Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Thursday, November 19, 2020

Radiotherapy for Resectable and Borderline Resectable Pancreas Cancer: When and Why?

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Abstract

The role of (chemo) radiation in the perioperative management of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma is controversial. Herein, we review and interpret existing data relating to the ability of (chemo) radiation to "downstage" pancreatic tumors, delay recurrence, and prolong patients' survival. In sum, the evidence suggests that while neoadjuvant (chemo) radiation may impact pathologic metrics favorably, it rarely converts anatomically unresectable tumors to resectable ones. And while data do support the ability of (chemo)radiation to delay cancer progression, its ability to prolong longevity has not been confirmed. It is possible that (chemo)radiation is effective in prolonging the survival of select patients, but to date, this cohort remains undefined due to heterogeneity in both the populations studied and the regimens used to treat them. Based on our interpretation of existing data, we currently administer n eoadjuvant and adjuvant (chemo)radiation selectively to patients with localized pancreatic cancer who we consider at highest risk for local progression. We may also use it as an alternative to pancreatectomy in patients who are poor candidates for surgery. Ultimately, the role of (chemo)radiation in these settings is evolving. Better studies of patients most likely to benefit from its local effects are necessary to clearly define its place within the perioperative treatment algorithms used for patients with localized pancreatic cancer.

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Alteration of FBXW7 is Associated with Worse Survival in Patients Undergoing Resection of Colorectal Liver Metastases

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Abstract

Background

For patients undergoing resection of colorectal liver metastases (CLMs), the prognostic role of somatic gene alterations is increasingly recognized. F-box/WD repeat–containing protein 7 (FBXW7) is a tumor suppressor gene found in approximately 10% of patients with colorectal cancer. The aim of this study is to assess the association of FBXW7 with overall survival after CLM resection.

Methods

Patients who underwent initial CLM resection during 2001–2016 and had genetic sequencing data were studied. Risk factors for overall survival (OS) were evaluated with Cox proportional hazards models using backward elimination.

Results

Of 2045 patients who underwent CLM resection during the study period, 476 were included. The majority (90.5%) underwent prehepatectomy chemotherapy. A total of 27 patients (5.7%) had FBXW7 alteration, along with 240 (50.4%) RAS, 337 (70.8%) TP53, 51 (10.7%) SMAD4, and 27 (5.7%) BRAF. Cox proportional hazards model analyses including 5 somatic gene alteration status and 12 clinicopathologic factors revealed FBXW7(hazard ratio [HR] 1.99, P = 0.015), BRAF (HR 2.47, P = 0.023), RAS (HR 2.42, P < 0.001), TP53 (HR 2.00, P < 0.001), and SMAD4 alterations (HR 1.90, P = 0.004) as significantly associated with OS, together with three clinicopathologic factors, prehepatectomy chemotherapy > 6 cycles (HR 1.51, P = 0.021), number of CLM (HR 1.05, P = 0.007), and largest liver metastasis diameter (HR 1.07, P = 0.023). The covariate-adjusted 5-year OS was significantly lower in patients with FBXW7 alteration than in patients with FBXW7 wild-type (40.4% vs.59.4%, P = 0.015).

Conclusions

FBXW7 alterations are associated with worse survival after CLM resection. The information on multiple somatic gene alterations is imperative for risk stratification and patient selection for CLM resection.

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Targets for Intervention? Preoperative Predictors of Postoperative Ileus After Colorectal Surgery in an Enhanced Recovery Protocol

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Abstract

Background

Postoperative ileus occurs in up to 30% of colorectal surgery patients and is associated with increased length of stay, costs, and morbidity. While Enhanced Recovery Protocols seek to accelerate postoperative recovery, data on modifiable preoperative factors associated with postoperative ileus in this setting are limited. We aimed to identify preoperative predictors of postoperative ileus following colorectal surgery in Enhanced Recovery Protocols, to determine new intervention targets.

