\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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\r\n\tIt has been said that oxidation- reduction(redox) reactions are the foundation of life – an accurate reflection in that much of cellular anabolic and catabolic metabolism is based on enzyme-catalyzed redox reactions. Oxidoreductases consist of a huge class of enzymes catalyzing the electrons transfer from an electron donor (reductant) to an electron acceptor (oxidant) molecule, taking several co-factors as nicotinamide adenine dinucleotide phosphate (NADP) or nicotinamide adenine dinucleotide (NAD) or Flavin dinucleotide (FAD). As there are several chemical and biochemical transformations reactions that comprise oxidation/reduction processes, it has long been an important goal in biotechnology to develop applications of oxidoreductases enzymes. During the last few years, significant breakthrough has been made in the development of oxidoreductase-based diagnostic tests. The proper names of oxidoreductases are in a form of "donor:acceptor oxidoreductase"; while in most cases "donor dehydrogenase" is much more common. Common names also sometimes appeared as "acceptor reductase", such as NAD+ reductase. "Donor oxidase" is a special case when O2 serves as the acceptor.
\r\n\r\n\tOxidoreductase have several functions. Oxidoreductase enzymes play significant roles in both aerobic and anaerobic metabolism. They have an important role in biological procedures like glycolysis, TCA cycle, oxidative phosphorylation, and amino acid metabolism. In glycolysis, glyceraldehydes-3-phosphate dehydrogenase accelerates the reduction of NAD+ to NADH in aerobic and anaerobic conditions. However, the re-oxidization of the generated NADH to NAD+ occurs in the oxidative phosphorylation pathway in order to maintain the redox state of the cell. In addition, during anaerobic glycolysis, the oxidation of NADH is accomplished through the reduction of pyruvate to lactate. The glycolysis product pyruvate takes part in the TCA cycle in a form of acetyl-CoA. Moreover, the pyruvate is further oxidized in the TCA cycle. All twenty of the amino acids, except for leucine and lysine, can be degraded to intermediates in TCA cycle, which allows the carbon skeletons of the amino acids to be converted into oxaloacetate and subsequently into pyruvate. The gluconeogenic pathway can then exploit the formed pyruvate.
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The problems of an open pneumothorax were already known by the ancient Greek Celsus around the year 30 AD noted: “as soon as the knife really penetrates to the chest, by cutting through the transverse septum, a sort of membrane which divides the upper from the lower parts, the man loses his life at once” [1].
\nAt that time, drainage of an empyema as described by Hippocrates (approx. 460–375 BC) was the only feasible operation [2]. The first report of a successful lung resection is attributed to Roland of Parma in 1499 who resected the herniating part of a lung, days after a penetrating chest trauma [3]. In 1846, general anesthesia with ether had been introduced by William Morton in Boston, an extremely important step in the history of surgery.
\nDuring the mid-nineteenth century, when tuberculosis reached its highest incidence, it was recognized that a state of rigidity of the mediastinum permitted an open pneumothorax. Estlander of Helsingfors was one of the first to describe wide thoracoplasty in order to “rest” a lung affected by tuberculosis (“decostalisation of the chest” in 1879) [4].
\nDuring the late nineteenth century, many experiments were carried out, mainly in animals, aimed at performing lobectomy and pneumonectomy. Usually these experiments were done in stages, the first procedure aiming at creating a state of fixation of the mediastinum. The world still was not ready yet for primary lung resections.
\nFurther in this chapter, a historical overview and an overview of modern surgical techniques for the treatment of lung cancer are outlined. The focus is on the introduction of open surgery as well as the minimally invasive surgery. In addition, a short introduction to upcoming techniques and modalities is given.
\nDuring the late nineteenth century, Joseph Lister, based on Louis Pasteur’s theory of micro-organisms, introduced the concept of asepsis in 1867. Surgeon’s hands, instruments, and surgical wounds were sterilized with 5% carbolic acid (phenol) solution and a mist of phenol was sprayed into the surgical field [5]. This policy led to an extreme reduction of post-operative mortality and for this reason, Lister is regarded as the father of modern surgery. Caroline Hampton, chief nurse and later on the wife of William Halsted, one of the founding fathers of the John’s Hopkins Hospital, developed severe dermatitis due to frequent exposure to phenol and mercuric chloride. This provoked Halsted to ask the Goodyear Company to develop rubber gloves to protect the hands of the surgical team. These became available at the end of 1890 and were soon used throughout the world [6].
\nThe aftermath of the nineteenth century saw the discovery of X-ray by William Konrad Rontgen in 1895. For the first time in mankind, it became possible to identify large tumors in the chest when not shaded by the heart and other mediastinal structures. At the turn of the twentieth century, the major barrier to enable one stage intrathoracic surgery was that of the open pneumothorax. This is remarkable since the anatomist Vesalius in 1543 had extensively studied respiration and already studied tracheotomy and positive pressure ventilation. His ideas would be dormant for about 3.5 centuries [7]. Based on this concept that there should be a pressure difference between the intra-alveolar pressure and the atmospheric pressure, Sauerbruch, still an assistant of von Mikulicz, developed the negative pressure chamber [8]—a genius idea, but quite unpractical. Only two of these operation theaters were built worldwide, one in Germany and the other one in the German Hospital (today the Lenox-Hill hospital) in New York where the surgeon Willy Meyer, emigrated to the USA from Germany in 1884, added a small positive pressure chamber over the patients head in 1909, this was called the super chamber but it was never clinically used [9]. Willy Meyer would become one of the founding fathers of the American Association for Thoracic Surgery (AATS) in 1918.
\nIn the same year, 1909, and also in New York, Meltzer and his son-in-law Auer launched their concept of positive pressure ventilation, using a flexible silk woven tracheal catheter and a continuous stream of air mixed with ether [10]. Their concept was the birth of modern anesthesia. Recognizing that this was an enormous step forward, Meltzer was invited to become the first president of the AATS. In a speech delivered at the founding meeting of the AATS, Willy Meyers stated: “The thorax was the last fortress to be attacked and it has been laid open safely to the surgeon’s knife” [9].
