Peripheral blood platelet counts identify prognostically diverse clinical phenotypes in hepatocellular carcinoma.

Background: The factors responsible for hepatocellular carcinoma (HCC) growth are not precisely known. Aims: To study the clinical parameters associated with increases in maximum tumor diameter (MTD). Methods: A new cohort of 944 prospectively accrued HCC patients was analyzed for large size associations. Results: Patients were ordered into MTD terciles. Blood platelets, GGT and AST levels significantly increased and total bilirubin decreased with increase in MTD. Similar results were found only for platelets, in patients with low alpha-fetoprotein (AFP) levels, for whom biomarkers are scanty. Survival significantly decreased for patients with high platelet or GGT levels, even when AFP levels were low.Comparison of patients with low and high platelet levels showed that in the ≤6cm MTD group, patients with higher platelet numbers had lower total bilirubin and AST, and higher albumin, hemoglobin and percent patients with portal vein thrombosis (PVT) than those with lower platelets. Univariable logistic analysis on HCCs >6cm versus ≤6cm revealed significantly higher odds ratios for elevated blood platelet, AFP, GGT and ALKP levels. Cox regression analysis on death showed that in ≤6cm MTD patients, significant hazard ratios were for platelets, GGT, AFP, ALKP and PVT; but not for >6cm MTD patients, suggesting different mechanisms. Given the association of higher platelets with larger tumors and good liver function, their precursors are suggested to be small tumors with higher platelets and endogenous tumor factors. However, patients with low platelets and larger HCCs might have a different HCC lineage, likely associated with liver inflammation factors. Conclusions: Blood platelet levels are a potential marker for HCC phenotype and prognosis, including in patients with low AFP. They may also be a therapeutic target.

Flt3 agonist enhances immunogenicity of arenavirus vector-based simian immunodeficiency virus vaccine in macaques.

Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens are capable of inducing efficacious humoral and cellular immune responses in nonhuman primates. Several studies have evaluated the use of immune modulators to further enhance vaccine-induced T-cell responses. The hematopoietic growth factor Flt3L drives the expansion of various bone marrow progenitor populations, and administration of Flt3L was shown to promote expansion of dendritic cell populations in spleen and blood, which are targets of arenaviral vectors. Therefore, we evaluated the potential of Flt3 signaling to enhance the immunogenicity of arenaviral vaccines encoding SIV immunogens (SIVSME543 Gag, Env, and Pol) in rhesus macaques, with a rhesus-specific engineered Flt3L-Fc fusion protein. In healthy animals, administration of Flt3L-Fc led to a 10- to 100-fold increase in type 1 dendritic cells 7 days after dosing, with no antidrug antibody (ADA) generation after repeated dosing. We observed that administration of Flt3L-Fc fusion protein 7 days before arenaviral vaccine increased the frequency and activation of innate immune cells and enhanced T-cell activation with no treatment-related adverse events. Flt3L-Fc administration induced early innate immune activation, leading to a significant enhancement in magnitude, breadth, and polyfunctionality of vaccine-induced T-cell responses. The Flt3L-Fc enhancement in vaccine immunogenicity was comparable to a combination with αCTLA-4 and supports the use of safe and effective variants of Flt3L to augment therapeutic vaccine-induced T-cell responses.IMPORTANCEInduction of a robust human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell response through therapeutic vaccination is considered essential for HIV cure. Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens have demonstrated strong immunogenicity and efficacy in nonhuman primates. Here, we demonstrate that the immunogenicity of arenaviral vectors encoding SIV immunogens can be enhanced by administration of Flt3L-Fc fusion protein 7 days before vaccination. Flt3L-Fc-mediated increase in dendritic cells led to robust improvements in vaccine-induced T- and B-cell responses compared with vaccine alone, and Flt3L-Fc dosing was not associated with any treatment-related adverse events. Importantly, immune modulation by either Flt3L-Fc or αCTLA-4 led to comparable enhancement in vaccine response. These results indicate that the addition of Flt3L-Fc fusion protein before vaccine administration can significantly enhance vaccine immunogenicity. Thus, safe and effective Flt3L variants could be utilized as part of a combination therapy for HIV cure.

