Percutaneous intentional extraluminal revascularization was first described in 1990 as an alternative to transluminal angioplasty. Up until that point, the widely accepted technique was to remain within the lumen of the artery, with accidental entry of the catheter into the subintimal space typically being an indication to abort the procedure. However, the early literature reports a case where accidental entry of the catheter into the subintimal space and subsequent return into the true lumen led to successful revascularization after the  angioplasty balloon  was inflated within the subintimal space. [ 9 ]


Portal vein embolization  ( PVE ) is a preoperative procedure performed in  interventional radiology  to initiate hypertrophy of the anticipated future liver remnant a couple weeks prior to a major  liver resection  procedure. The procedure involves injecting the right or left portal vein with embolic material to occlude portal blood flow. By occluding the blood flow to areas of the liver that will be resected away, the blood is diverted to healthy parts of the liver and induces  hyperplasia . This may allow for a more extensive resection or stage bilateral resections that would otherwise be  contraindicated  resulting in better  oncological  treatment outcomes. [ 1 ]


Indications for PVE depend on the ratio of future liver remnant (FLR) to total estimated liver volume (TELV) and liver condition. Although there is no consensus to the absolute minimum liver volume required for adequate post-resection liver function, a FLR/TELV ratio of at least 25% is recommended in patients with otherwise normal livers. [ 2 ]  The recommendation for those with chronic liver disease such as  cirrhosis  is a FLR/TELV ratio of at least 40%. In these patients a PVE may be indicated to increase the FLR and the FLR/TELV ratio. Preoperative patients receiving extensive chemotherapy with a FLR/TELV less than 30% should also receive PVE prior to resection; conversely, chemotherapy does not preclude subsequent PVE.


Other important considerations before a PVE include co-morbidities such as diabetes, procedure type and the extent of planned resection.  Insulin resistance  has been associated with slower rates of regeneration and higher likelihood of inadequate FLR growth after PVE. [ 2 ]  Additionally, if the resection requires more extensive surgery such as a resections of the pancreas or small bowel, a greater FLR/TELV ratio may be needed for safe recovery. [ 2 ]


Preoperative PVE is a very well tolerated procedure with extremely low mortality rates (0.1 percent) and technical failure rates (0.4 percent). [ 3 ]  Complication rates from the procedure are low as well (2–3 percent) and include portal vein thrombosis, liver infarction, necrosis, infection,  pneumothorax , and other risks as listed above. [ 3 ]  Success of PVE is determined by degree of regenerative response, which again depends on factors such as baseline liver condition, technical approach and pre-existing co-morbidities. Five-year survival in patients with originally unresectable tumors as a result of inadequate future liver remnant and received PVE with subsequent resection was found in one study to be 29%. [ 4 ]


Originally, there was concern that PVE could promote tumor growth and increase recurrence rates, however a systematic review has found that there was no significant difference observed in postoperative hepatic recurrence or 3 and 5 year overall survival rates. [ 5 ]  This suggests that PVE does not have any significant adverse effects on the risk of oncogenesis. Overall, PVE is an important technique that can allow for patients with inadequate predicted FLR/TELV ratios an opportunity for resection and potential cure of their liver conditions.


Portal hypertension  is an absolute contraindication, as these patients are not surgical candidates and are at higher risk of significant complications from PVE. Additionally, complete lobar portal vein occlusion of either lobe would preclude expected increases in FLR from PVE due to already existing diversion of portal flow. Patients with extrahepatic metastatic disease are also not candidates for resection, and therefore PVE is contraindicated. In the past patients with bi-lobar disease were not considered for PVE, however now there may be a role of PVE in combination with a two-stage hepatectomy. [ 2 ] [ 6 ]   Additionally, patients who have an inadequate predicted FLR post PVE should not be considered. Other contraindications include any conditions that make a patient unfit for surgery or intervention (poor cardiopulmonary status,  sepsis ,  kidney failure , etc.).


PVE has been shown to have the following risks: [ 1 ]


PVE has been shown to have the following benefits:


Portal vein embolization is a preoperative procedure performed in  interventional radiology  to initiate hypertrophy of the anticipated future liver remnant a couple weeks prior to a major liver resection procedure. Future liver remnant (FLR) is defined as the predicted volume of functional liver after resection. There are specific FLR thresholds depending on the status of the liver (otherwise normal, chronic hepatitis, cirrhosis, etc.) that are required for safe liver resection. When the predicted FLR is below threshold, portal vein embolization may increase the FLR and bring it to threshold. [ 1 ]  The majority of preoperative PVEs usually target the right  portal vein  in preparation of a major right-sided resection. Though rare, the left portal vein may be embolized prior to a left-sided resection.


The increase in FLR is a result of cellular hyperplasia and not cellular  hypertrophy . This means that it is an increase in the number of hepatocytes that accounts for the growth rather than the increase in size of existing hepatocytes. The liver is unique in that it is an organ with regenerative potential. When blood flow to one section of the liver is occluded in PVE, the flow is diverted to other areas and this increase in blood flow stimulates the regenerative response. [ 7 ]  Regeneration begins within hours of occlusion and factors important to this response include  hepatocyte growth factor ,  epidermal growth factor ,  insulin ,  IL-6  and  TNF-alpha , among others. [ 7 ] [ 8 ]  The expected increase in FLR is approximately 10 percent; greater increases after four to six weeks can be observed, albeit at a lower rate of growth. An increase in FLR of greater than five percent for a normal liver and 10 percent for a cirrhotic liver is considered adequate and is associated with a reduced risk of post-resection liver failure. [ 9 ]


PVE was originally performed using an open approach, but the majority is now done percutaneously under conscious sedation and local anesthesia by an interventional radiologist. This can be done using either a transjugular or transhepatic approach. The most commonly used method is the direct transhepatic puncture of the portal vein. [ 10 ]  Several different  embolization agents  can be used and the choice of agents often depend on the expertise of the physician, availability and cost. As the agents differ in size, occlusive properties and side effect profiles, the choice of agent will also depend on the anatomy and locations of the tumors in a specific case. Some commonly used agents include cyanoacrylate, sodium tetradecyl sulfate foam, gelatin, metallic spherical particles, coils and absolute alcohol. [ 2 ]


To determinate whether there is a need for PVE the FLR needs to be measured. There are various imaging methods used in order to measure the liver volume such as contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) [ 11 ]  and the FLR can be traced either manually or using automatic or semi-automatic segmentation tools. FLR is measured with the chosen imaging method before PVE and then again 1–4 weeks after PVE calculating the hypertrophy of the FLR.


A technique tested so far in pigs in which a 3:1 mixture of iodinated oil and absolute ethanol was infused via lobar hepatic artery branches and into the portal system via the peribiliary plexus. The degree of FLR hypertrophy seen in the pigs with transarterial PVE compared to traditional percutaneous PVE were found to be nearly double. No significant adverse events were noted. The advantage to this new approach is a better safety profile (does not require direct hepatic puncture). However, this approach may be limited by the amount of embolic agent needed for successful embolization, as the amount needed for humans may exceed the threshold for pulmonary complications.


There are times when a patient who has undergone a PVE is no longer able to undergo a resection. In these instances, the patients are left with a permanently occluded portal vein that can exclude them from receiving other therapies. Therefore, PVE with absorbable materials such as powdered gelatin sponge dissolved in a 4:1 mixture of iodinated contrast medium and saline has been used and shown induce FLR hypertrophy. However, whether it can provide the comparable response to traditional PVE must still be studied. In the future, reversible PVE may also play a role in treating patients with chronic hepatic insufficiency to increase functional liver tissue, as opposed to just being used as an adjuvant therapy for liver resection.


Studies have shown that bone marrow-derived stem cells (specifically CD133+) play a role in liver regeneration. A study done by Esch, et al. [ 12 ]  showed that patients who received stem cells in addition to PVE had significant increases in both absolute and relative FLR growth than in patients who received PVE only. They found no significant differences between the groups in regards to major complications and mortality. This suggests that adjuvant stem cell transplantation can increase the efficacy of PVE without increasing risk.


Radiation lobectomy  is a form of  radiation therapy  used in  interventional radiology  to treat  liver cancer . It is performed in patients that would be surgical candidates for resection, but cannot undergo surgery due to insufficient remaining liver tissue. It consists of injecting small radioactive beads loaded with  yttrium-90  into the hepatic artery feeding the hepatic lobe in which the tumor is located. This is done with the intent of inducing growth in the contralateral hepatic lobe, not dissimilarly from  portal vein embolization  (PVE).


