Assessing the Therapeutic Impacts of HAMLET and FOLFOX on BRAF-Mutated Colorectal Cancer: A Study of Cancer Cell Survival and Mitochondrial Dynamics In Vitro and Ex Vivo.

Background and Objectives: Colorectal cancer (CRC) is a major global health challenge. The BRAF V600E mutation, found in 8-12% of CRC patients, exacerbates this by conferring poor prognosis and resistance to therapy. Our study focuses on the efficacy of the HAMLET complex, a molecular substance derived from human breast milk, on CRC cell lines and ex vivo biopsies harboring this mutation, given its previously observed selective toxicity to cancer cells. Materials and Methods: we explored the effects of combining HAMLET with the FOLFOX chemotherapy regimen on CRC cell lines and ex vivo models. Key assessments included cell viability, apoptosis/necrosis induction, and mitochondrial function, aiming to understand the mutation-specific resistance or other cellular response mechanisms. Results: HAMLET and FOLFOX alone decreased viability in CRC explants, irrespective of the BRAF mutation status. Notably, their combination yielded a marked decrease in viability, particularly in the BRAF wild-type samples, suggesting a synergistic effect. While HAMLET showed a modest inhibitory effect on mitochondrial respiration across both mutant and wild-type samples, the response varied depending on the mutation status. Significant differences emerged in the responses of the HT-29 and WiDr cell lines to HAMLET, with WiDr cells showing greater resistance, pointing to factors beyond genetic mutations influencing drug responses. A slight synergy between HAMLET and FOLFOX was observed in WiDr cells, independent of the BRAF mutation. The bioenergetic analysis highlighted differences in mitochondrial respiration between HT-29 and WiDr cells, suggesting that bioenergetic profiles could be key in determining cellular responses to HAMLET. Conclusions: We highlight the potential of HAMLET and FOLFOX as a combined therapeutic approach in BRAF wild-type CRC, significantly reducing cancer cell viability. The varied responses in CRC cell lines, especially regarding bioenergetic and mitochondrial factors, emphasize the need for a comprehensive approach considering both genetic and metabolic aspects in CRC treatment strategies.

Targeting AHR Increases Pancreatic Cancer Cell Sensitivity to Gemcitabine through the ELAVL1-DCK Pathway.

The aryl hydrocarbon receptor (AHR) is a transcription factor that is commonly upregulated in pancreatic ductal adenocarcinoma (PDAC). AHR hinders the shuttling of human antigen R (ELAVL1) from the nucleus to the cytoplasm, where it stabilises its target messenger RNAs (mRNAs) and enhances protein expression. Among these target mRNAs are those induced by gemcitabine. Increased AHR expression leads to the sequestration of ELAVL1 in the nucleus, resulting in chemoresistance. This study aimed to investigate the interaction between AHR and ELAVL1 in the pathogenesis of PDAC in vitro. AHR and ELAVL1 genes were silenced by siRNA transfection. The RNA and protein were extracted for quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Direct binding between the ELAVL1 protein and AHR mRNA was examined through immunoprecipitation (IP) assay. Cell viability, clonogenicity, and migration assays were performed. Our study revealed that both AHR and ELAVL1 inter-regulate each other, while also having a role in cell proliferation, migration, and chemoresistance in PDAC cell lines. Notably, both proteins function through distinct mechanisms. The silencing of ELAVL1 disrupts the stability of its target mRNAs, resulting in the decreased expression of numerous cytoprotective proteins. In contrast, the silencing of AHR diminishes cell migration and proliferation and enhances cell sensitivity to gemcitabine through the AHR-ELAVL1-deoxycytidine kinase (DCK) molecular pathway. In conclusion, AHR and ELAVL1 interaction can form a negative feedback loop. By inhibiting AHR expression, PDAC cells become more susceptible to gemcitabine through the ELAVL1-DCK pathway.

Association between AHR Expression and Immune Dysregulation in Pancreatic Ductal Adenocarcinoma: Insights from Comprehensive Immune Profiling of Peripheral Blood Mononuclear Cells.

