Caveolin-1 protein expression as a prognostic biomarker of gastrointestinal tumours: A systematic review and meta-analysis.

BACKGROUND: Gastrointestinal (GI) cancers remain a major threat worldwide, accounting for over 30% of cancer deaths. The identification of novel prognostic biomarkers remains a challenge despite significant advances in the field. The CAV1 gene, encoding the caveolin-1 protein, remains enigmatic in cancer and carcinogenesis, as it has been proposed to act as both a tumour promoter and a tumour suppressor. METHODS: To analyse the differential role of caveolin-1 expression in both tumour cells and stroma in relation to prognosis in GI tumours, we performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; PROSPERO registration number: CRD42022299148. RESULTS: Our analysis showed that high levels of caveolin-1 in tumour cells were associated with poor prognosis and inferior overall survival (OS) in oesophageal and pancreatic cancer and hepatocellular carcinoma (HCC), but not in gastric and colorectal cancer. Importantly, our study showed that higher stromal caveolin-1 expression was associated with significantly longer OS and disease-free survival in colorectal cancer. Analysis of stromal caveolin-1 expression in the remaining tumours showed a similar trend, although it did not reach statistical significance. CONCLUSIONS: The data suggest that caveolin-1 expression in the tumour cells of oesophageal, pancreatic cancer and HCC and in the stroma of colorectal cancer may be an important novel predictive biomarker for the clinical management of these diseases in a curative setting. However, the main conclusion of our analysis is that caveolin-1 expression should always be assessed separately in stroma and tumour cells.

Markers of tumor inflammation as prognostic factors for overall survival in patients with advanced pancreatic cancer receiving first-line FOLFIRINOX chemotherapy.

BACKGROUND: Identifying pretreatment blood markers that distinguish prognostic groups of patients with advanced pancreatic ductal adenocarcinoma (PDAC) under first-line FOLFIRINOX chemotherapy has the potential to improve management of this condition. Aim of this study was to determine the prognostic utility of a range of pretreatment, inflammation-related, blood cell markers in this group of patients. MATERIAL AND METHODS: Data from a training cohort were analyzed to identify potential pretreatment blood markers correlating to survival outcomes. The most informative markers were further analyzed in a validation cohort comprised patients from a geographically separate cancer center undergoing the same treatment. RESULTS: A total of 138 consecutive patients receiving FOLFIRINOX chemotherapy between 2010 and 2019, constituted the training cohort. Neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), and platelet/lymphocyte ratio (PLR) as well as the systemic inflammatory response index (SIRI) and CA19.9 showed prognostic significance in addition to tumor stage. A pretreatment SIRI score cutoff of 2.35 differentiated between a poor prognostic group with median overall survival (mOS) 5.1 months and a better prognostic group, mOS 12.5 months. SIRI ≤/> 2.35 was predictive of mOS in patients with locally advanced and metastatic PDAC. SIRI was confirmed as a prognostic marker in a validation cohort of 67 patients with mOS of 13.4 months and 6.3 months for those with SIRI ≤ 2.35 and >2.35, respectively. Additional analysis revealed baseline SIRI as being prognostic within additional subgroups of patients in both cohorts. CONCLUSIONS: This large, retrospective, analysis of real-world patients receiving first-line FOLFIRINOX chemotherapy for advanced PDAC has identified the pretreatment blood SIRI as a strong prognostic marker for survival. This will allow better counseling of patients with regards to the benefits of treatment, improved stratification within clinical trials, and potentially identify groups of patients for novel therapy trials as first-line treatment.

Real world data regarding the management of cancer-associated thrombosis.