Methods

We performed a retrospective single-center cohort study of patients ≥ 18 years old who underwent colorectal surgery via Enhanced Recovery Protocols (7/2015–7/2017). Postoperative ileus was defined as nasogastric tube insertion postoperatively or nil-per-os by postoperative day 4. Preoperative risk factors including comorbidities and medication use were identified using multivariable stepwise logistic regression.

Results

Of 530 patients, 14.9% developed postoperative ileus. On univariate analysis of perioperative and postoperative factors, postoperative ileus patients had increased psychiatric illness, antidepressant and antipsychotic use, American Society of Anesthesiologists classification, ileostomy creation, postoperative opioid use, complications, surgery duration, and length of stay (p < 0.05). Multivariable logistic regression model for preoperative factors identified psychiatric illness, preoperative antipsychotic use, and American Society of Anesthesiologists classification ≥ 3 as significant predictors of postoperative ileus (p < 0.05).

Discussion

Postoperative ileus remains a common complication following colorectal surgery under Enhanced Recovery Protocols. Patients with pre-existing psychiatric comorbidities and preoperative antipsychotic use may be a previously overlooked cohort at increased risk for postoperative ileus. Additional research and preoperative interventions within Enhanced Recovery Protocols to reduce postoperative ileus for this higher-risk population are needed.

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Impact of palladium nanoparticles (Pd-NPs) on the biology of neutrophils in vitro and on leukocyte attraction in vivo

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Abstract

Recently, palladium nanoparticles (Pd-NPs) have been shown to possess pro-inflammatory activities. Herein, we investigated potential in vitro effects of Pd-NPs (primary size of 1–10 nm) on the biology of neutrophils, key player cells in inflammation. Also, the aim of this study was to evaluate the pro-inflammatory activity of Pd-NPs using the murine air pouch model, a model previously proposed to be used as a standard assay for testing in vivo pro-inflammatory effects of NPs. Although the positive controls used in vitro give the expected results in all biological functions tested, Pd-NPs do not affect the production of reactive oxygen species and that of interleukin-1β (IL-1β), IL-6, and IL-8. Pd-NPs moderately increase cellular adhesion of neutrophils onto human endothelial cells and significantly increase the capacity of neutrophils to migrate and to delay apoptosis. We conclude that Pd-NPs possess some pro-inflammatory activity in vitro but do not a ttract leukocytes in vivo regardless of sex.

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Colloidal stability and aggregation kinetics of nanocrystal CdSe/ZnS quantum dots in aqueous systems: effects of pH and organic ligands

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Abstract

Advancing the understanding of stability behavior and aggregation mechanisms of quantum dot (QD) nanoparticles in natural systems is fundamental to elucidate their fate and transport, bioavailability, environmental toxicity, and subsequent risks to environmental and public health. This study investigates the aggregation kinetics and colloidal stability of QDs as a function of pH and organic ligands—acetate, oxalate, and citrate. Results indicated an influence of solution chemistry upon both the aggregation kinetics and colloidal stability of QDs. The zeta potential of QDs, with a point of zero charge (pHPZC) between pH 1.5 and 3.5, decreased (from positive to negative) with increasing solution pH. The diameter of QD aggregates was ~500 nm in the region of pHPZC and decreased with pH when pH > pHPZC to 40–50 nm. Organic ligands enhanced the negative zeta potentials of QDs at pH = 1.5 and pH = 3.5. The impact of ligands on the levels and rates of aggregation was pH dependent; furthermore, the presence of ligands increased the diameters of all QD nanoaggregates at pH 3.5 (e.g., 817 nm for 0.001 M citrate). QDs and organic ligand-QD nanoparticle complexes remained stable across pH values 5–9. In terms of environmental and toxicological risk assessments, results revealed that QDs and organic ligand-QD nanoparticle complexes remain stable across a significant range of pH values (5–9), indicating that this stability behavior could enhance the mobility, transport, and residence time of QDs in terrestrial and aqueous environments, and facilitate the bioavailability of QDs, therefore augmenting the adverse effects of QDs in the environment.