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), has an immune suppressive environment that allows tumour cells to evade the immune system. The aryl-hydrocarbon receptor (AHR) is a transcription factor that can be activated by certain exo/endo ligands, including kynurenine (KYN) and other tryptophan metabolites. Once activated, AHR regulates the expression of various genes involved in immune responses and inflammation. Previous studies have shown that AHR activation in PDAC can have both pro-tumorigenic and anti-tumorigenic effects, depending on the context. It can promote tumour growth and immune evasion by suppressing anti-tumour immune responses or induce anti-tumour effects by enhancing immune cell function. In this study involving 30 PDAC patients and 30 healthy individuals, peripheral blood samples were analysed. PDAC patients were categorized into Low (12 patients) and High/Medium (18 patients) AHR groups based on gene expression in peripheral blood mononuclear cells (PBMCs). The Low AHR group showed distinct immune characteristics, including increased levels of immune-suppressive proteins such as PDL1, as well as alterations in lymphocyte and monocyte subtypes. Functional assays demonstrated changes in phagocytosis, nitric oxide production, and the expression of cytokines IL-1, IL-6, and IL-10. These findings indicate that AHR's expression level has a crucial role in immune dysregulation in PDAC and could be a potential target for early diagnostics and personalised therapeutics.

Editorial for the Special Issue "Acute and Chronic Pancreatitis, Pancreatic Malignancies".

Pancreatic diseases, especially acute pancreatitis and pancreatic cancer, are associated with high rates of complications, difficult treatment that may not always be effective, and high mortality in complex cases [...].

HAMLET effect on cell death and mitochondrial respiration in colorectal cancer cell lines with KRAS/BRAF mutations.

PURPOSE: Treatment of advanced colorectal cancer (CRC) depends on the correct selection of personalized strategies. HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a natural proteolipid milk compound that might serve as a novel cancer prevention and therapy candidate. Our purpose was to investigate HAMLET effect on viability, death pathway and mitochondrial bioenergetics of CRC cells with different KRAS/BRAF mutational status in vitro. METHODS: We treated three cell lines (Caco-2, LoVo, WiDr) with HAMLET to evaluate cell metabolic activity and viability, flow cytometry of apoptotic and necrotic cells, pro- and anti-apoptotic genes, and protein expressions. Mitochondrial respiration (oxygen consumption) rate was recorded by high-resolution respirometry system Oxygraph-2 k. RESULTS: The HAMLET complex was cytotoxic to all investigated CRC cell lines and this effect is irreversible. Flow cytometry revealed that HAMLET induces necrotic cell death with a slight increase in an apoptotic cell population. WiDr cell metabolism, clonogenicity, necrosis/apoptosis level, and mitochondrial respiration were affected significantly less than other cells. CONCLUSION: HAMLET exhibits irreversible cytotoxicity on human CRC cells in a dose-dependent manner, leading to necrotic cell death and inhibiting the extrinsic apoptosis pathway. BRAF-mutant cell line is more resistant than other type lines. HAMLET decreased mitochondrial respiration and ATP synthesis in CaCo-2 and LoVo cell lines but did not affect WiDr cells' respiration. Pretreatment of cancer cells with HAMLET has no impact on mitochondrial outer and inner membrane permeability.

Dysregulation of Peripheral Blood Mononuclear Cells and Immune-Related Proteins during the Early Post-Operative Immune Response in Ovarian Cancer Patients.

Surgical treatment is a cornerstone of ovarian cancer (OC) therapy and exerts a substantial influence on the immune system. Immune responses also play a pivotal and intricate role in OC progression. The aim of this study was to investigate the dynamics of immune-related protein expression and the activity of peripheral blood mononuclear cells (PBMCs) in OC patients, both before surgery and during the early postoperative phase. The study cohort comprised 23 OC patients and 20 non-cancer controls. A comprehensive analysis of PBMCs revealed significant pre-operative downregulation in the mRNA expression of multiple immune-related proteins, including interleukins, PD-1, PD-L1, and HO-1. This was followed by further dysregulation during the first 5 post-operative days. Although most serum interleukin concentrations showed only minor changes, a distinct increase in IL-6 and HO-1 levels was observed post-operatively. Reduced metabolic and phagocytic activity and increased production of reactive oxygen species (ROS) were observed on day 1 post-surgery. These findings suggest a shift towards immune tolerance during the early post-operative phase of OC, potentially creating a window for treatment. Further research into post-operative PBMC activity could lead to the development of new or improved treatment strategies for OC.