\nLung cancer was a very rare disease in the beginning of the twentieth century. In 1919, Alton Ochsner, as a medical student was invited with his whole class to witness an autopsy of a patient who died of lung cancer. The pathologist announced that no one in that class would ever again see another such case [11]. It took 17 years before Ochsner, who had become a surgeon, saw his second case, followed by 8 other cases in the 6 following months. All of these patients were male and had served as soldiers in World War I and in the line of duty they had taken up the habit of smoking, provoked by mass advertisements promoting smoking. Ochsner was amongst the first surgeons to correlate smoking to the development of lung cancer [12]. With the lung cancer epidemic which started after World War I, the number of patients with potentially resectable lung cancer increased significantly. Two major surgical items had to be settled; should a lung resection for cancer be a lobectomy or a pneumonectomy and what is the best surgical technique? Is it mass hilar ligation or anatomical dissection? The first report on lobectomy for lung cancer was that of Edward Churchill (Boston) in 1932 [13]. One year later, Evarts Graham, while intending to perform a lobectomy, was forced to perform a pneumonectomy because the tumor was very centrally located in the hilum at the origin of the left upper lobe (bronchoplastic procedures such as sleeve resection had not been developed yet) [14]. For a considerably long period, pneumonectomy was regarded as the golden standard for all lung cancer patients. Lobectomy by many was considered inferior and compared with lumpectomy without resection of loco-regional lymph nodes in breast cancer [15]. Only in 1962, a large case series between pneumonectomy and lobectomy were compared showing that lobectomy was equivalent to pneumonectomy as a cancer operation but with a lower rate of complications and mortality [16].
\nWith respect to surgical technique, there was no consensus on hilar control; mass ligation or anatomical dissection and step-by-step control of the hilar structures. Cadaveric studies performed by Blades and Kent in the early 1940s pushed the world toward the latter, later supported by several publications of Boyes on the intrahilar anatomy of the lung segments [10, 17].
\nWith this knowledge, Clement Thomas Price (London, 1947) introduced the concept of parenchyma sparing operations, having done the first anatomical segmentectomy in a lung cancer patient [18]. The first sleeve resection for bronchogenic carcinoma was performed in 1952 [19]. Consequently, it was around the mid-1950s the four main operations in lung cancer as we know today were in the armamentarium of the thoracic surgeon: pneumonectomy, lobectomy, sleeve lobectomy, and segmentectomy.
\nA major step forward was the introduction of double lumen endo-tracheal tube by Carlens in 1949 [20]. With this selective single lung ventilation concept, modern lung surgery is greatly facilitated, particularly, the endoscopic and robotic techniques used nowadays (discussed later in this chapter).
\nDiagnostic techniques were still very primitive in that era compared with today’s standards. Besides standard chest X-ray, there was rigid bronchoscopy, bronchography, planography, and cytology. The concept of staging had to be developed yet. Exploratory thoracotomy in “operable patients” was performed with a very low threshold, not to lose time. Some authors reported up to 50% inoperability [21]. In the Amsterdam University Hospital between 1955 and 1960 in a series of 100 exploratory thoracotomies in patients who were found to be inoperable, 54% of patients had complications and 9 of the 100 patients died due to post-operative complications [22]. In 63% of the cases, mediastinal ingrowth or large irresectable nodes were found. In 23%, there was in growth in heart and/or major vessels, 12% ingrowth into the thoracic wall, 1% in growth in the diaphragm, and 1% pleural carcinomatosis. By far, mediastinal involvement was the leading cause of inoperability. In 1959, Carlens had published his experience with 100 mediastinoscopies [20]. The morbidity of this technique was 2.5% and the mortality was less than 0.5%, way better then exploratory thoracotomy. The Amsterdam team embraced mediastinoscopy and combined this in a series of operable patients with bronchoscopy and on indication diagnostic pneumothorax. Due to the mediastinoscopy findings, the resection rate in Amsterdam rose from 60 to 94% with 12% false positive mediastinoscopies [20]. Years later, in 1984, Griffith Pearson published a landmark paper showing that when positive mediastinal nodes were found, any subsequent lung resection would not cure a patient [23].
\nThe world was waiting for methods to better identify loco-regional progression and distant metastases. Hounsfield, by combining tomography images with the calculating power of a computer, constructed the first computed tomography (CT) scanner, first for brain scans only, but in 1975 he and his team built the first whole body scanner. The computed tomography (CT) scanner was soon to be followed by the magnetic resonance imaging (MRI) scanner in 1977, while the next big step was the combination of positron emission tomography (PET) and CT scanners in 1991. The use of mediastinoscopy has declined after the introduction of ultrasound-guided examinations of the mediastinum and the hilum (endo-esophageal ultrasound (EUS) and endo-bronchial ultrasound bronchoscopy (EBUS)), but is still used on a regular base when the latter techniques fall short.
\nFor decades, postero-lateral thoracotomy has been the preferred entrance for most lung resections (Figure 1A). However, the price of an excellent exposure to the lung hilum came with high percentages of long standing post-operative pain, discomfort, and functional loss.
\nOverview of the surgical approaches for treatment of lung cancer. (A) Postero-lateral thoracotomy, (B) 3 ports, video-assisted thoracic surgery (VATS), (C) uniportal video-assisted thoracic surgery (UVATS), (D) robotic-assisted thoracic surgery (RATS), and (E) endo-bronchial surgery.
The Swedish internist Jacobeus is often positioned as the founding father of thoracoscopy but in fact, it was the British surgeon Francis Richard Cruse who already had published this technique in 1865 [24].
\nThe first thoracoscopic resections were not immediately embraced by the surgical community. Ralph Lewis was the first one to publish a series of 100 lobectomies done thoracoscopically [25]. Lacking experience, tailor-made instruments, and specific endo-staplers, these resections were performed using a mass stapling technique. In Los Angeles, Robert McKenna worked out a standardized approach for video-assisted thoracic surgery (VATS) lobectomy (Figure 1B), working through the hilum from anterior to posterior; in 2006, he published a series of 1100 cases [26].