RL is performed in people with liver cancer, both primary such as  hepatocellular carcinoma  and metastatic such as from  colon adenocarcinoma . Surgical resection is considered the only curative treatment for liver cancer (other than liver transplantation for hepatocellular carcinoma) but it can only be performed in patients with sufficient remnant liver after resection (amongst other criteria). Both PVE and RL are performed in patients who are not surgical candidates due to insufficient future liver remnant (FLR), which is advised to be between 20-30% and 30-40% of the native liver volume in healthy and cirrhotic livers, respectively. [ 1 ]


Radiation lobectomy is a relatively new application of  radioembolization  and results are mainly reported in the form of retrospective chart review studies and case reports, without any prospective validation. Most authors report a comparable future liver remnant hypertrophy between portal vein embolization and RL, ranging between 10 and 47% [ 2 ] [ 3 ] [ 4 ] [ 5 ]  with cases reaching up to 119% with RL. [ 6 ]  The main difference between the two is the time interval necessary for appropriate hypertrophy, greater for RL. PVE requires a shorter time frame to achieve comparable results, ranging between 2–6 weeks, [ 7 ] [ 8 ]  while the hypertrophy kinetics of RL are slower but more constant, without significant plateau (some studies report continued hypertrophy up to 9 months). [ 2 ]  Some authors have even raised concerns regarding PVE and the potential interval disease progression in the embolized and treatment naive lobes while allowing hypertrophy, which is of less concern with RL due to its added tumoricidal effect. [ 9 ]  Additionally, RL has been demonstrated to aid surgical resection in some cases by inducing a “vascular shift” of tumor masses via necrosis and contraction away from major vascular pedicles, converting patients to resectable status. [ 4 ]  One study has shown preliminary 600-day survival in 12 out of 13 patients who received RL and subsequent resection. [ 4 ]  Ultimately, further studies are needed to prospectively compare survival and recurrence outcomes in patients receiving RL versus PVE. [ citation needed ]


Common side effects include fatigue, abdominal pain, nausea and anorexia, usually self-limiting. Post-radioembolization syndrome occurs in 20-70% of patients that undergo traditional radioembolization, presenting with shakes, chills, fatigue, nausea/vomiting, abdominal pain/discomfort, and/or cachexia and possibly hemodynamic changes, rarely requiring admission. Unfortunately, most data, if not all, is derived from traditional radioembolization outcomes studies and more will be needed to assess the actual incidence and risk of post-radioembolization syndrome in RL. [ 10 ] [ 11 ]


Complications are abscess formation, biliary complications (biloma, radiation induced cholecystitis and cholangitis, biliary necrosis), gastrointestinal complications (diarrhea, radiation induced gastritis and gastrointestinal ulceration), radiation induced pancreatitis, dermatitis, pneumonitis and lymphopenia. [ 10 ] [ 11 ] [ 2 ]


RL is performed by an interventional radiologist in the  angiography  suite, in a fashion similar to radioembolization. The procedure is composed of two different portions, a planning phase and the actual radiation lobectomy, usually performed in two different sessions: [ 10 ]


Patients undergo cross-sectional imaging at approximately 30–60 days from the procedure for evaluation of the degree of  hypertrophy  undergone by the contralateral side (as assessed by future liver remnant) and to assess tumor burden. At this time, the surgeons and/or a multi-specialty tumor board will convene to determine if the patient can/should undergo safe surgical resection.


Radiofrequency ablation  ( RFA ), also called  fulguration , [ 1 ]  is a medical procedure in which part of the  electrical conduction system of the heart ,  tumor ,  sensory nerves  or a dysfunctional  tissue  is  ablated  using the heat generated from  medium frequency   alternating current  (in the range of 350–500 kHz). [ 2 ] [ 3 ]  RFA is generally conducted in the  outpatient  setting, using either a  local anesthetic [ 3 ]  or  twilight anesthesia . When it is delivered via  catheter , it is called radiofrequency  catheter ablation .


Two advantages of  radio frequency  current (over previously used low frequency AC or pulses of DC) are that it does not directly stimulate nerves or heart muscle, and therefore can often be used without the need for  general anesthesia , and that it is specific for treating the desired tissue without significant collateral damage. [ 3 ] [ 4 ]  Due to this, RFA is an alternative for eligible patients who have  comorbities  or do not want to undergo surgery. [ 3 ] [ 5 ] [ 6 ]


Documented benefits have led to RFA becoming widely used during the 21st century. [ 3 ] [ 5 ] [ 7 ] [ 8 ] [ 9 ]  RFA procedures are performed under image guidance (such as X-ray screening,  CT scan  or  ultrasound ) by an interventional pain specialist (such as an anesthesiologist),  interventional radiologist ,  otolaryngologists , a gastrointestinal or surgical endoscopist, or a  cardiac electrophysiologist , a subspecialty of  cardiologists .


RFA may be performed to treat tumors in the lung, [ 10 ] [ 11 ] [ 12 ]  liver, [ 13 ]  kidney, and bone, as well as other body organs less commonly. Once the diagnosis of tumor is confirmed, a needle-like RFA probe is placed inside the tumor. The radiofrequency waves passing through the probe increase the temperature within tumor tissue, which results in destruction of the tumor. RFA can be used with small tumors, whether these arose within the organ (primary tumors) or spread to the organ ( metastases ). The suitability of RFA for a particular tumor depends on multiple factors. [ citation needed ]


RFA can usually be administered as an outpatient procedure, though may at times require a brief hospital stay. RFA may be combined with locally delivered chemotherapy to treat hepatocellular carcinoma (primary liver cancer). A method currently in phase III trials uses the low-level heat (hyperthermia) created by the RFA probe to trigger release of concentrated chemotherapeutic drugs from heat-sensitive liposomes in the margins around the ablated tissue as a treatment for  hepatocellular carcinoma  (HCC). [ 14 ]
Radiofrequency ablation is also used in pancreatic cancer and bile duct cancer. [ 15 ]


RFA has become increasingly important in the care of benign bone tumors, most notably  osteoid osteomas . Since the procedure was first introduced for the treatment of osteoid osteomas in the 1990s, [ 16 ]  it has been shown in numerous studies to be less invasive and expensive, to result in less bone destruction and to have equivalent safety and efficacy to surgical techniques, with 66 to 95% of people reporting freedom from symptoms. [ 17 ] [ 18 ] [ 19 ]  While initial success rates with RFA are high, symptom recurrence after RFA treatment has been reported, with some studies demonstrating a recurrence rate similar to that of surgical treatment. [ 20 ]  RFA is also increasingly used in the palliative treatment of painful  metastatic bone disease  in people who are not eligible or do not respond to traditional therapies ( i.e.  radiation therapy ,  chemotherapy , palliative surgery,  bisphosphonates  or analgesic medications). [ 21 ]


Radiofrequency energy is used in heart tissue or normal parts to destroy abnormal electrical pathways that are contributing to a  cardiac arrhythmia . It is used in recurrent  atrial flutter  (Afl),  atrial fibrillation  (AF),  supraventricular tachycardia  (SVT),  atrial tachycardia ,  Multifocal Atrial Tachycardia  (MAT) and some types of  ventricular arrhythmia . The energy-emitting probe (electrode) is at the tip of a catheter which is placed into the heart, usually through a vein. This catheter is called the  ablator . The practitioner first "maps" an area of the heart to locate the abnormal electrical activity ( electrophysiology study ) before the responsible tissue is eliminated. Radiofrequency ablation technique can be used in AF, either to block the  atrioventricular node  after implantation of a pacemaker or to block conduction within the  left atrium , especially around the  pulmonary veins . Radiofrequency ablation for AF can be unipolar (one electrode) or bipolar (two electrodes). [ 22 ]  Although bipolar can be more successful, it is technically more difficult, resulting in unipolar being used more often. [ 22 ]  But bipolar is more effective in preventing recurrent atrial arrhythmias. [ 23 ]


Ablation is now the standard treatment for SVT and typical atrial flutter, In some conditions, especially forms of intra-nodal re-entry (the most common type of SVT), also called atrioventricular nodal reentrant tachycardia or AVNRT, ablation can also be accomplished by cryoablation (tissue freezing using a coolant which flows through the catheter) which avoids the risk of complete heart block – a potential complication of radiofrequency ablation in this condition. Recurrence rates with cryoablation are higher, though. [ 24 ]  Microwave ablation, where tissue is ablated by the microwave energy "cooking" the adjacent tissue, and ultrasonic ablation, creating a heating effect by mechanical vibration, or laser ablation have also been developed but are not in widespread use. [ citation needed ]


A new indication for the use of radiofrequency technology has made news in the last few years.  Hypertension  is a very common condition, with about 1 billion people over the world, nearly 75 million in the US alone. Complications of inadequately controlled hypertension are many and have both individual and global impact. Treatment options include medications, diet, exercise, weight reduction and meditation. Inhibition of the neural impulses that are believed to cause or worsen hypertension has been tried for a few decades. Surgical sympathectomy has helped but not without significant side effects. Therefore, the introduction of non-surgical means of renal denervation using a radiofrequency ablation catheter was enthusiastically welcomed. Although the initial use of radiofrequency-generated heat to ablate nerve endings in the renal arteries to aid in management of 'resistant hypertension' were encouraging, the most recent phase 3 studying looking at catheter-based renal denervation for the treatment of resistant hypertension failed to show any significant reduction in systolic blood pressure. [ 25 ]


Radiofrequency  ablation [ 26 ]  is a dermatosurgical procedure by using various forms of alternating current. Types of radiofrequency are electrosection, electrocoagulation, electrodessication and fulguration. The use of radiofrequency ablation has obtained importance as it can be used to treat most of the skin lesions with minimal side effects and complications. [ citation needed ]


Radiofrequency ablation is a minimally invasive procedure used in the treatment of  varicose veins . It is an alternative to the traditional stripping operation. Under ultrasound guidance, a radiofrequency catheter is inserted into the abnormal vein and the vessel treated with radio-energy, resulting in closure of the involved vein. Radiofrequency ablation is used to treat the  great saphenous vein , the  small saphenous vein , and the  perforator veins . The latter are connecting veins that transport blood from the superficial veins to the deep veins. Branch varicose veins are then usually treated with other minimally invasive procedures, such as  ambulatory phlebectomy ,  sclerotherapy , or  foam sclerotherapy . Currently, the VNUS ClosureRFS stylet is the only device specifically cleared by FDA for endovenous ablation of perforator veins. [ 27 ]


The possibility of skin burn during the procedure is very small, because the large volumes (500 cc) of dilute Lidocaine (0.1%) tumescent anesthesia injected along the entire vein prior to the application of radiofrequency provide a heat sink that absorbs the heat created by the device. Early studies have shown a high success rate with low rates of complications. [ 28 ]


RFA was first studied in  obstructive sleep apnea  (OSA) in a pig model. [ 29 ]  RFA has been recognized as a  somnoplasty  treatment option in selected situations by the  American Academy of Otolaryngology [ 29 ]  but was not endorsed for general use in the  American College of Physicians  guidelines. [ 30 ]


The clinical application of  RFA in obstructive sleep apnea  is reviewed in that main article, including controversies and potential advantages in selected  medical situations .
Unlike other electrosurgical devices, [ 31 ]  RFA allows very specific treatment targeting of the desired tissue with a precise  line of demarcation  that avoids collateral damage, which is crucial in the head and neck region due to its high density of major nerves and blood vessels. RFA also does not require high temperatures. However, overheating from misapplication of RFA can cause harmful effects such as coagulation on the surface of the electrode, boiling within tissue that can leave "a gaping hole", tears, or even charring. [ 32 ]


RFA, or  rhizotomy , was developed by  Nikolai Bogduk  to treat chronic pain arising from the  facet joints  in the lower ( lumbar ) back.  Radiofrequency waves  are used to produce heat on specifically identified nerves surrounding the  facet joints  called the lumbar medial branches of the  dorsal ramus of the spinal nerves . [ 33 ]   By generating heat around the nerve, the nerve is ablated, thus destroying its ability to transmit signals to the brain.


