bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of SUMOylation modulates the immunosuppressive microenvironment of pancreatic cancer
Authors: Erdem S , Narayanan J S , Mohottige Don N , Worni M , White R R , Chen Y 
Published: June 2022

Abstract

Objective
Pancreatic cancer (PC) is a highly aggressive disease that is poorly responsive to available immunotherapy approaches, such as checkpoint inhibitors. Post-translational protein modification (PTM) by small ubiquitin-like modifier (SUMO) is upregulated in cancer, and high expression of SUMOylation-related factors correlates with poor survival in PC. TAK-981 is a novel inhibitor of SUMOylation that has demonstrated induction of anti-tumor immune responses in preclinical models. Our hypothesis is that TAK-981 will decrease SUMOylated proteins and subsequently modulate the tumor microenvironment to increase anti-tumor immunity.

Methods
In order to recapitulate the microenvironment of human PC, a 3-dimensional organoid cell line derived from a genetically-engineered “KPC” mouse was used. Organoids were injected orthotopically into the head of the pancreas via laparotomy. Once tumors reached 5–7 mm in diameter on ultrasound imaging, mice were randomized to one of two treatment groups: Control/Vehicle versus TAK-981 (15 mg/kg) delivered daily via intraperitoneal injection. Tumors were harvested on day 14 for gene expression analysis by quantitative real time PCR (RT-qPCR).

Results
Tumor growth (Fig. 1) in the TAK-981 15 mg/KG daily group (mean + SD volume = 207 + 109 mm3) was significantly inhibited compared to the vehicle group (595 + 141 mm3, p &lt; 0.01). Immunohistochemical staining for CD 31 (Fig. 2) and Caspase 3 indicated a reduction of angiogenesis and increased apoptosis of tumor cells, consistent with the well-established roles of SUMOylation in angiogenesis and tumorigenesis. Gene expression analysis of tumor lysates showed a 26-fold increase in expression of Interferon beta (p&lt;0.05), and an almost 2-fold increase in expression of genes related to dendritic cell activation, including CD80 (p&lt;0.05) and CD86 (p=0.14) in the TAK-981 group, suggesting a modulation of the immune microenvironment.

Conclusion
Our results suggest that the inhibition of SUMOylation with TAK-981 is associated with improved local tumor control and changes in the immunosuppressive tumor microenvironment. We expect that TAK-981 will improve PC responsiveness to immunotherapy, such as with checkpoint inhibitors.
Systematic review on the use and management of drainages in pancreatic surgery
Authors: Pietrogiovanna L , Canovi S , Probst P , Hauswirth F , Müller M K , Renzulli P 
Published: June 2022

Abstract

Objective
The use of drains in pancreatic surgery, both in distal pancreatectomy (DP) and partial pancreaticoduodenectomy (PD) is controversial. The aim of this meta-analysis was to assess the potential benefit of drainage use in pancreatic surgery on postoperative outcomes.

Methods
A systematic literature search was performed in MEDLINE, Web of Science and CENTRAL. All RCTs investigating the use and management of any drainage in patients undergoing pancreatectomy were included. Data on mortality, postoperative complications and length of hospital stay (LOS) were analysed. A random-effects model for Mantel-Haenzsel and inverse variance analysis was used. Cochrane RoB 2.0 tool and GRADE approach was used for assessment of risk of bias and certainty of evidence.

Results
Ten RCTs investigating drainage vs no drainage, timing of drainage removal or type of drainage in PD such as DP with a total of 2004 patients were included. Drainage vs no drainage: Three RCTs (two with PD and DP, one with PD only). Neither mortality (OR 1.57, 95%-CI: 0.62 to 3.93 p=0.34) nor overall complications (OR 0.88, 95%-CI: 0.71 to 1.08, p=0.21) differed between both groups (certainty of evidence: low). However, one trial was stopped prematurely because of higher 90-day mortality in the no drainage group. Early vs late drainage removal: Four RCTs (two with PD and DP, two with PD only). Early drain removal resulted in both a significant reduction of chyle leak (OR 0.22, 95%-CI: 0.06 to 0.59, p&lt;0.01) as well as a shortening of LOS (mean difference -2.64 days, 95%CI: -4.63 to -0.65, p&lt;0.01). For both outcomes the certainty of evidence was moderate. Mortality, postoperative pancreatic fistula and hemorrhage showed no difference between early vs late drainage removal (certainty of evidence: low). Active vs passive drainage: Three RCTs (one with PD and DP, two with PD only). None of the studies found any significant difference in outcome with regard to the type of drainage.