\nThis provoked surgeons around the world to adapt this technique and today in many hospitals, it is the preferred approach for the majority of cases. In 2019, Eric Lim published the results of the VIOLET trial, a prospective randomized trial between VATS and thoracotomy in lung cancer patients. VATS showing to be superior with respect to major adverse events, less pain on post-operative day 2 and shorter median hospital stay with an equal oncological outcome (number of lymph nodes harvested and upstaged and R-0 resections) [27].
\nStudies on chronic pain (pain for which patients visit a doctor 3 months post-operative), however, did not show a major difference in pain between thoracotomy patients and VATS patients 3–6 months post-operatively [28]. Chronic pain after VATS is often contributed to the insult of multiple intercostal nerves by trocars and instruments. It has to be seen whether the explanation is that simple, however, it moved surgeons to search for even less invasive methods, eventually leading to the concept of uniportal VATS (UVATS), first proposed by Rocco in 2004 [29] (Figure 1C).
\nThere is still no proof that an UVATS approach leads to less pain, discomfort, and loss of functionality compared with multiple port VATS.
\nWith the idea of intercostal nerve damage in mind, surgeons have also explored other VATS-assisted intrathoracic pathways like subxiphoid and cervical approaches [30, 31]. Others are exploring a hybrid approach, combining 5 mm intercostal ports with a subxiphoid approach [32].
\nAlmost parallel with the introduction and evolution of VATS, the world saw the introduction of robotic-assisted thoracic surgery (RATS), first published by Franca Melfi and her team [33] (Figure 1D).
\nUp till now, no significant differences have been shown in complications and outcome between VATS, UVATS, and RATS [34]. The major reason that the introduction of RATS lagged behind in many institutions is a financial reason; it is not cost-efficient. In the meantime, VATS has evolutionized to three-dimensional VATS (3D VATS) and robotic-like instruments have become available for laparoscopic and VATS procedures.
\nDuring the last decade, there is a growing interest in lung parenchyma-sparing resections. This need is more highlighted by the results of the two largest population based national screening studies (NLST, 2011 and NELSON, 2018) showing that discovery and resection of early stage lung cancer through screening programs lead to significantly better survival of patients [35, 36]. The NLST study showed a reduction of 20% in lung cancer mortality for annual screening over 3 years with low-dose CT with a greater benefit for screening in women. The NELSON study showed for screening with low-dose CT, a 26% reduction of lung cancer mortality in high-risk men and up to 61% reduction of lung cancer mortality in high-risk women over a 10-year period. Nowadays, there is a trend toward sub-lobar resection as segmentectomy, making the oncological lung surgery even more challenging. Moreover, this makes the role of peri-operative diagnostic tools as fluorescent indocyanine green (ICG) [37], 3D-CT modalities, and (navigational) bronchoscopy interventions (next section, Figure 1E) indispensable. Because of its anatomical complexity, many surgeons hesitate to perform segmentectomy. For this reason, in 2012, Hiroaki Nomori and Morihito Okada published the book “Illustrated Anatomical Segmentectomy for Lung Cancer” which is an essential book for surgeons starting a segmentectomy program at their centers. In 2019, segmentectomy is mostly performed in countries of Eastern Asia, such as Japan, followed by few centers in the USA and Western Europe.
\nOver the past few decades, imaging modalities such as CT, PET-CT, and standard chest X-ray imaging have played a key role in the non-invasive diagnostic work-up of thoracic disease. In addition, these imaging modalities are an essential part of the preoperative planning process of thoracic surgical procedures. Even though there is a broad range of clinical indications for various thoracic imaging modalities and the information provided by all different modalities is different, the purpose of this section is not to undertake a comprehensive evaluation of the characteristics of these imaging modalities. Specifically, this section will focus on innovative preoperative and intraoperative imaging modalities as a surgical planning and navigation tools and provide a brief overview of new developments in medical imaging, especially in the context of (oncologic) pulmonary resections.
\nIn the setting of oncologic thoracic surgery, a standard chest CT scan can be used to evaluate the extensiveness of disease in terms of pleural, mediastinal, chest wall, or vascular involvement. In addition, the CT scan is used to study the surgical anatomy of the pulmonary artery (and its major branches), pulmonary vein, and bronchial structures when a resection of the lung parenchyma is planned. Due to the establishment and development of more modern multislice CT scanners, it has become easier to detect smaller peripheral tumors. While this has enabled more diagnostic accuracy, it has resulted in an increased clinical use of sublobar anatomic resections. Specifically, in the setting of anatomic segmental pulmonary resections, which are technically and anatomically more demanding and complex, there is a need for more accurate imaging modalities that enables better preoperative knowledge of the surgical anatomy (such as bronchial and vascular anatomy in sublobar/segmental levels). Recently, an increasing number of scientific reports have been published on the use of preoperative three-dimensional (3D)-CT reconstruction as a surgical planning tool before anatomic resection of pulmonary segments or lobes [38, 39, 40, 41, 42]. According to some of these studies, the preoperative use of 3D-CT reconstructed images is feasible and safe and, in some cases, associated with shorter operative time due to better preoperative understanding of surgical anatomy [38, 42]. In order to obtain 3D-CT image reconstructions, different methods are described and various (free open-source) software packets are available [42, 43, 44]. However, there are also limitations regarding the utility of software to reconstruct 3D images of CT scans. For example, the identification and separation of the pulmonary artery and vein may be a challenging and time-consuming process. Moreover, in some cases, a contrast-enhanced CT scan is required to create 3D-simulations, which increases the risks of radiation exposure. In addition, the reconstruction commonly requires technical support and the assistance of radiology and information and communication technology (ICT) experts.
\nOizumi et al. reported a study on the use of 3D reconstruction of multidetector CT (MDCT) images in order to plan and guide pulmonary segmentectomy preoperatively and during surgery [38]. It was noted that after the introduction of 3D-CT reconstruction, the number of (fairly) difficult classified segmentectomies that have been performed increased significantly, suggesting that preoperative 3D-CT simulation contributes fairly to the efficacy of surgical planning of complex segmentectomies. In addition, in a retrospective analysis of patients undergoing thoracoscopic segmentectomy reported by Xue et al., the authors found that when preoperative 3D-CT reconstruction was used to make operation plans, in 19% of the cases, the operation plan was changed due to the results of 3D simulation [42]. The original surgical plan of these cases was changed due to the expectation of an inadequate resection margin distance, based on pre-operative simulation results. This indicates that preoperative 3D simulation not only contributes to technical feasibility and efficacy of surgery, but also to the decision-making process from an oncological point of view.