Impact of Concomitant Traumatic Pancreatic and Colon Injuries on Outcomes.

BACKGROUND: Colon and pancreatic injuries have both long been independently associated with intraabdominal infectious complications in trauma patients. The goal of this study was to evaluate the impact of concomitant pancreatic injury on outcomes in patients with traumatic colon injuries. METHODS: Consecutive patients over a 3-year period who underwent operative management of colon injuries were identified. Patient characteristics, severity of injury and shock, presence and grade of pancreatic injury, and intraoperative packed red blood cell (PRBC) transfusions were recorded. Outcomes including intraabdominal abscess formation and suture line failure were collected and compared. Multivariable logistic regression analysis was then performed to determine the impact of concomitant pancreatic injury on intraabdominal abscess formation. RESULTS: 243 patients with traumatic colon injuries were identified. 17 of these also had pancreatic injuries. Patients with combined colon and pancreatic injuries were clinically similar to those with isolated colon injuries with respect to age, gender, penetrating mechanism of injury, admission lactate, ISS, suture line failure, and admission systolic blood pressure. Both intraabdominal abscess rates (88.2% vs 29.6%, P < .001) and intraoperative PRBC transfusions (8 vs 1 units, P = .004) were higher in the combined pancreatic and colon injury group. Multivariable logistic regression identified both intraoperative PRBC transfusions (odds ratio, 1.09; 95% confidence interval, 1.04-1.15; P < .001) and concomitant pancreatic injury (odds ratio, 14.8; 95% confidence interval, 3.92-96.87; P < .001) as independent predictors of intraabdominal abscess formation. DISCUSSION: Both intraoperative PRBC transfusions and presence of concomitant pancreatic injury are independent predictors of intraabdominal abscess formation in patients with traumatic colon injuries.

The effect of free flap surgery for oral cancer on laryngeal grade and intubation difficulty.

OBJECTIVE: The purpose of this study was to evaluate the change in laryngeal grade and intubation difficulty at subsequent surgery in patients with prior free flap reconstruction for oral cancer. STUDY DESIGN: This retrospective case series included patients with a diagnosis of oral cancer who underwent free flap reconstruction (FFR) (S1) followed by a subsequent surgery (S2) which required intubation. The primary predictor variable was FFR. The primary outcome variable was the change in laryngeal grade, based on the classification of Cormack and Lehane, after FFR. Secondary outcomes were intubation difficulty and number of intubation attempts. RESULTS: Thirty-three patients were included in the study. At S1, the average laryngeal grade was 1.1. There were 5 difficult intubations. The average time to S2 was 19 months. At S2, average laryngeal grade was 1.4. There were 17 difficult intubations. Analysis showed a significant association between FFR and a more obstructed view of the glottis at S2 (P = .007; 95% CI 0.101-0.808). FFR increased the odds of having >1 intubation attempt nearly 7-fold (OR 6.74; 95% CI 1.35-33.75), and the odds of a difficult intubation nearly 6-fold (OR 5.95; 95% CI 1.84-19.19) at S2, both of which were significant (P = .011 and P = .002, respectively) CONCLUSIONS: This investigation found an association between FFR for patients with oral cancer and a higher laryngeal grade - that is, a more obstructed view of the glottis - at subsequent surgery, in addition to increased intubation difficulty and greater number of intubation attempts.

Transplant and non-transplant HCC patients at a single institution.