Conclusion
There is no evidence that drainages after pancreatic surgery should be standard of care. However, there is also no evidence that placing a drain leads to worse outcomes. If a drainage is used it should be removed early to avoid chyle leak and accelerate hospital discharge.
Prevention and management of anastomotic leakage after colorectal surgery: A Swiss national consensus
Authors: Lázaro-Fontanet E , Clerc D , Girardin T , Martin D , Hübner M , Hahnloser D 
Published: June 2022

Abstract

Objective
Anastomotic leakage (AL) is one of the most feared complications of colorectal surgery. Despite surgical improvements, AL incidence remains significant and guidance on its prevention and management is lacking. The aim of the study was to achieve a Swiss nationwide consensus on clinical prevention and management of AL.

Methods
A three-step Delphi consensus meeting was performed in 2020 involving 78 Swiss surgeons from 40 centers. A steering-group drafted the questions, gathered best available evidence which was discussed in meetings prior answering the questions. Consensus was defined as ≥70% of agreement.

Results
The three consensus meetings were attended by 66, 57 and 37 surgeons, respectively. Surgeons’ median experience was 14 years, with 47% performing &gt;50 colorectal resections yearly. Consensus was reached on routine use of preoperative nutritional screening (100%) using nutritional scores (88%) and &gt;10% weight loss (95%). but not low BMI (63%) or low albumin (64%). Consensus was reached for no bowel preparation (BP) prior to right colectomy (RC) (76%) and for mechanical BP with oral antibiotics prior anterior resections (AR) (70%). No consensus was found on BP prior left colectomy (LC). Respondents favored a side-to-side anastomosis (76%) after RC, with extra-corporeal confection (70%), without consensus on the anastomosis being stapled or hand-sewn; an end-to-end (73%), stapled (80%) anastomosis after LC and a stapled anastomosis (86%) after AR, irrespective of the anastomosis configuration type. Anastomotic control with transanal leak-test was supported by 92%, while ICG control did not reached consensus (67%). After TME, routine diversion was favored (73%), irrespective of neoadjuvant therapy (94%) or not (70%). Consensus was reached on routine postoperative CRP monitoring (94%). CT-scan with rectal contrast enema was the preferred investigation for suspected AL after RC or LC (82%) and AR (76%). Conservative management of AL, provided appropriate clinical state, was an acceptable option after LC (72%), AR with stoma (95%), but not after RC (59%) or AR without stoma (53%).

Conclusion
Consensus was reached on several clinical aspects for prevention and management of AL among Swiss colorectal surgeons, providing national guidance. Further data is required on intraoperative aspects of anastomosis confection and control to ensure broader consensus.
Combined expression of fascin-1 and MAP17 in colorectal cancer: A group of patients in high risk
Authors: Tampaki E C , Nonni A , von Flüe M , Felekouras E , Nikiteas N , Tampakis A 
Published: June 2022

Abstract

Objective
Fascin and MAP17 are two well-known stem cell markers that have been previously shown to be associated with aggresive clinical features in cancer. This study aimed to assess their expression patterns and clinical significance in colorectal cancer.

Methods
Immunohistochemistry was used to assess the expression of fascin-1 and MAP17 in 111 specimens from patients with primary resectable colorectal cancer. Results were correlated with clinicopathological characteristics and survival data.

Results
Fascin-1 and MAP17 expression levels were associated with progressive anatomic disease extent (p=0.005), higher T classification (p=0.033), lymph node metastasis (p=0.002), high grade tumors (p=0.002), and vascular invasion (p=0.021). All patients with combined high fascin-1 and MAP17 expression died within 46 months after surgery, whereas patients with low fascin-1 and MAP17 expression had an excellent 5-year overall survival rate of 92.8% (95% CI: 83–98). Concerning 3-year PFS, only 14.3% (95%CI: 11–30) of patients with combined high expression of both biomarkers did not experience recurrence or death within 30 months of surgery.