\nEven though an increasing number of studies on the use of 3D-CT simulation are being published, the majority of them do not report on the differences in parameters of clinical outcome (such as perioperative blood loss, post-operative stay, and conversion rates to thoracotomy) but focus more on technical aspects and feasibility of 3D-simulation and surgery. However, the majority of reports do recognize the following advantages of preoperative 3D-simulation in the context of (sub-)lobar pulmonary resection: (1) classification and identification of anatomical (vascular and bronchial) abnormalities; (2) identification of unsuitable surgical cases for segmentectomy; (3) training of less experienced thoracic surgeons and surgical residents; (4) preoperative estimation of proper surgical resection margin; (5) a step-wise preoperative surgical planning; and (6) intraoperative navigation for identification of anatomical structures [38, 40, 41, 42].
\n3D-CT-mediated preoperative surgical planning and intraoperative guidance of (oncological) pulmonary surgery could contribute significantly to the development of more accurate and safer (sublobar) anatomic resections. In the near future, this technology will become more common in thoracic surgery. However, in order to reach that stage, some (mostly technical) limitations need to be overcome.
\nVirtual reality (VR) is a technology that enables users to interact with a computer-generated virtual 3D interface (Figure 2). More interestingly, in augmented reality (AR), the user is able to overlay aspects of the VR world within the real physical world. Finally, mixed reality (MR) allows users to create a hybrid physical and virtual world and offers the possibility to interact and analyze objects in the physical world by virtual projections [45, 46].
\nAn example of virtual reality application during minimally invasive lung cancer surgery in the operating theater.
Recently, surgical intraoperative navigation as well as preoperative surgical simulation based on VR, MR, and AR have been developed and successfully used in various surgical fields including neurosurgery, liver surgery, kidney surgery, and orthopedic surgery [47, 48, 49, 50, 51]. In contrast to 2D interfaces (e.g. conventional CT scans), VR, MR, and AR enable not only visualization of anatomical structures but also allow interactive manipulation of the digital information (e.g. anatomic structures) provided by (wearable) computer-integrated devices (such as the Microsoft Hololens or the Google Glass). It has been suggested that these new interfaces might have the potential to benefit both the surgeon and the patient. For surgeons, this benefit comes by the way of improved preoperative surgical planning, better and more accurate intraoperative imaging guidance, and a better preoperative awareness of anatomical abnormalities. Patients will potentially benefit from shorter operative time, shorter length of hospital stay, and improved outcomes. Additionally, AR, VR, and MR offer the possibility to simulate surgical situations as well as facilitating training for surgeons and residents. In the field of thoracic surgery, some of these modalities have been used over the past few years in order to train surgical residents and surgeons to master the techniques necessary for minimally invasive lung surgery [52].
\nHowever, only very few reports are available on the use of AR, VR, or MR for surgical planning or intraoperative navigation for lung surgery [53, 54, 55]. Frajhof et al. recently published a study on the use of AR, VR, and MR technology in the preoperative planning of a technically demanding VATS left upper lobectomy [53]. In another study from Rouzé et al., augmented reality was used as a navigation tool in combination with cone beam CT (CBCT) to guide intraoperative localization of pulmonary nodules for wedge resection through VATS. The investigators firstly localized the lesions by CBCT intraoperatively. Subsequently, a 3D reconstruction of the nodule was created by using software. After this, an augmented fluoroscopic 3D image of the pulmonary nodule was projected on a screen in front of the operating table. By this, the surgeon was able to localize the lesion intraoperatively and perform a wedge resection safely [54].
\nInterestingly, also some reports are available on the use of VR 3D reconstruction of the airways, known as virtual bronchoscopy, specifically used as a diagnostic aid tool in the assessment of airway masses and stenosis [56, 57]. Virtual bronchoscopy contributes fairly to the diagnostic process since it enables diagnostic maneuvers, such as assessing bronchial anatomy distally from stenoses, which are not possible with standard flexible bronchoscopy. Moreover, virtual bronchoscopy is a noninvasive method and does not bear any additional risks (e.g. radiation exposure or iatrogenic airway damage) for patients. Despite these advantages, virtual bronchoscopy is not expected to completely replace flexible bronchoscopy due to some limitations. For example, tumor boundaries can be misjudged by intrabronchial secretions that might lead to a false-positive result. Moreover, it has shown not to be sensitive and effective enough for detecting small mucosal abnormalities (e.g. erythema and erosion), dynamic stenoses (caused by, for example, the respiratory cycle or vocal cords), and in differentiating mucus plugs from a mass. Finally, virtual bronchoscopy has the limitation that it does not enable biopsies.
\nIn the past two decades, there has been an increase in the development of innovative technologies to facilitate more accurate, efficient, and safe (minimally invasive) thoracic interventions. Specifically, there have been some reports on the progress of innovative therapeutic modalities that approach lung cancer through other minimally invasive methods than direct surgery. Examples of these therapeutic options are thermal ablation, including radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation of malignant lung lesions. This section will touch on some of these developments and review some outcomes of thermal ablation therapy.
\nAmongst various thermal ablation therapies, RFA is a well-studied method, especially in the treatment of liver cancer [58, 59]. Due to favorable outcomes in the treatment of liver cancer, specifically hepatocellular carcinoma, the application of this technology to malignant lesions in other organs, including the lungs, has been growing. RFA involves the insertion of a probe inside the affected target tissue. The electrode on the probe generates frictional heat that creates coagulation necrosis of the surrounding (tumor) lung parenchyma. In pulmonary surgery, the use of RFA has been reported in the treatment of various malignant lesions including inoperable lung cancer [60, 61, 62], primary or metastatic pulmonary tumors of less than 3.5 cm in size [63], and stage I-4 non-small cellular lung cancer (NSCLC) not eligible for surgery [64, 65, 66, 67]. Results from retrospective studies on RFA of primary malignant lung lesions have suggested reasonable overall 1-year survival rates ranging from 78 to 94% in patients with early stage lung cancer [66, 68, 69, 70]. A 5-year survival rates have been reported to be significantly lower and in the range of 25–58% [66, 71, 72]. Important prognostic factors in RFA therapy of lung cancer, in terms of survival, are the additional use of targeted systemic therapies, lesions less than 3 cm (diameter), a Charlson comorbidity index (an index of associated comorbidities) >5, and lower stage disease [66, 73].
