\\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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The FUS/TLS (Fused in sarcoma Protein/Translocated in liposarcoma) gene encodes a 526-amino acid protein that belongs to the TET (TAF15, EWS, and TLS) family, which is implicated in multiple aspects of RNA metabolism. The FUS gene was initially identified as an oncogene in multiple cancers. FUS fuses with the transcription repressor C/EBP homologous protein 10 (CHOP) in myxoid liposarcomas. It was identified for its role as an activator of ETS-related gene (ERG) in acute myeloid leukemia [1, 2] and in Ewing’s sarcoma tumors [3]. Subsequently, mutations in FUS were linked to motor neuron diseases, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) [4, 5].
FUS protein is ubiquitously expressed in both the nucleus and cytoplasm of many cell types; however, it is predominantly found in the nucleus of glial cells and neurons in the central nervous system. A small fraction of FUS shuttles between the nucleus and cytoplasm under various stimuli, for example, sodium arsenite-induced oxidative stress [6, 7]. A previous study revealed that FUS binds RNA in vivo to engage in nucleo-cytoplasmic shuttling [8]. Another study showed that FUS is localized to dendritic spines as an RNA-protein complex and associates with mRNA encoding an actin-stabilizer protein, which indicates a regulatory role of FUS in actin/cytoskeleton processes in dendrites [9]. Interestingly, in response to stress-induced by sorbitol, FUS redistributes to the cytoplasm and localizes to cytoplasmic stress granules [10], a complex comprised of mRNA, ribosomes, RNA-binding proteins, transcription factors and nucleases that form in response to induced stress, such as oxidative stress and heat shock to maintain the stability of selected mRNAs and protein activities [11, 12]. The redistribution of FUS on stress granules is regulated by posttranslational modification, methylation, and highly related with cell survival from the stress [10]. FUS protein contains an SYGQ-rich region at its N terminal, followed by a RGG box (RGG1), an RRM motif, a second RGG box (RGG2), a zinc finger (ZnF) motif, and a third RGG box (RGG3). The C-terminus contains a nonclassical nuclear localization signal (NLS) with conserved proline and tyrosine residues (PY-NLS). The 13 terminal amino acids (514–526) containing the NLS sequence were shown to be necessary, but not sufficient, for nuclear import of FUS [13]. FUS can bind with RNA and both single-stranded (ss) as well as double-stranded (ds) DNA [14]. FUS is associated with multiple roles in RNA processing, including splicing, transcription, and transport. Studies have highlighted that FUS has a transcriptional regulatory role in global or specialized components of transcriptional machinery [15]. A Clip-seq based study revealed that FUS regulates alternative splicing of pre-mRNAs and processing of long-intron containing transcripts, and the RNAs targeted by FUS are associated with neurogenesis and gene expression regulation; interestingly, some of FUS’ mRNA targets are involved in DNA damage response and repair pathways [16].
The prevalence of ALS has been observed to be non-uniform geographically but ranges between 0.6 and 3.8 per 100,000 population worldwide. The rate of ALS incidence appears to be rising according to the recent epidemiological studies, despite the geographical differences [17]. Notably, the incidence and prevalence of ALS are greater in men than in women [18]. It has been reported that the male: female ratio is between 1 and 3 and changes in an age-dependent manner [19]. In approximately 90% of ALS cases the cause is unknown, and, as such, they are considered sporadic (SALS); while, around 10% of ALS patients have a clear family history (FALS). In 2009, two independent studies identified that FUS R521 is mutated in FALS cases and that mutation is characterized pathologically with enhanced cytoplasmic inclusions of FUS and motor neuron degeneration [4, 5]. FUS mutations have also been linked to cases of SALS [20, 21, 22]. The FUS gene is composed of 15 exons and most mutations are clustered in exon15. Exon15 encodes the NLS domain, implying a possible involvement of its nuclear import defects. These mutations/truncations include 495X, R521C/G/H/L/S, R522G, P525L, and so on. R521 is the most commonly mutated site in ALS, whereas P525 mutations are highly related with early onset and severe progress of ALS [23, 24, 25]. Mutations also occur in domains other than NLS. For example, G187S within Gly-rich domain, G399V in RGG domain, and P431L in ZnF domain [26], which is believed to induce functional defects of FUS. Autosomal dominant mutations in the gene encoding the FUS protein have been detected in approximately 5% of FALS patients and a small subset (~1%) of SALS cases.
