COVID-19-Associated Portal Vein Thrombosis Post-Cholecystitis.

This case study describes a 45-year-old Caucasian male with a past medical history of obesity, hypertension, and non-insulin-dependent diabetes mellitus, who in the setting of coronavirus disease 2019 (COVID-19) pneumonia, developed portal vein thrombosis (PVT) presenting as an acute abdomen after hospital discharge from a cholecystitis episode. PVT is a very infrequent thromboembolic condition, classically occurring in patients with systemic conditions such as cirrhosis, malignancy, pancreatitis, diverticulitis, autoimmunity, and thrombophilia. PVT can cause serious complications, such as intestinal infarction, or even death, if not promptly treated. Due to the limited number of reports in the literature describing PVT in the COVID-19 setting, its prevalence, natural history, mechanism, and precise clinical features remain unknown. Therefore, clinical suspicion should be high for PVT, in any COVID-19 patient who presents with abdominal pain or associated signs and symptoms. To the best of our knowledge, this is the first report of COVID-19-associated PVT causing extensive thrombosis in the portal vein and its right branch, occurring in the setting of early-stage cirrhosis after a preceding episode of cholecystitis.

Portomesenteric Vein Thrombosis in Patients Undergoing Sleeve Gastrectomy: an Updated Systematic Review and Meta-Analysis of 101,914 Patients.

INTRODUCTION: Portomesenteric vein thrombosis (PMVT) is a rare but potentially fatal complication of sleeve gastrectomy (SG). The rising prevalence of SG has led to a surge in the occurrence of PMVT, while the associated risk factors have not been fully elucidated. This study aims to determine the incidence and risk factors of PMVT in patients undergoing SG. METHODS: A comprehensive literature search was performed in PubMed and EMBASE databases. Proportion and regression meta-analyses were conducted. RESULTS: In a total of 76 studies including 101,914 patients undergoing SG, we identified 357 patients with PMVT. Mean follow-up was 14.4 (SD: 16.3) months. The incidence of PMVT was found to be 0.50% (95%CI: 0.40-0.61%). The majority of the population presented with abdominal pain (91.8%) at an average of 22.4 days postoperatively and PMVT was mainly diagnosed with computed tomography (CT) (96.0%). Hematologic abnormalities predisposing to thrombophilia were identified in 34.9% of the population. Advanced age (p=0.02) and low center volume (p <0.0001) were significantly associated with PMVT, while gender, BMI, hematologic abnormality, prior history of deep vein thrombosis or pulmonary embolism, type of prophylactic anticoagulation, and duration of prophylactic anticoagulation were not associated with the incidence of PMVT in meta-regression analyses. Treatment included therapeutic anticoagulation in 93.4% and the mortality rate was 4/357 (1.1%). CONCLUSION: PMVT is a rare complication of sleeve gastrectomy with an incidence rate <1% that is associated with low center volume and advanced age but is not affected by the duration or type of thromboprophylaxis administered postoperatively.

Anastomotic Leak and Perioperative Outcomes of Esophagectomy for Esophageal Cancer during the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

Background and Objectives: The coronavirus disease-2019 (COVID-19) pandemic influenced the healthcare system tremendously, as well as the number of elective surgical procedures worldwide. The aim of this study is to investigate the COVID-19 pandemic's impact on esophagectomies. Materials and Methods: The MEDLINE (via PubMed), Cochrane Library, and Google Scholar bibliographical databases were systematically searched. Original clinical studies investigating the outcomes of esophageal cancer surgery during the COVID-19 pandemic were deemed eligible. After exclusion criteria were applied, eight studies were considered eligible for inclusion. Results: Eight studies with non-overlapping populations, reporting on patients undergoing esophagectomy for resectable esophageal cancer during the COVID-19 pandemic, were included in our analysis, with a total of 18548 patients. Background characteristics for age, lung disease, smoking history as well as Body Mass Index and age were equal among the groups. The background of diabetes presented a statistically significant difference among the groups. Perioperative outcomes like reoperation rates, the length of intensive care unit stay, or readmission rates were not significantly increased during the pandemic. The 30-day readmission, and 30- and 90-day mortality were not affected either. The length of hospital stay was significantly lower in the non-pandemic period. Conclusions: The results of our study support the evidence that in the context of the COVID-19 pandemic, esophageal cancer operations took place safely and effectively, similarly to the standards of the non-COVID-19 era.