Background and Aim: Patients with hepatocellular carcinoma (HCC) are managed in various hospital departments, which complicates the assessment of the overall picture. In our large liver transplant institute, we evaluate all HCC patients in a weekly multi-disciplinary liver tumor board, and their data are prospectively collected in an institutional HCC database to evaluate HCC causes, tumor features, treatments, and survival. Materials and Methods: Baseline data for patients (n=1322) were prospectively recorded, including hepatitis status, routine clinical serum parameters, radiological assessment of maximum tumor diameter (MTD), tumor number, presence of macroscopic portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP) levels. Results: Cirrhosis was found in 81.1% of patients; 58.5% had hepatitis B virus (HBV), 14.9% hepatitis C virus (HCV), 8.9% cryptogenic cirrhosis, and less than 2% had alcoholism. MTD was <5 cm in 61.95% of patients, and 31.9% had PVT. The median overall survival was more than six-fold greater for the 444 liver transplant patients than for those without surgery. Transplanted patients had smaller tumors, whereas larger tumors (MTD >10 cm) were primarily in the no-surgery group. Parallel differences were found for AFP levels (highest in the no-surgery group). PVT was present in similar proportions (25.0% for transplant, 28.0% for no-surgery). The presence of cirrhosis was higher in the transplant group. MTD and levels of serum AFP, gamma-glutamyl transferase (GGT), and blood platelets were prognostic parameters for transplant. Furthermore, AFP and GGT levels were prognostic for transplanted PVT patients. Only albumin was prognostic in the no-surgery patients. Conclusion: Transplanted HCC patients have longer survival, smaller tumors, and more severe liver damage than no-surgery patients. Prognostic subsets were identified within the surgery and the PVT groups.

HBV viral load and tumor and non-tumor factors in patients with HBV-associated HCC.

Background and Aim: Several tumor and non-tumor factors affect the prognosis of hepatocellular carcinoma (HCC) patients. This study aimed to investigate the effects of hepatitis B virus (HBV) viral load on tumor and non-tumor factors in patients with HBV-associated HCC. Materials and Methods: Patients with hepatitis B and HCC who presented to the HCC council at the Faculty of Medicine, Marmara University Liver Transplantation Institute, were included in our study. Patients were divided into two groups according to the presence or absence of HBV-DNA, and it was determined whether there were differences between these two groups with respect to tumor and non-tumor parameters. Results: Comparison of serum alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), hepatitis B surface antigen (HBsAg), and C-reactive protein (CRP) levels between HBV-DNA negative and positive patients showed significant differences (respectively p<0.01, p<0.01, p<0.05, and p<0.05). A major finding was a very significant difference between the two patient groups in terms of portal vein invasion (PVI) and venous invasion (p<0.001 and p<0.01, respectively). However, there was no significant difference in metastasis or lymph node involvement between HBV-DNA negative and positive patients. Conclusion: Our findings suggest that HBV viral load plays an important role in PVI in HCC patients, and there is a significant relationship between HBV viral load and inflammation.

Microvascular Invasion in Hepatocellular Carcinoma: Some Puzzling Facets.

BACKGROUND/AIMS: Hepatocellular carcinoma is the main type of primary liver cancer. Macroscopic vascular invasion is usually identified during imaging, whereas microvascular invasion is usually determined by histopathological evaluation. We aim to identify the association between microvascular invasion and other markers of tumor aggressiveness and to identify the role of microvascular invasion in the prognosis of patients who were treated by liver transplantation for hepatocellular carcinoma. MATERIALS AND METHODS: This is a single-center retrospective analysis of prospectively collected data. Patients who received liver transplantation for hepatocellular carcinoma were included in the study. Data were collected regarding sociodemographic variables, criteria of selection for liver transplantation, pretransplant alpha-fetoprotein, presence or absence of microvascular invasion, presence or absence of recurrence, overall survival, and disease-free survival. Data were analyzed using Statistical Package for the Social Sciences. RESULTS: Sociodemographic laboratory values and radiologic tumor characteristics were found to be similar in patients with or without microvascular invasion. Our study revealed that microvascular invasion is associated with increased recurrence, decreased diseasedfree survival, and decreased overall survival, only for patients with hepatocellular carcinoma beyond Milan criteria at the time of liver transplantation. CONCLUSION: For patients beyond Milan criteria, but not within Milan criteria, microvascular invasion plays a significant role in predicting recurrence and shorter survival after liver transplantation.

Venovenous Extracorporeal Membrane Oxygenation Usage Following Bullet Embolism to the Pulmonary Artery.

Background: Pulmonary artery embolus is a rare complication following gunshot wounds that creates a unique and serious challenge for trauma surgeons. While the majority of bullets that embolize through the vascular system end in the peripheral circulation, approximately one-third enter the central venous circulation. Case Report: We present the case of a bullet embolus to the left pulmonary artery following gunshot wounds to the right chest and the abdomen, with the abdominal ballistic traversing the liver before entering the vena cava and embolizing. The patient's course was complicated by the development of severe acute respiratory distress syndrome that was successfully managed by venovenous extracorporeal membrane oxygenation. Conclusion: Venovenous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome after bullet embolization to the pulmonary tree and surgical embolectomy is a viable option in appropriately selected patients.