\nA major drawback of RFA therapy compared with surgical resection is the poor results of local progression control [74]. This limitation might be explained by the fact that in RFA therapy no systematic lymph node dissection is carried out and, additionally, no good method exists to check for local adequate treatment margins. With regard to complications, pneumothorax is one of the most common complications associated with RFA. However, it is most often (>80%) treated conservatively without the need for chest tube drainage [75]. In addition, pleural effusion might develop after RFA, however, similar to pneumothorax, does not often (<5%) require intervention [75]. In summary, RFA therapy seems an effective and relatively safe intervention for treating lung cancer, however, a careful patient selection is necessary. Moreover, more future long-term and large randomized controlled trials are necessary to compare the clinical outcomes between RFA, surgical resection, and other modalities of thermal ablation therapy.
\nMWA involves hyperthermia-mediated ablation of tissue by causing friction between water molecules in the target tissue. By creating a dipole excitation, hyperthermia is generated and coagulation necrosis results in the lesion and surrounding tissue [76, 77]. The placement of the probes is commonly guided by CT/CT-fluoroscopy. MWA has been successfully used to create larger ablation zones than RFA. Compared with RFA, MWA technology is thought to be more effective in creating larger zones of coagulation necrosis due to the elimination of heat loss through heat sink (the loss of heat through blood flow inside the target tissue) [76].
\nStudies and long-term data after MWA as a thermal ablation modality are limited when compared with RFA. In a recent review, Yuan and colleagues reported a meta-analysis of clinical outcomes after RFA and MWA for primary and metastatic pulmonary malignancies [75]. The authors identified 11 studies based on MWA compared with 42 studies based on RFA therapy, all with a retrospective study design. In this meta-analysis, it was demonstrated that RFA seems to be superior to MWA with regard to overall survival (up to 5 years) for both primary and metastatic pulmonary malignancies. However, the authors note that the results of lung metastasis should be interpreted carefully, since small groups of patients were included in the analysis based on only a few retrospective studies. With regard to local tumor progression free survival, RFA and MWA showed similar results. In addition, similar to RFA, MWA is a relatively safe intervention which is not associated with high complication rates. Yuan et al. reported comparable rates of pneumothorax and pleural effusion after ablation by MWA and RFA [75]. Concerning prognostic factors negatively affecting survival and local tumor progression control, more advanced disease stage, tumors >3 cm (diameter), and emphysematous lungs have been identified [78].
\nAn opposite method of hyperthermia induced ablation, termed cryoablation, creates protein denaturation, ischemia, cell rupture, and necrosis through local hypothermia (temperatures < −40°C) [79]. In this technique, compressed argon gas is used to create freezing temperatures that induce local injury to the tissue. Subsequently, helium is used to thaw the tissue. Comparable to MWA, in cryoablation, multiple probes can be used to increase the ablation area in the tissue and placement under the guidance of CT/CT-fluoroscopy. Although cryosurgery is a relatively old ablative technique, use of cryoablation in the context of lung cancer and long-term studies are limited. Besides percutaneous cryoablation, other methods of cryoablative strategies are endo-bronchial (for obstructive intrabronchial tumors) (Figure 1E) and intrathoracic (during surgery). Specific indications for each modality have been reviewed by Niu and colleagues and are beyond the scope of this chapter [80].
\nSince thermal ablation therapies are commonly reserved for patients not eligible for curative surgery, tumor recurrence after radiotherapy or patients who refuse surgery, even though they have resectable lesions, cryoablation is often offered as a therapy to palliate symptoms or to increase survival in advanced disease stage. Consequently, a number of reports have been published on the use of cryoablation for the treatment of medically inoperable NSCLC, advanced stages of NSCLC, and for pulmonary metastasis [80, 81, 82, 83, 84]. Niu et al. reported on a series of 840 patients with NSCLC who received percutaneous cryoablative therapy for various stages of NSCLC ranging from IIa to IV. The reported overall survival was 68, 52, 34, 26, and 17% for 1-, 2-, 3-, 4-, and 5-year, respectively. Local and peripheral recurrence rates were 28.3 and 47.2%, respectively, after a median follow-up of 34 months (range 4–63 months). For patients with less advanced NSCLC, better outcome is reported in terms of overall survival. In 2012, Yamauchi et al. demonstrated a 2-year overall survival of 88% in medically inoperable patients with stage I NSCLC who were treated with percutaneous cryoablation [84]. In addition, Moore and colleagues published a study in which an overall survival rate of 67.8% was reported in patients with stage I NSCLC after 5 years [82].
\nRegarding cryoablation therapy in metastatic lung lesions, studies have also proven the efficacy and safety of percutaneous cryoablation. For example, Yamauchi et al. reported a 3-year progression free survival rate of 59% for patients with metastatic colorectal carcinoma treated with cryoablation [85]. Factors associated with local tumor progression or poor prognosis have been studied by multivariate analyses. Interestingly, most of these factors (e.g. tumor size <3 cm and stage of disease) are comparable to the factors in other modalities of thermal ablation [78, 80]. Regarding the safety profile of cryoablation compared with other modalities of thermal ablation, comparable rates of pneumothorax and pleural effusion are reported in the literature [77, 80]. However, incidental reports of transient recurrent laryngeal nerve neuropraxia have also been documented [86].