The nerves to be ablated are identified through injections of local anesthesia (such as  lidocaine ) around the medial branches prior to the RFA procedure to first confirm the diagnosis. If the  local anesthesia  injections provide temporary pain relief, the injection is repeated a second time to confirm the diagnosis. Then RFA is performed on the nerve(s) that responded well to the injections.


RFA is a minimally invasive procedure which can usually be done in day-surgery clinics, going home shortly after completion of the procedure. The person is awake during the procedure, so risks associated with general anesthesia are avoided. Whether for back or knee pain, a drawback for this procedure is that nerves recover function over time, so the pain relief achieved lasts only temporarily (3–15 months) in most people. [ 9 ]


Radiofrequency ablation of sensory nerves in the knee, also called  genicular neurotomy  or  genicular RFA , is clinically preceded by confirming pain reduction upon anesthetizing the main knee sensory nerves in a test procedure called  genicular nerve block . [ 3 ] [ 34 ] [ 35 ]  Genicular nerve block is a short (10-30 minutes), outpatient procedure usually performed weeks before genicular RFA. [ 3 ] [ 36 ] [ 37 ]  The extent of pain reduction by injecting a local anesthetic, such as  bupivacaine , at specific locations of the target genicular nerves, is self-assessed by the person for hours after the procedure, leading to confirmation with the physician of the need for RFA. [ 3 ] [ 37 ]


In the procedure for genicular RFA, a guide cannula is first directed under local anesthesia and imaging ( ultrasound  or  fluoroscopy ) to each target genicular nerve, then the radiofrequency electrode is passed through the cannula, and the electrode tip is heated to about 80 °C (176 °F) for one minute to  cauterize  a small segment of the nerve. [ 3 ] [ 34 ]  The heat destroys that segment of the nerve, which is prevented from sending pain signals to the brain. [ 3 ] [ 34 ]


As of 2019, several hundred publications showed promise for substantial, long-term (6 months or longer) reduction of knee pain following genicular RFA. [ 3 ] [ 38 ]


The US  Food and Drug Administration  had approved in 2017 a commercial device using cooled RFA, with effects lasting for up to a year of pain relief from  knee arthritis . [ 9 ] [ 39 ]  As of 2023, reviews of clinical outcomes indicated that efficacy for reducing knee pain was achieved by ablating three or more branches of the genicular nerve (one of the  articular  branches of the  tibial nerve ). [ 36 ] [ 38 ] [ 40 ] [ 41 ]  Other sources indicate 4-5 genicular nerve targets may be justified for ablation to optimize pain relief, [ 35 ] [ 36 ]  while a 2022 analysis indicated that as many as 10 genicular nerve targets for RFA would produce better long-term relief of knee pain. [ 42 ]


Knee pain relief of 50% or more following genicular RFA may last from several months to two years, [ 3 ] [ 40 ] [ 41 ]  and can be repeated by the same outpatient procedure when pain recurs. [ 3 ]


An anatomical study of  cadaver  knees indicated that ultrasound-guided bony landmarks could be used to effectively target the superior medial geniculate nerve, superior lateral geniculate nerve, and inferior medial geniculate nerve – the three nerves commonly targeted for knee RFA [ 3 ]  – with average nerve-to-needle distances of 1.7, 3.2, and 1.8 mm, respectively. [ 43 ]


Radiofrequency ablation has been shown to be a safe and effective treatment for  Barrett's esophagus . The balloon-based radiofrequency procedure was invented by Robert A. Ganz, Roger Stern and Brian Zelickson in 1999 (System and Method for Treating Abnormal Tissue in the Human Esophagus). While the person is sedated, a catheter is inserted into the esophagus and radiofrequency energy is delivered to the diseased tissue. This outpatient procedure typically lasts from fifteen to thirty minutes. Two months after the procedure, the physician performs an upper endoscopic examination to assess the esophagus for residual Barrett's esophagus. If any Barrett's esophagus is found, the disease can be treated with a focal RFA device. Between 80 and 90% or greater of people in numerous clinical trials have shown complete eradication of Barrett's esophagus in approximately two to three treatments with a favorable safety profile. The treatment of Barrett's esophagus by RFA is durable for up to 5 years. [ 44 ] [ 45 ] [ 46 ] [ 47 ] [ 48 ]


Radiofrequency ablation has been used successfully on benign thyroid nodules for decades, most notably in Europe, South America and Korea. [ citation needed ]  In the United States, the FDA approved the use of RFA techniques for thyroid nodules in 2018. Since then, professional guidelines reflect its use as a viable treatment modality for thyroid nodules, and the procedure is increasingly applied. [ citation needed ]


- 2023: the  American Thyroid Association  issued the position statement "Thyroid ablative procedures provide valid alternative treatment strategies to conventional surgical management for a subset of patients with symptomatic benign thyroid nodules. [ 49 ]


- 2022: the  American Association of Clinical Endocrinologists  published an update in Endocrine Practice, stating that the "new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses". [ 50 ]


- 2018: FDA approved the RFA procedure for treatment of benign thyroid nodules. [ citation needed ]


The procedure is similar to a thyroid biopsy, although instead of using a needle to remove cells from the nodule, a probe delivers heat to the interior of the nodule that effectively  cauterizess  the tissue. [ medical citation needed ]  Over the course of 3-6 months, the nodule will continue to shrink, typically achieving a 50-80% reduction total size. [ medical citation needed ]


In order to qualify for an RFA procedure, a person must have a clearly benign thyroid nodule, usually proven by two fine needle aspiration biopsies. [ medical citation needed ]


As of 2020, RFA is not recommended for the treatment of  malignant  thyroid nodules, although research into this topic is ongoing. [ 51 ]


RFA is also used in radiofrequency lesioning for vein closure in areas where intrusive surgery is contraindicated by trauma, and in liver resection to control bleeding (hemostasis) and facilitate the transection process. [ citation needed ]


This process has also been used to treat  TRAP sequence  in multiple gestation pregnancies. This has an acceptable success rate for saving the 'pump' twin in recent studies compared to previous methods including laser photocoagulation. [ citation needed ]


RFA is used to treat  uterine fibroids  using the heat energy of radio frequency waves to ablate the fibroid tissue. The Acessa device [ 52 ]  obtained FDA approval in 2012. [ 53 ]  The device is inserted via a laparoscopic probe and guided inside the fibroid tissue using an ultrasound probe. The heat shrinks the fibroids. Clinical data on the procedure show an average of 45% shrinkage.


RFA is also used in the treatment of  Morton's neuroma [ 54 ]  where the outcome appears to be more reliable than alcohol injections. [ 55 ]


Renal sympathetic denervation  (RSDN) is a minimally invasive, endovascular catheter based procedure using  radiofrequency ablation  or ultrasound ablation aimed at treating resistant  hypertension  (high  blood pressure  not controlled by medication). [ 1 ]   Nerves in the wall of the  renal artery  are ablated by applying radiofrequency pulses or ultrasound to the renal arteries. This causes reduction of sympathetic afferent and efferent activity to the  kidney  and blood pressure can be decreased. [ 2 ]  Early data from international clinical trials without sham controls was promising - demonstrating large blood pressure reductions in patients with treatment-resistant hypertension. [ 2 ] [ 3 ]  However, in 2014 a prospective, single-blind, randomized, sham-controlled clinical trial failed to confirm a beneficial effect on blood pressure. [ 4 ]  A 2014 consensus statement from The Joint UK Societies did not recommend the use of renal denervation for treatment of resistant hypertension on current evidence. [ 5 ]   More recent sham-controlled trials suggest renal denervation can lead to lower systolic blood pressure. [ 6 ] [ 7 ] [ 8 ]


Prior to pharmacological management of hypertension, surgical  sympathectomy  was a recognized treatment for hypertension. [ 9 ]  This was often successful in reducing blood pressure but due to its non-selective nature the side effects of the procedure were poorly tolerated. Side effects included orthostatic hypotension, palpitations, anhydrosis, intestinal disturbances, loss of ejaculation, thoracic duct injuries and atelectasis. [ 10 ]   Modern antihypertensive pharmacological interventions have improved the control of hypertension, but only 34–66% of people with hypertension in England, US and Canada have blood pressure at or below target levels. [ 11 ]  Resistant hypertension is defined as blood pressure above target (140/90mm Hg) despite concomitant use of three or more anti-hypertensives – one of which should be a diuretic. [ 12 ]  It has been estimated that 8–10% of people with hypertension fall into this category. [ 5 ]


Several commercial devices exist. [ 13 ]   These include Medtronic's Symplicity Renal Denervation System, St. Jude Medical's EnligHTN System, Boston Scientific's Vessix V2 Renal Denervation System, Covidien's OneShot System, Recor's Paradise System, Terumo's Iberis System and Cordis Corporation's RENLANE Renal Denervation System.