Anastomotic Leak in Ovarian Cancer Cytoreduction Surgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: Anastomotic leaks (AL) following ovarian cytoreduction surgery could be detrimental, leading to significant delays in commencing adjuvant chemotherapy, prolonged hospital stays and increased morbidity. The aim of this study was to investigate risk factors associated with anastomotic leaks after ovarian cytoreduction surgery. MATERIAL AND METHODS: The MEDLINE (via PubMed), Cochrane Library, EMBASE and Scopus bibliographical databases were searched. Original clinical studies investigating risk factors for AL in ovarian cytoreduction surgery were included. RESULTS: Eighteen studies with non-overlapping populations reporting on patients undergoing cytoreduction surgery for ovarian cancer (n = 4622, including 344 cases complicated by AL) were included in our analysis. Patients undergoing ovarian cytoreduction surgery complicated by AL had a significantly higher rate of 30-day mortality but no difference in 60-day mortality. Multiple bowel resections were associated with an increased risk of postoperative AL, while no association was observed with body mass index (BMI), American Society of Anesthesiologists (ASA) score, age, smoking, operative approach (primary versus interval cytoreductive, stapled versus hand-sewn anastomoses and formation of diverting stoma), neoadjuvant chemotherapy and use of hyperthermic intraperitoneal chemotherapy (HIPEC). DISCUSSION: Multiple bowel resections were the only clinical risk factor associated with increased risk for AL after bowel surgery in the ovarian cancer population. The increased 30-day mortality rate in patients undergoing ovarian cytoreduction complicated by AL highlights the need to minimize the number of bowel resections in this population. Further studies are required to clarify any association between neoadjuvant chemotherapy and decreased AL rates.

Systemic inflammatory changes and their clinical implications following thoracic cancer surgery.

Trauma that follows every surgical procedure triggers an inflammatory response, which in the majority of the cases reflects the associated tissue damage. Tissue regeneration, postoperative outcomes, and systemic antibacterial activity are highly dependent on the initial inflammatory response elicited by surgical trauma. More specifically, in thoracic surgery, systemic cytokine and cellular changes have an impact on several measured postoperative outcomes. Lastly, the introduction of video-assisted and robotic-assisted thoracic surgery has been shown to provide improved postoperative outcomes with altered systemic inflammatory response, when compared to open thoracic surgery. This review outlines the major systemic inflammatory changes observed in thoracic cancer surgery as well as its clinical significance.

Circulating microRNAs and Clinicopathological Findings of Papillary Thyroid Cancer: A Systematic Review.

BACKGROUND/AIM: Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a rising incidence. There is a need for a non-invasive preoperative test to enable better patient counselling. The aim of this systematic review was to investigate the potential role of circulating microRNAs (miRNAs) in the diagnosis and prognosis of PTC. MATERIALS AND METHODS: A systematic literature search was performed using MEDLINE, Cochrane, and Scopus databases (last search date was December 1, 2021). Studies investigating the expression of miRNAs in the serum or plasma of patients with PTC were deemed eligible for inclusion. RESULTS: Among the 1,533 screened studies, 39 studies met the inclusion criteria. In total, 108 miRNAs candidates were identified in the serum, plasma, or exosomes of patients suffering from PTC. Furthermore, association of circulating miRNAs with thyroid cancer-specific clinicopathological features, such as tumor size (13 miRNAs), location (3 miRNAs), extrathyroidal extension (9 miRNAs), pre- vs. postoperative period (31 miRNAs), lymph node metastasis (17 miRNAs), TNM stage (9 miRNAs), BRAF V600E mutation (6 miRNAs), serum thyroglobulin levels (2 miRNAs), 131I avid metastases (13 miRNAs), and tumor recurrence (2 miRNAs) was also depicted in this study. CONCLUSION: MiRNAs provide a potentially promising role in the diagnosis and prognosis of PTC. There is a correlation between miRNA expression profiles and specific clinicopathological features of PTC. However, to enable their use in clinical practice, further clinical studies are required to validate the predictive value and utility of miRNAs as biomarkers.