Transaxillary gasless endoscopic thyroidectomy versus conventional open thyroidectomy: systematic review and meta-analysis.

AIM: This systematic review and meta-analysis evaluates surgical outcome and safety results of conventional (OT) versus endoscopic transaxillary gasless thyroidectomies (ET). MATERIAL AND METHODS: A systematic literature search was performed. The weighted mean differences or the odd ratios with corresponding 95% CIs were examined for surgical outcomes and complications. The results were analysed using fixed- or random-effects models. The heterogeneity was checked by the Cochran Q test and the extent of inconsistency was evaluated by the I2 statistic. RESULTS: Ten studies and 1597 patients were included. All studies found that ET required longer operative time. Postoperative pain was significantly lower after ET on day 1 and day 7. No statistical difference was found in complication rates. CONCLUSIONS: ET has disadvantages such as longer surgery time, but it is a feasible and safe procedure with lower postoperative pain and comparable complication rates to OT. However, good quality prospective randomised studies are necessary to draw firmer conclusions.

Dynamic perfusion CT - A promising tool to diagnose pancreatic ductal adenocarcinoma.

BACKGROUND AND OBJECTIVE: This study deals with an important issue of setting the role and value of the dynamic computed tomography (CT) perfusion analysis in diagnosing pancreatic ductal adenocarcinoma (PDAC). The study aimed to assess the efficacy of perfusion CT in identifying PDAC, even isodense or hardly depicted in conventional multidetector computed tomography. METHODS: A total of 56 patients with PDAC and 56 control group patients were evaluated in this study. A local perfusion assessment, involving the main perfusion parameters, was evaluated for all the patients. Sensitivity, specificity, positive, and negative predictive values for each perfusion CT parameter were defined using cutoff values calculated using receiver operating characteristic curve analysis. We accomplished logistic regression to identify the probability of PDAC. RESULTS: Blood flow (BF) and blood volume (BV) values were significant independent diagnostic criteria for the presence of PDAC. If both values exceed the determined cutoff point, the estimated probability for the presence of PDAC was 97.69%. CONCLUSIONS: Basic CT perfusion parameters are valuable in providing the radiological diagnosis of PDAC. The estimated BF and BV parameters may serve as independent diagnostic criteria predicting the probability of PDAC.

Epigenetic Regulation of APAF-1 Through DNA Methylation in Pancreatic Cancer.

BACKGROUND/AIM: Apoptotic peptidase activating factor 1 (APAF-1) is essential regulator of apoptosis and inactivation by DNA methylation is common event in numerous cancer types. We investigated the regulation of APAF-1 through DNA methylation in pancreatic cancer. MATERIALS AND METHODS: Datasets from 44 patients after pancreatoduodenectomy and the pancreatic adenocarcinoma (PDAC) cell lines Capan-2 and MIA PaCa-2 treated with decitabine were analyzed by RT-PCR, immunoblotting, methylation-specific PCR analysis, apoptosis and viability assays to identify effects of APAF-1 regulation. RESULTS: APAF-1 mRNA and protein levels were significantly down-regulated, and APAF-1 methylation status was associated with perineural invasion in PDAC. Decitabine inhibited cell viability and increased apoptosis rates, however failed to restore APAF-1 mRNA and protein levels in cells. CONCLUSION: APAF-1 gene hypermethylation may contribute to the progression of PDAC through perineural invasion. Decitabine could sensitize pancreatic cancer cells to apoptosis and growth retardation, however, not directly through the APAF-1 demethylation process.

Long-Term Impact of Iatrogenic Bile Duct Injury.