PURPOSE OF REVIEW: Patients with cancer are at high risk for thrombotic events, mainly deep vein thrombosis and pulmonary embolism. Low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the current treatment options for cancer-associated thrombosis (CAT). We assessed real world data (RWD) regarding treatment patterns of CAT from 1 September 2018 to 31 January 2020. RECENT FINDINGS: RWD showed that LMWHs were the most common initial anticoagulation treatment for CAT. Based on these data DOACs had a lower risk of recurrent venous thromboembolism compared with LMWHs and warfarin. However, the selection bias and the small number of patients in these studies might explain this difference and these limitations should be taken into consideration. Moreover, there was no statistical difference regarding adverse events during anticoagulant treatment between LMWHs and DOACs with the limitations of RWD. As far as the duration of the treatment is concerned, the adherence ranged from 100% to 67.3% at 6 months. SUMMARY: The current review of RWD illustrates that LMWHs and DOACs are used for the treatment of CAT. LMWHs are most commonly used for the initial management of CAT. Data regarding recurrence of CAT, adverse events, compliance and duration of anticoagulant treatment should be analyzed with caution as RWD are observational studies with many limitations. Further research is needed to elucidate the best algorithm for the management of CAT.

Predictive factors of thromboembolic complications in patients with esophagogatric adenocarcinoma undergoing preoperative chemotherapy.

BACKGROUND: Thromboembolic events (TEEs) represent a significant treatment and disease complication for cancer patients. In the present study we assessed the incidence of TEEs in patients receiving preoperative chemotherapy for esophagogastric adenocarcinoma. The risk factors for TEE development and their impact on prognosis were further analyzed. MATERIAL AND METHODS: Data from 590 patients with esophagogastric adenocarcinoma, who received preoperative epirubicin-cisplatin with capecitabine (ECX) or 5-fluorouracil (ECF) between 2009 and 2016 in three UK hospitals were retrospectively collected. RESULTS: Twenty-one percent had stomach primary and 98% received ECX chemotherapy. In total, 52 patients (9%) had a venous and 22 (4%) an arterial event. Of those patients with venous TEEs (vTTEs), 39 had pulmonary embolism and 13 deep vein thrombosis, whereas in patients with arterial TEEs (arTTEs), 7 developed a myocardial infarct, 8 developed limb ischemia, 4 developed cerebrovascular accidents and 3 developed superior mesenteric artery thrombosis. ArTEEs were associated with a much higher inoperability rate compared to cases without TEE or with vTEE (77% vs. 20% vs. 31%, respectively, p < .001). Independent risk factors of vTEEs were primary site being the stomach (Odds ratio [OR] 3.24, 95%CI 1.72-6.12, p < .001), being overweight (OR 3.11, 95%CI 1.33-7.26, p = .009) or obese (OR 4.52, 95%CI 1.85-11.09, p = .001) and the presence of central venous access device (OR 3.40, 95%CI 1.00-11.55, p = .050). In contrast, anticoagulant treatment was independently associated with a lower risk of vTEE (OR 0.22, 95%CI 0.06-0.83, p = .026). Khorana score of 4-5 was an independent risk factor of arTEE (OR 6.38, 95%CI 1.85-22.04, p = .003). Finally, arTEEs were an independent poor prognostic factor for OS, when adjusted for baseline patient, tumor and treatment characteristics (Hazard ratio 3.02, 95%CI 1.85-4.95, p < .001). CONCLUSION: Preoperative ECX/ECF chemotherapy for patients with resectable esophagogastric adenocarcinoma was associated with relatively high incidence of TEEs. However, only arTEEs affected patient survival outcomes.

Pseudomyxoma Peritonei: A Challenging Clinical Diagnosis. Case Report and Review of the Literature.

Background: Pseudomyxoma peritonei (PMP) is a clinical entity of subtle onset abdominal pain, ascites, and distention associated with characteristic imaging. In most cases, laparoscopic exploration will give the definitive diagnosis and histopathologic verification. However, usually there are difficulties in the diagnosis of this disease. Case Report: Herein, we present a case of a 51-year-old female who developed ascites over 5 months. An investigational laparotomy established the diagnosis of PMP, after the discovery of a mucinous, grey-brown tumor that was CK20 positive and CK7 negative. Subsequently, chemotherapy with oxaliplatin combined with 5-FU (FOLFOX4 regimen), was initiated and the patient survived for 30 months. We also present a comprehensive review of the English literature concerning the different symptoms and radiological findings of this rare entity. According to the literature review, 35 cases of PMP with different clinical and radiological findings have been described. In the majority of the cases, ultrasound, computed tomography or magnetic resonance imaging was orientating towards a proper diagnosis before a diagnostic laparotomy. Conclusion: The combination of a clinical picture with the characteristic imaging findings enables a prompt diagnosis of PMP, making prognosis more favorable.

Exploring the biology of cancer of unknown primary: breakthroughs and drawbacks.

BACKGROUND: Cancer of unknown primary (CUP) ranks among the ten most common malignancies worldwide. Cancer of unknown primary presents as disseminated disease, has a dismal prognosis and remains a diagnosis of exclusion. The natural history and biology of the disease is poorly understood, and efforts are focused on identifying the specific 'CUP signature'. MATERIALS AND METHODS: We collected and analysed all published research in the biology of CUP from 1974 till present (Medline, Embase, ASCO and ESMO Congresses). RESULTS: Current scientific evidence suggests that aneuploidy and karyotype changes are frequent, while more subtle molecular aberrations, such as epidermal growth factor receptor family proteins, cKit/PDGFR are frequently overexpressed, although without prognostic significance. Loss of function of tumour suppressor genes, active angiogenesis, a hypoxic genetic programme and a mesenchymal transitory phenotype have been reported in CUP and may be indicative of unfavourable prognosis. Molecular pathway analyses have identified various biomolecules impacting on survival (pAKT, pMAPK, c-Met, p21 and pPRS6). Finally, circulating tumour cells have recently been reported as a frequent phenomenon in CUP. CONCLUSIONS: Overall, advances in understanding CUP biology have been weak and the application of gene expression profiling failed to identify an as yet elusive 'CUP molecular signature'. MicroRNA, epigenetic and proteomic studies are warranted to better characterize the biological profile of CUP and unravel its mystery.

Hyperthermic intraperitoneal chemotherapy for management of gastrointestinal and biliary tract malignancies: a systematic review and meta-analysis of randomized trials.

Background: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) promised to transform the management of peritoneal carcinomatosis (PC). Forty years since the introduction of the technique, published data from randomized controlled trials (RCTs) remain scarce. We assessed the cumulative comprehensive available evidence on the use of HIPEC in gastrointestinal (GI) and biliary tract malignancies and established the current benchmark for GI HIPEC research in both the prevention and treatment of peritoneal metastases. Methods: RCTs were identified through a systematic search of Medline, Cochrane and Embase databases. Overall survival and progression-free survival were the outcomes of interest. Results: The search resulted in 13 RCTs for gastric cancer (10 on prophylactic and 3 on therapeutic HIPEC), 4 for colorectal cancer (2 on prophylactic and 2 on therapeutic HIPEC), and 1 for pancreatic cancer. No RCTs were identified that included other types of GI or biliary tract cancers. Current randomized evidence does not support any overall survival benefit from the use of HIPEC in the adjuvant setting for gastric cancer or for colorectal cancer in any setting. Despite the survival benefit noticed in the treatment of PC from gastric cancer (risk ratio 0.85, 95% confidence interval 0.77-0.93; P<0.001), the results were derived from only 190 patients. Conclusions: The current evidence from RCTs does not support the use of HIPEC in the treatment/prevention of PC in GI and biliary tract malignancies. HIPEC should continue to be considered experimental until level 1 evidence from properly designed international multicenter studies becomes available.

Metformin: A Promising Radiosensitizer in Neoadjuvant Rectal Cancer Treatment.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) decreases the risk of local recurrence after surgery in patients with locally advanced rectal cancer (LARC) and metformin is constantly gaining scientific interest due to its potentially radiosensitizing effect. OBJECTIVE: This review article aims to better clarify the role of metformin as a radiosensitizer in patients with LARC undergoing neoadjuvant concurrent chemoradiotherapy. METHODS: We used the PubMed database to retrieve journal articles and the inclusion criteria were all human studies that illustrated the effective role of metformin in the neoadjuvant setting of locally advanced rectal cancer. RESULTS: Our search resulted in 17 citations, of which 10 eventually fulfilled the inclusion criteria of our study. Promising results (improved tumor and nodal regression as well as higher pathologic complete response rate) have been occasionally documented with metformin use in some of the included studies. However, regarding survival and all-cause mortality, no significant difference has been found. CONCLUSION: Metformin might constitute a highly promising radiosensitizer in neoadjuvant LARC treatment attracting much scientific interest. Due to the lack of studies with high evidence, further advanced research is required to enhance the existing knowledge about its potential value in this field.

COVID-19 Emotional and Mental Impact on Cancer Patients Receiving Radiotherapy: An Interpretation of Potential Explaining Descriptors.

Background: Significant changes in the accessibility and viability of health services have been observed during the COVID-19 period, particularly in vulnerable groups such as cancer patients. In this study, we described the impact of radical practice and perceived changes on cancer patients' mental well-being and investigated potential outcome descriptors. Methods: Generalized anxiety disorder assessment (GAD-7), patient health (PHQ-9), and World Health Organization-five well-being index (WHO-5) questionnaires were used to assess anxiety, depression, and mental well-being. Information on participants, disease baseline information, and COVID-19-related questions were collected, and related explanatory variables were included for statistical analysis. Results: The mean score values for anxiety, depression, and mental well-being were 4.7 ± 5.53, 4.9 ± 6.42, and 72.2 ± 18.53, respectively. GAD-7 and PHQ-9 scores were statistically associated (p < 0.001), while high values of GAD-7 and PHQ-9 questionnaires were related to low values of WHO-5 (p < 0.001).Using the GAD-7 scale, 16.2% of participants were classified as having mild anxiety (GAD-7 score: 5−9).Mild to more severe anxiety was significantly associated with a history of mental health conditions (p = 0.01, OR = 3.74, 95% CI [1.372−10.21]), and stage category (stage III/IV vs. I/II, p = 0.01, OR = 3.83, 95% CI [1.38−10.64]. From the participants, 36.2% were considered to have depression (PHQ-9 score ≥ 5). Depression was related with older patients (p = 0.05, OR = 1.63, 95% CI [1.16−2.3]), those with previous mental health conditions (p = 0.03, OR = 14.24, 95% CI [2.47−81.84]), those concerned about the COVID-19 impact on their cancer treatment (p = 0.027, OR = 0.19, 95% CI [0.045−0.82]) or those who felt that COVID-19 pandemic has affected mental health (p = 0.013, OR = 3.56, 95% CI [1.30−9.72]). Additionally, most participants (86.7%) had a good well-being score (WHO-5 score ≥ 50). Mental well-being seemed more reduced among stage I−III patients than stage IV patients (p = 0.014, OR = 0.12, 95% CI [0.023−0.65]). Conclusion: There is a necessity for comprehensive cancer care improvement. These patients' main concern related to cancer therapy, yet the group of patients who were mentally affected by the pandemic should be identified and supported.

The Mental Health Burden of Patients with Colorectal Cancer Receiving Care during the COVID-19 Pandemic: Results of the PICO-SM Study.

The COVID-19 pandemic has resulted in unprecedented changes to the lives of patients with cancer. To evaluate the impact of the COVID-19 pandemic on the mental health and well-being of patients with colorectal cancer, we conducted a prospective longitudinal questionnaire study at a UK tertiary cancer centre. In total, 216 participants were included: mean age 65 years, 57% (n = 122) male, 92% (n = 198) of white ethnicity. Amongst participants who completed the screening psychometric questionnaire, 24% (n = 48/203) reported anxiety (GAD-7 ≥ 5), 15% (n = 31/204) depressive symptoms (PHQ-9 ≥ 10), 3% (n = 5/190) probable post-traumatic stress disorder (PC-PTSD-5 ≥ 4), and 31% (n = 66/213) poor well-being (WHO-5 < 50). In the subgroup (n = 95/216, 44%) who consented to and completed a follow-up survey 6 months later, there was a significant increase in the number of participants at risk of depression (4% vs. 13%, p = 0.021). Self-reported concern about the COVID-19 pandemic impacting one's mental health is associated with increased likelihood of anxiety, depression, and poor well-being, in respective multivariate analyses. In conclusion, screening for the mental health impact of the COVID-19 pandemic is essential to ensure timely action from all key stakeholders and to avoid potentially longer-term detrimental consequences.

Comparing health-related quality of life of cancer patients under chemotherapy and of their caregivers.

INTRODUCTION: Cancer is a major disorder physically and psychologically affecting both patients and their caregivers. In this study, health-related quality of life (HRQoL) of patient-caregiver dyads during the period of chemotherapy was assessed. MATERIAL AND METHODS: Two hundred twenty-two cancer patient-caregiver dyads were enrolled in the study, which was conducted from October 2008 to March 2009. HRQoL was evaluated with EQ-5D. RESULTS: The mean age of the sample was 57.4 and 48.9 for patients and caregivers, respectively. The EQ-5D descriptive system indicates that female patients more frequently experience anxiety and depression than male patients. Male and higher-education caregivers had higher VAS scores, while demographic factors did not seem to influence patients' HRQoL. Anxiety and depression of caregivers were correlated with patients' problems in self-care and usual activities. CONCLUSIONS: Quality of life is highly influenced during the period of chemotherapy for both patients and caregivers and is often under reported. Interventions that can improve HRQoL, especially in the domain of mental health for both cancer patients and their caregivers, need to be implemented.

Pancreaticobiliary Malignancies in the Emergency Room: Management of Acute Complications and Oncological Emergencies.

BACKGROUND: Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In this review, we focus on the management of oncological emergencies in PB malignancies and the potential complication of associated therapeutic interventions. METHODS: Biobliographic review of current evidence on the management of oncological emergencies, their potential complications, as well as synthesis of recommendations was performed. The pathogenesis, frequency, related symptoms as well as appropriate investigations are presented. RESULTS: The oncologic emergencies in PB patients were summarised in six categories: (1) hematological (including febrile neutropaenia, thrombocytopenia, coagulopathies), (2) gastrointestinal (gastric outlet and biliary obstruction, gastrointestinal bleeding), (3) thromboembolic events, (4) ascites, (5) metabolic disorders and (6) neurologic complications. The pathogenesis, frequency, related symptoms as well as appropriate investigations are also presented. CONCLUSION: Patients with PB malignancies are at increased risk of a wide variation of medical emergencies. Clinical knowledge, early recognition and collaboration with the relevant specialties are critical to manage these complications effectively, tailoring overall management around the actual prognosis and individuals' expectations.

Prognostic significance and therapeutic implications of Caveolin-1 in gastrointestinal tract malignancies.

Caveolin-1 (CAV1) is expressed in several solid tumors both in cancerous cells as well as in tumor stroma and is reported to be related to cancer progression, metastasis, therapy resistance and clinical outcomes. Many studies report contrasting functions of this protein depending on the tumor cell model, the tumor type, or the stage of cancer studied. This protein is reported to function both as tumor suppressor and as tumor promoter. In this review, we aim to summarize translational and clinical studies that provide evidence of the role of CAV1 in tumor progression and survival outcome focusing on tumors of the gastrointestinal (GI) tract. Towards this aim, a detailed search has been performed for studies on the expression and the role of CAV1 in oesophageal, gastric, colorectal, pancreatic cancer and cholangiocarcinoma prognosis. We also review and discuss the implication of CAV1 in the outcome of pharmacological interventions. We conclude that CAV1 has the potential to become an important prognostic, and possibly predictive, biomarker in GI malignancies. It may also become a novel target towards the development of improved cancer therapies. However, it is obvious that there remains a lack of consensus on important issues such as the methodologies and cut-off levels in caveolin assessment. This ultimately result in many studies being contradictory not only in terms of the role of CAV1 as a tumor-promoting or suppressing gene but also in terms of the tumor compartment in which the levels of this protein may be of clinical significance. Addressing these important technical issues, in conjunction with a further elucidation of the role of CAV1 in tumor formation and progression, will delineate the importance of CAV1 in prognostic and therapeutic perspectives.

Cutaneous soft tissue sarcomas: survival-related factors.

Cutaneous sarcomas are a heterogeneous group of rare mesenchymal neoplasms representing less than 1% of malignant tumors. Histology report remains the cornerstone for the diagnosis of these tumors. The most important clinicopathologic parameters related to prognosis include larger tumor size, high mitotic index, head and neck location, p53 mutations, depth of infiltration and histological grade, vascular and perineural invasion as well as the surgical margins status. Applying advanced biopsy techniques might offer more precise assessment of surgical margins, which constitutes a significant precondition for the management of these tumors. The management of cutaneous soft tissue sarcomas requires a multidisciplinary approach. Surgery remains the standard treatment, nonetheless adjuvant therapy may be required, consisting of radiotherapy, chemotherapy, and molecular targeted therapies to improve treatment outcomes. The role of molecular profiling in the treatment of uncontrolled disease is promising, but it may be offered to a relatively small proportion of patients and its use is still considered experimental in this setting. Due to the rarity of the disease, there is a need for knowledge and experience to be shared, pooled, organized and rationalized so that recent developments in medical science can have a major impact on the disease course. Multicenter clinical trials are needed to improve the care of patients with cutaneous sarcomas.

