In multivariate analysis, only rituximab was associated with OS HR 0.07 (95% CI 0.015–0.312, P = 0.001) and PFS HR 0.19 (95% CI 0.55–0.626, P = 0.007) following transformation.
There is a moderate risk of transformation in limited-stage follicular lymphoma treated with curative intent RT, and it substantially impacts outcome in these patients. Treatment with rituximab at the time of transformation appears to improve survival in this otherwise poor-risk population.
Mechanisms of Climate Warming at the End of the Paleocene Bains, Santo; Corfield, Richard M.; Norris, Richard D.
Science (American Association for the Advancement of Science),
07/1999, Letnik:
285, Številka:
5428
Journal Article
Recenzirano
An abrupt episode of global warming marked the end of the Paleocene epoch. Oxygen and carbon isotope records from two widely separated sites support the notion that degassing of biogenic methane ...hydrate may have been an important factor in altering Earth's climate. The data show evidence for multiple injections of methane, separated by intervals in which the carbon cycle was in stasis. Correlations between the two sites suggest that even these small-scale events were global in nature.
The onset of the Palaeocene/Eocene thermal maximum (about 55 Myr
ago) was marked by global surface temperatures warming by 5-7 °C
over approximately 30,000 yr (ref. 1),
probably because of enhanced ...mantle outgassing and the pulsed
release of ∼1,500 gigatonnes of methane carbon from decomposing
gas-hydrate reservoirs. The aftermath of this rapid,
intense and global warming event may be the best example in the geological
record of the response of the Earth to high atmospheric carbon dioxide concentrations
and high temperatures. This response has been suggested to include an intensified
flux of organic carbon from the ocean surface to the deep ocean and its subsequent
burial through biogeochemical feedback mechanisms. Here we
present firm evidence for this view from two ocean drilling cores, which record
the largest accumulation rates of biogenic barium-indicative of export
palaeoproductivity-at times of maximum global temperatures and peak
excursion values of δ13C. The unusually rapid return
of δ13C to values similar to those before the methane
release and the apparent coupling of the accumulation rates
of biogenic barium to temperature, suggests that the enhanced deposition of
organic matter to the deep sea may have efficiently cooled this greenhouse
climate by the rapid removal of excess carbon dioxide from the atmosphere.
We present the initial results of a 3-mm spectral-line survey towards 83 methanol maser-selected massive star-forming regions. Here, we report observations of the J = 5–4 and 6–5 rotational ...transitions of methyl cyanide (CH3CN) and the J = 1–0 transition of HCO+ and H13CO+. CH3CN emission is detected in 58 sources (70 per cent of our sample). We estimate the temperature and column density for 37 of these using the rotational diagram (RD) method. The temperatures we derive range from 28–166 K, and are lower than previously reported temperatures, derived from higher J transitions. We find that CH3CN is brighter and more commonly detected towards ultracompact H ii (UCH ii) regions than towards isolated maser sources. Detection of CH3CN towards isolated maser sources strongly suggests that these objects are internally heated and that CH3CN is excited prior to the UCH ii phase of massive star formation. HCO+ is detected towards 82 sources (99 per cent of our sample), many of which exhibit asymmetric line profiles compared to H13CO+. Skewed profiles are indicative of inward or outward motions, however, we find approximately equal numbers of red- and blue-skewed profiles among all classes. Column densities are derived from an analysis of the HCO+ and H13CO+ line profiles. 80 sources have mid-infrared (mid-IR) counterparts: 68 seen in emission and 12 seen in absorption as ‘dark clouds’. Seven of the 12 dark clouds exhibit asymmetric HCO+ profiles, six of which are skewed to the blue, indicating infalling motions. CH3CN is also common in dark clouds, where it has a 90 per cent detection rate.
PDF