BACKGROUND: Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including anastomotic strictures, recurrent cholangitis, and secondary biliary cirrhosis. METHODS: We provide a comprehensive overview of current literature on the long-term outcome of BDI. Considering the availability of only limited data regarding treatment of anastomotic strictures in literature, we also retrospectively analyzed patients with anastomotic strictures following a hepaticojejunostomy (HJ) from a prospectively maintained database of 836 BDI patients. RESULTS: Although clinical outcomes of endoscopic, radiologic, and surgical treatment of BDI are good with success rates of around 90%, quality of life (QoL) may be impaired even after "clinically successful" treatment. Following surgical treatment, the incidence of anastomotic strictures varies from 5 to 69%, with most studies reporting incidences around 10-20%. The median time to stricture formation varies between 11 and 30 months. Long-term BDI-related mortality varies between 1.8 and 4.6%. Of 91 patients treated in our center for anastomotic strictures after HJ, 81 (89%) were treated by percutaneous balloon dilatation, with a long-term success rate of 77%. Twenty-four patients primarily or secondarily underwent surgical revision, with recurrent strictures occurring in 21%. CONCLUSIONS: The long-term impact of BDI is considerable, both in terms of clinical outcomes and QoL. Treatment should be performed in tertiary expert centers to optimize outcomes. Patients require a long-term follow-up to detect anastomotic strictures. Strictures should initially be managed by percutaneous dilatation, with surgical revision as a next step in treatment.

CT- and MRI-Based Assessment of Body Composition and Pancreatic Fibrosis Reveals High Incidence of Clinically Significant Metabolic Changes That Affect the Quality of Life and Treatment Outcomes of Patients with Chronic Pancreatitis and Pancreatic Cancer.

Background and Objectives: Both chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) may lead to cachexia, sarcopenia, and osteoporosis due to different mechanisms. Neither patient gender, age, nor body weight are good predictors of these metabolic changes having a significant negative impact on the quality of life (QOL) and treatment outcomes. The aim of this study was to evaluate radiological changes in body composition and to compare them with manifestations of exocrine and endocrine pancreatic insufficiency, body mass, and QOL among patients with CP and PDAC. Materials and Methods: Prospectively collected data of 100 patients with diagnosed CP or PDAC were used for analysis. All patients underwent dual-energy X-ray absorptiometry (DXA), computed tomography (CT), and magnetic resonance imaging (MRI). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) was used to assess QOL. Diabetes and changes in fecal elastase-1 were also assessed. Results: There was no significant difference in skeletal muscle mass (SMM) among patients with CP and PDAC (p = 0.85). Significantly more underweight patients had low SMM (p = 0.002). Patients with CP had more pronounced pancreatic fibrosis (PF) (p < 0.001). Data showed a significant relationship between a high degree of PF and occurrence of diabetes (p = 0.006) and low fecal elastase-1 levels (p = 0.013). A statistically significant lower QOL was determined in patients with PF ≥ 50% and in the CP group. Conclusions: Sarcopenia and osteoporosis/osteopenia are highly prevalent among patients with chronic pancreatitis and pancreatic cancer, and CT- and MRI-based assessment of body composition and pancreatic fibrosis could be a potentially useful tool for routine detection of these significant metabolic changes.

Stimulated upregulation of HO-1 is associated with inadequate response of gastric and ovarian cancer cell lines to hyperthermia and cisplatin treatment.

Heme oxygenase (HO)-1 is a heat shock protein induced by hyperthermia, responsible for cellular resistance to temperature. The aim of this in vitro study was to clarify the response of gastric and ovarian cancer cells to hyperthermic intraperitoneal chemotherapy, following the modulation of HO-1 expression. AGS and OVCAR-3 cells were treated with different temperature regimens, either alone or in combination with an IC50 dose of cisplatin for 1 h. Prior to treatment, HO-1 expression was silenced by short interfering RNA transfection. In OVCAR-3 cells, cisplatin increased HO-1 mRNA expression by 3.73-fold under normothermia and 2.4-fold under hyperthermia; furthermore, these factors similarly increased HO-1 protein expression levels. Exposure to cisplatin under hyperthermia reduced the viability of OVCAR-3 cells by 36% and HO-1-silencing enhanced this effect by 20%. HO-1-silencing under normothermia increased apoptotic rates in cisplatin-treated OVCAR-3 cells by 2.07-fold, and hyperthermia enhanced the effect by 3.09-fold. Semi-quantitative polymerase chain reaction (PCR) cell analysis indicated that exposure to cisplatin decreased the cell index under normothermia, and that hyperthermia boosted this effect in OVCAR-3. In AGS cells, only temperature increased cellular HO-1 levels. Silencing HO-1 in AGS cells at 37°C reduced viability by 16% and increased apoptotic rates 2.63-fold. Hyperthermia did not affect AGS viability; however, apoptosis was increased 6.84-fold. PCR analysis indicated no additional effects of hyperthermia on the AGS cell index. HO-1 is induced in cancer cells by different stressors in a variable manner. In tumors with highly inducible HO-1, prior silencing of this gene could improve the cellular response to hyperthermia and cisplatin.