\nUntil the late nineteenth century, the inside of the chest cavity was a no-go area for complex surgical interventions. The world still was not ready yet for primary lung resections. To make the lung surgery possible, several giant steps were undertaken: the introduction of aseptic concept by Joseph Lister in 1867, the discovery of X-ray by William Konrad Rontgen in 1895, and the introduction of positive pressure ventilation by Meltzer and Auer in 1909. With the lung cancer epidemic after World War I, the number of patients with potentially resectable lung cancer increased significantly. Surgeons around the world were debating on the preferable resection (lobectomy vs. pneumonectomy) and the best surgical technique: mass hilar ligation versus anatomical dissection. While the first report on lobectomy for lung cancer in 1932, it took almost 30 years to report that lobectomy was the preferred resection for lung cancer surgery. In the same period, the anatomical dissection technique gained wider application. This all together with the discovery of double lumen endo-tracheal tube by Carlens in 1949 paved the way for modern lung resection techniques. The introduction of diagnostic tools as CT, MRI, PET-CT, and later EUS and EBUS facilitated even better tumor localization and mediastinal evaluation decreasing the surgical mortality.
\nThe next major challenge was decreasing the morbidity of thoracotomy: high percentages of long standing post-operative pain, discomfort, and functional loss. The solution led to the development of modern minimally invasive lung surgery. In 2006, Robert McKenna published a standardized approach for VATS lobectomy in a series of 1100 cases leading to global adaptation of VATS for lung surgery. While VATS showing to be superior with respect to major adverse events, less pain on post-operative day 2 and shorter median hospital stay with an equal oncological outcome, studies on chronic pain, however, did not show a major difference in pain between thoracotomy and VATS. This moved surgeons to search for even less invasive methods, eventually leading to the concept of uniportal VATS, first proposed by Rocco in 2004, subxiphoid and cervical approaches, and hybrid approach combining 5 mm intercostal ports with a subxiphoid approach. At the same time, the world witnessed the introduction of RATS by Franca Melfi and her team, however, because of the financial reasons, the introduction of RATS in many centers lagged behind. In the meantime, VATS has evolutionized to 3D-VATS and robotic like instruments have become available for laparoscopic and VATS procedures. Whether all these approaches will lead to reduction of chronic pain is yet to be determined.
\nThe results of major screening programs have shifted the trend of lung resection toward sub-lobar resection as segmentectomy, making the lung surgery even more challenging. Moreover, this makes the role of peri-operative imaging tools as fluorescent indocyanine green (ICG), 3D-CT modalities, and (navigational) bronchoscopy interventions indispensable.
\nThe upcoming VR, AR, and MR enable a more naturalistic 3D presentation of human anatomy in a digital interface. As a diagnostic tool, it can provide physicians with a more realistic view of the patient’s anatomy and might enable diagnostic assessment, preoperative surgical planning, and intraoperative guidance. In addition, it can provide training and learning platform for students, residents, and surgeons. It has already proven its added value for a broad range of surgical procedures; however, AR/VR/MR has not been used widely in thoracic surgery yet. Considering the speed of development of this technology in other areas, it is expected that it will make its way into the world of thoracic surgery in the near future. In this perspective, hybrid operating theaters including 3D-CT and (robotic-assisted) navigational bronchoscopy tools are already on their way. To address this, however, it is essential that thoracic surgeons have an active and open attitude toward the introduction of innovative (digital) applications.
\nWith respect to endo-bronchial interventions, thermal ablation therapy seems to provide an efficacious and safe alternative for surgical therapy of lung cancer and lung cancer metastasis. However, patient’s selection should be carried out with caution and should be personalized for each patient based on type of cancer (e.g. NSCLC), comorbidities, tumor size, and disease stage. Specifically, thermal ablation therapy could offer a palliative or even a life-prolonging treatment option for non-surgical candidates. Hopefully future long-term and larger prospective (randomized controlled) trials will answer the remaining questions. For example, it will be necessary to study the impact of combining thermal ablation therapy with other conventional (e.g. systemic or radiotherapy) therapies for the treatment of lung cancer. In addition, more data are warranted on the determination of the best therapy for incomplete ablations and/or local recurrence of disease. More interestingly, biomarkers or novel imaging techniques to follow-up on ablative therapies are also required, especially since the radiological follow-up of recently ablated lung tissue is very challenging. More data and confirmation of these data are therefore necessary and need to be generated by future multicenter trials.
\nTo conclude, this chapter provides a historical overview and a summary of state-of-the-art surgical techniques in the treatment of lung cancer today. The journey of lung surgery was and is a very challenging one, with major hurdles to overcome. It departed from a “no-go” era, leaving behind the golden standard of pneumonectomy and thoracotomy, to arrive in the current era of minimally invasive and robotic-assisted surgery. The journey continues toward the horizon of non-intubated operations, sub-lobar resections, virtual reality imaging modalities, navigational bronchoscopy interventions, and hybrid procedures. We are heading toward the era of incisionless, natural orifice surgery: an almost science fiction vision, yet nothing is more real.
\nThe contribution of Egied Simons (Simons Productions, Mathenesserdijk 236A, 3026 GL, Rotterdam, The Netherlands) and Chris Hordijk (Medical VR, van Eeghenstraat 98, 1071JL, Amsterdam, The Netherlands) in generating the figures is highly appreciated. We would like to thank Dr. F. Incekara (Departments of Neurosurgery and Radiology, Erasmus Medical Center, Rotterdam, The Netherlands) for his helpful advice.