Alpha-fetoprotein and albumin inversely relate to each other and to tumor parameters in patients with hepatocellular carcinoma.

Background and Aim: Alpha-fetoprotein (AFP), an oncofetal protein and biomarker in hepatocellular carcinoma (HCC), has unclear roles and actions.To evaluate the relationships between AFP, liver function tests, and HCC aggressiveness. Materials and Methods: A retrospective analysis of an HCC patient database was conducted to examine the relationships between baseline serum AFP values, liver function tests, and tumor characteristics. Results: Statistically significant positive trends were observed between AFP levels and both AST and bilirubin, along with negative trends between AFP and albumin. Significant correlations were also found between AFP and MTD, multifocality, and PVT. Increases in MTD, multifocality, and PVT were noted even at low AFP levels, indicating both AFP-independent and AFP-dependent processes. However, these parameter changes were minimal compared to the substantial changes in AFP levels. Relationships between AFP-related liver and tumor characteristics were found to be similar but inverse to those for albumin, with normal albumin levels associated with more favorable tumor characteristics. Additionally, serum levels of albumin and AFP were inversely related. Conclusion: AFP and albumin levels significantly, but inversely, correlate with tumor parameters, suggesting that albumin may suppress HCC functions and could serve as a potential prognostic marker.

Are higher odontogenic infection severity scores associated with difficult intubations?

PURPOSE: This study aimed to determine if there is a relation between odontogenic infection severity score (OISS) and difficult intubation at the time of surgical treatment for severe odontogenic infections (SOI). A secondary goal of this study was to determine the utility of OISS as a predictor of difficult intubations. METHODS: This retrospective cohort study was composed of consecutive patients admitted and surgically treated in the operating room (OR) for SOIs. Patients with an OISS ≥ 5 were designated as Group 1 and < 5 Group 2. RESULTS: There was a statistically significant difference in difficult intubations between the two groups (p = 0.018). Patients with an OISS ≥ 5 were nearly four times more likely to be difficult intubations compared to patients with an OISS < 5 (OR 3.70, 95% CI 1.19-11.45). When OISS ≥ 5 was used to predict difficult intubation, the sensitivity was 69%, the specificity was 63%, the positive predictive value was 23%, and the negative predictive value was 93%. CONCLUSION: OISS ≥ 5 was associated with a higher prevalence of difficult intubations compared to an OISS < 5. OISS may provide clinically relevant data that can be used with established risk factors, laboratory values, and clinical judgment.

Discordance among aggressiveness characteristics of hepatocellular carcinoma: Portal vein thrombosis and multifocality, related to tumor size, but not to serum alpha-fetoprotein level.

Background and aims: Hepatocellular carcinoma (HCC) is characterized by several clinically important prognostic parameters, including portal vein thrombosis (PVT), tumor multifocality, and serum alpha-fetoprotein (AFP) levels, in addition to maximum tumor diameter (MTD). However, associations among these parameters have not been thoroughly examined. Thus, the study aimed to investigate the correlations among these HCC characteristics in a prospectively collected database. Methods: An 8080 HCC patient database derived from our weekly HCC council meeting was examined with respect to the correlations at baseline patient presentation between increases in MTD and changes in the percentage of patients with PVT, multifocality, or AFP levels. Results: The percentage of patients with PVT and with multifocality (tumor nodule numbers ≥3) significantly increased with enlarging MTD, regardless of the serum AFP level, showing the independence of PVT and multifocality on AFP. The percentage of patients with multifocality increased with enlarging MTD, in the presence or absence of PVT, showing the independence of multifocality from PVT. Therefore, discordance was found between different tumor parameters. Conclusions: A statistically significant association was found between PVT and MTD and between multifocality and MTD, all three of which are independent of AFP. PVT and multifocality appeared to be independent of each other. Although PVT and multifocality were independent of AFP, they were also augmented with high serum AFP levels. The results suggest the possibility of multiple pathways of tumor progression in the later stages of HCC development.