Hyperthermia potentiates cisplatin cytotoxicity and negative effects on mitochondrial functions in OVCAR-3 cells.

The aim of this study was to determine the effects of hyperthermia, cisplatin and their combination on mitochondrial functions such as glutamate dehydrogenase (GDH) activity and mitochondrial respiration rates, as well as survival of cultured ovarian adenocarcinoma OVCAR-3 cells. Cells treated for 1 h with hyperthermia (40 and 43 °C) or cisplatin (IC50) or a combination of both treatments were left for recovery at 37 °C temperature for 24 h or 48 h. The obtained results revealed that 43 °C hyperthermia potentiated effects of cisplatin treatment: combinatory treatment more strongly suppressed GDH activity and expression, mitochondrial functions, and decreased survival of OVCAR-3 cells in comparison to separate single treatments. We obtained evidence that in the OVCAR-3 cell line GDH was directly activated by hyperthermia (cisplatin eliminated this effect); however, this effect was followed by GDH inhibition after 48 h recovery. A combination of 43 °C hyperthermia with cisplatin induced stronger GDH inhibition in comparison to separate treatments, and negative effects exerted on GDH activity correlated with suppression of mitochondrial respiration with glutamate + malate. Cisplatin did not induce uncoupling of oxidative phosphorylation in OVCAR-3 cells but induced impairment of the outer mitochondrial membrane in combination with 43 °C hyperthermia. Hyperthermia (43 °C) potentiated cytotoxicity of cisplatin in an OVCAR-3 cell line.

Heme Oxygenase-1 Polymorphism Is Associated With the Development of Necrotic Acute Pancreatitis Via Vascular Cell Adhesion Molecule-1 and the E-Selectin Expression Regulation Pathway.

OBJECTIVES: Severe acute pancreatitis can lead to systemic complications. Here, we explore the mechanisms based on our previous study associated with the deregulation of heme oxygenase-1 (HO-1) and development of severe acute pancreatitis. METHODS: Acute pancreatitis patients (n = 135) and age- and sex-matched healthy controls (n = 108) were studied. The polymerase chain reaction products were analyzed with an ABI 3130 genetic analyzer and GeneMapper software. A short allele was defined ≤27 dinucleotide (GT) repeats, whereas a long allele was defined >27 GT. Levels of 12 different cytokines in blood serum were measured by enzyme-linked immunosorbent assay. All samples in this study were consistently stored in -80°C. RESULTS: Patients with the long long genotype expressed E-selectin and vascular cell adhesion molecule-1 at statistically significantly higher levels in serum compared with short short genotype or short long genotypes. Vascular cell adhesion molecule-1 and E-selectin serum levels significantly correlate with the total allele length of the HO-1 promoter region. CONCLUSION: Polymorphism of the GT repeats in the HO-1 promoter region may be a risk factor for developing acute necrotizing pancreatitis due to deregulation of the immune response.

Detailed methylation map of LINE-1 5'-promoter region reveals hypomethylated CpG hotspots associated with tumor tissue specificity.

BACKGROUND: Long interspersed nuclear elements (LINE-1) sequences constitute a substantial portion of the human genome, and their methylation often correlating with global genomic methylation. Previous studies have highlighted the feasibility of using LINE-1 methylation to discriminate tumors from healthy tissues. However, most studies are based on only a few specific LINE-1 CpG sites. METHODS: Herein, we have performed a systematic fine-scale analysis of methylation at 14 CpGs located in the 5'-region of consensus LINE-1, in bladder, colon, prostate, and gastric tumor tissues using a global degenerate approach. RESULTS: Our results reveal variable methylation levels between different CpGs, as well as some tissue-specific differences. Trends toward hypomethylation were observed in all tumors types to certain degrees, showing statistically significance in bladder and prostate tumors. Our data points toward the presence of unique LINE-1 DNA methylation patterns for each tumor type and tissue, indicating that not the same CpGs will be informative for testing in all tumor types. CONCLUSION: This study provides an accurate guide that will help to design further assays that could avoid artifacts and explain the variability of obtained LINE-1 methylation values between different studies.