It is important to note that many ALS patients (36–51%) also exhibit cognitive impairment, with about 20% developing FTD, also called frontotemporal lobar degeneration (FTLD) [27], a disorder characterized by cognitive, behavioral, and linguistic dysfunction. The reverse is also seen, wherein patients with FTD can develop ALS [28]. FTD accounts for 10–15% of dementias, making it the second most common type of dementia for people under the age of 65, after Alzheimer’s disease. The overlap between ALS and FTD indicates a likely common molecular basis between FUS and cognitive deficits. After the discovery of FUS mutation in ALS, a novel subtype of FTD with FUS pathology was identified, although no FUS mutation was seen [29]. In 2010, Oriane Broustal et al. identified three exonic FUS variants, c. 1562G > A (p.Arg521His), c. 1566G > A (p.Arg522Arg), and c.188A > G (pAsn63Ser) from 317 patients including 144 patients with familial FTD and 173 patients with FTD-ALS. Interestingly, the three variants were found only in patients with both FTD and ALS [27].
The molecular mechanisms of FUS-ALS are complex and ambiguous, typically described by both loss of function and gain of toxicity hypotheses. Although controversial, loss of function is not entirely supported by animal models: FUS knockout mice and zebrafish do not develop ALS-like phenotypes [30, 31, 32]. As mentioned in the previous section, FUS plays multiple roles in RNA metabolism. In fact, thousands of RNA targets have been identified that bind to FUS in various cell lines and brain tissue from both patients and animal models [33]. The dysregulation and disturbance of RNA processing are considered to be one mechanism that leads to neurodegeneration. Depletion of FUS in mouse nervous system has been shown to alter the levels of splicing of over 950 mRNAs [34]; FUS knockout in neuroblastoma cells disturbs the splicing of more than 400 introns [35]. Expression of FUS P525L mutant was shown to inhibit splicing of minor introns by trapping U11 and U12 small nuclear RNAs (snRNAs) in these aggregates [35], and expression of R521G and R522G mutations influence RNA transcription and splicing but in a different way [36]. Besides, mRNA transport and stabilization are also affected by ALS-linked FUS mutations [37, 38].
The majority of the mutations occur in the NLS region of FUS, which induces its cytoplasmic accumulation. The widespread FUS mislocalization has been considered a hallmark of ALS [39]. Mutant, but not the wild-type FUS was shown to be assembled into stress granules in cytoplasm in response to oxidative stress or heat shock [7, 40], which potentially contributes to neurotoxicity by impairing mRNA translation [41, 42]. In fact, mutations in RNA-binding proteins (RBPs) are highly related to ALS. The interaction between mistranslocated FUS and other RBPs was recently investigated. These studies show that the cytoplasmic mislocalization caused by FUS P525L mutation impairs its interaction with other ALS-associated RBPs including shnRNPA1, hnRNPA2B1, EWSR1, and TAF15, which facilitates the nucleation of toxic cytoplasmic FUS aggregates. In addition, high cytoplasmic FUS levels exhibit defects in protein degradation and reduced protein levels of RBPs, shedding lights on the FUS-ALS pathology linked to the homeostasis of multiple ALS-associated RBPs [43].
In addition to RNA dysregulation, there has been a lot of focus on the genome instability caused by FUS mutation in ALS patients since FUS was first linked to DNA damage repair by multiple studies. In human cells, one major source of genome damage is the reactive oxygen species (ROS) accumulation-induced oxidative stress. ROS that defined as a group of reactive molecules derived from oxygen including but not limited to free radicals (superoxide, O2−), hydroxyl radical (·OH), or non-radicals (hydrogen peroxide) can be balanced by various antioxidant systems, while the imbalance between ROS production and antioxidant defenses causes oxidative stress, leading to oxidation of lipid, protein, and DNA in cells [44]. Accumulation of oxidative DNA damge has been linked to multiple neurodegenerative diseases like Parkinson’s disease (PD) and Huntington’s disease (HD) [45, 46]. In addition to DNA damage, mutation in the genes of specific DNA repair pathways that lead to DNA damage repair (DDR) is another challenge for the central nervous system [47]. For example, nucleotide excision repair (NER) is defective in xeroderma pigmentosum (XP) and Cockayne syndrome (CS), base excision/single-strand break repair (BER/SSBR) defects in ataxia with oculomotor apraxia type 1 (AOA1) [48], spinocerebellar ataxia with axonal neuropathy (SCAN1) [49] and ALS [50], and defective DDR signaling and DNA double-strand break repair (DSBR) in ataxia telangiectasia (A-T) and Nijmegen break-age syndrome. FUS is found to be phosphorylated by DDR proteins ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK) in response to DSB-inducing agents. FUS was identified to interact with histone deacetylase 1 (HDAC1) in primary mouse cortical neurons, and the interaction is believed to modulate the homologous recombination (HR) and non-homologous end joining (NHEJ), two major pathways for DSB repair. Besides, FUS was shown to be recruited at DNA damage tracks induced by microirradiation (MIR) at wavelengths of 405 or 351 nm, in a PARP1-depedent manner and accompanied with PARylation by PARP1 [51, 52, 53]. Notably, MIR causes clusters of different types of DNA damage including oxidized base lesions, single-strand breaks (SSBs), and DSBs. It is generally believed that UVA (wavelength between 320 and 400 nm) predominantly induces SSBs via elevated ROS, while UVA may also induce secondary DSBs due to clustered SSBs [54]. Thus, recruitment of FUS at MIR with wavelength of 351 nm suggests its potential role in the repair of SSBs.