Trends in Primary Gallbladder Cancer Incidence and Incidence-based Mortality in the United States, 1973 to 2015.

OBJECTIVES: Primary gallbladder cancer (GBC) is the most common biliary tract cancer with poor survival despite aggressive treatment. This study aimed to investigate the trends of GBC incidence and incidence-based mortality (IBM) over the last 4 decades. MATERIALS AND METHODS: GBC cases diagnosed between 1973 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Incidence rates, IBM rates, and annual percent changes (APCs) were calculated and stratified according to population and tumor characteristics. RESULTS: The cohort consisted of 10,792 predominantly white (81%) and female (71%) GBC patients. The overall GBC incidence decreased by 1.65% (95% confidence interval [CI]: 1.45% to 1.84%) per year since 1973, but has plateaued since 2002. IBM decreased by 1.69% (95% CI: 1.22% to 2.16%) per year from 1980 to 2015; the rate of decrease in IBM rates was lower during 1997 to 2015 (APC: -1.19%, 95% CI: -1.68% to -0.71%) compared with 1980 to 1997 (APC: -3.13%, 95% CI: -3.68% to -2.58%). CONCLUSIONS: The incidence and IBM rates of GBC have been decreasing over the last 40 years, but the decrease plateaued over the last 2 decades. The effects of treatment modalities, including laparoscopic cholecystectomy, adjuvant chemotherapy, and radiation on the incidence and IBM of GBC need to be further investigated.

Delayed intracranial hemorrhage of patients with mild traumatic brain injury under antithrombotics on routine repeat CT scan: a systematic review and meta-analysis.

BACKGROUND: Patients on antithrombotics experiencing mild traumatic brain injury (mTBI) may benefit from a routine repeat CT scan to detect delayed intracranial hemorrhage (dICH). OBJECTIVES: The primary outcome was the incidence of dICH on routine repeat CT scans of mTBI patients on antithrombotics within an intra-hospital observation period of up to 48 hours. The secondary outcomes were potential risk factors, readmissions, neurosurgical interventions, and mortality. METHODS: A systematic review and a meta-analysis of single proportions were performed according to the PRISMA and PRESS guidelines. The risk of bias was assessed using Newcastle-Ottawa Scale. RESULTS: Eighteen studies with 4613 patients were included. The pooled incidence of dICH was 2% [95% CI 1-2%] with similar rates between different antithrombotic regimens, even in combination. Of the 67 patients with dICH reported (1.45%), eleven required surgery (0.24%), while six died (0.13%). Loss of consciousness was a risk factor of dICH (risk ratio 3.04 [95%CI 0.96; 9.58]). A total of 48 patients were reported for readmission without associated death or surgical intervention. CONCLUSION: The contribution of this routine repeat CT scan should be questioned due to the low incidence, the limited clinical significance, and the unsubstantiated clinical benefit of early or systematic detection of dICH.

Autonomic Neuromodulation for Atrial Fibrillation Following Cardiac Surgery: JACC Review Topic of the Week.