In August 2023, the US FDA panel recommended the device from ReCor while rejecting the device from Medtronic. [ 14 ] [ 15 ]


The procedure involves  endovascular access   via  the  femoral artery  with advancement of a catheter-mounted device into the renal artery. The device uses radiofrequency or ultrasound to ablate the renal nerves. Typically, numerous ablations are applied at a different longitudinal and rotational positions to ensure maximal denervation. [ 13 ]  The procedure does not involve a permanent implant. [ citation needed ]


The most widely discussed studies to date are the Symplicity HTN-1, HTN-2 and HTN-3 trials, conducted with Medtronic's Symplicity RDN System. [ citation needed ]


Symplicity HTN-1 [ 3 ]  looked at outcomes in 153 patients that underwent catheter-based renal denervation. Three-year follow-up data have demonstrated an average blood pressure reduction of -33/-19mm Hg.


Symplicity HTN-2 was a randomized, [ 2 ]  controlled trial that compared 54 control patients with 52 patients who underwent catheter-based renal denervation. Six month follow-up data demonstrated a blood pressure reduction of -32/12 mm Hg in the treated group compared with a change of 1/0 mm Hg in the control group.


Meta-analyses of renal denervation have yielded conflicting results. [ 16 ]  Whilst office systolic blood pressure reductions typically average around 30 mmHg, reductions observed on ambulatory blood pressure monitoring are typically much smaller, around 10 mmHg. [ 17 ]  Explanations offered for this mismatch include renal denervation obliterating the white coat response, thereby disproportionately reducing clinic pressures, [ 16 ]  or inadvertent bias arising from the unblinded design and lack of sham control procedure in almost all renal denervation trial designs to date. [ 17 ] [ 18 ]


A study published in 2014, Symplicity HTN-3, was a prospective, single-blind, randomised, sham-controlled trial in which 535 patients with severe resistant hypertension were randomized to undergo renal denervation or a sham procedure (in a 2:1 ratio). The results showed no statistically significant difference between renal denervation and the sham procedure. [ 4 ]


Following the publication of Symplicity HTN-3 the Joint UK Societies produced a consensus statement that did not recommend the use of renal denervation for treatment of resistant hypertension in routine clinical practice. However they advocated further research with better designed randomised studies. [ 5 ]


More recent sham-controlled trials suggest renal denervation can lead to lower systolic blood pressure. [ 6 ] [ 7 ] [ 8 ] [ 19 ]


The Symplicity HTN-1, HTN-2 and HTN-3 trials have demonstrated acceptable safety profiles for catheter based renal denervation. Patients may experience pain during application of radiofrequency pulses and intraprocedural  bradycardia  requiring  atropine  has also been reported. [ 2 ]   Other documented procedure related complications include femoral artery  pseudoaneurysm  and renal artery dissection. [ citation needed ]


Of particular concern is the theoretical risk of damage to renal arteries during delivery of radiofrequency energy. An animal study using swine showed no damage to the renal arteries at 6 month follow up.  This finding is further supported in human studies in the HTN-1 and HTN-2 trial where follow up imaging has not demonstrated renal vascular damage. [ 20 ]


Other diseases may be associated with an overactive sympathetic drive and therefore, in theory, renal denervation could be of benefit. Congestive heart failure (CHF), left ventricular hypertrophy (LVH), atrial fibrillation (AF), obstructive sleep apnea (OSA), and insulin resistance/type 2 diabetes mellitus (DM) all have been associated with increased activity of the sympathetic nervous system. [ citation needed ]  Current clinical trials are examining the effect of renal denervation in these conditions. [ 21 ]


Resuscitative endovascular balloon occlusion of the aorta  ( REBOA ) is a minimally-invasive procedure performed during resuscitation of critically-injured trauma patients. Originally developed as a less invasive alternative to  emergency thoracotomy  with aortic cross clamping, REBOA is performed to gain rapid control of non-compressible truncal or junctional hemorrhage. [ 1 ] [ 2 ]  REBOA is performed first by achieving access to the common femoral artery (CFA) and advancing a catheter within the aorta. [ 1 ]  Upon successful catheter placement, an occluding balloon may be inflated either within the descending  thoracic aorta  (Zone 1) or infrarenal  abdominal aorta  (Zone 3). [ 1 ] [ 2 ]  REBOA stanches downstream hemorrhage and improves  cardiac index , cerebral perfusion, and coronary perfusion. [ 1 ] [ 3 ] [ 4 ]  Although REBOA does not eliminate the need for definitive hemorrhage control, it may serve as a temporizing measure during initial resuscitation. [ 1 ]  Despite the benefits of REBOA, there are significant local and systemic ischemic risks. [ 1 ] [ 5 ]  Establishing standardized REBOA procedural indications and mitigating the risk of ischemic injury are topics of ongoing investigation. [ 1 ] [ 4 ]  Although this technique has been successfully deployed in adult patients, it has not yet been studied in children. [ 6 ]


Severe hemorrhagic shock caused by non-compressible traumatic injury to the torso and junctional regions remains a major cause of death among civilian and military trauma victims. [ 1 ] [ 2 ] [ 3 ] [ 4 ]  In contrast to peripheral hemorrhage caused by injury to an extremity, traumatic injuries to the torso and junctional regions are not amendable to direct pressure or  tourniquet  application. [ 1 ] [ 2 ] [ 4 ]  Because non-compressible torso hemorrhages are not amendable to external interventions, these injuries account for approximately 90% of exsanguinating deaths. [ 4 ]  Severe hemorrhage is managed either with vascular embolization or damage control surgical techniques such as abdominal packing or removal of non-essential organs. [ 2 ]  However, in patients with severe hemorrhagic shock at risk for cardiovascular collapse, emergency thoracotomy with aortic cross clamping may be performed though outcomes are typically poor. [ 2 ] [ 3 ]


REBOA was developed as a rapidly deployable, minimally invasive alternative to emergency thoracotomy with aortic cross-clamping. Although there is no single indication criteria for the procedure, it is typically performed for patients with either blunt or penetrating traumatic injuries to the torso with severe hemorrhage refractory to blood product resuscitation. [ 7 ]  REBOA is performed by gaining access to the common femoral artery and inserting a small endovascular catheter with an inflatable balloon within the aorta. [ 1 ]  Upon inflation of the occluding balloon, blood flow across the descending aorta is either partially or completely obstructed which subsequently stanches downstream bleeding. [ 1 ] [ 2 ] [ 3 ]  The adjustable catheter design of the REBOA device allows for variable positioning of the occluding balloon within the aorta based on the suspected source of bleeding. [ 1 ] [ 2 ]  Zone 1 positioning in the descending thoracic aorta minimizes blood flow below the diaphragm and significantly reduces bleeding within the abdomen, pelvis, and lower extremities. [ 2 ]  Alternatively, Zone 3 placement within the infrarenal descending abdominal aorta reduces bleeding within the pelvis and lower extremities while preserving blood supply within the abdomen. [ 2 ]  Although REBOA does not replace the need for definitive surgical management, it may act as a temporizing measure by temporarily augmenting cardiac index to preserve cerebral and myocardial perfusion. [ 1 ] [ 3 ] [ 4 ]  Immediately following successful REBOA deployment, patients must be considered for emergent surgical intervention. [ 1 ] [ 2 ] [ 7 ] [ 8 ]


The safety and efficacy of REBOA in the treatment of severe hemorrhagic shock is an area of ongoing research. Early studies reported conflicting data regarding mortality and failed to establish any clear benefit of REBOA when compared to emergency thoracotomy with aortic cross clamping. [ 1 ] [ 2 ] [ 4 ]  However, design improvements of the REBOA device and continuously evolving patient selection criteria have subsequently improved REBOA outcomes. [ 1 ]  Current literature demonstrates a survival benefit of REBOA deployment in patients with severe hemorrhagic shock who do not require  cardiopulmonary resuscitation (CPR) . [ 1 ]  However, despite REBOA demonstrating its greatest efficacy when deployed prior to cardiovascular collapse, recent data has also shown promise when deployed during CPR. [ 1 ]  Closed cardiopulmonary compressions with the REBOA device deployed has demonstrated improved cardiac compression fraction and end-tidal CO 2  when compared to emergency thoracotomy with aortic cross clamping and cardiac massage. [ 1 ]  Additionally, some centers have promoted REBOA deployment in patients with hypotension at risk for progression to severe hemorrhagic shock but who do not yet meet criteria for emergency thoracotomy with aortic cross clamping. [ 3 ]  The variability in REBOA outcomes likely reflects the variability in institutional patient selection and indications criteria which highlights the need for ongoing evaluation. [ 2 ]


Access to the common femoral artery is first achieved using ultrasound guided, open, or percutaneous technique. [ 1 ]  The REBOA device is then positioned either within Zone 1 (descending thoracic aorta) or Zone 3 (infrarenal abdominal aorta) before the occluding balloon is inflated with saline. [ 1 ]  Upon successful definitive hemorrhage control, the occluding balloon is slowly deflated and the patient is monitored for recurrent bleeding or metabolic derangement. [ 1 ]  Finally, the REBOA sheath is removed and the patient is monitored for access site complications or potential ischemic complications. [ 1 ]


Despite the minimally invasive nature of the REBOA device, there are significant risks associated with its use. Although occlusion of the aorta may temporarily augment cardiac index to preserve cardiac and coronary perfusion, there is a significant risk of downstream ischemia which may lead to local ischemic changes or systemic metabolic derangement. [ 2 ] [ 3 ]  Significant complications such as limb amputation,  metabolic acidosis , and severe  reperfusion injury  have all been reported with REBOA use and are the subjects of ongoing research. [ 1 ] [ 2 ] [ 3 ]  Although there is no definitive consensus within the academic or surgical communities, many centers recommend balloon occlusion times of less than 30 minutes whenever possible to minimize the risk of clinically significant ischemia. [ 3 ]  Alternatively, some institutions have recommended partial aortic occlusion or intermittent balloon deflation to minimize the effect of downstream ischemia. [ 3 ]  Although intermittent balloon deflation is less technically difficult to perform, partial occlusion of the aorta has been demonstrated to reduce uncontrolled hemorrhage while simultaneously limiting distal ischemia and extending safe occlusion times. [ 3 ]


Additional potential complications are listed below:


The  Seldinger technique , also known as  Seldinger wire technique , is a  medical procedure  to obtain safe access to  blood vessels  and other hollow  organs . It is  named after   Sven Ivar Seldinger  (1921–1998), a  Swedish   radiologist  who introduced the procedure in 1953. [ 1 ]


The Seldinger technique is used for  angiography , insertion of  chest drains  and  central venous catheters , insertion of  PEG  tubes using the push technique, insertion of the leads for an  artificial pacemaker  or  implantable cardioverter-defibrillator , and numerous other interventional medical procedures.