A comprehensive investigation by our group described the mechanistic role of FUS in BER/SSBR, a major pathway to repair oxidative DNA damage. Our study utilized multiple in vitro and in vivo model systems, including, CRISPR/Cas9-mediated FUS knockout (KO) human embryonic kidney (HEK)293 cells, FALS patient-derived induced pluripotent stem cells (iPSCs) with FUS mutations R521H and P525L, motor neurons induced from these iPSC lines, and ALS patients spinal cord tissues with FUS pathology. We discovered that the DNA integrity is substantially affected in the spinal cord tissues and the motor neurons derived from ALS patients. Both downregulation and pathological mutation of FUS were associated with DNA SSB accumulation and SSBR defects. Finally, we identified that FUS directly interacts with PARP1, XRCC1, and LigIII in response to oxidative stress and FUS facilitates the recruitment of XRCC1/LigIII to DNA damage sites in a PARP1 activity-dependent manner. FUS enhances the ligation activity of LigIII, which is critical for an optimal SSBR in neurons (Figure 1). The SSBR deficiency due to ALS-linked FUS mutations can be rescued by the correction of those mutations via Crisper/Cas9 technology [50]. Furthermore, FUS regulates PARP1’s PARylation activity in motor neurons and thus could affect neuronal energy metabolism by uncoupling NAD+/NADH levels.
Model of FUS involving DNA damage response in the nucleus. In response to DNA SSBs, FUS is PARylated and recruited to DNA damage sites by PARP1 and the recruitment facilitates the loading of XRCC1 and nuclear LigIII (nLigIII) complex, where FUS enhances the ligation activity of LigIII for an optimal SSB ligating. While in response to DSB, FUS is associated with HDAC1, which is required for an efficient NHEJ and HR-mediated DSB repair. FUS is also phosphorylated by ATM and DNA-PK, although the underlying mechanism is not known. Due to its role in the functional activation of LigII, which is involved in MMEJ-mediated DSB repair, it is likely that FUS also affects MMEJ, which needs to be investigated.
During DDR, PARP1 plays an important role in regulating DNA damage repair. In response to DNA damage, PARP1 is self-activated by its auto-PARylation and transfers ADP-ribose to create long and branched poly(ADP-ribose) on target DNA repair proteins to facilitate their recruitment; for example, PARP1 recruits XRCC1 by its PARylation. A study showed that PARP1 likely plays a major role for the poly(ADP-ribose) synthesis induced by alkylating agents, since the amount of poly(ADP-ribose) can be reduced for around 10 folds (from 60 pmol per mg of DNA to 5.85 pmol per mg of DNA) in PARP1 KO cells in the presence of MNNG [55], which activates DNA mismatch repair. Consistantly, PARP1 knockout mice are highly susceptible to DNA damaging agents and are accumulated with DNA strand breaks accompanied with genomic instability in them [56, 57].
In response to DNA damage, FUS is recruited to DNA damage site in a PARP1 activity-dependent manner [51, 52]. FUS directly binds to PAR synthesized by activated PARP1 leading to the formation of damaged DNA-rich compartments contributed by its N-terminal low-complexity domain (LCD) and C-terminal RGG domains, and the compartments are dissociated by the hydrolysis of PAR by PARG [58], which indicates that PAR polymers play an essential role for the recruitment, likely through enhancing the FUS droplet formation [59]. While the activation of PARP1 can induce shuttling of FUS from nucleus to cytoplasm, which in turn enhances FUS aggregate formation and neurodegeneration [58, 60]. Furthermore, like FUS, the other two members in TET family, TAF15 and EWSR1 are also recruited to MIR-induced DNA damage tracks depending on PARP1 activity [53], while the molecular mechanism of the cross-talk between TET family proteins and PARP-1 has not been investigated.