Autonomic neuromodulation therapies (ANMTs) (ie, ganglionated plexus ablation, epicardial injections for temporary neurotoxicity, low-level vagus nerve stimulation [LL-VNS], stellate ganglion block, baroreceptor stimulation, spinal cord stimulation, and renal nerve denervation) constitute an emerging therapeutic approach for arrhythmias. Very little is known about ANMTs' preventive potential for postoperative atrial fibrillation (POAF) after cardiac surgery. The purpose of this review is to summarize and critically appraise the currently available evidence. Herein, the authors conducted a systematic review of 922 articles that yielded 7 randomized controlled trials. In the meta-analysis, ANMTs reduced POAF incidence (OR: 0.37; 95% CI: 0.25 to 0.55) and burden (mean difference [MD]: -3.51 hours; 95% CI: -6.64 to -0.38 hours), length of stay (MD: -0.82 days; 95% CI: -1.59 to -0.04 days), and interleukin-6 (MD: -79.92 pg/mL; 95% CI: -151.12 to -8.33 pg/mL), mainly attributed to LL-VNS and epicardial injections. Moving forward, these findings establish a base for future larger and comparative trials with ANMTs, to optimize and expand their use.

The Fanconi anemia pathway and Breast Cancer: A comprehensive review of clinical data.

The development of breast cancer depends on several risk factors, including environmental, lifestyle and genetic factors. Despite the evolution of DNA sequencing techniques and biomarker detection, the epidemiology and mechanisms of various breast cancer susceptibility genes have not been elucidated yet. Dysregulation of the DNA damage response causes genomic instability and increases the rate of mutagenesis and the risk of carcinogenesis. The Fanconi Anemia (FA) pathway is an important component of the DNA damage response and plays a critical role in the repair of DNA interstrand crosslinks and genomic stability. The FA pathway involves 22 recognized genes and specific mutations have been identified as the underlying defect in the majority of FA patients. A thorough understanding of the function and epidemiology of these genes in breast cancer is critical for the development and implementation of individualized therapies that target unique tumor profiles. Targeted therapies (PARP inhibitors) exploiting the FA pathway gene defects have been developed and have shown promising results. This narrative review summarizes the current literature on the involvement of FA genes in sporadic and familial breast cancer with a focus on clinical data derived from large cohorts.

Challenges of Hematopoietic Stem Cell Transplantation in the Era of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic raised unprecedented concerns in the hematopoietic stem cell transplant community. The diagnosis of COVID-19 in these transplant recipients may require extensive laboratory testing and high clinical suspicion, as atypical clinical manifestations or other respiratory viral infections are common in this patient population. The underlying malignancies, immunosuppressed state, frequently observed coinfections, and advanced age in some patients may also predispose them to worse clinical outcomes. Similar outcomes have been previously described with other human coronaviruses, including the severe acute respiratory syndrome coronavirus and the Middle East respiratory syndrome coronavirus. Many hematopoietic stem cell transplant organizations have issued elaborative guidelines that aim to prevent transmission and hence adverse patient outcomes. All potential donors are thoroughly screened, and donated products are cryopreserved in advance. Potential hematopoietic stem cell transplant recipients are also screened, and most nonurgent transplant cases with low risk of progression and/or death are deferred. Current hematopoietic stem cell transplant recipients should adhere to precaution and isolation measures, while their transplant units should also follow strict safety protocols, similar to other infectious outbreaks. The prolonged susceptibility of hematopoietic stem cell transplant recipients to respiratory viral infections might necessitate extending these measures even after the peak of the outbreak until a gradually return to normality is possible.

Imaging in the COVID-19 era: Lessons learned during a pandemic.

The first year of the coronavirus disease 2019 (COVID-19) pandemic has been a year of unprecedented changes, scientific breakthroughs, and controversies. The radiology community has not been spared from the challenges imposed on global healthcare systems. Radiology has played a crucial part in tackling this pandemic, either by demonstrating the manifestations of the virus and guiding patient management, or by safely handling the patients and mitigating transmission within the hospital. Major modifications involving all aspects of daily radiology practice have occurred as a result of the pandemic, including workflow alterations, volume reductions, and strict infection control strategies. Despite the ongoing challenges, considerable knowledge has been gained that will guide future innovations. The aim of this review is to provide the latest evidence on the role of imaging in the diagnosis of the multifaceted manifestations of COVID-19, and to discuss the implications of the pandemic on radiology departments globally, including infection control strategies and delays in cancer screening. Lastly, the promising contribution of artificial intelligence in the COVID-19 pandemic is explored.

