Survival After Recurrent Esophageal Carcinoma Has Not Improved Over the Past 18 Years

Background

Numerous patients will develop recurrent disease after esophagectomy for esophageal carcinoma (EC). In literature, survival after recurrent EC is poor with 6–8 months. In these studies, diagnostic imaging during follow-up (FU) is routinely performed. In the Netherlands, routine imaging is not part of FU and only performed on indication. The aim of this study was to determine survival after diagnosis of recurrent disease in patients after esophagectomy without routine imaging during FU.

Methods

All EC patients who underwent esophagectomy between 1993 and 2010 were included and followed for clinical evidence of recurrent EC. Location, symptoms, diagnosis, and treatment of recurrent disease were registered. Pattern of recurrence was compared between patients who underwent neoadjuvant therapy and patients who underwent surgery alone. Survival after detection of recurrence was determined in all patients and related to the year of surgery.

Results

A total of 493 of 1,088 patients (45 %) who underwent esophagectomy between 1993 and 2010 developed recurrent disease. Median interval between esophagectomy and recurrence was 10.5 months. Within the first 2 years after surgery, 33 % of patients developed recurrent EC. The majority of patients (51 %) were diagnosed with distant metastases. Locoregional recurrence occurred significantly less often among patients who underwent neoadjuvant therapy (6 vs 16 %, p = .017). Median survival after diagnosis of recurrent disease was 3 months. No relation was observed between the year of surgery and survival after recurrent disease (p = .931).

Conclusions

Survival after recurrent EC in patients who undergo FU without routine imaging after esophagectomy is approximately 3 months and has not improved over the past 18 years.     

Super‐resolution methods in MRI: Can they improve the trade‐off between resolution,signal‐to‐noise ratio,and acquisition time?

Improving the resolution in magnetic resonance imaging comes at the cost of either lower signal‐to‐noise ratio, longer acquisition time or both. This study investigates whether so‐called super‐resolution reconstruction methods can increase the resolution in the slice selection direction and, as such, are a viable alternative to direct high‐resolution acquisition in terms of the signal‐to‐noise ratio and acquisition time trade‐offs. The performance of six super‐resolution reconstruction methods and direct high‐resolution acquisitions was compared with respect to these trade‐offs. The methods are based on iterative back‐projection, algebraic reconstruction, and regularized least squares. The algorithms were applied to low‐resolution data sets within which the images were rotated relative to each other. Quantitative experiments involved a computational phantom and a physical phantom containing structures of known dimensions. To visually validate the quantitative evaluations, qualitative experiments were performed, in which images of three different subjects (a phantom, an ex vivo rat knee, and a postmortem mouse) were acquired with different magnetic resonance imaging scanners. The results show that super‐resolution reconstruction can indeed improve the resolution, signal‐to‐noise ratio and acquisition time trade‐offs compared with direct high‐resolution acquisition. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis

Hip osteoarthritis (HOA) is one of the most disabling and common joint disorders with a large genetic component that is, however, still ill-defined. To date, genome-wide association studies (GWAS) in osteoarthritis (OA) and specifically in HOA have yielded only few loci, which is partly explained by heterogeneity in the OA definition. Therefore, we here focused on radiographically measured joint-space width (JSW), a proxy for cartilage thickness and an important underlying intermediate trait for HOA. In a GWAS of 6,523 individuals on hip-JSW, we identified the G allele of rs12982744 on chromosome 19p13.3 to be associated with a 5% larger JSW (P = 4.8 × 10(-10)). The association was replicated in 4,442 individuals from three United Kingdom cohorts with an overall meta-analysis P value of 1.1 × 10(-11). The SNP was also strongly associated with a 12% reduced risk for HOA (P = 1 × 10(-4)). The SNP is located in the DOT1L gene, which is an evolutionarily conserved histone methyltransferase, recently identified as a potentially dedicated enzyme for Wnt target-gene activation in leukemia. Immunohistochemical staining of the DOT1L protein in mouse limbs supports a role for DOT1L in chondrogenic differentiation and adult articular cartilage. DOT1L is also expressed in OA articular chondrocytes. Silencing of Dot1l inhibited chondrogenesis in vitro. Dot1l knockdown reduces proteoglycan and collagen content, and mineralization during chondrogenesis. In the ATDC5 chondrogenesis model system, DOT1L interacts with TCF and Wnt signaling. These data are a further step to better understand the role of Wnt-signaling during chondrogenesis and cartilage homeostasis. DOT1L may represent a therapeutic target for OA.     