Liver Transplantation for Hepatocellular Carcinoma in Patients with Inherited Metabolic Liver Diseases: A Single-Center Analysis.

BACKGROUND/AIMS: Liver transplantation is an acceptable treatment for some selected hepatocellular carcinoma. We report our experience of 6 patients with liver transplantation for hepatocellular carcinoma with background inherited metabolic disease. MATERIALS AND METHODS: This is a single-center retrospective, descriptive study. Consecutive patients who underwent liver transplantation for hepatocellular carcinoma with background inherited metabolic disease were included in the study. The record of the patients was accessed, and the following data were extracted: sociodemographic variables, type of metabolic disease, date of liver transplantation, tumor characteristics, laboratory parameters, Model for End-Stage Liver Disease score, immediate- and long-term outcome after transplantation, disease-free survival, and overall survival. Data were analyzed using Statistical Package for the Social Sciences version 25.0. RESULTS: Six patients received liver transplantation for hepatocellular carcinoma with background inherited metabolic liver disease. The median age was 4.5 years. The median Model for End-Stage Liver Disease score was 29.30. The median maximum tumor diameter was 2.15 cm. Three patients had multiple tumor nodules. Half of the patients had microvascular invasion. Four of the patients had a moderately differentiated tumor. Progressive familial intrahepatic cholestasis type II is the commonest inherited metabolic disease seen in 3 patients. Median follow-up is 46.1 months. Half of the patients are currently more than 5 years post liver transplantation with no features of recurrence. The estimated survival rates at 1, 3, and 5 years are 100%, 83.3%, and 83.3%, respectively. CONCLUSION: Liver transplant for these categories of patients is associated with good disease-free and overall survival, even in the presence of some seemingly poor prognostic features.

The effect of mandibular advancement for mandibular deficiency dentofacial deformities on laryngeal grade and intubation difficulty: a preliminary study.

OBJECTIVE: The purpose of this study was to evaluate mandibular advancement for cases of mandibular deficiency with changes in vocal cord grade and intubation difficulty at subsequent surgery requiring intubation. STUDY DESIGN: This retrospective case series included patients with a diagnosis of mandibular deficiency (Class II skeletal dentofacial deformity) who underwent mandibular advancement surgery (T1) followed by a subsequent surgery (T2) which required intubation. The primary predictor variable was mandibular advancement. The primary outcome variable was the change in laryngeal grade-Cormack and Lehane-after mandibular advancement. A secondary outcome was intubation difficulty after mandibular advancement. RESULTS: Eight patients were included in the study. At T1, the average laryngeal grade was 1.6. There was 1 difficult intubation. The average time to T2 was 9 months. At T2, all patients were intubated on their first attempt, and all had a Cormack-Lehane Grade I view of the vocal cords. There were no difficult intubations at T2. Analysis showed a significant association between mandibular advancement and laryngeal grade at T2 (P = .03; 95% CI 0.07-1.13). CONCLUSIONS: This preliminary investigation found an association between mandibular advancement for cases of mandibular and improved laryngeal grade at subsequent intubation without any difficult intubations.

Parameters Predicting Microvascular Invasion and Poor Differentiation in Hepatocellular Carcinoma Patients with Normal Alpha-fetoprotein Level Before Liver Transplantation.