\nVATS | video-assisted thoracic surgery |
UVATS | uniportal video-assisted thoracic surgery |
RATS | robotic-assisted thoracic surgery |
3D | three-dimensional |
CT | computed tomography scanner |
AATS | American Association for Thoracic Surgery |
MRI | magnetic resonance imaging scanner |
PET | positron emission tomography |
EUS | endo-esophageal ultrasound |
EBUS | endo-bronchial ultrasound bronchoscopy |
ICG | indocyanine green |
ICT | information and communication technology |
MDCT | multidetector computed tomography |
VR | virtual reality |
AR | augmented reality |
MR | mixed reality |
CBCT | cone beam computed tomography |
RFA | radiofrequency ablation |
MWA | microwave ablation |
NSCLC | non-small cellular lung cancer |
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He is currently an associate professor at Department of Civil Engineering, Minia University, Egypt and the chairman of Department of Civil Engineering, High Institute of Engineering and Technology, Giza, Egypt. He is also a consultant engineer and head of structural group at Hamza Associates, Giza, Egypt. Dr. Moustafa was a senior research associate at Vanderbilt University and a JSPS fellow at Kyoto and Nagasaki Universities. He has more than 40 research papers published in international journals and conferences. He acts as an editorial board member and a reviewer for several regional and international journals. 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El-Hemaly\nProfessor OB/GYN & Urogynecology\nFaculty of medicine, Al-Azhar University \nPersonal Information: \nMarried with two children\nWife: Professor Laila A. Moussa MD.\nSons: Mohamad A. M. El-Hemaly Jr. MD. Died March 25-2007\nMostafa A. M. El-Hemaly, Computer Scientist working at Microsoft Seatle, USA. \nQualifications: \n1.\tM.B.-Bch Cairo Univ. June 1963. \n2.\tDiploma Ob./Gyn. Cairo Univ. April 1966. \n3.\tDiploma Surgery Cairo Univ. Oct. 1966. \n4.\tMRCOG London Feb. 1975. \n5.\tF.R.C.S. Glasgow June 1976. \n6.\tPopulation Study Johns Hopkins 1981. \n7.\tGyn. Oncology Johns Hopkins 1983. \n8.\tAdvanced Laparoscopic Surgery, with Prof. Paulson, Alexandria, Virginia USA 1993. \nSocieties & Associations: \n1.\t Member of the Royal College of Ob./Gyn. London. \n2.\tFellow of the Royal College of Surgeons Glasgow UK. \n3.\tMember of the advisory board on urogyn. FIGO. \n4.\tMember of the New York Academy of Sciences. \n5.\tMember of the American Association for the Advancement of Science. \n6.\tFeatured in �Who is Who in the World� from the 16th edition to the 20th edition. \n7.\tFeatured in �Who is Who in Science and Engineering� in the 7th edition. \n8.\tMember of the Egyptian Fertility & Sterility Society. \n9.\tMember of the Egyptian Society of Ob./Gyn. \n10.\tMember of the Egyptian Society of Urogyn. \n\nScientific Publications & Communications:\n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Asim Kurjak, Ahmad G. Serour, Laila A. S. Mousa, Amr M. Zaied, Khalid Z. El Sheikha. \nImaging the Internal Urethral Sphincter and the Vagina in Normal Women and Women Suffering from Stress Urinary Incontinence and Vaginal Prolapse. Gynaecologia Et Perinatologia, Vol18, No 4; 169-286 October-December 2009.\n2- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nFecal Incontinence, A Novel Concept: The Role of the internal Anal sphincter (IAS) in defecation and fecal incontinence. Gynaecologia Et Perinatologia, Vol19, No 2; 79-85 April -June 2010.\n3- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nSurgical Treatment of Stress Urinary Incontinence, Fecal Incontinence and Vaginal Prolapse By A Novel Operation \n"Urethro-Ano-Vaginoplasty"\n Gynaecologia Et Perinatologia, Vol19, No 3; 129-188 July-September 2010.\n4- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n5- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n6- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n7-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n8-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n9-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n10-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n11-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n12- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n13-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n14- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n15-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n\n16-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n17- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis\n\n18-Maternal Mortality in Egypt, a cry for help and attention. The Second International Conference of the African Society of Organization & Gestosis, 1998, 3rd Annual International Conference of Ob/Gyn Department � Sohag Faculty of Medicine University. Feb. 11-13. Luxor, Egypt. \n19-Postmenopausal Osteprosis. The 2nd annual conference of Health Insurance Organization on Family Planning and its role in primary health care. Zagaziz, Egypt, February 26-27, 1997, Center of Complementary Services for Maternity and childhood care. \n20-Laparoscopic Assisted vaginal hysterectomy. 10th International Annual Congress Modern Trends in Reproductive Techniques 23-24 March 1995. Alexandria, Egypt. \n21-Immunological Studies in Pre-eclamptic Toxaemia. Proceedings of 10th Annual Ain Shams Medical Congress. Cairo, Egypt, March 6-10, 1987. \n22-Socio-demographic factorse affecting acceptability of the long-acting contraceptive injections in a rural Egyptian community. Journal of Biosocial Science 29:305, 1987. \n23-Plasma fibronectin levels hypertension during pregnancy. The Journal of the Egypt. Soc. of Ob./Gyn. 13:1, 17-21, Jan. 1987. \n24-Effect of smoking on pregnancy. Journal of Egypt. Soc. of Ob./Gyn. 12:3, 111-121, Sept 1986. \n25-Socio-demographic aspects of nausea and vomiting in early pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 35-42, Sept. 1986. \n26-Effect of intrapartum oxygen inhalation on maternofetal blood gases and pH. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 57-64, Sept. 1986. \n27-The effect of severe pre-eclampsia on serum transaminases. The Egypt. J. Med. Sci. 7(2): 479-485, 1986. \n28-A study of placental immunoreceptors in pre-eclampsia. The Egypt. J. Med. Sci. 7(2): 211-216, 1986. \n29-Serum human placental lactogen (hpl) in normal, toxaemic and diabetic pregnant women, during pregnancy and its relation to the outcome of pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:2, 11-23, May 1986. \n30-Pregnancy specific B1 Glycoprotein and free estriol in the serum of normal, toxaemic and diabetic pregnant women during pregnancy and after delivery. Journal of the Egypt. Soc. of Ob./Gyn. 12:1, 63-70, Jan. 1986. Also was accepted and presented at Xith World Congress of Gynecology and Obstetrics, Berlin (West), September 15-20, 1985. \n31-Pregnancy and labor in women over the age of forty years. Accepted and presented at Al-Azhar International Medical Conference, Cairo 28-31 Dec. 1985. \n32-Effect of Copper T intra-uterine device on cervico-vaginal flora. Int. J. Gynaecol. Obstet. 