The initial puncture is with a sharp instrument, and this may lead to  hemorrhage  or  perforation  of the organ in question.  Infection  is a possible complication, and hence  asepsis  is practiced during most Seldinger procedures.


Loss of the guidewire into the cavity or blood vessel is a significant and generally preventable complication. [ 2 ]


The desired vessel or cavity is punctured with a sharp hollow needle, with  ultrasound  guidance if necessary. A round-tipped guidewire is then advanced through the  lumen  of the needle, and the needle is withdrawn. A sheath or blunt  cannula  can now be passed over the guidewire into the cavity or vessel. Alternatively, drainage tubes are passed over the guidewire (as in chest drains or  nephrostomies ). After passing a sheath or tube, the guidewire is withdrawn. [ 1 ]


An introducer sheath can be used to introduce  catheters  or other devices to perform endoluminal (inside the hollow organ) procedures, such as  angioplasty .  Fluoroscopy  may be used to confirm the position of the catheter and to manoeuvre it to the desired location. Injection of  radiocontrast  may be used to visualize organs. Interventional procedures, such as  thermoablation , angioplasty, embolisation or  biopsy , may be performed.


Upon completion of the desired procedure, the sheath is withdrawn. In certain settings, a sealing device may be used to close the hole made by the procedure.


A modified technique, known as the accelerated Seldinger technique, has also been described where the needle, guidewire, dilator, and sheath are inserted as one unit. [ 3 ]


Prior to the description of the Seldinger technique, sharp  trocars  were used to create lumens through which devices could be passed. This had a high rate of complications. [ 4 ]  However, with the introduction of the Seldinger technique,  angiography  became a relatively risk-free procedure, and the field of  interventional radiology  blossomed.


Building on the work of Seldinger,  Charles Dotter  and  Andreas Gruentzig  developed  angioplasty .


Selective aortic arch perfusion  ( SAAP ) is an experimental treatment for  haemorrhage -induced  traumatic cardiac arrest . It has been shown in animal studies to be superior to Zone 1  REBOA  once cardiac arrest has occurred. [ 1 ] [ 2 ]


Selective internal radiation therapy  (SIRT), also known as  transarterial radioembolization  (TARE),  radioembolization  or  intra-arterial micro brachytherapy  is a form of  radionuclide therapy  used in  interventional radiology  to treat  cancer . It is generally for selected patients with surgically unresectable cancers, especially  hepatocellular carcinoma  or  metastasis  to the  liver . The treatment involves injecting tiny  microspheres  of  radioactive  material into the  arteries  that supply the  tumor , where the spheres lodge in the small vessels of the tumor. Because this treatment combines  radiotherapy  with  embolization , it is also called  radioembolization . The chemotherapeutic analogue (combining  chemotherapy  with embolization) is called chemoembolization, of which  transcatheter arterial chemoembolization  (TACE) is the usual form.


Radiation therapy  is used to kill cancer cells; however, normal cells are also damaged in the process. Currently, therapeutic doses of radiation can be targeted to tumors with great accuracy using  linear accelerators  in  radiation oncology ; however, when irradiating using  external beam radiotherapy , the beam will always need to travel through healthy tissue, and the normal liver tissue is very sensitive to radiation. [ 1 ]  The radiation sensitivity of the  liver parenchyma  limits the radiation dose that can be delivered via external beam radiotherapy. SIRT, on the other hand, involves the direct insertion of radioactive  microspheres  to a region, resulting in a local and targeted deposition of radioactive dose. It is therefore well-suited for treatment of liver tumors. Due to the local deposition, SIRT is regarded as a type of locoregional therapy (LRT). [ citation needed ]


The liver has a dual blood supply system; it receives blood from both the  hepatic artery  and the  portal vein . The healthy liver tissue is mainly perfused by the portal vein, while most liver malignancies derive their blood supply from the hepatic artery. Therefore, locoregional therapies such as transarterial chemoembolization or radioembolization, can selectively be administered in the arteries that are supplying the tumors and will preferentially lead to deposition of the particles in the tumor, while sparing the healthy liver tissue from harmful side effects. [ 2 ]


In addition, malignancies (including primary and many metastatic liver cancers) are often  hypervascular ; tumor blood supplies are increased compared to those of normal tissue, further leading to preferential deposition of particles in the tumors. [ citation needed ]


SIRT can be performed using several techniques, including whole liver treatment, lobar or segmental approaches. Whole liver SIRT targets the entire liver in one treatment and can be used when the disease is spread throughout the liver. Radiation lobectomy targets one of the two  liver lobes  and can be a good treatment option when only a single lobe is involved or when treating the whole liver in two separate treatments, one lobe at the time. The segmental approach, also called radiation  segmentectomy , is a technique where a high dose of radiation is delivered in one or two Couinaud  liver segments  only. The high dose results in eradication of the tumor while damage to healthy liver tissue is contained to the targeted segments only. This approach results in effective  necrosis  of the targeted segments. Segmentectomy is only feasible when the tumor(s) are contained in one or two segments. Which technique is applied is determined by  catheter  placement. The more  distally  the catheter is placed, the more localized the technique. [ 3 ]


Candidates for radioembolization include patients with:


SIRT is currently considered as a salvage therapy. It has been shown to be safe and effective in patients for whom surgery is not possible, and chemotherapy was not effective. [ 4 ] [ 5 ] [ 11 ] [ 7 ] [ 8 ]  Subsequently, several large  phase III trials  have been started to evaluate the efficacy of SIRT when used earlier in the treatment scheme or in combination treatments with systemic therapy.


SIRT, when added to first line therapy for patients with metastases of colorectal cancer, was evaluated in the SIRFLOX, [ 12 ]  FOXFIRE [ 13 ]  and FOXFIRE Global [ 14 ]  studies. For primary liver cancer (HCC), two large trials comparing SIRT with standard of care chemotherapy,  Sorafenib , have been completed, namely the SARAH [ 15 ]  and SIRveNIB [ 16 ]  trials.


Results of these studies, published in 2017 and 2018, reported no superiority of SIRT over chemotherapy in terms of overall survival (SARAH, [ 17 ]  SIRveNIB, [ 18 ]  FOXFIRE [ 19 ] ). In the SIRFLOX study, better progression-free survival was also not observed. [ 20 ]  These trials did not give direct evidence supporting SIRT as a first-line treatment regime for liver cancer. However, these studies did show that SIRT is generally better tolerated than systemic therapy, with less severe adverse events. Simultaneously, for HCC, data derived from a large retrospective analysis showed promising results for SIRT as an earlier stage treatment, particularly with high dose radiation segmentectomy and lobectomy. [ 21 ]


More studies and cohort analyses are underway to evaluate subgroups of patients who benefit from SIRT as a first-line or later treatment, or to evaluate the effect of SIRT in combination with chemotherapy (EPOCH, [ 22 ]  SIR-STEP, [ 23 ]  SORAMIC, [ 24 ]  STOP HCC [ 25 ] ).


For HCC patients currently ineligible for liver transplant, SIRT can sometimes be used to decreases tumor size allowing patients to be candidates for curative treatment. This is sometimes called bridging therapy. [ 26 ]


When comparing SIRT with transarterial chemoembolization (TACE), several studies have shown favorable results for SIRT, such as longer time to progression, [ 27 ]  higher complete response rates and longer progression-free survival. [ 28 ]


There are currently three types of commercially available microsphere for SIRT. Two of these use the radionuclide  yttrium-90  ( 90 Y) and are made of either  glass  ( TheraSphere ) or  resin  ( SIR-Spheres ). The third type uses  holmium -166 ( 166 Ho) and is made of  poly(l-lactic acid) , PLLA, (QuiremSpheres). The therapeutic effect of all three types is based on local deposition of radiation dose by high-energy  beta particles . All three types of microsphere are permanent implants and stay in the tissue even after radioactivity has decayed.