BACKGROUND/AIMS: The aim of this study is to evaluate the parameters that might be associated with pathologically diagnosed microvascular invasion and poor differentiation, using complete blood count and routine clinical biochemistry test results, in hepatocellular carcinoma patients before liver transplantation. MATERIALS AND METHODS: The data of patients who underwent liver transplantation for hepatocellular carcinoma at our institute, between March 2006 and November 2021, was researched retrospectively. RESULTS: The incidence of microvascular invasion was 28.6%, poor differentiation rate was 9.3%, hepatocellular carcinoma recurrence rate after liver transplantation was 12.1%, and median time to recurrence was 13 months, in the patients with normal alpha-fetoprotein levels. After univariate and multivariate analysis, maximum tumor diameter >4.5 cm and the number of nodules (n > 5) were found to be independent risk factors for microvascular invasion, and number of nodules >4 and mean platelet volume ≤8.6 fL were found to be independent risk factors for poor differentiation. Serum alpha-fetoprotein levels were still within the normal range at the recurrence time, in 53% of the patients who had recurrence after liver transplantation, but surprisingly were elevated in 47% of the patients at time of hepatocellular carcinoma recurrence. CONCLUSIONS: In hepatocellular carcinoma patients with normal alpha-fetoprotein levels before liver transplantation, independent risk factors of the presence of microvascular invasion were maximum tumor diameter and number of nodules, and independent risk factors of poor differentiation were mean platelet volume and number of nodules. Furthermore, serum alpha-fetoprotein levels were still normal at time of recurrence in 53% of hepatocellular carcinoma patients whose alpha-fetoprotein levels were normal before liver transplantation but were elevated in 47% of the patients at recurrence time, despite having normal levels before liver transplantation.

Comparison of liver resection and living donor liver transplantation in patients with hepatocellular carcinoma within Milan criteria and well-preserved liver function.

Background and Aim: Liver resection (LR) and liver transplantation (LT) are curative treatments for hepatocellular carcinoma (HCC). The main purpose of this study was to compare the survival of LR and LDLT in patients with HCC within the Milan criteria. Materials and Methods: The results of the LR (n=67) and LDLT (n=391) groups were compared for overall survival (OS) and disease-free survival (DFS). Twenty-six of the HCCs in the LRs met the Milan and Child A criteria. Also, 200 of the HCC patients in the LDLTs met the Milan criteria, of which 70 also met the Child A criteria. Results: Early mortality was higher in the LDLT group (13.9% vs 1.47%; p=0.003). The 5-year OS was higher in the LDLTs than the LRs, but not statistically significant (84.6% vs 74.2%; p=0.287). However, 5-year DFS was better in the LDLT group (96.8% vs 64.3%; p<0.001). When the LRs (n=26) and the LDLTs (n=70) that met both Milan and Child A criteria were compared, 5-year OS was similar (81.4% vs 74.2%; p=0.512), but DFS was better in the LDLTs (98.6% vs 64.3%; p<0.001). Conclusion: LR can be justified as the first-line treatment for HCC patients who meet Milan and Child A criteria in terms of early mortality and OS.

Serum Inflammation Parameters and Survival in Hepatocellular Carcinoma Patients: Importance of Albumin and Gamma-Glutamyltranspeptidase.

INTRODUCTION: Many single and combination blood tests that reflect local or systemic inflammation have been shown to be useful prognosticators in patients with a variety of tumor types. To try to clarify, this issue in patients with nonsurgically treatable hepatocellular carcinoma, multiple serum parameters were evaluated for their relationship to survival. METHODS: A prospectively collected database was interrogated of 487 patients with known hepatocellular carcinoma and documented survival and having all the inflammation parameters of interest in this study, together with baseline tumor characteristics from CT scans. Serum parameters included NLR, PLR, CRP, ESR, albumin, and GGT. RESULTS: All the parameters had significant hazard ratios on Cox regression model. Combination double parameters with hazard ratios >2.0 were: ESR plus GGT, albumin plus GGT, albumin plus ESR. The triplet combination of albumin plus GGT plus ESR had a hazard ratio of 6.33. Using Harrell's concordance index (C-index), the highest inflammation-based 2-parameter prognostic score was for albumin plus GGT. When clinical characteristics of patients with high values for albumin plus low values for GGT were compared to low values for albumin plus high values for GGT (worse prognosis), statistically significant differences were found for tumor size, tumor focality, macroscopic portal vein invasion, and serum alpha-fetoprotein levels. Addition of ESR did not provide additional tumor information. CONCLUSION: The combination of serum albumin plus GGT levels was the most prognostically useful among the inflammation parameters that were tested, and reflected significant differences in tumor aggressiveness characteristics.

Understanding the Drawbacks of the Current Tumor Staging Systems: How to Improve?

Tumor stage definition is required for the description of the diagnosis and the development and use of treatment guidelines, as well as to enable clinical research (including clinical trials) and cancer surveillance [...].