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Discovering Decolorization Potential of Triphenylmethane Dyes by Actinobacteria from Soil

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Abstract

This study investigates the decolorization potential of actinobacteria from soil towards toxic triphenylmethane (TPM) dyes, i.e., malachite green (MG), methyl violet (MV), crystal violet (CV), and cotton blue (CB). The actinobacterial isolates were first isolated from fresh soil samples, plated onto actinomycetes isolation agar (AIA), and both live and dead cells were prepared to evaluate their decolorization efficiency (DE). Isolates with positive decolorization activities were identified via partial sequencing of the 16S rRNA region. They were revealed as species of Nocardiopsis (N. alba), Streptomyces (S. puniceus, S. bacillaris, S. albolongus, S. acidiscabies, S. albulus, S. pratensis, S. luridiscabiei, S. rubiginosus, S. albidochromogenes), Rhodococcus (R. sovatensis), and Kitasatospora (K. albolonga). Results indicated that all 12 actinobacterial strains (live cells and dead cells) were able to decolorize TPM dyes, although with varying degree of effectiveness. Isolate N. alba (live cells) achieved the highest DE, with 97.0, 95.1, 95.8, and 83.8% (day 14) for MG, MV, CV, and CB, respectively. This was followed by live cells of S. bacillaris with 94.7, 95.1, 90.5, and 63.9% of DE for the same dyes. Live cells appeared to be more effective in decolorizing TPM dyes, suggesting the possible biosorption and biodegradation of dyes. It is concluded that soil actinobacteria tested in this study have the potential for removal of TPM dyes.

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Open abdomen in the trauma ICU patient: who? when? why? and what are the outcome results?

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Abstract

Purpose

Temporary abdominal closure is a component of damage control surgery and may decrease mortality rates. The ultimate aim in managing an open abdomen is to achieve definitive fascial closure. The aim of this study is to assess the previously known predictors for failure to achieve definitive fascial closure and identify new predictors in order to achieve a better outcome.

Methods

An 11-year retrospective chart review included open abdomen cases at Inkosi Albert Luthuli Hospital Trauma ICU in KZN (Ethics Approval BCA207-09). The evaluated outcomes were definitive fascial closure, open abdomen and mortality. Variables included age, co-morbidities, albumin levels, renal failure, multiple blood transfusions, type of blood products given, entero-atmospheric fistulas, TAC, anastomosis, intra-abdominal abscess, type of nutrition, ACS, number of re-laparotomies, deep site infections (peritonitis), systemic infections (bloodstream), ventilator acquired pneumonia, head injury, and type of fluids given.

Results

This study reviewed 188 cases, 46.8% (88) arrived from elsewhere with an open abdomen while 53.2% (100) did not; 46.8% suffered blunt trauma, 45.2% suffered gunshots, while 8.0% were stabbed. Ninety deaths (47.9%) occurred during the index admission with 57 (30.3%) within the first 30 days. For both death within 30 days and death as final outcome, the majority were blunt abdominal trauma, 51.1 and 52.6%, respectively. Out of 188 patients, 27.1% had definitive fascial closure and 26.6% remained with an open abdomen. The relevant variables related to failure to achieve fascial closure were hypoalbuminemia (p = 0.002, p = 0.036), anastomotic leak (p < 0.05), VAP (p = 0.007), age (p = 0.002), intra-abdominal abscesses (p = 0.006), ACS (p = 0.005), multiple re-laparotomies (p = 0,028), deep surgical site infection (p < 0.05) and multi- organ failure (p = 0.003).

Conclusion

This study identified the predictors of failed fascial closure and mortality. While not directly modifiable, hypoalbuminaemia, anastomotic leak and sepsis, leading to multiple re-laparotomy, preclude early closure and portend high mortality.

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