Chronic Pancreatitis Is Characterized by Distinct Complication Clusters That Associate With Etiological Risk Factors.

OBJECTIVES: Chronic pancreatitis (CP) is characterized by several disease-related complications and multiple etiological risk factors. Past studies of associations between complications and risk factors have mostly been limited to single complications or highly focused on single etiologies. Using an objective data-driven approach (cluster analysis), we characterized complication clusters and their associations with etiological risk factors in a large cohort of patients with CP. METHODS: This was a multicenter, cross-sectional study including 1,071 patients with CP from the Scandinavian and Baltic countries. Complications to CP were classified according to the M-ANNHEIM system, and treelet transform was used to derive complication clusters. Cluster complication frequencies were analyzed for their association with main etiological risk factors (smoking and alcohol). RESULTS: The mean age of participants was 57 years and 66% were men. Alcohol (55%) and smoking (53%) were the most common etiological risk factors and seen in combination in 36% of patients. Cluster analysis identified 3 distinct complication clusters characterized by inflammation, fibrosis, and pancreatic insufficiencies. An independent association between inflammatory complications and alcoholic etiology was seen (odds ratio [OR] 2.00 [95% CI [confidence interval], 1.38-2.90], P < 0.001), whereas smoking was associated with fibrosis-related complications (OR 2.23 [95% CI, 1.56-2.3.20], P < 0.001) and pancreatic insufficiencies (OR 1.42 [95% CI, 1.00-2.01], P = 0.046). DISCUSSION: Three distinctive clusters of complications to CP were identified. Their differing associations with alcoholic and smoking etiology indicate distinct underlying disease mechanisms.

Human antigen R mediated post-transcriptional regulation of inhibitors of apoptosis proteins in pancreatic cancer.

AIM: To determine the association of human antigen R (HuR) and inhibitors of apoptosis proteins (IAP1, IAP2) and prognosis in pancreatic cancer. METHODS: Protein and mRNA expression levels of IAP1, IAP2 and HuR in pancreatic ductal adenocarcinoma (PDAC) were compared with normal pancreatic tissue. The correlations among IAP1/IAP2 and HuR as well as their respective correlations with clinicopathological parameters were analyzed. The Kaplan-Meier method and log-rank tests were used for survival analysis. Immunoprecipitation assay was performed to demonstrate HuR binding to IAP1, IAP2 mRNA. PANC1 cells were transfected with either anti-HuR siRNA or control siRNA for 72 h and quantitative reverse transcription polymerase chain reaction (RT-PCR), western blot analysis was carried out. RESULTS: RT-PCR analysis revealed that HuR, IAP1, IAP2 mRNA expression were accordingly 3.3-fold, 5.5-fold and 8.4 higher in the PDAC when compared to normal pancreas (P < 0.05). Expression of IAP1 was positively strongly correlated with HuR expression (P < 0.05, r = 0.783). Western blot analysis confirmed RT-PCR results. High IAP1 expression, tumor resection status, T stage, lymph-node metastases, tumor differentiation grade, perineural and lymphatic invasion were identified as significant factors for shorter survival in PDAC patients (P < 0.05). Immunohistological analysis showed that HuR was mainly expressed in the ductal cancer cell's nucleus and less so in cytoplasm. RNA immunoprecipitation analysis confirmed IAP1 and IAP2 post-transcriptional regulation by HuR protein. Following siHuR transfection, IAP1 mRNA and protein levels were decreased, however IAP2 expression levels were increased. CONCLUSION: HuR mediated overexpression of IAP1 significantly correlates with poor outcomes and early progression of pancreatic cancer. Further studies are needed to assess the underlying mechanisms.

Magnetic Resonance Imaging as a Valid Noninvasive Tool for the Assessment of Pancreatic Fibrosis.

