Current professional standing of young medical oncologists in Spain : a nationwide survey by the Spanish Society of Medical Oncology + MIR section

There is a lack of knowledge about the career paths and employment situation of young medical oncologists. The aim of our study was to evaluate the current professional standing of these professionals in Spain. The Spanish Society of Medical Oncology + MIR section conducted a national online survey in May 2021 of young medical oncology consultants (< 6 years of expertise) and final year medical oncology residents. A total of 162 responses were eligible for analysis and included participants from 16 autonomous communities; 64% were women, 80% were consultants, and 20% were residents. More than half of the participants performed routine healthcare activity and only 7% research activity. Almost three quarters (73%) were subspecialized in a main area of interest and almost half of these chose this area because it was the only option available after residency. Half of the respondents (51%) considered working abroad and 81% believed the professional standing in Spain was worse than in other countries. After finishing their residency, only 22 were offered a job at their training hospital. Just 16% of participants had a permanent employment contract and 87% were concerned (score of ≥ 5 on a scale of 1-10) about their job stability. In addition, one quarter of the participants in our study showed an interest in increasing their research activity. The choice of subspecialty in medical oncology may depend on job opportunities after residency rather than personal interest. The abundance of temporary contracts may have influenced the job stability concerns observed. Future mentoring strategies should engage in building a long-term career path for young medical oncologists. The online version contains supplementary material available at 10.1007/s12094-022-02989-3

Evaluating radiological response in pancreatic neuroendocrine tumours treated with sunitinib : comparison of Choi versus RECIST criteria (CRIPNET_ GETNE1504 study)

The purpose of our study was to analyse the usefulness of Choi criteria versus RECIST in patients with pancreatic neuroendocrine tumours (PanNETs) treated with sunitinib. A multicentre, prospective study was conducted in 10 Spanish centres. Computed tomographies, at least every 6 months, were centrally evaluated until tumour progression. One hundred and seven patients were included. Median progression-free survival (PFS) by RECIST and Choi were 11.42 (95% confidence interval [CI], 9.7-15.9) and 15.8 months (95% CI, 13.9-25.7). PFS by Choi (Kendall's τ = 0.72) exhibited greater correlation with overall survival (OS) than PFS by RECIST (Kendall's τ = 0.43). RECIST incorrectly estimated prognosis in 49.6%. Partial response rate increased from 12.8% to 47.4% with Choi criteria. Twenty-four percent of patients with progressive disease according to Choi had stable disease as per RECIST, overestimating treatment effect. Choi criteria predicted PFS/OS. Changes in attenuation occurred early and accounted for 21% of the variations in tumour volume. Attenuation and tumour growth rate (TGR) were associated with improved survival. Choi criteria were able to capture sunitinib's activity in a clinically significant manner better than RECIST; their implementation in standard clinical practice shall be strongly considered in PanNET patients treated with this drug

Dysregulation of splicing variants and spliceosome components in breast cancer.

The dysregulation of the splicing process has emerged as a novel hallmark of metabolic and tumor pathologies. In breast cancer (BCa), which represents the most diagnosed cancer type among women worldwide, the generation and/or dysregulation of several oncogenic splicing variants have been described. This is the case of the splicing variants of HER2, ER, BRCA1, or the recently identified by our group, In1-ghrelin and SST5TMD4, which exhibit oncogenic roles, increasing the malignancy, poor prognosis, and resistance to treatment of BCa. This altered expression of oncogenic splicing variants has been closely linked with the dysregulation of the elements belonging to the macromolecular machinery that controls the splicing process (spliceosome components and the associated splicing factors). In this review, we compile the current knowledge demonstrating the altered expression of splicing variants and spliceosomal components in BCa, showing the existence of a growing body of evidence supporting the close implication of the alteration in the splicing process in mammary tumorigenesis

Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli

Although protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin-like deacetylase, and patZ, the best-known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified. Nearly 65%of these proteins are related to metabolism. The global activity of CobB contributes to the deacetylation of a large number of substrates and has a major impact on physiology. Apart from the regulation of acetyl-CoA synthetase, we found that CobB-controlled acetylation of isocitrate lyase contributes to the fine-tuning of the glyoxylate shunt. Acetylation of the transcription factor RcsB prevents DNA binding, activating flagella biosynthesis and motility, and increases acid stress susceptibility. Surprisingly, deletion of patZ increased acetylation in acetate cultures, which suggests that it regulates the levels of acetylating agents. The results presented offer new insights into functional roles of protein acetylation in metabolic fitness and global cell regulation

Evaluating radiological response in pancreatic neuroendocrine tumours treated with sunitinib: comparison of Choi versus RECIST criteria (CRIPNET_ GETNE1504 study)

[Background] The purpose of our study was to analyse the usefulness of Choi criteria versus RECIST in patients with pancreatic neuroendocrine tumours (PanNETs) treated with sunitinib. [Method] A multicentre, prospective study was conducted in 10 Spanish centres. Computed tomographies, at least every 6 months, were centrally evaluated until tumour progression. [Results] One hundred and seven patients were included. Median progression-free survival (PFS) by RECIST and Choi were 11.42 (95% confidence interval [CI], 9.7–15.9) and 15.8 months (95% CI, 13.9–25.7). PFS by Choi (Kendall’s τ = 0.72) exhibited greater correlation with overall survival (OS) than PFS by RECIST (Kendall’s τ = 0.43). RECIST incorrectly estimated prognosis in 49.6%. Partial response rate increased from 12.8% to 47.4% with Choi criteria. Twenty-four percent of patients with progressive disease according to Choi had stable disease as per RECIST, overestimating treatment effect. Choi criteria predicted PFS/OS. Changes in attenuation occurred early and accounted for 21% of the variations in tumour volume. Attenuation and tumour growth rate (TGR) were associated with improved survival. [Conclusion] Choi criteria were able to capture sunitinib’s activity in a clinically significant manner better than RECIST; their implementation in standard clinical practice shall be strongly considered in PanNET patients treated with this drug