Although, recent reports from our group and others demonstrate a complex, but the direct role of FUS in maintaining genome integrity, whether FUS RNA-binding activity plays a role in regulating the expression of DDR factors has not been investigated. FUS regulates several key steps of RNA metabolism that impairs various biological processes. CLIP-seq has been used to identify RNAs that FUS targeted in multiple studies [16, 34, 61, 62, 63, 64, 65], which reveals an indirect role of FUS involving in DDR by regulating RNA transcription. One report shows that FUS regulates alternative splicing of pre-mRNAs and processing of long-intron containing transcripts in HeLa cells, and FUS binds RNA encoding proteins important for DNA damage response and repair pathways. By comparing with other CLIP-based assays, a map of FUS RNA targets to DNA DSBR by NHEJ and HR is generated in the report and in which, a number of key DDR factors such as ATM, 53BP1, MRN11, NBS1 are included [16]. We recently performed RT2 PCR arrays for DNA repair and DDR signaling pathways in CRISPR/cas9 FUS knockout (KO) cells, patient-derived FUS-mutant cells, as well as FUS-ALS patient spinal cord autopsy tissue, which revealed significant downregulation of DDR factors BRCA1, MSH complex, RAD23B, and DNA ligase 4. Notably, BRCA1 depletion has been linked to neuronal DNA DSB accumulation and cognitive defects in Alzheimer’s disease. The ubiquitin receptor RAD23 functions both in nucleotide excision repair and the proteasomal protein clearance pathway and is thus linked to amyloid load in neurodegeneration. This study provides evidence of FUS pathology-mediated perturbation in the expression of DNA repair and DDR signaling factors and thus highlights the intricate connections between FUS, genome instability, and neurodegeneration.
As early as 1982, the defective DNA repair and its possible role in ALS pathology was first proposed by Bradley et al. [66], where they hypothesize that abnormal DNA in ALS may arise from a deficiency of an isozyme of a DNA repair factor. Subsequently, growing evidence suggests that defective DNA repair is a common feature of not only ALS but also several other neurodegenerative diseases, underscoring the needs of studying the implications of unrepaired DNA damage in neurons affected by neurodegeneration [67], which may lead to novel therapeutic strategies.
Our recent studies made a critical breakthrough in this direction by first time shedding lights on the molecular insights into the involvement of ALS and FTD-associated FUS and other RNA/DNA-binding proteins in specific DNA repair failure mechanisms, such as DNA ligation deficiency. While this study suggests a potential for DNA ligase complementation strategy, several key questions should be addressed to develop DNA repair-based interventions for ALS. These are: (1) The role of FUS in mitochondrial genome stability maintaining. The linkage between FUS and mitochondrial integrity has been established by a number of studies. Deng et al. demonstrated interactions between FUS and two mitochondrial proteins, mitochondrial chaperonin HSP60 and ATP synthase beta subunit ATP5B, in different studies. HSP60 mediates the translocation of FUS into mitochondria, and downregulating of HSP60 rescues mitochondrial defects and neurodegenerative phenotypes in FUS transgenic flies. While interaction between FUS and ATP5B indicates a involvement of FUS in the dysregulation of mitochondrial ATP synthesis: expression of wild-type or FUS P525L mutant disrupts the formation of the mitochondrial ATP synthase supercomplexes and suppresses the activity of ATP synthase, resulting in mitochondrial cristae loss followed by mitochondrial fragmentation [68, 69]. Nakaya and Maragkakis et al. found that expression of human FUS R495X in mouse embryonic stem cell-differentiated neurons disturbs the translation efficiency of mitochondria-associated genes and results in significant reduction of mitochondrial size [70]. Although ALS-FUS has been linked with the dysfunction of mitochondria, the role of FUS in mitochondrial genome integrity has not been explored. (2) The role of FUS in microhomology-mediated end joining (MMEJ) repair. We have established a relationship between FUS and XRCC1/LigIII, which is required for an optimal SSBR. While LigIII, together with XRCC1 and PARP1, also participates in the MMEJ-mediated DSB repair pathway, the role of which in primary neurons is unknown (Figure 1). We hypothesized that the MMEJ contributes DSBR in motor neurons and the loss of FUS may affect MMEJ and lead to genomic instability, which we are currently pursuing. (3) The role of FUS in maintaining genome integrity in astrocytes. Recent studies have shown that expression of ALS-linked mutant FUS and other ALS causative factors in astrocytes induces motor neuron death [71, 72, 73]. It will, therefore, be critical to investigate FUS toxicity-induced ligation activity defects in astrocytes and the collateral influence on motor neurons. (4) Whether DNA ligase I (LigI) rescues FUS mutant-mediated LigIII defects. Mammalian cells express three DNA ligases including ligase IV (LigIV), LigIII, and LigI. LigIV specifically participates in NHEJ-mediated DSB repair; LigIII has nuclear and mitochondrial isoforms. Both the nuclear and mitochondrial isoforms have ~98% similarity and function in BER/single-strand break repair (SSBR); LigI has been shown to functionally overlap with LigIII and is believed a back-up of LigIII, however, the level of LigI expression in non-cycling, postmitotic cells like neurons is negligible due to lack of replication-associated repair. Very likely, the induction of LigI into motor neurons with FUS pathology can rescue the LigIII ligation activity defects caused by FUS mutation.