Conclusion
Conclusions; Combined high expression of fascin-1 and MAP17 identifies a group of patiens with poor early overall survival, indicating therefore targeted therapy's necessity.
A pilot, prospective, observational study to investigate the value of NGS liquid biopsies to predict tumor response after neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer: The LiBReCa study
Authors: Roesel R , Epistolio S , Saletti P , De Dosso S , Valli M , Franzetti-Pellanda A , Deantonio L , Bigioggero M , Spina P , Popeskou S G , Mongelli F , Frattini M , Christoforidis D 
Published: June 2022

Abstract

Objective
Circulating tumor DNA (ctDNA) has been shown to correlate with therapy response in different types of cancer.Little is known about the value of liquid biospies in locally advanced rectal cancer (LARC) to select patients for non-operative management. Our aim was to explore the value of serial liquid biopsies for response monitoring after neo-adiuvant chemoradiation therapy (nCRT) in LARC.

Methods
Twenty-five consecutive LARC patients undergoing long course nCRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded tissue (diagnostic biopsy and surgical specimen)and from plasma ctDNA collected at different time points: on the first and last day of radiotherapy (T0, Tend), at 4 (T4), 7 (T7) weeks after radiotherapy, at the day of surgery (Top) prior to resection, and 3–7 days after surgery (Tpost-op). At the day of surgery a mesenteric vein sample was also collected (Timv). The relationship between the ctDNA at those time-points and the Tumor Regression Grade (TRG) of the surgical specimen was statistically explored.

Results
ctDNA was detected in 87% of samples at baseline but only in 13%, 10%, 25% and 17% at T4, T7, Top and Tpost-op respectively. Pathological complete response (TRG1) was not statistically associated with gradual negativization of ctDNA mutations in plasma samples obtained in the aforementioned time points compared to tissue biopsy. However a positive liquid biopsy at Top was significantly associated to no response to nCRT (TRG 4) .

Conclusion
ctDNA evaluation by NGS technology was not a good marker for defining LARC patients that are more prone to develop complete response to nCRT, however persistence of ctDNA molecular alterations after this treatment could be a marker of poor-response.
Impact of gut microbiota and immune contexture on effectiveness of neo-adjuvant chemo-radiotherapy in locally advanced rectal cancer (LARC)
Authors: Roesel R , Basso C , Epistolio S , Djordjevic J , Sorrenti E , Terzaghi L , Galafassi J , Spina P , Popeskou S G , Mongelli F , Frattini M , Iezzi G , Christoforidis D 
Published: June 2022

Abstract

Objective
Among patients affected by Locally Advanced Rectal Cancer (LARC), 15–20% ultimately reveal a complete pathological response to the neo-adjuvant chemo-radiotherapy nCRT), which might render the surgical resection no longer necessary. However, the possibility to adopt alternative management options, such as a “wait and see” strategy, is hampered by the lack of reliable indicators of complete responsiveness to nCRT. Our hypothesis is that the composition of LARC-associated microbiome and immune contexture may predict the responsiveness to nCRT. We therefore proceed to a quantitative and qualitative evaluation of gut microbiome composition and immune contexture in LARC bioptic tissues and we then comparatively evaluated those markers in complete responders (Tumor regression grade, TRG,1) versus others (TRG2-3-4).

Methods
FFPE (Formalin Fixed Paraffin Embedded) LARC tissues from diagnostic biopsies and corresponding resections from patients treated at our hospital from 2012 to December 2019 were collected. Following sample deparaffinization, n. 71 genomic DNA (gDNA) and total cellular RNA were extracted. DNA used for microbiome analysis, upon amplification and sequencing of the hypervariable V3-V4 region of 16S gene. Expression of immune cell genes was evaluated by the Nanostring PanCancer Immune profiling panel on extracted RNA.

Results
Regarding the Microbiome profile we found no difference in terms of biodiversity between complete responders and others. However, we found some species significantly disregulated, in particular an over-expression of Alloprevotella Rava and down-expression of Porphyromonas Asaccharolytica, Turicibacter Sanguinis, Leptotrichia Trevisanii, Fusobacterium Nucleatum. The immune contexture analysis revealead a significant disregulation of 41 genes.