Patients with Crohn's disease have longer post-operative in-hospital stay than patients with colon cancer but no difference in complications' rate

BACKGROUNDRight hemicolectomy or ileocecal resection are used to treat benign conditions like Crohn's disease (CD) and malignant ones like colon cancer (CC).AIMTo investigate differences in pre- and peri-operative factors and their impact on post-operative outcome in patients with CC and CD.METHODSThis is a sub-group analysis of the European Society of Coloproctology's prospective, multi-centre snapshot audit. Adult patients with CC and CD undergoing right hemicolectomy or ileocecal resection were included. Primary outcome measure was 30-d post-operative complications. Secondary outcome measures were post-operative length of stay (LOS) at and readmission.RESULTSThree hundred and seventy-five patients with CD and 2,515 patients with CC were included. Patients with CD were younger (median = 37 years for CD and 71 years for CC (P &lt; 0.01), had lower American Society of Anesthesiology score (ASA) grade (P &lt; 0.01) and less comorbidity (P &lt; 0.01), but were more likely to be current smokers (P &lt; 0.01). Patients with CD were more frequently operated on by colorectal surgeons (P &lt; 0.01) and frequently underwent ileocecal resection (P &lt; 0.01) with higher rate of de-functioning/primary stoma construction (P &lt; 0.01). Thirty-day post-operative mortality occurred exclusively in the CC group (66/2515, 2.3%). In multivariate analyses, the risk of post-operative complications was similar in the two groups (OR 0.80, 95%CI: 0.54-1.17; P = 0.25). Patients with CD had a significantly longer LOS (Geometric mean 0.87, 95%CI: 0.79-0.95; P &lt; 0.01). There was no difference in re-admission rates. The audit did not collect data on post-operative enhanced recovery protocols that are implemented in the different participating centers.CONCLUSIONPatients with CD were younger, with lower ASA grade, less comorbidity, operated on by experienced surgeons and underwent less radical resection but had a longer LOS than patients with CC although complication's rate was not different between the two groups

The impact of stapling technique and surgeon specialism on anastomotic failure after right?sided colorectal resection: an international multicentre, prospective audit

Aim There is little evidence to support choice of technique and configuration for stapled anastomoses after right hemicolectomy and ileocaecal resection. This study aimed to determine the relationship between stapling technique and anastomotic failure. Method Any unit performing gastrointestinal surgery was invited to contribute data on consecutive adult patients undergoing right hemicolectomy or ileocolic resection to this prospective, observational, international, multicentre study. Patients undergoing stapled, side?to?side ileocolic anastomoses were identified and multilevel, multivariable logistic regression analyses were performed to explore factors associated with anastomotic leak. Results One thousand three hundred and forty?seven patients were included from 200 centres in 32 countries. The overall anastomotic leak rate was 8.3%. Upon multivariate analysis there was no difference in leak rate with use of a cutting stapler for apical closure compared with a noncutting stapler (8.4% vs 8.0%, OR 0.91, 95% CI 0.54–1.53, P = 0.72). Oversewing of the apical staple line, whether in the cutting group (7.9% vs 9.7%, OR 0.87, 95% CI 0.52–1.46, P = 0.60) or noncutting group (8.9% vs 5.7%, OR 1.40, 95% CI 0.46–4.23, P = 0.55) also conferred no benefit in terms of reducing leak rates. Surgeons reporting to be general surgeons had a significantly higher leak rate than those reporting to be colorectal surgeons (12.1% vs 7.3%, OR 1.65, 95% CI 1.04–2.64, P = 0.04). Conclusion This study did not identify any difference in anastomotic leak rates according to the type of stapling device used to close the apical aspect. In addition, oversewing of the anastomotic staple lines appears to confer no benefit in terms of reducing leak rates. Although general surgeons operated on patients with more high?risk characteristics than colorectal surgeons, a higher leak rate for general surgeons which remained after risk adjustment needs further exploration

Relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit

Aim: The anastomosis technique used following right-sided colonic resection is widely variable and may affect patient outcome. This study aimed to assess the association between leak and anastomosis technique (stapled vs handsewn). Method: This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a 2-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30\ua0days of surgery, determined using a prespecified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random-effect variable. Results: This study included 3208 patients, of whom 78.4% (n\ua0=\ua02515) underwent surgery for malignancy and 11.7% (n\ua0=\ua0375) underwent surgery for Crohn's disease. An anastomosis was performed in 94.8% (n\ua0=\ua03041) of patients, which was handsewn in 38.9% (n\ua0=\ua01183) and stapled in 61.1% (n\ua0=\ua01858). Patients undergoing handsewn anastomosis were more likely to be emergency admissions (20.5% handsewn vs 12.9% stapled) and to undergo open surgery (54.7% handsewn vs 36.6% stapled). The overall anastomotic leak rate was 8.1% (245/3041), which was similar following handsewn (7.4%) and stapled (8.5%) techniques (P\ua0=\ua00.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted OR\ua0=\ua01.43; 95% CI: 1.04\u20131.95; P\ua0=\ua00.03). Conclusion: Despite being used in lower-risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe