Considered parameters in Comprehensive geriatric Assessment.
\r\n\tWith this goal in mind, together with the US Prof. John M. Ballato and the InechOpen publishing house since 2011 we have published in 2011, 2013, 2015 and 2017 4 books of our serial “Optoelectronics” and the book “Excitons”, edited in 2018 by Prof. Sergei L. Pyshkin. Publishing the new book “Luminescence” we are pleased to note the growing number of countries participating in this undertaking as well as for a long time fruitfully cooperating scientists from the United States and the Republic of Moldova.
\r\n\tSpecialists from all over the world have published in edited by us books their works in the field of research of the luminescent properties of various materials suitable for use in optoelectronic devices, the development of new structures and the results of their application in practice.
Hepatocellular carcinoma (HCC) is characterized by high clinical and biological variability [1]. Diagnosis and treatment of HCC always require multidisciplinary approaches.
\nTreatment requires commonly to make a decision between several specific interventions and to choose the one that allows the best risk-benefit ratio for a chosen patient.
\nTherapeutical approach shall take into account acute cirrhotic impairment risk and patient management experience, thus to avoid iatrogenic prognosis worsening.
\nNowadays, patients older than 75 years account for 22% of HCC patients [2]. That is due to treatment and technological advancements which allow to reach an overall survival of decades, if therapy is well pondered; patients are kept in lifelong follow-up and intervention is timed well.
\nTherapeutical approaches to treat HCC can be divided into surgical approaches, such as major hepatic resection, minor hepatic resection, and wedge resection. Nonsurgical approaches are interventional radiology, chemotherapy, and most recently hadrontherapy. Since people older in age frequently have several comorbidities, often a specific less invasive therapeutical approach is needed.
\nAge is not a good outcome predictor: fit elderly patients may tolerate radical and invasive approaches, while unfit patients may not [3]. Treatment of older adults must take into account multiple issues related to the condition of aging itself. First of all, patient’s frailty, thus invasive approaches are commonly excluded in patients advanced in age; on the other hand, noninvasive treatments are often palliative and do not achieve a satisfactory disease-free survival (DFS) or long-term survival (LTS) [3, 4]. Into this complex scenario, treatment strategies should also consider obstacles to cure the patients either physical or psychological, illness awareness, linguistic or cultural barriers, poverty, depression, and family environment.
\nGiving indication for or against invasive treatments is arduous in elderly. A decision for intervention shall consider either oncological principles and radical excision on one side or performance status, tolerability of treatment, and actual life expectancy on the other. HCC patients are not only in need for specific treatments, they must also be guided through routine activities in order to ameliorate their own hepatopathic condition, such as lifestyle correction (diet, water and salt assumption, physical activity, and smoking); instructions to the patient himself and to his family for therapeutical adhesion and instruction for early recognition of cirrhotic impairment or therapeutical side effects.
\nPhysiological age is a new fundamental concept which is crucial in evaluating an advance in aged patient’s performance status beyond his chronological age, which is still today too often used as a threshold to exclude or include a patient into specific treatment protocols [4].
\nThe aim of this chapter is to give guidelines about management of elderly patients suffering from HCC and to give indications to treat those suffering from HCC as primary malignancy, recurrent illness, or metastatic disease either.
\nHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality. In almost all populations, males have higher liver cancer rates than females, with male/female ratios usually averaging between 2:1 and 4:1 [1, 2].
\nHCC global distribution varies by region, incidence rate, sex, and also, by etiology. Normally, HCC incidence in female peaks 5 years later than males. Age-specific onset patterns are likely related to differences in the dominant hepatitis virus in population, age at viral infection, and the existence of other risk factors. As for average age at infection, normally, HCV carriers became infected in adulthood, while HBV carriers tend to become infected in childhood [2].
\nRecently, a significant increase in HCC incidence in hepatitis-free patients was noted; this index had a boost and went from 22% in 2000–2004 to 31% in 2010–2014 (database ITALICA) [5]. Among nonvirus-related hepatopathy, incidence of HCC in Alcoholic fatty liver disease patients (AFLD-patients) remains stable (17 vs. 19%), while a significant incidence increase was seen in Non Alcoholic fatty liver disease Patients (NAFLD-Patients) or in patients suffering from cryptogenic cirrhosis (0.5 vs. 9%) [5].
\nOften NAFLD-patients are demanding to treat; patients in this group have commonly several comorbidities such as metabolic syndrome; therefore, they need a more accurate and multidimensional clinical evaluation in order to choose the best treatment and achieve the best outcome from their condition.
\nHCV interferon-mediated clearance, associated with mild to severe fibrosis reduces hepatopathy progression and cirrhosis incidence, thus HCC’s incidence reduction in SVR patients is expectable.
\nHCC hazard in HBV replication-controlled infection is reduced but not abolished, although effective antiviral therapy reduces HCC incidence in HBV- or HCV-positive patients [6].
\nSudden HCC recurrence was reported by several papers after Direct Acting Antiretrovirals (DAA) mediated HCV clearance [7]. Other papers have found similar incidence of HCC after DAA-mediated HCV clearance when compared to IFN-mediated SVR but considering an overall 24-month follow-up [7]. HCC incidence after HCV clearance is still not sufficiently evaluated.
\nMore than two-third of patients newly diagnosed with HCC are aged >65 years [8], and this number is expected to increase as the world population ages. Furthermore, there is heterogeneity in the aging process, which further contributes to the complexity of treatment decisions. These factors contribute to age-related variations in treatment patterns and outcomes, potentially resulting in increased likelihood of under- or overtreatment, which can influence both risk of treatment toxicity and survival [9].
\nGeriatric patients may be extremely complex to treat due to comorbidities that may affect them. Therefore, a clinical evaluation is fundamental to assess the best treatment for each patient.
\nAspects that must be considered comprehend not only biological age, HCC stage, and liver status, but also general patient conditions, performance status, and, in particular, individual and familial psychological frame, will to fight against the disease, and treatment tolerability. All these parameters are included into the concept of physiological age which goes far beyond chronological age and considers many crucial aspects of aging which is an extremely individual process.
\nSince chronologic age alone is a poor descriptor of heterogeneity in the aging process, a systematic and evidence-based way to assess physiological age is needed to guide treatment decisions.
\nComprehensive geriatric assessment (CGA) is defined as a multidimensional, interdisciplinary diagnostic process focusing on determining an older person’s medical, psychosocial, and functional capabilities to develop a coordinated and integrated plan for treatment and long-term follow-up [10] (Table 1).
\nConsidered parameters in Comprehensive geriatric Assessment.
Important reasons to perform GA in older patients with cancer are detection of unidentified problems and risks for which targeted interventions can be applied and prediction of adverse outcomes (e.g., toxicity, other relevant items such as functional or cognitive decline, postoperative complications); and better estimation of residual life expectancy and lethality of the malignancy in the context of competing comorbidities and general health problems. There is clear evidence that GA items independently predict OS in a variety of oncology diseases and treatment settings. Poorer OS in older patients with cancer and deficits identified in geriatric domains might potentially be explained by several factors (e.g., increased risk of death resulting from causes other than cancer, increased death resulting from cancer because of less aggressive treatment, or death resulting from complications of cancer treatment) [9].
\nPatients with risk factors, in particular if older in age, must be lifelong under clinical surveillance for HCC onset. Principal conditions that require normally a twice per year follow-up are advanced cirrhosis, active HCV infection or cleared HCV infection, and HBV-controlled infection. Surveillance is made by liver-US and serum α-fetoprotein assessment. Oncological-marker-only surveillance is not recommendable and since cirrhotic parenchyma is on average poorly explorable, imaging shall be performed by a hepatobiliary dedicated team. Suspect nodules shall be further investigated by CT scan or hepatospecific MRI, which allows to make in the same session either a noninvasive diagnosis or staging when nodule is >10 mm in diameter [11]. Noninvasive diagnosis is cost-effective and a big advantage especially for elderly in poor performance status.
\nPatients older in age are the cohort that receives the highest benefit in early cancer detection since lower stage HCCs are associated with less invasive interventions, faster recovery, lower mortality rate, and better QoL [4].
\nTherefore, geriatric patients shall be educated to strictly comply to follow-up timing and to change their lifestyle in order to ameliorate liver function and reduce liver damage.
\nHCC shall never be considered as a single-cell malignancy: it is a whole organ malignancy; cell transformation is due to liver damage from hepatotropic viruses, toxins, and metabolic syndrome [2, 4]. Even a radical liver resection that cures the single malignancy does not exclude the onset of further lesions and rarely metastases after radical resection is possible [12].
\nThe aim of HCC treatment is to freeze the disease into a chronic stage and to treat lesions as they show. There are several possible treatments that allow in some cases extremely long survival, even in metastatic patients [12].
\nManagement of HCC patients can be extremely complex, so only dedicated multidisciplinary teams shall treat these patients who are regularly discussed into liver units [4].
\nHepatic resection is the gold standard in noncirrhotic liver. In western countries, HCC incidence is raising, mostly due to NAFLD and metabolic syndrome [13].
\nPatients with these pathologic conditions can develop HCC in the absence of cirrhosis or severe fibrosis [14], although hepatic parenchyma shall not be considered healthy since steatosis is determinable in 50% of patients and steatohepatitis (NASH) in 25% [15, 16]. A multicentric study confirmed that HCC patients suffering from metabolic syndrome have higher postoperative hepatic failure, mortality, and morbidity rates [15, 16].
\nNevertheless, hepatic resection on metabolic syndrome-liver has excellent oncologic effectiveness and leads to long-time survival [16].
\nIn cirrhotic patients, hepatic resection is the first-line treatment for single HCC nodule and preserved hepatic function, strict indications for hepatic resection are serum-bilirubin <1.5 mg/dl and Hepatic Portal-Venous Gradient (HPVG) ≤10 mmHg or platelets ≥100,000 [17].
\nResection in patients with light portal hypertension and nonenrollable for liver transplant shall be well weighted against locoregional treatments [17].
\nCirrhotic liver resection can be a safe practice in well-selected patients with low morbidity and mortality rates [18]. Selection shall be lead through a global, multiparametric evaluation of the patient and shall pass beyond a dogmatic data interpretation.
\nAll guidelines agree that is needed to select cirrhotic patients for hepatic resection thus to achieve the best outcome, but selection criteria are not universally accepted, the ones suggested from several surgical groups are not based on strong evidence. Therefore, it is necessary to develop a multiparametric evidence-based prognostic score to allow to evaluate a “tailored” operative risk and expected survival.
\nTailored-risk evaluation is even more important in elderly patients since aging is a strict-individual process, multidimensional evaluation, and CGA score, in particular, are crucial to assess whether advanced in aged patients can be either enrolled or not for surgery with a deep gap in quality of life and overall survival [4].
\nChild-Pugh class B patients are routinely excluded from surgery; however, in some cases, satisfying outcome was achieved by performing limited hepatic resections in strictly selected patients, with mild serum bilirubin raise (≤2 mg/dl) and without portal hypertension [19] (Table 2).
\nIndications to liver resection in HCC patient.
Laparoscopic or robotic approaches could widen indications to Child-Pugh class B patients due to their little invasivity.
\nIn elderly patients, these approaches are extremely interesting.
\nHepatic surgery obtains excellent results in elderly patients, even if cirrhotic. Advance age alone is no more a contraindication to surgery.
\nHowever, elderly patients, cirrhotic or not, are often excluded from surgery due to comorbidities that rise ASA score and operative risk. Mini-invasive procedures on the one hand make operative time longer and worsen blood-gases control; on the other hand, they allow to spare hepatic parenchyma and shorten hospitalization and recovery [20]. Therefore, patients treated with mini-invasive surgery vs. open achieve a better outcome, especially if elderly, who often suffer longer hospitalizations either physically (reduced physical activity and nosocomial infection risk) and psychologically (depression, confusion, and dizziness) [20].
\nAs reported by a recent meta-analysis, even better outcome is achieved with surgery (open or mini-invasive) vs. transarterial chemoembolization (TACE), which is the most used palliative care technique for HCC, whose advantage remains consistent even in advance HCC, even if vascular invasion is present, so up to stage Barcelona Clinic Liver Cancer (BCLC) stageC [17, 21].
\nPortal hypertension is often associated with hepatic damage. However, several studies proved that hepatic residual functionality and not portal hypertension affects short- and long-time outcome of hepatic resections [22, 23].
\nPatients with mild portal hypertension and preserved hepatic functionality can receive limited resections with morbidity, mortality, and OS similar to patients without portal hypertension [19].
\nHCC frequently develops and spreads through the portal system and that is why several authors recommend performing anatomical resections; these studies prove a better OS and local disease control for anatomic resection vs. wedge resection [24, 25].
\nMore recently, a large Japanese retrospective study (more than 72,000 patients) proved superiority of anatomical resection only for HCC diameter >2 and <5 cm. Superiority is not proven if HCC diameter is <2 cm since portal diffusion risk is very low or >5 cm because other factors influence prognosis [26].
\nIt is also possible to match a parenchyma-sparing surgery with anatomical resection, thanks to subsegmental US-guided resections [27]. This technique with laparoscopic subglissonian or extraglissionan approach is not of common use, due to its technical difficulty and exclusion criteria, that are ascites and moderate to severe portal hypertension. The approach remains interesting and future technical development is possible, especially thanks to robotic surgery. Subsegmental resection shall not be performed for advanced HCC (diameter >2 cm) in order to respect oncologic principles of a radical resection [27]. The procedure allows to spare liver parenchyma, and it may be really interesting for elderly even if cirrhotics with an early-HCC diagnosis.
\nLiver transplantation (LT) is considered the first-line treatment for cirrhotic patients. LT indications are given following the Milan criteria: single HCC nodules (diameter <5 cm) or less than 3 HCC nodules all <3 cm and in any case nonresectable [17].
\nA modest expansion to Milan criteria was given by “up to seven criteria,” which had achieved satisfactory results in patients without extrahepatic metastases and/or macrovascular invasion. A prospective validation is needed [28].
\nAn increasing number of older patients with end-stage liver disease (ESLD) are evaluated for liver transplantation (LT). In fact, patients aged ≥65 years represent one of the fastest-growing patient populations in LT [29]. The most extreme of these patients, those aged ≥70 years, are associated with several difficult clinical dilemmas. Firstly, advanced patient age is associated with higher risk and poorer outcomes after complex surgical procedures [30]. LT in advanced age patients is associated with increased risk for infection and cardiovascular impairment, increased resource utilization, and lower patient survival [31]. Since the number of adult candidates on the waiting list continues to rise and organ availability remains unable to fully meet this demand, proper organ allocation and utilization are critically important.
\nEquivalent outcomes can be achieved in elderly recipients and age alone should not be used as a barrier to LT.
\nRecent data for waitlist registrants on the SRTR registry suggest that <12% of waitlisted patients are aged ≥65 years, but this proportion has steadily increased over the past decade. Continued improvements in care in pre- and posttransplant medicine and surgery suggest that this age group will continue to grow on the waiting list. With this demographic shift in the ESLD, more elderly patients will be considered for LT, and the use of scarce donor livers will need to be addressed because these recipients have a shorter life expectancy compared with younger patients. Despite the shortened lifespan, single-centered reports have shown equivalent posttransplant survival in super-selected patients [32, 33].
\nDue to physical and psychological impairment, elderly patients are often considered unfit for liver transplantation, since in super-selected groups only satisfying result in LT is achieved, surgical resection remains, for elderly, the first-line approach when performable.
\nPercutaneous radiofrequency thermoablation (RFTA) and microwave thermoablation (MWA) are considered the standard care for patients with BCLC 0-A HCC, who are not eligible for surgical treatment.
\nPercutaneous ablation techniques are indicated for HCC nodules <2 cm, while nodules with diameter between 2 and 3 cm need to be discussed in a multidisciplinary unit in order to determine an appropriate management plan (Table 3). In patients with a single HCC nodule less than 2 cm in diameter, a complete necrosis ratio of 97% is expected [34].
\nIndications to Radio-Frequency Thermal Ablation.
Several randomized studies have documented the superiority of surgical resection over percutaneous ablation techniques in terms of efficacy, while thermoablation has shown lower morbidity, mortality, hospitalization rates, and costs [35].
\nMWA and RFTA have shown comparable safety and effective results, although MWA seems to have certain theoretical advantages compared to RFTA: shorter procedure, higher ablation temperature, larger area of necrosis, lower probability of biliary duct injury, and reduction in the heat-sink effect through a more uniform heating in the volume of ablation. However, these advantages have not been confirmed in clinical practice. Although EASL guidelines recommend the use of MWA for nodules up to 4 cm, a recent phase II trial, comparing the two techniques in patients with similar mean lesion volumes, showed no significant difference between them in terms of outcome and recurrence ratio [36].
\nRFTA and MWA can also be safely and effectively performed via a video laparoscopic (VL) approach [37]. VL allows the operator to treat nodules that would normally not be eligible for a percutaneous approach due to nonaccessible locations and allows for hybrid management of patients with multiple nodules (e.g., surgical resection and RFTA on additional nonresectable nodules).
\nPercutaneous ablation techniques are a precious tool in management of elderly patients with multiple comorbidities.
\nHCC is often methacronous and new nodules are expected to develop during follow-up after the first tumor. Therefore, it is crucial to perform an appropriate follow-up in patients who have been treated for HCC, in order to detect new nodules at an early stage, so that the least invasive treatment available can be delivered. This is particularly relevant in elderly patients, or those who have already undergone extensive hepatic resection, who might not be eligible for surgery.
\nPercutaneous ablation is a recommended treatment modality, when indicated, due to its mini-invasive nature, high effectiveness, low rates of adverse events, short hospitalization times, and its relatively few contraindications.
\nTransarterial chemoembolization (TACE) is a palliative treatment that is routinely used in patients with HCC that are neither eligible for surgery nor for percutaneous ablation, and in stage BCLC B HCC. TACE is indicated for asymptomatic patients in Child-Pugh class up to B7 and PS ≤ 1 [17] (Table 4).
\nIndications to Trans Arterial Chemo-Embolization.
A study found no significant difference in survival following TACE in patients with Child-Pugh Class 8–9 compared to class 7; however, patients with Child-Pugh 8–9 had a significant worse prognosis and more dangerous side effects [38].
\nTACE is not indicated for patients with signs of HCC vascular invasion, metastases, untreatable ascites, jaundice, thrombosis of a major portal vessel, and HCC nodules >10 cm. In these cases, due to an already compromised liver function, there is a high risk of liver failure and eventually death.
\nDrug-eluting beads TACE (DEB-TACE) is a more recent variation of conventional TACE (cTACE) that uses embolizing beads eluted with doxorubicin as a chemotherapeutic agent. It has shown overall similar effectiveness, but less systemic side effects compared to cTACE.
\nRandomized trials have found superior outcomes with DEB-TACE compared to cTACE in patients with Child-Pugh class B and/or PS ≥ 1 [39, 40].
\nAlthough contrast-enhanced CT (CECT) or MRI with hepatospecific contrast agent is recommended for TACE outcome evaluation, contrast-enhanced US (CEUS) could be an appropriate alternative in patients with less than four nodules [41].
\nIf imaging follow-up detects residual or recurrent HCC nodules, TACE can be repeated up to three times per nodule. Treatment failure is considered when there are no signs of lesion response, as assessed using the mRECIST criteria, after two treatments or if there is no complete response after three treatments [42]; in eastern countries, different staging criteria, RECICIL, are actually in use [43].
\nTACE has been proved safe and effective in elderly as well as in younger patients. In particular, a prospective study found that elderly patients suffered from the same complication rates as nonelderly, while effectiveness rates were similar [44].
\nMore important than age is the liver functional status, and the patient’s performance status that mostly affects the safety profile of TACE. Therefore, TACE can be an effective palliative treatment able to give benefits in terms of disease control and improved quality of life in elderly patients with HCC.
\nTACE can also be combined with percutaneous ablation, particularly in patients with tumor recurrence within 1 year since the initial treatment, those with tumor diameters of 3.1–5.0 cm, and those with tumor recurrences after initial treatment with thermoablation, where sequential TACE-thermoablation might be the best treatment option [45].
\nThe benefit of this sequential approach is due to the occlusion of hepatic arterial flow by means of embolization before ablation. Furthermore, lipiodol and gelatine sponge particles used in TACE reduce the portal flow around the tumor by filling the peripheral portal vein via multiple arterioportal communications. Therefore, the reduced cooling effect of the hepatic blood flow on ablation-induced thermal coagulation allows the achievement of an enlarged ablation zone which might reduce recurrence rates.
\nTransarterial radioembolization (TARE) is a palliative brachytherapy for HCC. Radioactive substances (I131-lipidol or Y90-beads) are delivered into the tumor by injecting them selectively into its feeding arteries.
\nThis is a complex technique that requires a high-level specialization and has potentially severe side effects such as hepatic, intestinal, and lung toxicity [17]. Therefore, it should only be performed in specialized centers, with high volume activity and experience with this procedure.
\nGiven the fact that TARE has minimal embolizing effects, it can be safely performed even in patients with thrombosis of the portal vein or its branches.
\nIt can be used as a first-line treatment when TACE is not recommended, such as in the case of large or multifocal HCC or if there are signs of portal thrombosis. However, liver function must be conserved (Child-Pugh ≤7, bilirubin ≤2.0 mg/dl, no ascites) [17].
\nTARE has also been shown to be an appropriate bridge or downstaging treatment in order to meet liver transplantation criteria [17, 46].
\nFurthermore, TARE can be used as a second-line treatment in patients who did not respond to TACE or who are intolerant to chemotherapy [17, 47].
\nMean survival for Child-Pugh class A or B patients who underwent TARE is, respectively, 17.2 and 7.7 months [48, 49]. Mean survival for patients with portal vein thrombosis is 9 months, while for those with intrahepatic portal thrombosis is 17 months [50].
\nA study has revealed similar results in terms of overall survival (OS) and toxicity between cTACE and TARE in patients with nonresectable HCC [51]; another study has shown a better time-to-progression (TTP) and lower toxicity following TARE compared to TACE [52].
\nTARE cannot be performed in patients with a pulmonary shunt >20% or if other vascular anomalies may cause irradiation of visceral organs (stomach and intestine) [17].
\nIndications for this treatment are often controversial and should only be discussed in dedicated multidisciplinary teams. The difficulty in determining the precise indications of TARE is in part due to the lack of cost-effectiveness studies and the fact that its therapeutical equivalence to TACE has only been proved in selected patients. TARE is usually indicated in patients with stage BCLC C HCC, especially those with portal vein thrombosis and preserved liver function.
\nTARE is usually not indicated in elderly patients, who often have a compromised liver function, and therefore, risks of liver failure and death are high. TARE can be performed in elderly with good performance status and liver functionality as a second-line treatment in patients with treatment failure following TACE.
\nTARE has not been shown superior to sorafenib in treating advanced HCC; therefore, sorafenib could be a safer treatment in elderly patients who can tolerate chemotherapy [53].
\nPEI induces cell necrosis through dehydration, protein denaturation, and small vessel disruption. It is not often used since it can only be performed in lesions <2 cm and it has a higher recurrence ratio than percutaneous ablation. It has indication only in lesions that are not considered safe for ablation due to their localization [54].
\nCompared to PEI, RF has shown better outcomes in terms of overall survival, survival at 1, 2, and 3 years, and cancer-free survival at 1, 2, and 3 years. This is probably due to the better performance of RF in terms of complete necrosis of the lesion and the low percentage of local recurrence [54].
\nRF requires fewer treatment sessions and shorter hospitalization than ethanol injection: although the quality of life of these patients was not evaluated, there was a decrease in hospitalization rates [54].
\nCell death with cryoablation is different than that with thermal ablation. The freezing process results in both intracellular and extracellular ice formation, both of which can result in cellular death, but by different mechanisms. Since the ablation zone is reperfused after the ice ball melts, the result is a rapid release of cellular debris into the systemic circulation. This probably explains the systemic complications of cryoablation (i.e., cryoshock) that are rare with heat-based ablation. Thermoablation is the preferred ablation method for treating HCC in patients with cirrhosis because of the increased risk of bleeding and of disseminated intravascular coagulation-like reaction (called cryoshock) associated with cryoablation [55, 56]. Therefore, although many studies have shown that small-volume cryoablation is feasible in patients with cirrhosis and HCC, it is difficult to justify the additional risk of cryoablation in these patients when viable heat-based alternatives are available [55].
\nThe term laser ablation refers to the thermal tissue destruction by conversion of absorbed light (usually infrared) into heat. Infrared energy penetrates tissue for 12–15 mm in depth; heat is conducted beyond this range thereby creating a larger ablation area. Optical penetration has been shown to be increased in malignant tissue compared to normal parenchyma [57].
\nLocal tissue properties, in particular perfusion, have a significant impact on the size of the ablation zone. Highly perfused tissue and large blood vessels act as a heat sink, since infrared energy is absorbed by erythrocytic heme and transported away from the target area. This phenomenon makes normal liver parenchyma relatively more resistant to LA than tumor tissue and this is the rationale for using hepatic inflow occlusion techniques such as arterial embolization (TACE) in conjunction with laser therapy [57].
\nLight transmission into tissues and the size of the ablation zone increase with higher laser power, as does the local tissue temperature reached during ablation, with consequent higher risk of overheating and carbonization of the adjacent normal tissue.
\nThe use of water-cooled laser application sheaths allows the use of a higher laser power output while preventing carbonization [58]. When using multiple water-cooled higher power fibers, ablation zones of up to 80 mm diameter can be obtained.
\nMajor complications of LA are liver failure, segmental infarction, hepatic abscess, cholangitis, bile duct injury, and hemorrhage. The technique is considered safe by rates of 1.8% for major complications and a mortality rate of 0.1% [59] and can also be used safely in elderly patients with advanced liver disease up to Child–Pugh class B [57]. Tumor seeding after percutaneous biopsy and ablative therapies is a well-known phenomenon, but it has rarely been reported following laser ablation [57].
\nA recent study compared LA and TACE in patients with a single large HCC and found a significant superiority in multifiber-LA vs. TACE in terms of recurrence rates, especially in nodules >4 cm, while OS was similar between both groups [60].
\nAblation size is critical to predict outcome; patients with lesions >6 cm or with multifocal disease (more than five nodules) are usually managed with other treatment modalities.
\nLA can be used with a curative intent only in patients with early-stage HCC. In this setting, it has shown similar outcomes compared to RFTA when treating nodules <3 cm [57, 60].
\nIn patients with advanced local HCC, LA should only be used as a palliative treatment. The use of laser ablation is not currently extensively adopted for the treatment of HCC, but given the promising outcomes shown in recent studies and the expected technical advancements, it could become an increasingly more important treatment modality for HCC in the near future.
\nSystemic therapy is recommended for HCC patients in stage BCLC-C with conserved liver functionality (Child-Pugh A), good performance status, advanced disease, and/or extrahepatic diffusion. Systemic therapy is also recommended for patients with progressive HCC after locoregional treatments or HCC with vascular invasion not enrollable for other local treatments [17].
\nTarget therapy with sorafenib proved to give survival benefits versus either placebo or cytotoxic and hormonal therapy [61].
\nObservational studies suggest that sorafenib administration in Child-Pugh B patients is as safe as administration in class A patients [62].
\nRecently, RESORCE trial showed survival benefit in regorafenib administration vs. placebo for HCC patients that went to tumor progression after sorafenib administration; all patients had tyrosine kinases-associated adverse effects [63].
\nCytotoxic chemotherapy, such as doxorubicin or FOLFOX4 scheme, can be considered in patients with conserved liver functionality and after that sorafenib therapy has suspended for adverse effects [17] (Table 5).
\nMost common adverse effects of Sorafenib.
Adverse effects of sorafenib especially dermatological, hypertension, or diarrhea in the first month of treatment are a frequent cause of treatment failure; it was proved that half-dose administration after adverse effects is associated with survival benefits [64].
\nIn some cases, for fit and super-selected patients, intolerant to sorafenib, in case of oligometastatic disease, a different disease management can be done. Mini-invasive surgical therapy along with intervention radiology may be able to remove several metastases and treat them as they show; once the primitive tumor is surgically resected, a chronic metastatic disease can be surgically controlled with survival benefits [12]. Only case reports on this field have been published, but these authors believe that more research shall be done with multicentric clinical trials to prove what has been shown only in case reports.
\nElderly can hardly ever be treated with surgical therapy due to their frailty and low PS even if in many cases, biological age does not correspond to chronological age. Sorafenib showed similar results in terms of safety and effectiveness in elderly and younger HCC populations. When administering systemic therapy, careful baseline evaluation is needed for patient’s selection in elderly population, including discussion about antiplatelet therapy discontinuation, and caution in PS ≥ 1 patients, as well as active management of toxicity.
\nAsthenia and bleeding are more frequent in the elderly. The higher frequency of bleeding is explained by concomitant antiplatelet treatments, and major asthenia is frequent in PS ≥ 1 elderly patients [65].
\nA multidimensional evaluation is crucial for elderly patients and also in advanced HCC, and decision to start systemic therapy shall be made by experienced and dedicated units.
\nPalliative treatments and supportive care aim at ameliorating patients QoL and at giving relief by symptoms. Terminal-stage HCC may have several symptoms associated with liver dysfunction due to cirrhosis, such as ascites, esophageal hemorrhage, and hepatic encephalopathy. Abdominal pain and asthenia are common.
\nParacetamol and opioids are the safest drugs for pain control in hepatopathics; Non Steroideal Antinflammatory Drugs (NSAIDs) shall be avoided due to hemorrhage risk, kidney dysfunction risk, and resistant ascites development.
\nRadiotherapy is effective in pain control due to bone metastases; control results complete in 50% of patients and partial in 80–90% [66].
\nPercutaneous cementoplasty is effective in controlling HCC vertebral metastases’ pain [67]. Brain metastases are rare and selected cases can be treated with stereotaxic radiotherapy [68].
\nMalnutrition and cachectic-state is common in end-stage oncological patients, in particular if affected by noncontrolled cirrhosis which enhances weight loss and muscular tissue loss.
\nNutritional state assessment is important in HCC patients and was observed that prognostic nutritional index can predict survival expectancy in HCC patients [69].
\nHadrontherapy or heavy charged particle therapy (CPT) is one of the newest palliative treatments available against HCC.
\nHadrontherapy technology is based on charged particles (carbon ions), which accelerated by cyclotrons or synchrotrons are conveyed into a beam to irradiate the tumor. Different from X-rays, charged particles have a sharp Bragg’s peak which is even sharper than the one of protons; therefore, they release a great part of their energy at a specific level of tissue penetration which is proportional to their kinetic energy.
\nThis technology allows to concentrate cellular damage into a very small area; therefore, CPT has higher tumor control probability (TCP) and relative biological effectiveness (RBE) than other radiotherapy techniques, it can also reduce organs at risk (OAR) and nonmalignant tissue complications probability (NTCP) [70].
\nDue to the physical properties of charged particles and, in particular, the possibility to generate a heavy concentrated damage, hypofractioning is possible with good results in terms of adverse effects.
\nClinical trials on CPT are still running; first data are hopeful; in a Japanese study that used CPT in nontreatable HCC, a 5-year local control rate was 81% and survival was 33%; results are similar to those for proton therapy with 20 fractions, but by using a total of 4 fractions in 2 days [71]. Good results are also obtained with difficult to treat porta-hepatis HCC [69]. As for HCC metastases, they can be treated with a 50.4 Gy irradiation in 12 fractions [12, 71].
\nThese treatments are still experimental but results of trials until now are encouraging, in the next future hadrontherapy may be one of the pillaRs of advance HCC treatment.
\nHadrontherapy may be extremely interesting as a treatment also for elderlies, since it has little adverse effect and thanks to hypofractioning and noninvasivity; in the future, it may become a treatment of choice for difficult-to-treat HCC in elderly and for metastatic disease. It may ensure long-time tumor control and good QoL even in people advanced in age; the only issue of this treatment is its high cost-effectiveness ratio, even though cost-effectiveness trials for CPT are not still published a CPT apparatus costs around US$ 200 million; only three carbon ion centers are available in Western Europe, seven in Asia (Japan and China), and none in US [65] (Figure 1).
\nSummary—HCC treatment decision chart in elderly recipients.
The aim of this chapter is to give information and indications about the most recent operative and nonoperative existing techniques to treat HCC. Focus on older adults’ case evaluation is of extreme importance; because lifespan enlargement will produce, in next decades, a sharp rise in HCC incidence among elderlies [2].
\nIt is strongly believed, by this multidisciplinary team, that early diagnosis is the key for HCC eradication in general population and in particular in elderly: dealing with a lower-staged cancer allows to use both less invasive and more radical treatments. Patients would then suffer less hospitalization time; would have faster recovery and lower infection risk [4]. Hospitalization time and subsequent infections are the most common cause of death for hospitalized elderly patients. Early-HCCs grow slowly when they develop in elderlies and when removed surgically or with interventional radiology mean (RFTA or MWA) recurrences appear after a sufficient time latency thus to make it possible to chronicize the disease and allow to reach survival rates not different from general population [4].
\nThe elderlies are a very heterogenic population; therefore, this kind of patients cannot be treated with a standardized protocol, but a tailored approach is needed. Each patient has its own comorbidities that must be taken into account; moreover, aging itself is an extremely individual process and different patients may have wide differences in performance status and therefore different treatment indications. Life expectancy, comorbidities, liver functionality, cancer progression, patient’s therapy compliance, psychological status, and performance status shall be all taken into account when cases are discussed into multidisciplinary teams in order to assure the best treatment, and therefore, the best OS and QoL.
\nEdited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. 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His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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Saxena",hash:"105e347b2d5dbbe6b593aceffa051efa",volumeInSeries:1,fullTitle:"Influenza - Therapeutics and Challenges",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}]},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}]},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",slug:"current-topics-in-neglected-tropical-diseases",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Alfonso J. Rodriguez-Morales",hash:"61c627da05b2ace83056d11357bdf361",volumeInSeries:3,fullTitle:"Current Topics in Neglected Tropical Diseases",editors:[{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}]},{type:"book",id:"7839",title:"Malaria",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7839.jpg",slug:"malaria",publishedDate:"December 11th 2019",editedByType:"Edited by",bookSignature:"Fyson H. Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",biography:"Dr. Kasenga is a graduate of Tumaini University, Kilimanjaro Christian Medical College, Moshi, Tanzania and Umeå University, Sweden. He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). Dr. Kasenga is married to Grace and blessed with three children, a son and two daughters: Happy, Lettice and Sungani.",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}]}]},openForSubmissionBooks:{paginationCount:7,paginationItems:[{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",hash:"8d41fa5f3a5da07469bbc121594bfd3e",secondStepPassed:!0,currentStepOfPublishingProcess:4,submissionDeadline:"March 24th 2022",isOpenForSubmission:!0,editors:[{id:"335401",title:"Prof.",name:"Margherita",surname:"Mori",slug:"margherita-mori",fullName:"Margherita Mori"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11460",title:"Pluralistic Approaches for Conservation and Sustainability in Biodiversity",coverURL:"https://cdn.intechopen.com/books/images_new/11460.jpg",hash:"ab014f8ed1669757335225786833e9a9",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"April 22nd 2022",isOpenForSubmission:!0,editors:[{id:"101105",title:"Dr.",name:"Gopal",surname:"Shukla",slug:"gopal-shukla",fullName:"Gopal Shukla"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11475",title:"Food Security Challenges and Approaches",coverURL:"https://cdn.intechopen.com/books/images_new/11475.jpg",hash:"090302a30e461cee643ec49675c811ec",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 5th 2022",isOpenForSubmission:!0,editors:[{id:"292145",title:"Dr.",name:"Muhammad",surname:"Haseeb Ahmad",slug:"muhammad-haseeb-ahmad",fullName:"Muhammad Haseeb Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11450",title:"Environmental Impacts of COVID-19 Pandemic on the World",coverURL:"https://cdn.intechopen.com/books/images_new/11450.jpg",hash:"a58c7b02d07903004be70f744f2e1835",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 10th 2022",isOpenForSubmission:!0,editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11477",title:"Public Economics - 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Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"80546",title:"Streptococcal Skin and Skin-Structure Infections",doi:"10.5772/intechopen.102894",signatures:"Alwyn Rapose",slug:"streptococcal-skin-and-skin-structure-infections",totalDownloads:48,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Streptococcal Infections",coverURL:"https://cdn.intechopen.com/books/images_new/10828.jpg",subseries:{id:"3",title:"Bacterial Infectious Diseases"}}}]},subseriesFiltersForOFChapters:[{caption:"Parasitic Infectious Diseases",value:5,count:1,group:"subseries"},{caption:"Viral Infectious Diseases",value:6,count:1,group:"subseries"},{caption:"Bacterial Infectious Diseases",value:3,count:2,group:"subseries"}],publishedBooks:{paginationCount:0,paginationItems:[]},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{paginationCount:249,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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