Addressing these critical follow-up questions is an unmet need in the FUS-ALS field, which will help to develop a mechanism-based DNA-repair-targeted therapy. With recent emerging studies, the stage is set for such a paradigm shift.
The research was supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institute of Health (NIH) under the award numbers R01NS088645, RF1NS112719 and the Houston Methodist Research Institute funds. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Intestinal obstruction is a clinical manifestation that occurs since the passage of the intestinal contents, which should be into the distal levels, is prevented in any part of the passage. It is a condition frequently encountered in the emergency department, which gives positive results with early diagnosis and accurate treatment methods but may have negative consequences if it is not managed well. The patients usually present with the complaints of nausea and vomiting, colic abdominal pain, and inability to defecate. Intestinal obstruction accounts for 5–15% of the patients presenting to the emergency department with acute abdomen [1, 2, 3].
In parallel with the development of medical technology and the increasing experience of us, the surgeons, morbidity and mortality rates due to intestinal obstruction have decreased, but difficulties in diagnosis and treatment remain. Now, the cases may present with more complex conditions, and treatment may become more complicated. Nowadays, when minimally invasive and conservative methods are more popular, there is no doubt that nonoperative approach should be the preferred approach for intestinal obstruction. However, unfortunately, surgery should not be delayed, and appropriate intervention should be performed in the presence of a condition that requires absolute surgery in its etiology.
Obstruction can occur at any point in the gastrointestinal tract. Correct diagnosis and appropriate treatment of the patient is essential. Another important point, especially in surgical treatment, is to prevent brid formation which may cause re-obstruction. In addition, absolute oncological principles should be followed in obstructions caused by tumors, etc.
Intestinal obstructions can be due to very simple benign causes that need to be considered or malignant causes where no intervention apart from palliative surgical interventions can be performed [1, 2, 3, 4, 5, 6]. Here, we will examine this entity with a wide clinical, treatment, and follow-up margin.
Mechanical intestinal obstructions may be present due to various reasons. Etiology should be learned well to be able to determine the appropriate treatment option. The causes of intestinal obstruction can be broadly classified into three categories [3].
Intraluminal
Intramural
Extrinsic factors
Intraluminal causes can be defined as factors causing obstruction by not allowing intestinal passage. These can be exemplified as gallstones, foreign bodies such as bezoar, and solidified ileal content.
Tumors of the small intestine, inflammatory small bowel diseases such as Crohn’s disease, intramural hematoma, invagination, and stricture due to radiotherapy can be considered as intramural causes.
This part, which is classified as extrinsic factors, appears more than the sum of the other two parts. We know that adhesions secondary to previous abdominal surgery account for approximately 75% of small intestinal obstructions. In addition, we encounter with a considerable amount of hernias, congenital anomalies, and carcinomatosis due to intra-abdominal tumors [7, 8].
According to the mechanism of formation, there are also paralytic ileus, spastic ileus, and chronic intestinal pseudo-obstruction as well as mechanical intestinal obstruction. While paralytic ileus can be observed as a result of insufficient nerve conduction due to excessive analgesic use or electrolyte imbalance, spastic ileus occurs in cases of increased nerve conduction, such as metal poisoning [2, 7, 8, 9].
Small intestinal obstructions usually present with colic abdominal pain, nausea, vomiting, and constipation. If obstruction is at proximal levels, vomiting is more prominent, while if it is at distal levels, abdominal distension is more prominent. Although intestinal sounds, by listening, may increase in the early period, they decrease in later periods. Strangulation or ischemia should be considered if there is severe abdominal pain that is not correlated with mild distention, and the diagnosis and treatment should be made without any delay [9].
Although it is known by the world of medicine that a good anamnesis is necessary for the diagnosis, it has been shown to be more important in the diagnosis of ileus. The presence of previous abdominal surgery and intra-abdominal disease (Crohn’s disease, tumor, etc.) should be questioned in the anamnesis, and the inguinal region should be checked for hernias during the examination.
Plain abdominal radiography in the standing position should be first obtained for the radiological imaging of the patient. Plain radiography is an examination that has been used for about half a century. The radiograph should be checked for enlarged small intestinal loop and air-fluid level. If present, it should be noted whether this is from the small intestine or the large intestine (Figures 1 and 2). It should not be forgotten that obstructions proximal to the small intestine may be overlooked as they may not be able to produce air-fluid level on the radiograph. Nevertheless, it is still used as the cheapest, most practical, and easiest diagnostic method in appropriate patients [3, 10, 11].
Volvulus view on plain radiography (from the archive of Burhan Hakan Kanat).
Enlarged small intestinal loop and air-fluid levels in the radiograph (from the archive of Burhan Hakan Kanat).