Modification to Systemic Anticancer Therapy at the Start of the COVID-19 Pandemic and its Overall Impact on Survival Outcomes in Patients with Colorectal Cancer.

BACKGROUND: Since the beginning of the COVID-19 pandemic, multiple changes to the provision of cancer care has been introduced to maximize patient safety and protect staff. We aimed to identify factors influencing clinicians' decision on treatment modification during the initial phase of the pandemic, and to assess its impact on outcomes in patients with colorectal cancer. PATIENTS AND METHODS: Electronic records of patients seen in a large United Kingdom tertiary cancer center was reviewed. The frequency and type of changes to systemic anticancer therapy , as well as the factors predicting clinicians' decision were assessed. RESULTS: A total of 418 patients; mean age 63 ± 12 years and 57% male were included. More than half of the patients had modification to their treatment; with treatment delay (21%) or cancellation (10%), being the most common. Majority of patients on neoadjuvant treatment (97%) proceeded with treatment, with some form of treatment modification in 20%. Half of patients on adjuvant treatment had their treatment plan modified. Overall, a change in treatment was more likely in older patients (OR 1.028 [95% CI 1.010-1.047]; P = .002), and in patients who had already received higher number of cycles of systemic anticancer therapy (OR 1.040 [95% CI 1.016-1.065]; P = .001). A change in treatment was less likely further out of the first national lockdown (OR 0.837 [95% CI 0.758-0.925]; P < .001). Patients on third-line treatment were most likely to have alterations to their treatment plan (69%, n=33/48). CONCLUSION: During the first wave of COVID-19 in the United Kingdom, clinicians adapted clinical practice in accordance to local and national guidance, especially amongst older patients and those on third-line treatment. Further real-world data are needed to document the important impact of changes to treatment on outcomes in patients with cancer.

Next-Generation Sequencing of Circulating Tumor DNA Can Optimize Second-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer after Progression on anti-EGFR Therapy: Time to Rethink Our Approach.

BACKGROUND: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge. SUMMARY: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions. KEY MESSAGES: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

The COVID-19 survey pandemic: a critical approach.

COVID-19 pandemic has obviously affected patients' behavior towards seeking medical help as well as physicians' decision in the management of emergencies. Our recent experience as surgeons at a COVID-19 referral hospital revealed cases which share an alerting characteristic: the delay in appropriate management. Unfortunately for COVID-19 negative patients a "coronacentric" health system has been adopted. In view of measures applied to avoid spread of the disease, a significant delay in patients' presentation as well as in their in-hospital management is observed. We present cases where delay in appropriate management affected the patients' outcome and underline the fact that balancing between COVID-19 safety measures and a patient who needs urgent treatment can be very challenging and stressful.

YAP/Hippo Pathway and Cancer Immunity: It Takes Two to Tango.

Hippo pathway with its main molecule YAP is a crucial pathway for development, tissue homeostasis, wound healing, tissue regeneration, and cancer. In this review, we discuss the multiple effects of the YAP/Hippo pathway in the immune system and cancer. We analyzed a series of effects: extracellular vesicles enhanced immunity through inhibition of LATS1/2, ways of modulation of the tumor microenvironment, YAP- and TAZ-mediated upregulation of PDL1, high expression of YAP and PDL1 in EGFR-TKI-resistant cells, enhanced YAP activity in inflammation, and the effect of the Hippo pathway on T cells, B cells, Tregs, macrophages, and myeloid-derived suppressor cells (MDSCs). These pleiotropic effects render the YAP and Hippo pathway a key pathway for exploitation in the future, in order to enhance our immunotherapy treatment strategies in oncology.