23:2, 153-156, April 1985. \n33-Factors affecting the occurrence of post-Caesarean section febrile morbidity. Population Sciences, 6, 139-149, 1985. \n34-Pre-eclamptic toxaemia and its relation to H.L.A. system. Population Sciences, 6, 131-139, 1985. \n35-The menstrual pattern and occurrence of pregnancy one year after discontinuation of Depo-medroxy progesterone acetate as a postpartum contraceptive. Population Sciences, 6, 105-111, 1985. \n36-The menstrual pattern and side effects of Depo-medroxy progesterone acetate as postpartum contraceptive. Population Sciences, 6, 97-105, 1985. \n37-Actinomyces in the vaginas of women with and without intrauterine contraceptive devices. Population Sciences, 6, 77-85, 1985. \n38-Comparative efficacy of ibuprofen and etamsylate in the treatment of I.U.D. menorrhagia. Population Sciences, 6, 63-77, 1985. \n39-Changes in cervical mucus copper and zinc in women using I.U.D.�s. Population Sciences, 6, 35-41, 1985. \n40-Histochemical study of the endometrium of infertile women. Egypt. J. Histol. 8(1) 63-66, 1985. \n41-Genital flora in pre- and post-menopausal women. Egypt. J. Med. Sci. 4(2), 165-172, 1983. \n42-Evaluation of the vaginal rugae and thickness in 8 different groups. Journal of the Egypt. Soc. of Ob./Gyn. 9:2, 101-114, May 1983. \n43-The effect of menopausal status and conjugated oestrogen therapy on serum cholesterol, triglycerides and electrophoretic lipoprotein patterns. Al-Azhar Medical Journal, 12:2, 113-119, April 1983. \n44-Laparoscopic ventrosuspension: A New Technique. Int. J. Gynaecol. Obstet., 20, 129-31, 1982. \n45-The laparoscope: A useful diagnostic tool in general surgery. Al-Azhar Medical Journal, 11:4, 397-401, Oct. 1982. \n46-The value of the laparoscope in the diagnosis of polycystic ovary. Al-Azhar Medical Journal, 11:2, 153-159, April 1982. \n47-An anaesthetic approach to the management of eclampsia. Ain Shams Medical Journal, accepted for publication 1981. \n48-Laparoscopy on patients with previous lower abdominal surgery. Fertility management edited by E. Osman and M. Wahba 1981. \n49-Heart diseases with pregnancy. Population Sciences, 11, 121-130, 1981. \n50-A study of the biosocial factors affecting perinatal mortality in an Egyptian maternity hospital. Population Sciences, 6, 71-90, 1981. \n51-Pregnancy Wastage. Journal of the Egypt. Soc. of Ob./Gyn. 11:3, 57-67, Sept. 1980. \n52-Analysis of maternal deaths in Egyptian maternity hospitals. Population Sciences, 1, 59-65, 1979. \nArticles published on OBGYN.net: \n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n2- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n3- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n4-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n5-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n6-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n7-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n8-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n9- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n10-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n11- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n12-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n13-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n14- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis",institutionString:null,institution:{name:"Al Azhar University",country:{name:"Egypt"}}},{id:"113313",title:"Dr.",name:"Abdel-Aal",middleName:null,surname:"Mantawy",slug:"abdel-aal-mantawy",fullName:"Abdel-Aal Mantawy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ain Shams University",country:{name:"Egypt"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:1683},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"8"},books:[{type:"book",id:"10454",title:"Technology in Agriculture",subtitle:null,isOpenForSubmission:!0,hash:"dcfc52d92f694b0848977a3c11c13d00",slug:null,bookSignature:"Dr. Fiaz Ahmad and Prof. Muhammad Sultan",coverURL:"https://cdn.intechopen.com/books/images_new/10454.jpg",editedByType:null,editors:[{id:"338219",title:"Dr.",name:"Fiaz",surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10502",title:"Aflatoxins",subtitle:null,isOpenForSubmission:!0,hash:"34fe61c309f2405130ede7a267cf8bd5",slug:null,bookSignature:"Dr. Lukman Bola Abdulra'uf",coverURL:"https://cdn.intechopen.com/books/images_new/10502.jpg",editedByType:null,editors:[{id:"149347",title:"Dr.",name:"Lukman",surname:"Abdulra'uf",slug:"lukman-abdulra'uf",fullName:"Lukman Abdulra'uf"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10504",title:"Crystallization",subtitle:null,isOpenForSubmission:!0,hash:"3478d05926950f475f4ad2825d340963",slug:null,bookSignature:"Dr. Youssef Ben Smida and Dr. Riadh Marzouki",coverURL:"https://cdn.intechopen.com/books/images_new/10504.jpg",editedByType:null,editors:[{id:"311698",title:"Dr.",name:"Youssef",surname:"Ben Smida",slug:"youssef-ben-smida",fullName:"Youssef Ben Smida"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10552",title:"Montmorillonite",subtitle:null,isOpenForSubmission:!0,hash:"c4a279761f0bb046af95ecd32ab09e51",slug:null,bookSignature:"Prof. Faheem Uddin",coverURL:"https://cdn.intechopen.com/books/images_new/10552.jpg",editedByType:null,editors:[{id:"228107",title:"Prof.",name:"Faheem",surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10572",title:"Advancements in Chromophore and Bio-Chromophore Research",subtitle:null,isOpenForSubmission:!0,hash:"4aca0af0356d8d31fa8621859a68db8f",slug:null,bookSignature:"Dr. Rampal Pandey",coverURL:"https://cdn.intechopen.com/books/images_new/10572.jpg",editedByType:null,editors:[{id:"338234",title:"Dr.",name:"Rampal",surname:"Pandey",slug:"rampal-pandey",fullName:"Rampal Pandey"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10581",title:"Alkaline Chemistry and Applications",subtitle:null,isOpenForSubmission:!0,hash:"4ed90bdab4a7211c13cd432aa079cd20",slug:null,bookSignature:"Dr. Riadh Marzouki",coverURL:"https://cdn.intechopen.com/books/images_new/10581.jpg",editedByType:null,editors:[{id:"300527",title:"Dr.",name:"Riadh",surname:"Marzouki",slug:"riadh-marzouki",fullName:"Riadh Marzouki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10582",title:"Chemical Vapor Deposition",subtitle:null,isOpenForSubmission:!0,hash:"f9177ff0e61198735fb86a81303259d0",slug:null,bookSignature:"Dr. Sadia Ameen, Dr. M. 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