Abdominal ultrasonography is an option that may be beneficial in cases where direct radiography is contraindicated such as pregnancy, although it is not in the first place in practice [3, 12].
Computed tomography has a sensitivity and specificity of approximately 80–90% in detecting small intestinal obstructions. Tomography may show the point causing small intestinal obstruction (transition zone), loss of diameter in large loops proximal to the transition zone and loops distal to the transition zone, and decompression in the colon due to lack of ileal content. Closed loop is visible, if present. Hematoma in the small intestinal wall, tumor, and invagination can also be observed if obstruction is due to an intramural cause. Gallstones, bezoars, and foreign bodies, which are among the intraluminal causes, can also be easily observed by computed tomography [10, 11, 12].
In laboratory tests, it should be kept in mind that the patient may be in a hemoconcentrated state following the intravascular volume decrease due to fluid loss to the third space. Dehydration may occur due to loss of intravascular volume. Hypokalemic-hypochloremic metabolic alkalosis may occur depending on the severity of vomiting. Leukocytosis may be added to the condition due to bacterial translocation, and lactate may increase as a finding of ischemia in the presence of closed loop [2, 13, 14].
Although some statements like “the sun should not rise” or “the sun should not set on the patient with the diagnosis of intestinal obstruction” have been made before, nonoperative approach is now applied to the patients with obstruction as in all areas of surgery. However, it should be kept in mind that complete obstruction and closed loop obstruction must be excluded for this approach [15].
Laboratory tests should be performed to see if there is an electrolyte imbalance. The dehydrated patient should be started on fluid therapy rapidly, and urinary catheter should be inserted to monitor urine output in the presence of additional diseases such as cardiac disorders. If necessary, central venous catheter insertion and CVP monitoring are among the treatment options for continuation of fluid therapy. When leukocytosis and CRP elevation are observed, prophylactic antibiotherapy should be started to prevent peritonitis secondary to bacterial translocation.
When air-fluid level is observed on standing plain abdominal radiograph, a nasogastric catheter should be inserted, and oral intake should be restricted. As a result of this decompression, aspiration, nausea, and vomiting can be prevented [16].
Computed tomography performed using water-soluble radiopaque materials such as gastrografin can show the location, characteristics of the obstruction, and whether complete obstruction occurred or not. Although it has not yet been proven in the literature, there are some authors who argue that gastrografin accelerating the passage inside the loop helps maintain local fluid-electrolyte balance.
After exclusion of closed loop and intestinal ischemia, the patient can be followed up with nonoperative approach. In this context, the presence of peritonitis and distention should be evaluated during regular abdominal examinations. Intermittent plain radiographs should be performed to see if the air-fluid levels seen in the first radiograph have decreased or replaced. Leukocyte and lactate values, gas-stool discharge, and nasogastric catheter flow rates should be closely monitored. Continuous mobilization of the patient during this follow-up reduces the length of hospital stay.
It was reported that no improvement was seen in approximately 5–15% of the patients within the first 48 h by nonoperative approach. Therefore, laparotomy option should be kept in mind for the patients who do not have significant improvement in their clinical findings after 48 h (Figures 3 and 4). It is known that the surgical decision taken after this 2-day waiting period does not increase mortality [17].
Surgery image of a patient with volvulus (from the archive of Burhan Hakan Kanat).
Bowel loop gone to necrosis due to internal herniation (from the archive of Burhan Hakan Kanat).
With the decrease of nasogastric catheter flow rate and the onset of gas-stool discharge, NG catheter can be withdrawn first, oral intake can be started over time, and food intake can be gradually increased.
Although open surgical technique is found in the first place in practice, there are also studies showing that laparoscopic surgery can be performed in selected cases. Important parameters such as early diagnosis, proximal obstruction, partial obstruction, and the number of previous abdominal surgeries are available [18]. The algorithm can be followed in follow-up and treatment (Algorithm).
Surgeons have an important duty especially in preventable mechanical obstructions due to adhesions. It is needed to pay attention to surgical rules such as minimal touching the intestines during surgery, preferring laparoscopic surgical procedures if possible, and minimizing perioperative fluid resuscitation. Transition to early oral nutrition, minimal NSAID and opioid use, administration of epidural anesthesia if possible, avoiding excessive fluid resuscitation, and close monitoring of electrolytes should be taken into consideration in the postoperative period.
The main goal in the treatment of the patients with intestinal obstruction should be to prevent unnecessary surgeries. Peristalsis-increasing agents may be given to provide anal discharge of gas in the intestine if there is no contraindication (mechanical obstruction, etc.). It is needed to prevent the introduction and production of new gas into the intestine. It may be necessary to insert a nasogastric catheter to allow the introduction of atmospheric air and easy release of air refluxing in the stomach. Although the nasogastric catheter is not very comfortable for the patient, it is very useful in some patients.