OBJECTIVES: The aim of this study was to evaluate the utility of magnetic resonance imaging (MRI) for the noninvasive assessment of pancreatic fibrosis (PF). METHODS: Fifty-two patients who underwent surgical resection of the pancreas, histological examination of resection margins, preoperative abdominal MRI, and fecal elastase-1 test were enrolled in the study. Pancreatic tissue was identified on the MRI T1-, T2-, and diffusion-weighted imaging sequences. Apparent diffusion coefficient (ADC) was measured at the expected resection margin of the pancreas. RESULTS: There was a significant negative correlation between the ADC mean and histologically determined PF (r = -0.752, P = 0.001). For equal to or greater than 25% of PF, the ADC cutoff value was 1.331 or less, with a sensitivity of 77% and specificity of 88%. The unenhanced T1-weighted signal intensity ratio (T1SI) cutoff value was 172.1 or less. For equal to or greater than 50% of PF, the ADC cutoff value was 1.316 or less with a sensitivity of 85% and specificity of 88%. The highest sensitivity was obtained by combining ADC and T1SI values. CONCLUSIONS: Combining both the ADC and T1SI measurement allows the detection of early PF with good sensitivity and specificity. Magnetic resonance imaging has the advantage of being noninvasive and widely used in the clinical setting, thus making our results easily transferable to routine clinical practice.

Swept-wavelength lasers based on GaSb gain-chip technology for non-invasive biomedical sensing applications in the 1.7-2.5 µm wavelength range.

The infrared spectral region beyond 1.7 µm is of utmost interest for biomedical applications due to strong overtone and combination absorption bands in a variety of important biomolecules such as lactates, urea, glucose, albumin, etc. In this article, we report on recent progress in widely tunable swept-wavelength lasers based on type-I GaSb gain-chip technology, setting a new state-of-the-art in the 1.7 - 2.5 µm range laser sources. We provide an application example for the spectroscopic sensing of several biomolecules in a cuvette as well as an experimental demonstration of a non-invasive in-vivo sensing of human serum albumin through the skin.

Predictors of postoperative hypocalcemia occurring after a total thyroidectomy: results of prospective multicenter study.

BACKGROUND: Thyroid surgeries are among the most common operations performed in the world. Hypocalcemia following total thyroidectomy is a common complication that is sometimes difficult to correct. The aim of this study is to determine the risk factors for hypocalcemia following total thyroidectomy and their clinical value. METHODS: From January 2015 through to April 2017, 400 patients were included in this prospective multicenter study. All patients underwent total thyroidectomy due to various thyroid diseases. The following risk factors were analyzed: pre-operative and post-operative biochemical blood parameters, clinical effects and factors related to surgery, the patient, and the disease. RESULTS: Post-operative hypocalcemia developed in 257 patients (64.2%). Of them, 197 patients (76.7%) were diagnosed with asymptomatic hypocalcemia. Clinical symptoms were present in 60 of the 257 patients with hypocalcemia (23.3%). The statistically significant predictors of hypocalcemia were decreased calcium and ionized calcium pre-operatively (p < 0.001), parathyroid hormone on day one following surgery (p < 0.001), thyrotoxicosis <10 years before surgery (odds ratio 1.65, 95% CI 1.01-2.70, p = 0.046), the number of parathyroid glands found during surgery (odds ratio 0.52, 95% CI 0.38-0.70, p < 0.001), ligation of the trunk of the left inferior thyroid artery (odds ratio 2.04, 95% CI 1.27-3.29, p = 0.003), ligation of the trunk of the right inferior thyroid artery (odds ratio 2.37, 95% CI 1.47-3.81, p < 0.001), and the number of transplanted parathyroid glands (odds ratio 1.87, 95% CI 1.12-2.97, p = 0.015). In the multivariate analysis, age (odds ratio 1.05, 95% CI 1.01-1.09, p = 0.029) and gender (odds ratio 5.94, 95% CI 1.13-31.26, p = 0.035) were statistically significant predictors. CONCLUSIONS: This study demonstrates that there is a number of different patient (gender, age, and duration of thyrotoxicosis <10 years before surgery) and surgical (number of parathyroid glands found during surgery, decreased calcium and ionized calcium before surgery, parathyroid hormone on day one following surgery, and ligation of the trunk of the left and right inferior thyroid artery) risk factors predictive of hypocalcemia following total thyroidectomy. Optimization of the surgical technique could possibly prevent the occurrence of hypocalcemia after total thyroidectomy in some cases; in other cases, identification of known risk factors post-operatively could permit early detection and effective treatment of these patients.