EMT and Inflammation: Crossroads in HCC.

Hepatocellular carcinoma is one of the major causes of cancer-related deaths worldwide and is associated with several inflammatory mediators, since 90% of HCCs occur based on chronic hepatitis B or C, alcoholism or increasingly metabolic syndrome-associated inflammation. EMT is a physiological process, with coordinated changes in epithelial gene signatures and is regulated by multiple factors, including cytokines and growth factors such as TGFß, EGF, and FGF. Recent reports propose a strong association between EMT and inflammation, which is also correlated with tumor aggressiveness and poor outcomes. Cellular heterogeneity results collectively as an outcome of EMT, inflammation, and the tumor microenvironment, and it plays a fundamental role in the progression, complexity of cancer, and chemoresistance. In this review, we highlight recent developments concerning the association of EMT and inflammation in the context of HCC progression. Identifying potential EMT-related biomarkers and understanding EMT regulatory molecules will likely contribute to promising developments in clinical practice and will be a valuable tool for predicting metastasis in general and specifically in HCC.

Critical overview of resection for Bismuth-Corlette type IV perihilar cholangiocarcinoma.

BACKGROUND: Current standard treatment for perihilar cholangiocarcinoma (pCCA) is surgical resection. Bismuth-Corlette (BC) type IV pCCA is accepted as an unresectable disease. In the present study, the results of non-transplant surgical approaches in patients with BC type IV pCCA were examined. METHODS: Medical records of consecutive patients with BC type IV pCCA between 2010 and 2021 were retrospectively reviewed. Patients were subdivided according to operation type. Postoperative survival rates were compared. RESULTS: Hemihepatectomy with caudate lobe and extrahepatic bile duct (EHBD) resection was performed in 15 patients and only EHBD resection was performed in 10 patients. Ten of the cases were found to be unresectable at the stage of laparotomy. Median follow-up was 41.3 (24.8-57.9) months. Overall survival rate for all 35 patients was 56.4% at 1 year, 32.2% at 2 years, and 16.1% at 3 years. When survivals were compared according to operation type, 1, 2, and 3-year survivals were 80%, 57.1% and 42.9% for the hepatectomy group; 55.6%, 44.4% and 11.1% for the EHBD resection group; 75%, 0% and 0% in laparotomy-only group, respectively (p = 0.13). The best survival rates were obtained in patients with pCCA who underwent hepatectomy and were lymph node negative, 100% for 1 year, 66.7 for 2 years and 50% for 3 years. CONCLUSION: It is difficult to achieve high survival rates in BC type IV pCCA. However, these patients mostly benefit from resective treatments. Acceptable survival rates can be achieved, especially in the R0N0 patient group.

Does implant placement using a minimally invasive technique increase early failures among trainees at an academic center?

PURPOSE: This study aims to identify whether dental implants placed using a flapless technique have a higher early failure rate, defined as failure within 6 months of placement, compared to implants placed with flap elevation when a surgical guide is not used. METHODS: A retrospective cohort study was conducted to evaluate implants placed with either flapless (FL) or mucoperiosteal flap (MF) surgery between 2006 and 2012 at the Philadelphia VA Medical Center (PVAMC). Implant status after FL or MF surgery was assessed using dental encounter and radiographs at subsequent follow-up appointments to assess for early implant failures within 6 months of implant placement. RESULTS: The FL technique was used to place 89 implants in 38 subjects, while the MF technique was used to place 381 implants in 139 subjects. Early failure occurred in 37 implants, of which 13 occurred in the FL group and 24 occurred in the MF group. FL surgery was found to be associated with a 265% increase in early implant failure (OR 2.653; 95% CL 1.287-5.469) and was statistically significant (p = 0.0064). Residents were over 200% more likely to have an early implant failure when using the FL technique (OR 2.314; 95% CL 1.112-4.816), CONCLUSIONS: Analysis revealed flapless implant placement was associated with higher early implant failure rates. In addition, early failures were more likely to occur when residents placed an implant using the flapless technique. While FL surgery can result in long-term success, it is a more technique-sensitive approach that requires greater clinical skill and stricter case selection to perform.