Elevated albuminuria associated with increased risk of recurrent venous thromboembolism: results of a population-based cohort study

This study examined the risk of recurrent venous thromboembolism (VTE) in patients with elevated albuminuria. In 1997-1998, inhabitants of Groningen, the Netherlands, aged 28-75 years (n=85,421), were invited to participate in the PREVEND (Prevention of REnal and Vascular ENd stage Disease) Study, an observational, population-based cohort study. Albuminuria was measured and VTE occurrence was monitored in responding subjects (n=40,856). Patients with first VTE between study entry and January 2009, identified through databases of the national registry of hospital discharge diagnoses, death certificates, regional anticoagulation clinic and medical records, were used for analysis. Of 351 subjects with first VTE, 37 subjects developed a recurrence during a median follow-up period of 3.3 (interquartile range, 1.1-6.4) years. The annual incidence of recurrence in subjects with elevated albuminuria (≥ 20 mg/l) was 5.00% [95% confidence interval (CI); 2.16-9.85], compared to 2.38% (95%CI; 1.59-3.41) in subjects with normal albuminuria (<20 mg/l). Hazard ratio for recurrence was 1.95 (95%CI; 0.89-4.30) after adjustment for age and sex. This hazard ratio was 3.35 (95%CI; 1.18-9.47) in patients with first unprovoked, and 1.12 (95%CI; 0.25-5.01) in those with a first provoked event. This study showed that subjects with elevated albuminuria who experience an unprovoked VTE are at an increased risk of recurrence, independent of age and sex.     

Trapped in my lungs and fighting a losing battle. A phenomenological study of patients living with chronic obstructive and pulmonary disease

Chronic obstructive and pulmonary disease (COPD) has detrimental effects on individuals with the disease. COPD causes breathlessness, morbidity and associated psychosocial distress. This study was guided by the phenomenological question what is it like to have COPD and situated in Van Manen's phenomenology of practice. Experiential material was gathered through phenomenological interviews. Four themes emerged from the lived experiences of patients living with COPD: breath as a possibility; being vigilant; fighting a losing battle; and feeling isolated from others. For patients with COPD, breathing becomes ever-present and shifts from the invisible background of daily living to the central activity around which everyday life is organised. COPD patients always monitor their own breath and scrutinise the environment on possible dangers that can affect their breathing. Whenever moving or being involved in an activity, a part of their mind is preoccupied with the breathing. Although COPD patients realise that no amount of good behaviour will matter and that the decline of their lungs is inevitable, they make every effort to take good care of their body. They anticipate and avoid triggers of breathlessness isolating them from social interactions and activities. The appearance of the body as a source of social embarrassment also has an isolating effect. This study shows that breathlessness is a constant horizon that frames the experience of COPD patients. It is a limiting factor and determines their entire life. A more profound understanding of these experiences in healthcare professionals will contribute to person-centred care for COPD patients.     

Divergent chemokine receptor expression and the consequence for human IgG4 B cell responses

IgG4 antibodies are unique to humans. IgG4 is associated with tolerance during immunotherapy in allergy, but also with pathology, as in pemphigus vulgaris and IgG4-related disease. Its induction is largely restricted to nonmicrobial antigens, and requires repeated or prolonged antigenic stimulation, for reasons poorly understood. An important aspect in generating high-affinity IgG antibodies is chemokine receptor-mediated migration of B cells into appropriate niches, such as germinal centers. Here, we show that compared to IgG1 B cells, circulating IgG4 B cells express lower levels of CXCR3, CXCR4, CXCR5, CCR6, and CCR7, chemokine receptors involved in GC reactions and generation of long-lived plasma cells. This phenotype was recapitulated by in vitro priming of naive B cells with an IgG4-inducing combination of T_FH/T_H2 cytokines. Consistent with these observations, we found a low abundance of IgG4 B cells in secondary lymphoid tissues in vivo, and the IgG4 antibody response is substantially more short-lived compared to other IgG subclasses in patient groups undergoing CD20⁺ B cell depletion therapy with rituximab. These results prompt the hypothesis that factors needed to form IgG4 B cells restrain at the same time the induction of a robust migratory phenotype that could support a long-lived IgG4 antibody response.