90 Y, a pure beta emitter, has half-life 2.6 days, or 64.1 hours.  166 Ho emits both beta and  gamma rays  emitter, with half-life 26.8 hours. Both  90 Y and  166 Ho have mean tissue penetration of a few millimeters.  90 Y can be imaged using  bremsstrahlung   SPECT  and  positron emission tomography  (PET). Bremsstrahlung SPECT uses of the approximately 23000 Bremsstrahlung photons per  megabecquerel  that are produced by interaction of beta particles with tissue. The positrons needed for PET imaging come from a small branch of the  decay chain  ( branching ratio   32 × 10 −6 ) that gives positrons. [ 29 ]   90 Y's low bremsstrahlung photon and positron yield make it difficult to perform quantitative imaging. [ 30 ]


166 Ho's additional gamma emission (81 KeV, 6.7%) makes  166 Ho microspheres quantifiable using a  gamma camera . Holmium is also  paramagnetic , enabling visibility and quantifiability in  MRI  even after the radioactivity has decayed. [ 31 ]


1.85 (50.0%)


Theraspheres (glass  90 Y microspheres) are  FDA  approved under a humanitarian device exemption for hepatocellular carcinoma (HCC). SIR-spheres (resin  90 Y microspheres) are FDA approved under premarket approval for colorectal metastases in combination with chemotherapy. [ 40 ]


SIR-Spheres were  CE-marked  as a  medical device  in 2002, for treating advanced inoperable liver tumors, and Theraspheres in 2014, for treating  hepatic neoplasia . [ 37 ]
QuiremSpheres (PLLA  166 Ho microspheres) received their CE mark in April 2015 for treating unresectable liver tumors and are currently only available for the European market. [ 37 ] [ 41 ]


90 Y microsphere treatment requires patient-individualized planning with cross-sectional imaging and  arteriograms . [ 42 ]  Contrast  computed tomography  and/or contrast-enhanced  magnetic resonance imaging  of the liver is required to assess tumor and normal liver volumes,  portal vein  status, and extrahepatic tumor burden. Liver and kidney function tests should be performed; patients with irreversibly elevated  serum bilirubin ,  AST  and  ALT  are excluded, as these are markers of poor liver function. [ 43 ]  Use of  iodinated contrast  should be avoided or minimized in patients with  chronic kidney disease . Tumor marker levels are also evaluated. Hepatic artery  technetium (99mTc) macro aggregated albumin  (MAA) scan is performed to evaluate hepatopulmonary shunting (resulting from  hepatopulmonary syndrome ). Therapeutic radioactive particles travelling through such a shunt can result in a high  absorbed radiation dose  to the lungs, possibly resulting in  radiation pneumonitis . Lung dose >30  gray  means increased risk of such pneumonitis. [ 44 ]


Initial  angiographic  evaluation can include an abdominal  aortogram ,  Superior mesenteric  and  Celiac  arteriograms, and selective right and left liver arteriograms. These tests can show gastrointestinal vascular anatomy and flow characteristics. Extrahepatic vessels found on angiographic evaluation can be  embolized , to prevent nontarget deposition of microspheres, that can lead to gastrointestinal  ulcers . Or the catheter tip can be moved more distally, past the extrahepatic vessels. [ 45 ]  Once the branch of the  hepatic artery  supplying the tumor is identified and the tip of the  catheter  is selectively placed within the artery, the  90 Y or  166 Ho microspheres are infused. If preferred, particle infusion can be alternated with  contrast  infusion, to check for stasis or backflow. Radiation dose absorbed, depends on microsphere distribution within the tumor vascularization. Equal distribution is necessary to ensure tumor cells are not spared due to ~2.5mm mean tissue penetration, with maximum penetration up to 11mm for  90 Y [ 46 ]  or 8.7mm for  166 Ho. [ 47 ]


After treatment, for  90 Y microspheres, bremsstrahlung SPECT or PET scanning may be done within 24 hours after radioembolization to evaluate the distribution. For  166 Ho microspheres, quantitative SPECT or MRI can be done. Weeks after treatment,  computed tomography  or MRI can be done to evaluate anatomic changes.  166 Ho microspheres are still visible on MRI after radioactivity has decayed, because holmium is paramagnetic.  FDG  positron emission tomography may also be done to evaluate changes in metabolic activity.


Complications include postradioembolization syndrome (PRS), hepatic complications,  biliary  complications,  portal hypertension  and  lymphopenia . Complications due to extrahepatic deposition include  radiation pneumonitis , gastrointestinal  ulcers  and vascular injury. [ 48 ]


Postradioembolization syndrome (PRS) includes fatigue, nausea, vomiting, abdominal discomfort or pain, and  cachexia , occurring in 20-70% of patients. Steroids and  antiemetic  agents may decrease the incidence of PRS. [ 49 ]


Liver complications include  cirrhosis  leading to  portal hypertension , radioembolization-induced liver disease (REILD), transient elevations in liver enzymes, and fulminant liver failure. [ 49 ]  REILD is characterized by  jaundice ,  ascites ,  hyperbilirubinemia  and  hypoalbuminemia  developing at least 2 weeks-4 months after SIRT, absent tumor progression or biliary obstruction. It can range from minor to fatal and is related to (over)exposure of healthy liver tissue to radiation. [ 49 ] [ 50 ]


Biliary complications include  cholecystitis  and biliary  strictures .


Investigation of  yttrium-90  and other radioisotopes for cancer treatment began in the 1960s. Many key concepts, such as preferential blood supply and tumor vascularity, were discovered during this time. Reports of initial use of resin particles of  90 Y in humans were published in the late 1970s. In the 1980s, the safety and feasibility of resin and glass yttrium-90 microsphere therapy for liver cancer were validated in a  canine  model. Clinical trials of yttrium-90 applied to the liver continued throughout the late 1980s to the 1990s, establishing the safety of the therapy. More recently, larger trials and  RCTs  have shown safety and efficacy of  90 Y therapy for the treatment of both primary and metastatic liver malignancies. [ 40 ] [ 51 ]


Development of holmium-166 microspheres started in the 1990s. The intention was to develop a microsphere with therapeutic radiation dose similar to  90 Y, but with better imaging properties, so that distribution of microspheres in the liver could be assessed more precisely. In the 2000s, development progressed to animal studies.  166 Ho microspheres for SIRT were first used in humans in 2009, which was first published in 2012. [ 52 ]  Since then, several trials have been performed showing safety and efficacy of  166 Ho SIRT, [ 53 ]  and more studies are ongoing. [ 54 ]


In  medicine , a  stent  is a tube usually constructed of a metallic  alloy  or a polymer. It is inserted into the  lumen  (hollow space) of an anatomic vessel or duct to keep the passageway open.


Stenting  refers to the placement of a stent. The word "stent" is also used as a  verb  to describe the placement of such a device, particularly when a disease such as  atherosclerosis  has  pathologically  narrowed a structure such as an  artery .


A stent is different from a  shunt . A shunt is a tube that connects two previously unconnected parts of the body to allow fluid to flow between them. Stents and shunts can be made of similar materials, but perform two different tasks.


There are various types of stents used for different medical purposes.  Coronary stents  are commonly used in  coronary angioplasty , with  drug-eluting stents  being the most common type. Vascular stents are used for peripheral and cerebrovascular disease, while ureteral stents ensure the patency of a ureter.


Prostatic stents can be temporary or permanent and are used to treat conditions like  benign prostatic hyperplasia . Colon and esophageal stents are palliative treatments for advanced colon and  esophageal cancer . Pancreatic and biliary stents provide drainage from the  gallbladder ,  pancreas , and bile ducts to the  duodenum  in conditions such as obstructing  gallstones . There are also different types of bare-metal, drug-eluting, and bioresorbable stents available based on their properties.


The term "stent" originates from  Charles Stent , an English  dentist  who made advances in denture-making techniques in the 19th century. The use of coronary stents began in 1986 by Jacques Puel and Ulrich Sigwart to prevent vessel closure during coronary surgery.


Coronary stents  are placed during a  coronary angioplasty . The most common use for coronary stents is in the  coronary arteries , into which a  bare-metal stent , a  drug-eluting stent , a bioabsorbable stent,  a  dual-therapy stent  (combination of both drug and bioengineered stent), or occasionally a covered stent is inserted.
 [ 1 ]


The majority of coronary stents used today are drug-eluting stents, which release medication to prevent complications such as blood clot formation and restenosis (re-narrowing). Stenting is performed through a procedure called percutaneous coronary intervention (PCI), where the cardiologist uses angiography and intravascular ultrasound to assess the blockage in the artery and determine the appropriate size and type of stent. The procedure is typically done in a catheterization clinic, and patients may need to stay overnight for observation. While stenting has been shown to reduce chest pain (angina) and improve survival rates after a heart attack, its effectiveness in stable angina patients has been debated.


Studies have found that most heart attacks occur due to plaque rupture rather than an obstructed artery that would benefit from a stent. Statins, along with PCI/stenting and anticoagulant therapies, are considered part of a broader treatment strategy. Some cardiologists believe that coronary stents are overused, but there is evidence of under-use in certain patient groups like the elderly. Ongoing research continues to explore new types of stents with biocompatible coatings or absorbable materials.


Vascular stents are a common treatment for advanced  peripheral  and  cerebrovascular disease . Common sites treated with vascular stents include the  carotid ,  iliac , and  femoral  arteries. Because of the external compression and mechanical forces subjected to these locations, flexible stent materials such as  nitinol  are used in many peripheral stents. [ 2 ]


Vascular stents made of metals can lead to  thrombosis  at the site of treatment or to inflammation scarring.  Drug-eluting stents  with pharmacologic agents or as drug delivery vehicles have been developed as an alternative to decrease the chances of restenosis. [ medical citation needed ]


Because vascular stents are designed to expand inside a blocked artery to keep it open, allowing blood to flow freely, the mechanical properties of vascular stents are crucial for their function: they need to be highly elastic to allow for the expansion and contraction of the stent within the blood vessel, they also need to have high strength and fatigue resistance to withstand the constant physiological load of the arteries, they should have good biocompatibility to reduce the risk of thrombosis and vascular restenosis, and to minimize the body's rejection of the implant. [ 3 ] [ 4 ] [ 5 ]


Vascular stents are commonly used in angioplasty, a surgical procedure that opens blocked arteries and places a stent to keep the artery open. This is a common treatment for heart attacks and is also used in the prevention and treatment of strokes. Over 2 million people receive a stent each year for coronary artery disease alone. Vascular stents can also be used to prevent the rupture of aneurysms in the brain, aorta, or other blood vessels. [ 6 ] [ 7 ]


Ureteral stents  are used to ensure the patency of a  ureter , which may be compromised, for example, by a  kidney stone . This method is sometimes used as a temporary measure to prevent damage to a kidney caused by a kidney stone until a procedure to remove the stone can be performed.