Conclusion
FFPE tissues from diagnostic biopsies proved suitable for the analysis of LARC-associated microbiome and immune contexture.
A specific microbiome signature appears to be associated with responsiveness to neo-adjuvant chemoradiotherapy. Defined immune related genes, in particular those associated with IFN-gamma response, are up-regulated in tumors exhibiting complete response. A possible associations between the bacterial species significantly disregulated and this favorable immune contexture is currently under investigation.
Risk factors for chronic postsurgical pain in visceral surgery: A matched case-control analysis
Authors: Perrodin S , Trinh W-H , Streitberger K , Di Pietro Martinelli C , Holzgang M , Candinas D , Beldi G 
Published: June 2022

Abstract

Objective
Chronic postsurgical pain (CPSP) is defined as new and persisting pain three months after a surgical procedure, whereby other causes of pain have been excluded. Although CPSP following orthopedic or gynecological surgery has been well investigated, we are lacking data for patients undergoing abdominal visceral surgery. We aim to identify the risk factors for CPSP in this patient population.

Methods
We performed a retrospective case-control matched analysis including all patients diagnosed with CPSP after abdominal visceral surgery between 2016 and 2019, matched to a control group of patients who did not develop CPSP. Excluded were patients for whom no follow-up was available 3 months or more after surgery. Two-to-one case-control matching was based on operation category (hepato-pancreatico-biliary, upper gastrointestinal, colorectal, transplantation, bariatric and others) and date of surgery. The influence of personal, surgical and pain management factors were explored and multivariate logistic regression analysis was performed.

Results
176 patients were diagnosed with CPSP during the study period. They were matched to a sample of 394 control patients extracted from the cohort of 3554 patients without CPSP. The incidence proportion of CPSP was 4.7%. Multivariate logistic regression analysis showed that age under 65 years (OR 2.22, CI 1.34-3.69, p=0.002), preexisting chronic pain of any origin (OR 3.39, CI 2.04-5.62, p=0.000), previous abdominal surgery (OR 1.71, CI 1.07-2.71, p=0.024), acute postoperative pain (2.62, CI 1.55-4.42, p=0.000) and length of stay over three days (OR 2.11, CI 1.26-3.53, p=0.004) were independent risk factors for CPSP. Preoperative Pregabalin intake was protective (OR 0.04, CI 0.01-0.33, p=0.003).

Conclusion
The identification of these risk factors allows for a preventive and personalized health care approach to our at-risk patients, for whom the optimization of postoperative acute pain management and an additional follow-up consultation 3 months after surgery might be indicated to avoid a delay in diagnosing CPSP. A possible explanation for the protective effect of Pregabalin is that in these patients, preexisting chronic pain might be better controlled in the preoperative phase, and they might have additional follow-up in the postoperative phase, be it from a pain specialist or their general practitioner.
Low-energy fractures of the pelvis in the elderly and mortality
Authors: Ramser M 
Published: June 2022

Abstract

Objective
While the prognostic impact of hip fractures in the elderly is widely accepted, the risk and excess mortality associated with pelvic fragility fractures is still underestimated and receives considerably less attention. Morbidity and mortality might thereby be related to fracture morphology and/or patient characteristics. The aim of this project is to investigate the prognostic value of specific fracture characteristics with respect to overall survival and to compare it with an established classification system.

Methods
Retrospective analysis of patients ≥60 years, treated conservatively for a CT-scan verified, low-energy pelvic ring fracture diagnosed between August 2006 and December 2018. Survival data was available from patients’ charts and cantonal or national registries.
The prognostic value of fracture characteristic describing the anterior and posterior involvement of the pelvic ring was investigated. This analysis was repeated after patients were stratified into a high-risk vs a low-risk group according to patient characteristic (age, gender, comorbidities, mobility, living situation). This allowed to assess the impact of the different fracture morphologies on mortality in fit vs. frail senior patients separately

Results
Overall, 428 patients (83.4% female) with a mean age of 83.7 years were included. Two thirds of patients were still living in their home and mobile without walking aid at baseline. In-hospital mortality was 0.7%, overall, one-year mortality 16.9%. An independent and significant association of age, gender and comorbidities to overall survival was found. Further, the occurrence of a horizontal sacral fracture as well as a ventral comminution or dislocation was associated with an increased mortality. The effect of a horizontal sacral fracture was more accentuated in low-risk patients while the ventral fracture components showed a larger effect on survival in high-risk patients. No association of the FFP classification with survival was observed.