Fluid-electrolyte balance can rapidly change in these patients. It is needed to be on the alert for this condition, and the patient should be closely followed up. Fluid-electrolyte imbalance is the most important pathology that prevents physiological gas absorption from the intestinal wall. If fluid-electrolyte imbalance is corrected quickly and accurately, intestinal mucosal cell functions will be improved, and therefore a large amount of CO2 can be transferred through the lumen into the blood.
There are different approaches for some patients especially those with tumor-induced obstruction. Temporary ostomy and definitive surgery can be performed after bowel cleansing in order to keep patient comfort at a better level. Or appropriate surgery can be performed in a single session considering the general condition and additional diseases of the patient.
It is recommended to follow up some of the patients requiring surgery in the secondary or intensive care units in the postoperative period. There are important steps in early follow-up and treatment of the patients. Pulse rate, respiration rate, blood pressure, oxygen saturation, and body temperature should be closely monitored. There is no standard protocol for their monitoring frequency. Many clinics or intensive care units have standardized blood test monitoring. The laboratory values to be controlled are arranged depending on the factors such as size and duration of surgery, intraoperative interventions, renal functions, etc. Blood count, bleeding-coagulation panel, and renal and liver function tests are the most frequently studied parameters. The acid–base balance of the patient is also monitored, especially if the operation is prolonged. The patient’s intake and discharge should be closely monitored, and fluid intake should be adjusted accordingly. Fluid-electrolyte balance is especially important [19].
In these patients, multimodal management of nausea and vomiting, use of nasogastric catheter, application of urinary catheter and withdrawal time, stimulation of gastrointestinal motility, appropriate analgesia, when to feed the patient, and especially early mobilization are important in the postoperative period [20, 21].
The application of nasogastric catheters was first performed by Levine and Paine to reduce nausea, vomiting, and distension occurring after abdominal surgery. It has continued to be used in the same way since those years. Although many recent studies do not recommend its routine use, a considerable number of surgeons apply it traditionally [22]. Nasogastric catheter poses risks in terms of both comfort and complications for patients.
Despite advances in surgical treatment methods and increased experience of surgeons, postoperative pain is the most common symptom experienced by patients and is a condition that adversely affects patient comfort. Postoperative pain has a negative effect on the quality of life of patient and prolongs the period of return to daily activities and hospital stay. Thus, it increases the cost. Postoperative pain management is an issue that needs to be meticulously addressed. It may cause anxiety both in patients and their relatives, especially in hospitalized patients. The aim of providing analgesia is to minimize or prevent the patient’s discomfort, to protect against side effects, to reduce the length of hospital stay, and to prevent recurrence of pain complaints. Pharmacological and non-pharmacological methods are used in postoperative pain management [23, 24].
Malnutrition is one of the most important patient-related factors affecting morbidity and mortality in surgical patients. The most important step in nutrition is to identify the patient with malnutrition or the patient with the possibility of developing malnutrition. There are several screening methods for this. It is essential to provide adequate support when preparing the patient for surgery. Nutritional support can be provided by direct oral intake, enteral feeding tube, and parenteral route both preoperatively and postoperatively. Each alternative has its own advantages and disadvantages. Many hospitals have nutrition teams that follow up patients and provide adequate support. There are also some authors who argue that excessive feeding in the preoperative period triggers the risk of infection due to hyperglycemia [25].
Nutritional status of the patient should be closely monitored, and necessary support should be provided for early recovery. It is recommended to gradually start oral intake after sarcoma surgeries, if there is no intervention to the gastrointestinal organs. The preferred and recommended route is the enteral route as in any patient.
Every surgical intervention has a skin scar that appears from the outside. What about inside? Adhesion formation after surgery is inevitable but it is possible to minimize it. Minimally invasive surgery (robotic, laparoscopic, endoscopic), to which traditional open surgery is gradually giving way, can be considered as the first step to reduce adhesion formation. Minimally invasive surgery is very valuable in reducing brid formation by shortening the duration of surgery, eliminating intestinal contact, and reducing the amount of bleeding.
Bleeding during surgery and insufficient clearance of bleeding-related clots and inadequate intra-abdominal washing are predisposing factors for postoperative adhesions. On the other hand, the amount of contact with the intestines during abdominal surgery is correlated with brid formation.
Surgical planning should be made as soon as possible in infective pathologies (perforation, appendicitis, etc.). The elapsed waiting time will increase postoperative adhesion formation.