An ureteral stent it is typically inserted using a cystoscope, and one or both ends of the stent may be coiled to prevent movement. Ureteral stents are used for various purposes, such as temporary measures to prevent damage to a blocked kidney until a stone removal procedure can be performed, providing drainage for compressed ureters caused by tumors, and preventing spasms and collapse of the ureter after trauma during procedures like stone removal. The thread attached to some stents may cause irritation but allows for easy removal by pulling gently.


Stents without threads require cystoscopy for removal. Recent developments have introduced magnetic retrieval systems that eliminate the need for invasive procedures like cystoscopy when removing the stent. The use of magnets enables simple extraction without anesthesia and can be done by primary care physicians or nurses rather than urologists. This method has shown high success rates across different patient groups including adults, children, and kidney transplant patients while reducing costs associated with operating room procedures.


Prostatic stents  are placed from the  bladder  through the  prostatic  and  penile urethra  to allow drainage of the bladder through the  penis . This is sometimes required in  benign prostatic hyperplasia .


A prostatic stent is used to keep the male urethra open and allow for the passage of urine in cases of prostatic obstruction and lower urinary tract symptoms (LUTS). There are two types of prostatic stents: temporary and permanent. Permanent stents, typically made of metal coils, are inserted into the urethra to apply constant gentle pressure and hold open sections that obstruct urine flow. They can be placed under anesthesia as an outpatient procedure but have disadvantages such as increased urination, limited incontinence, potential displacement or infection, and limitations on subsequent endoscopic surgical options. On the other hand, temporary stents can be easily inserted with topical anesthesia similar to a Foley catheter, and allow patients to retain volitional voiding. However, they may cause discomfort or increased urinary frequency.


In the US, there is one temporary prostatic stent that has received FDA approval called The Spanner. It maintains urine flow while allowing natural voluntary urination. [ 8 ]  Research on permanent stents often focuses on metal coil designs that expand radially to hold open obstructed areas of the urethra.


These permanent stents are used for conditions like benign prostatic hyperplasia (BPH), recurrent bulbar urethral stricture (RBUS), or detrusor external sphincter dyssynergia (DESD). The Urolume is currently the only FDA-approved permanent prostatic stent. [ 9 ]


Colon and  esophageal  stents are a  palliative  treatment for advanced  colon  and  esophageal cancer .


A colon stent is typically made of flexible metal mesh that can expand and hold open the blocked area, allowing for the passage of stool. Colon stents are used primarily as a palliative treatment for patients with advanced colorectal cancer who are not candidates for surgery. They help relieve symptoms such as abdominal pain, constipation, and bowel obstruction caused by tumors or strictures in the colon.


The placement of a colon stent involves endoscopic techniques similar to esophageal stenting. A thin tube called an endoscope is inserted into the rectum and guided through the colon to locate the blockage. Using fluoroscopy or endoscopic guidance, a guidewire is passed through the narrowed area and then removed after positioning it properly. The stent is then delivered over the guidewire and expanded to keep open the obstructed section of the colon. Complications associated with colon stents include perforation of the intestinal wall, migration or dislodgment of the stent, bleeding, infection at insertion site, or tissue overgrowth around it. [ 10 ]


Colon stenting provides several benefits including prompt relief from bowel obstruction symptoms without invasive surgery in many cases. It allows for faster recovery time compared to surgical interventions while providing palliative care for patients with advanced colorectal cancer by improving quality of life and enabling better nutritional intake. However, there are potential risks associated with complications such as migration or obstruction that may require additional procedures or interventions to address these issues effectively. [ 11 ]


Pancreatic and biliary stents provide  pancreatic and bile drainage  from the  gallbladder ,  pancreas , and  bile ducts  to the  duodenum  in conditions such as  ascending cholangitis  due to obstructing  gallstones .


Pancreatic and biliary stents can also be used to treat biliary/pancreatic leaks or to prevent post-ERCP pancreatitis. [ 12 ]


In the case of gallstone pancreatitis, a gallstone travels from the gallbladder and blocks the opening to the first part of the small intestine (duodenum). This causes a backup of fluid that can travel up both the bile duct and the pancreatic duct. Gallbladder stones can lead to obstruction of the biliary tree via which gallbladder and pancreas enzymes are secreted into the duodenum, causing emergency events such as acute cholecystitis or acute pancreatitis. [ 12 ]


In conditions such as ascending cholangitis due to obstructing gallstones, these stents play a crucial role. They help in maintaining the flow of bile and pancreatic juices from the gallbladder, pancreas, and bile ducts to the duodenum1. Biliary stents are often used during endoscopic retrograde cholangiopancreatography (ERCP) to treat blockages that narrow your bile or pancreatic ducts. In cases of malignant biliary obstruction, endoscopic stent placement is one of the treatment options to relieve the obstruction. Biliary drainage is considered effective, particularly in bile duct conditions that are diagnosed and treated early. [ 12 ]


Glaucoma  drainage stents are recent developments and have been recently approved in some countries. [ 13 ]  They are used to reduce  intraocular pressure  by providing a drainage channel.


A stent graft or covered stent is type of vascular stent with a fabric coating that creates a contained tube but is expandable like a  bare metal stent . Covered stents are used in  endovascular surgical  procedures such as  endovascular aneurysm repair . Stent grafts are also used to treat  stenoses  in  vascular grafts  and  fistulas  used for  hemodialysis .


A bioresorbable stent is a tube-like device made from a material that can release a drug to prevent scar tissue growth. It is used to open and widen clogged heart arteries and then dissolves or is absorbed by the body. Unlike traditional metal stents, bioresorbable stents can restore normal vessel function, avoid long-term complications, and enable natural reconstruction of the arterial wall.


Metal-based bioresorbable scaffolds include iron, magnesium, zinc, and their alloys. Magnesium-based scaffolds have been approved for use in several countries around the world and show promising clinical results in delivering against the drawbacks of permanent metal stents. However, attention has been given to reducing the rate of magnesium corrosion through alloying and coating techniques.


Clinical research shows that resorbable scaffolds offer comparable efficacy and safety profiles to traditional drug-eluting stents (DES). The Magmaris resorbable magnesium scaffold has reported favorable safety outcomes similar to thin-strutted DES in patient populations. The Absorb naturally dissolving stent has also shown low rates of major adverse cardiac events when compared to DES. Imaging studies demonstrate that these naturally dissolving stents begin to dissolve between six months to two years after placement in the artery.


Drug-eluting stents (DES) are specialized medical devices used to treat coronary artery disease and peripheral artery disease. They release a drug that inhibits cellular growth into the blocked or narrowed arteries, reducing the risk of blockages. DES are commonly placed using percutaneous coronary intervention (PCI), a minimally invasive procedure performed via catheter. These stents have shown clear advantages over older bare-metal stents, improving patient outcomes and quality of life for cardiac patients. With over 90% of stents used in PCI procedures being drug-eluting as of 2023, DES have become the standard choice for interventional cardiologists.


DES gradually release drugs that prevent restenosis and thrombosis within the treated arteries, addressing common complications associated with previous treatments. While risks such as clot formation and bleeding exist, studies have demonstrated superior efficacy compared to bare-metal stents in reducing major adverse cardiac events like heart attacks and repeat revascularization procedures. Long-term outcomes are still being studied due to their relatively recent introduction; however, DES have revolutionized the treatment of coronary artery disease by significantly improving patient outcomes and enhancing their quality of life.


The currently accepted origin of the word  stent  is that it derives from the name of an English  dentist ,  Charles Thomas Stent  (1807–1885), notable for his advances in the field of denture-making. [ 14 ] [ 15 ]  He was born in  Brighton , England, on October 17, 1807, was a dentist in London, and is most famous for improving and modifying the denture base of the  gutta-percha , creating the stent's compounding that made it practical as a material for dental impressions.


Others attribute the noun  stent  to  Jan F. Esser , a Dutch plastic surgeon who in 1916 used the word to describe a dental impression compound invented in 1856 by Charles Stent, whom Esser employed to craft a form for facial reconstruction. The full account is described in the  Journal of the History of Dentistry . [ 16 ]   According to the author, from the use of Stent's compound as a support for facial tissues evolved the use of a stent to hold open various body structures.


The verb form "stenting" was used for centuries to describe the process of stiffening garments (a usage long obsolete, per the  Oxford English Dictionary ), and some [ who? ]  believe this to be the origin. According to the Merriam Webster Third New International Dictionary, the noun evolved from the Middle English verb  stenten , shortened from  extenten  'to stretch', which in turn came from Latin  extentus , the past participle of  extendō  'to stretch out'.


The first (self-expanding) "stents" used in medical practice in 1986 by  Ulrich Sigwart  in Lausanne were initially called "Wallstents" after their inventor, Hans Wallstén. [ 17 ] [ 18 ]
 Julio Palmaz   et al.  created a balloon-expandable stent that is currently used. [ 19 ]


The first use of a coronary stent is typically attributed to  Jacques Puel  [ fr ]  and  Ulrich Sigwart , who implanted a stent into a patient in Toulouse, France, in 1986. [ 14 ]  That stent was used as a scaffold to prevent a vessel from closing and to avoid  restenosis  in coronary surgery—a condition where scar tissue grows within the stent and interferes with vascular flow. Shortly thereafter, in 1987,  Julio Palmaz  (known for patenting a balloon-expandable stent  [ 20 ] ) and Richard Schatz implanted their similar stent into a patient in Germany.