Conclusion
Specific fracture characteristics such as horizontal sacral fracture, comminuted and dislocated ventral fractures may indicate a higher mortality risk of patients with a pelvic fragility fracture. Hence, they should be taken into account in future treatment algorithms and decisions on patient management.
Time to treatment initiation: An analysis of sarcoma patients treated at Multidisciplinary-Team/Sarcoma-Board (MDT/SB's) over a four-year period
Authors: Schärer M , Heesen P , Theus-Steinemann C , Bode B , Fuchs B 
Published: June 2022

Abstract

Objective
It is hypothesized that in the treatment of patients with soft tissue sarcomas (STS) the interval from establishing the diagnosis until initiation of treatment is relevant for the overall survival. Therefore, time to treatment initiation (TTI) was defined as a quality indicator for monitoring the treatment standard. The primary objective of this study was to find out how long (in days) it takes from establishing the sarcoma diagnosis through biopsy until initiation of treatment in patients suffering from STS. Secondary objectives were defined as the comparison between the different dignities, the different institutions and how the Swiss Sarcoma Network (SSN) cohort compares to the international standard.

Methods
This is a retrospective analysis of prospectively collected data from the SSN. All patients being presented to the MDT/SB within a four-year period from 2018 to 2022 were included in this study. TTI and secondary objectives were determined using non-parametric summary statistics and presented as median and interquartile range. Ethic approval was granted for this study.

Results
In total 383 patients were recorded in the respective time period in the SSN. In this study 278 patients with a malignant or intermediate STS according to WHO2020 were included. There were 66% (n=185) with a malignant and 44% (n=93) with an intermediate STS. The median TTI was 23 (8-52) days. In the malignant group, the median TTI was 21 (5-43) days and in the intermediate group 32 (11-59) days. In the different institutions the median TTI's were 10 (-6-30), 28 (12-78), 24 (10-58), 24 (10-53) and 12 (-12-54) days.

Conclusion
In the SSN cohort the overall median TTI was 23 days. In the literature, a TTI delay of more than 42 days led to a slightly reduced overall survival. Compared to the international standard, we conclude that within the SSN network, patients face an adequate waiting time until treatment initiation with no potential restrictions to overall survival.
Electrocautery smoke exposure and smoke evacuation in thoracic surgery: A prospective randomized study
Authors: Kocher G J , Dorn P , Hutterli M , Koss A 
Published: June 2022

Abstract

Objective
Worldwide, health care professionals working in operating rooms (ORs) are exposed to electrocautery smoke on a daily basis.
Aims of this study were to determine the composition and concentrations of electrocautery smoke in the OR using mass spectrometry and investigate whether smoke evacuation systems, operative technique and distance to the cautery source are effective in reducing exposure.

Methods
Single-center study at our thoracic surgical unit including 122 surgical procedures. Besides room air measurements away from the operating table (n=35) and direct breath analysis (n=3), 84 minimally invasive and open procedures were in each group 1:1 computer randomized to smoke evacuation system (SES) versus no SES use and hazardous compounds were measured at the height of the operating surgeons respiratory tract.

Results
Irritating, toxic, carcinogenic and mutagenic volaticle organic compounds (VOCs) were observed in OR air, with some exceeding permissible exposure limits (OSHA/NIOSH). Mean total concentration of harmful compounds at surgeon height without SES was 273ppb (±189ppb) with a maximum total concentration of harmful substances of 8991ppb .
Maximum total VOC concentrations were 1.6±1.2 ppm (minimally-invasive surgery) and 2.1±1.5 ppm (open surgery), and total maximum VOC concentrations were 1.8±1.3 ppm at the OR table and 1.4±1.0 ppm in OR air in general. Neither difference was statistically significant.
In open surgery, SES significantly reduced maximum concentrations of specific VOCs at surgeon height, including aromatics and aldehydes.

Conclusion
Our data indicate relevant exposure of health care professionals to volatile organic compounds in the OR. Surgical technique and distance to cautery devices did not significantly reduce exposure. SES reduced exposure to specific harmful VOC's during open surgery.