Diagnostic, Predictive and Prognostic Molecular Biomarkers in Pancreatic Cancer: An Overview for Clinicians.

Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and is associated with aggressive tumor behavior and poor prognosis. Most patients with PDAC present with an advanced disease stage and treatment-resistant tumors. The lack of noninvasive tests for PDAC diagnosis and survival prediction mandates the identification of novel biomarkers. The early identification of high-risk patients and patients with PDAC is of utmost importance. In addition, the identification of molecules that are associated with tumor biology, aggressiveness, and metastatic potential is crucial to predict survival and to provide patients with personalized treatment regimens. In this review, we summarize the current literature and focus on newer biomarkers, which are continuously added to the armamentarium of PDAC screening, predictive tools, and prognostic tools.

Laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma: An individual patient data survival meta-analysis.

BACKGROUND: We compared the outcomes of laparoscopic hepatectomy (LH) vs. open hepatectomy (OH) for intrahepatic cholangiocarcinoma (iCCA). METHODS: A systematic review of the MEDLINE, EMBASE, Scopus, and Cochrane Library databases was performed using PRISMA guidelines (end-of-search date: 08-June-2020). Individual patient data on overall survival (OS) and recurrence-free survival (RFS) were extracted. Random-effects meta-analyses, and one- and two-stage survival analyses were conducted. RESULTS: Eight retrospective cohort studies comparing LH (n = 544) vs. OH (n = 2256) were identified. LH demonstrated lower overall complication (Risk ratio [RR] = 0.64, 95% confidence interval [CI]: 0.46-0.90; p = 0.01), surgical lymphadenectomy (RR = 0.74, 95% CI: 0.58-0.93; p = 0.01) and margin-positive resection (RR = 0.78, 95% CI: 0.62-0.99; p = 0.04) rates, and higher recurrence-free rate (RR = 1.24, 95% CI: 1.01-1.51; p = 0.04) vs. OH. In Cox regression, no difference was observed regarding OS (Hazard Ratio [HR] = 1.11, 95% CI: 0.65-1.91; p = 0.70) and RFS (HR = 1.19, 95% CI: 0.74-1.90; p = 0.47). CONCLUSION: The use of LH should be considered when feasible in well-selected iCCA patients by hepatobiliary surgeons with experience in minimally-invasive surgery.

Magnetically Controlled Capsule Endoscopy Versus Conventional Gastroscopy: A Systematic Review and Meta-Analysis.

BACKGROUND: The introduction of magnetically controlled capsule endoscopy overcame the restriction of passive capsule endoscopy movement, thus allowing an improved visualization of the gastrointestinal lumen, where other imaging studies seem to be unhelpful. The aim of this study is to systematically review the performance of magnetically controlled capsule endoscopy and evaluate its potential as a less invasive diagnostic method in the detection of gastric lesions. METHODS: A systematic search was performed in PubMed (Medline), EMBASE, Google Scholar, Scopus, Who Global Health Library (GHL), Virtual Health Library (VHL), Clinicaltrials.gov, Cochrane Library, and ISI Web of Science databases. Proportion meta-analyses were performed to estimate the pooled sensitivity of magnetically controlled capsuled endoscopy in the detection of gastrointestinal lesions. RESULTS: Among the 3026 studies that were initially assessed, 7 studies were finally included, with a total of 916 patients and 745 gastric lesions. The mean capsule endoscopy examination time was 21.92±8.87 minutes. The pooled overall sensitivity of magnetically controlled capsule endoscopy was 87% [95% confidence interval (CI), 84%-89%]. Subgroup analysis showed that the sensitivity of identifying gastric ulcers was 82% (95% CI: 71%-89%), gastric polyps was 82% (95% CI: 76%-87%), and gastric erosions was 95% (95% CI: 86%-98%). In general, magnetically controlled capsule endoscopy was well tolerated by the participants with minimal adverse events. CONCLUSION: The magnetically controlled capsule endoscopy demonstrated an acceptable sensitivity of identifying gastric lesions. Further prospective comparative studies are needed to identify the risks and benefits of this new technique, as well as to determine its role as a replacement for conventional gastroscopy.

Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry.

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.

Validation of the 8th Edition American Joint Commission on Cancer (AJCC) Gallbladder Cancer Staging System: Prognostic Discrimination and Identification of Key Predictive Factors.

The scope of our study was to compare the predictive ability of American Joint Committee on Cancer (AJCC) 7th and 8th edition in gallbladder carcinoma (GBC) patients, investigate the effect of AJCC 8th nodal status on the survival, and identify risk factors associated with the survival after N reclassification using the National Cancer Database (NCDB) in the period 2005-2015. The cohort consisted of 7743 patients diagnosed with GBC; 202 patients met the criteria for reclassification and were denoted as stage ≥III by AJCC 7th and 8th edition criteria. Overall survival concordance indices were similar for patients when classified by AJCC 8th (OS c-index: 0.665) versus AJCC 7th edition (OS c-index: 0.663). Relative mortality was higher within strata of T1, T2, and T3 patients with N2 compared with N1 stage (T1 HR: 2.258, p < 0.001; T2 HR: 1.607, p < 0.001; Τ3 HR: 1.306, p < 0.001). The risk of death was higher in T1-T3 patients with Nx compared with N1 stage (T1 HR: 1.281, p = 0.043, T2 HR: 2.221, p < 0.001, T3 HR: 2.194, p < 0.001). In patients with AJCC 8th edition stage ≥IIIB GBC and an available grade, univariate analysis showed that higher stage, Charlson-Deyo score ≥ 2, higher tumor grade, and unknown nodal status were associated with an increased risk of death, while year of diagnosis after 2013, academic center, chemotherapy. and radiation therapy were associated with decreased risk of death. Chemotherapy and radiation therapy were associated with decreased risk of death in patients with T3-T4 and T2-T4 GBC, respectively. In conclusion, the updated AJCC 8th GBC staging system was comparable to the 7th edition, with the recently implemented changes in N classification assessment failing to improve the prognostic performance of the staging system. Further prospective studies are needed to validate the T2 stage subclassification as well as to clarify the association, if any is actually present, between advanced N staging and increased risk of death in patients of the same T stage.

The Epidemiology, Staging and Outcomes of Sarcomatoid Hepatocellular Carcinoma: A SEER Population Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) subtypes differ in terms of histopathology and prognosis. Sarcomatoid HCC is rare and literature concerning the survival of patients with sarcomatoid HCC is scarce. MATERIALS AND METHODS: Data of patients with sarcomatoid HCC, diagnosed from 1989 to 2016, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. We evaluated the baseline and tumor related data, overall survival (OS), disease-specific survival and the performance (Harrell's concordance index - OS c-index) of the eighth edition of the American Joint Committee on Cancer TNM staging system (AJCC8). In addition, univariate and multivariate forward stepwise cox regression analyses were performed to identify factors associated with increased risk of death. RESULTS: The SEER cohort consisted of 71 patients, mostly males (n=49, 69.0%), of White race (n=51, 71.8%) and the most common stage at presentation was stage IVB (n=30, 42.3%). The overall predictive ability of AJCC8 was mediocre, with an OS c-index=0.577 (SE=0.048). Surgery (hazard ratio=0.25, p<0.001) was significantly associated with reduced risk of death. Advanced TNM stage was not associated with increased risk of death. CONCLUSION: Sarcomatoid HCC, a rare subtype of HCC, is associated with poor outcomes in terms of overall and disease-specific survival across all disease stages. Surgery seems to be of utmost importance. The eighth edition of the AJCC8 for HCC underperforms in predicting the survival of patients with sarcomatoid subtype.

The Role of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review and Pooled Analysis of 2,402 Patients.