After surgery, intestinal function usually returns to normal within 5 days. If it persists for longer than this, it is considered a paralytic ileus. Recovering from an ileus depends on getting the proper treatment for the underlying cause. Ileus is a relatively common condition that is easy to treat. It is especially prevalent in those who have undergone recent abdominal or pelvic surgery. An awareness of the symptoms is key to improving the outlook and reducing the risk of complications. It is essential to seek prompt medical treatment as soon as symptoms appear.
The cornerstone of nonoperative management of small bowel obstruction caused by adhesions is starvation and stomach decompression using a nasogastric tube and fluid resuscitation. This approach seems uniform for younger and older patients. Nonoperative management should further include correction of electrolyte disturbances and nutritional support, especially in the frail older patient to avoid delirium, functional decline, and complications as a result of starvation and malnutrition. Nonoperative management is effective in approximately 70–90% of patients with adhesive small bowel obstruction in general. Though it has a significant failure rate, the nasogastric tube remains relevant in the conservative treatment of small bowel obstruction to initially relieve symptoms and avoid aspiration. An ongoing debate in the management of small bowel obstruction is the duration of nonoperative treatment that is deemed mandatory to resolve the bowel obstruction before the decision to operate. Most authors apply the 72-h safe-time rule for duration of initial nonoperative therapy irrespective of age [26, 27, 28, 29].
The term acute mechanical intestinal obstruction describes the condition of preventing the progression of the contents in the intestinal lumen for mechanical reasons [30]. Complaints and clinical findings can be quite guiding in the diagnosis of obstruction and can be meaningless or misleading. The accuracy rate of direct abdominal X-ray in the diagnosis of obstruction is approximately 50–70% among the initial examinations of patients with acute abdominal pain. However, it is possible to say the level and degree of obstruction in diagnostic direct abdominal X-rays and even the presence of some complications (such as perforation) [31, 32]. Today, computed tomography is the gold standard imaging method. It not only makes a diagnosis but also provides important information on determining the etiological cause, determining the level and degree of obstruction, presence of strangulation, monitoring, and treatment [33, 34].
Emergency colonoscopy, which has recently become prominent in distal intestinal obstructions, offers important diagnostic and therapeutic opportunities. Although colonoscopic examination performed in emergency conditions is more likely to not be performed optimally or fails and requires more experience, it not only shows the cause, level, degree, and presence of ischemia in cases where it is successful but also enables endoscopic treatment [30, 31, 32, 33, 34, 35, 36, 37]. There are many endoscopic methods used in the treatment of large bowel obstructions; the most preferred among these are procedures that reduce tumor size, tube administration, stenting, dilation, and detortion.
Endoscopic stenting is a frequently preferred method for both malignant and benign bowel obstructions. Stenting has two important advantages in malignant obstructions:
It is also known as bridging treatment, by eliminating the emergency, giving the patient the chance to perform elective surgery with much lower morbidity and mortality rates.
It provides palliation in patients with stage 4 disease or poor candidate for surgery, after the removal of the emergency after stenting, so that the patient does not have to live dependent on stoma in the remaining life [30].
Emergency colonoscopy should be in the first place for patients who are considered to have mechanical obstruction especially for the colon.
Although intestinal obstruction is rare in pregnancy, it is seen in the ratio of 1/10–16 thousand. Intestinal obstruction is most common in pregnancy at the beginning of the second trimester, at the end of pregnancy, and in the puerperium. The time of its appearance is parallel to the displacement of the intestines. Pregnancy can change or mask the signs and symptoms of the disease, so its diagnosis is more difficult [38, 39].
The most important cause of pregnancy intestinal obstructions is brids. Volvulus and intussusception are other common causes. It should be remembered that malignant and benign tumors can also be seen [40]. For diagnosis, abdominal ultrasonography should be the first choice since it does not contain radiation. If it is still preferred, computed tomography should be preferred instead of X-ray [39]. Colonoscopy may be preferred in patients who are considering volvulus. In treatment, surgery should be avoided as much as possible. However, there are the same treatment options as normal patients, if necessary [38].
General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed.
',metaTitle:"Horizon 2020 Compliance",metaDescription:"General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed. ",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
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\n\nMetadata for all publications is also automatically deposited in IntechOpen's OAI repository, making them available through the Open Access Infrastructure for Research in Europe's (OpenAIRE) search interface further establishing our compliance.
\n\nIn other words, publishing with IntechOpen guarantees compliance.
\n\nRead more about Open Access in Horizon 2020 here.
\n\nWhich scientific publication to choose?
\n\nWhen choosing a publication, Horizon 2020 grant recipients are encouraged to provide open access to various types of scientific publications including monographs, edited books and conference proceedings.
\n\nIntechOpen publishes all of the aforementioned formats in compliance with the requirements and criteria established by the European Commission for the Horizon 2020 Program.
\n\nAuthors requiring additional information are welcome to send their inquiries to funders@intechopen.com
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