BACKGROUND: Immune checkpoints inhibitors (ICIs) have emerged as a treatment option for several malignancies. Nivolumab, pembrolizumab, nivolumab plus ipilimumab, and atezolizumab plus bevacizumab have been approved for the management of advanced-stage hepatocellular carcinoma (HCC). We aimed to systematically review the literature and summarize the characteristics and outcomes of patients with HCC treated with ICIs. METHODS: A systematic literature search of PubMed, the Cochrane Library, and ClinicalTrials.gov was performed according to the PRISMA statement (end of search date: November 7, 2020). Quality of evidence assessment was also performed. RESULTS: Sixty-three articles including 2,402 patients were analyzed, 2,376 of whom received ICIs for unresectable HCC. Response to ICIs could be evaluated in 2,116 patients; the overall objective response rate (ORR) and disease control rate (DCR) were 22.7% and 60.7%, respectively, and the mean overall survival (OS) was 15.8 months. The ORR, DCR, and OS for nivolumab (n = 846) were 19.7%, 51.1%, and 18.7 months, respectively; for pembrolizumab (n = 435) they were 20.7%, 64.6% and 13.3 months, respectively. The combination of atezolizumab/bevacizumab (n = 460) demonstrated an ORR and DCR of 30% and 77%, respectively. The overall rate of treatment discontinuation because of adverse events was 14.9%. Fifteen patients received ICIs in the liver transplant (LT) setting (one pre-LT for bridging, 14 for post-LT recurrence); fatal graft rejection was reported in 40.0% (n = 6/15) and mortality in 80.0% (n = 12/15). CONCLUSION: ICIs are safe and effective against unresectable HCC, but caution is warranted regarding their use in the LT setting because of the high graft rejection rate. IMPLICATIONS FOR PRACTICE: This systematic review pooled the outcomes from studies reporting on the use of immune checkpoint inhibitors (ICIs) for the management of 2,402 patients with advanced-stage hepatocellular carcinoma (HCC), 2,376 of whom had unresectable HCC. The objective response rate and disease control rate were 22.7% and 60.7%, respectively, and the mean overall survival was 15.8 months. The overall rate of treatment discontinuation because of adverse events was 14.9%. Fifteen patients received ICIs in the liver transplant (LT) setting (one pre-LT for bridging, 14 for post-LT recurrence). Six of these patients experienced graft rejection (40.0%).

The anti-adhesive effect of anti-VEGF agents in experimental models: A systematic review.

Adhesions constitute a major problem in abdominal-pelvic and thoracic surgery with significant impact in the postoperative quality of life and healthcare services utilization. Adhesiogenesis is the result of increased fibrin formation, impaired fibrinolysis, angiogenesis, and fibrosis. Despite the recent advancements, the ideal anti-adhesive agent remains to be determined. To this end, we performed a comprehensive literature search in PubMed, EMBASE, and Scopus databases to identify studies investigating the antiadhesive role of anti-VEGF agents in peritoneal, pleural, and pericardial experimental adhesion models. Fifteen studies were eligible for inclusion with a total population of 602 animals (334 rats, 180 rabbits, and 88 mice). The majority of included studies (11/15) used bevacizumab, while three studies used other anti-VEGF antibodies and one study used an anti-VEGFR-antibody. A rat model was used in nine studies, while rabbit (n = 3) or mouse (n = 3) models were used less frequently. Eleven studies used peritoneal models, three studies used pleural models, and one study used a pericardial model. The scales (n = 12) and interval (Range: 1-42 days) used for the evaluation of adhesions varied between the studies. All studies demonstrated a significant decrease in adhesion scores between the anti-VEGF and control groups up to 42 days postprocedure. VEGF blockade resulted in decreased fibrosis in four out of five studies that used peritoneal models, while the effect on pleural models depended on the pleurodesis agent and was significant between 7 and 28 days. The effect of anti-VEGF agents on anastomosis integrity depends on the dose and the model that is used (inconclusive results).Current data support the anti-adhesive role of Anti-VEGF agents in all three serosal surfaces up to 6 weeks postprocedure. Further studies are needed to confirm the anti-adhesive role of anti-VEGF agents in pleural and pericardial adhesion experimental models and investigate any effect on anastomosis integrity in peritoneal models.