Though several doctors have been credited with the creation of the stent, the first  FDA -approved stent in the U.S. was created by Richard Schatz and coworkers. Named the Palmaz-Schatz ( Johnson & Johnson ), it was developed in 1987. [ 21 ]


To further reduce the incidence of restenosis, the  drug-eluting stent  was introduced in 2003. [ 22 ]  Research has led to general stent design changes and improvements since that time. [ 23 ]  Bioresorbable scaffolds have also entered the market, though a large-scale clinical trial showed higher acute risks compared to drug-eluding stents. As a result, the FDA issued an official warning for their use in 2013, and research on the design and performance optimisation of stents is ongoing. [ 24 ]


Surface-guided radiation therapy  (SGRT) (sometimes referred to as  Surface-image Guided Radiation Therapy ) is the process of using 3D imaging to position and track movement of  radiation therapy  patients during treatment.


SGRT can help to improve the safety, effectiveness and efficiency of radiation therapy treatments, by offering guidance across every step of the radiation therapy workflow, including simulation, planning, treatment and dose visualisation.


Developed as an advancement to  image-guided radiation therapy , SGRT relies on 3D imaging as opposed to an x-ray. [ 1 ]  SGRT uses cameras to feed data into a software program linked to the linear accelerator delivering the radiation. [ 2 ]  Each camera uses a projector and image sensors to create a 3D surface model of a patient, by projecting a red light containing a pseudo-random speckle pattern on their skin. [ 3 ]  The pattern allows the SGRT system to reference thousands of points on the skin, acting as virtual  medical tattoos . [ 4 ]  This imaging information is fed into the software to allow real-time tracking and sub-millimetric accuracy during radiotherapy treatments. Information on movements is fed back to the radiation therapist, who is alerted if the patient moves from the optimal position (as determined by their treatment plan). SGRT systems can be set to automatically stop the delivery of radiation if a patient moves outside of a certain tolerance level. [ 5 ]


SGRT can help to reduce errors in set-up and positioning, allow the margins around  target tissue  when planning to be reduced, and enable treatment to be adapted during its course, with the aim of overall improving outcomes. [ 6 ]


For breast cancer treatment, SGRT increases the patient setup information compared to laser‐based setup (LBS), by using the entire patient skin surface instead of only three skin marks. [ 7 ]  SGRT also enables clinicians to monitor a patient in real-time to replicate the same position during the CT scan for  sarcoma  patients. [ 8 ]


When used with  deep inspiratory breath-hold , SGRT supports initial positioning, both in free breathing (at mid-patient reference point) and in DIBH (at treatment isocenter). [ 9 ]  This process has been found to help reduce errors in set-up, positioning and improve overall outcomes for patients. It has also been used with  Stereotactic Body Radiation Therapy  to assist with the initial set-up and detect intrafraction patient motion throughout treatment. [ 3 ]  For  stereotactic surgery , SGRT allows a frameless system to be used to monitor the surface of the patient within an open-face immobilization mask. [ 10 ]


Thoracentesis   / ˌ θ ɔː r ə s ɪ n ˈ t iː s ɪ s / , also known as  thoracocentesis  (from  Greek     θώραξ  (thōrax,  GEN  thōrakos)  'chest,  thorax ' and    κέντησις  (kentēsis)  'pricking, puncture'),  pleural tap ,  needle thoracostomy , or  needle decompression  (often used term), is an invasive medical procedure to remove  fluid  or  air  from the  pleural space  for diagnostic or therapeutic purposes. A  cannula , or hollow needle, is carefully introduced into the thorax, generally after administration of  local anesthesia . The procedure was first performed by  Morrill Wyman  in 1850 and then described by  Henry Ingersoll Bowditch  in 1852. [ 1 ]


The recommended location varies depending upon the source. Some sources recommend the  midaxillary line , in the eighth, ninth, or tenth  intercostal space . [ 2 ]  Whenever possible, the procedure should be performed under ultrasound guidance, which has shown to reduce complications. [ 3 ] [ 4 ] [ 5 ]


Tension pneumothorax  is a  medical emergency  that requires needle decompression before a  chest tube  is placed. [ 6 ] [ 7 ]


This procedure is indicated when unexplained fluid accumulates in the chest cavity outside the lung. In more than 90% of cases analysis of pleural fluid yields clinically useful information. If a large amount of fluid is present, then this procedure can also be used therapeutically to remove that fluid and improve patient comfort and lung function.


The most common causes of pleural  effusions  are  cancer ,  congestive heart failure ,  pneumonia , and recent  surgery . In countries where  tuberculosis  is common, this is also a common cause of pleural effusions.


When cardiopulmonary status is compromised (i.e. when the fluid or air has its repercussions on the function of heart and lungs), due to air (significant  pneumothorax ), fluid ( pleural fluid ) or  blood  ( hemothorax ) outside the lung, then this procedure is usually replaced with  tube thoracostomy , the placement of a large tube in the pleural space.


An uncooperative patient or a  coagulation  disorder that cannot be corrected are relative contraindications. [ 9 ]  Routine measurement of coagulation profiles is generally not indicated, however; when performed by an experienced operator "hemorrhagic complications are infrequent after ultrasound-guided thoracentesis, and attempting to correct an abnormal INR or platelet level before the procedure is unlikely to confer any benefit". [ 10 ]


Relative contraindications include cases in which the site of insertion has known  bullous emphysema , use of  positive end-expiratory pressure  (PEEP, see  mechanical ventilation ) and only one functioning  lung  (due to diminished reserve). Traditional expert opinion suggests that the aspiration should not exceed 1 L to avoid the possible development of pulmonary edema, but this recommendation is uncertain as the volume removed does not correlate well with this complication. [ 5 ]


Major complications are  pneumothorax  (3–30%),  hemopneumothorax ,  hemorrhage , hypotension (low blood pressure due to a vasovagal response) and reexpansion  pulmonary edema .


Minor complications include a dry tap (no fluid return), subcutaneous  hematoma  or  seroma , anxiety,  dyspnea  and cough (after removing large volume of fluid).


The use of  ultrasound  for needle guidance can minimize the complication rate. [ 3 ] [ 4 ] [ 5 ]


While chest X-ray has traditionally been performed to assess for pneumothorax following the procedure, it may no longer be necessary to do so in asymptomatic, non-ventilated persons given the widespread use of ultrasound to guide this procedure. [ 11 ]


Several diagnostic tools are available to determine the  etiology  of pleural fluid.


First the fluid is either  transudate  or  exudate .


An exudate is defined as pleural fluid to serum total protein ratio of more than 0.5, pleural fluid to serum LDH ratio > 0.6, and absolute pleural fluid LDH > 200 IU or >  2 ⁄ 3  of the normal.


An exudate is defined as pleural fluid that filters from the circulatory system into lesions or areas of inflammation. Its composition varies but generally includes water and the dissolved solutes of the main circulatory fluid such as blood. In the case of blood it will contain some or all plasma proteins, white blood cells, platelets and (in the case of local vascular damage) red blood cells.


Exudate


Transudate


A high amylase level (twice the serum level or the absolute value is greater than 160 Somogy units) in the pleural fluid is indicative of either acute or chronic  pancreatitis , pancreatic  pseudocyst  that has dissected or ruptured into the pleural space,  cancer  or esophageal rupture.


Glucose  is considered low if pleural fluid value is less than 50% of normal serum value. The  differential diagnosis  for this is:


Normal pleural fluid pH is approximately 7.60.  A pleural fluid pH below 7.30 with normal arterial blood pH has the same differential diagnosis as low pleural fluid glucose.


Chylothorax  (fluid from  lymph vessels  leaking into the pleural cavity) may be identified by determining  triglyceride  and  cholesterol  levels, which are relatively high in  lymph . A triglyceride level over 110 mg/dl and the presence of chylomicrons indicate a  chylous effusion . The appearance is generally milky but can be  serous .


The main cause for chylothorax is rupture of the  thoracic duct , most frequently as a result of  trauma or malignancy (such as  lymphoma ).


The number of  white blood cells  can give an indication of infection. The specific subtypes can also give clues as to the type on infection. The amount of  red blood cells  are an obvious sign of bleeding.


If the effusion is caused by  infection ,  microbiological culture  may yield the infectious organism responsible for the infection, sometimes before other cultures (e.g. blood cultures and sputum cultures) become positive. A  Gram stain  may give a rough indication of the causative organism. A  Ziehl–Neelsen stain  may identify  tuberculosis  or other mycobacterial diseases.


Cytology  is an important tool in identifying effusions due to  malignancy . The most common causes for pleural fluid are  lung cancer ,  metastasis  from elsewhere and  pleural mesothelioma . The latter often presents with an effusion. Normal cytology results do not reliably rule out malignancy, but make the diagnosis more unlikely.


Transcatheter arterial chemoembolization  ( TACE ) is a  minimally invasive procedure  performed in  interventional radiology  to restrict a  tumor 's blood supply. Small  embolic  particles coated with  chemotherapeutic drugs  are injected selectively through a  catheter  into an  artery  directly supplying the tumor. These particles both block the blood supply and induce  cytotoxicity , attacking the tumor in several ways. [ citation needed ]


The radiotherapeutic analogue (combining  radiotherapy  with embolization) is called radioembolization or  selective internal radiation therapy  (SIRT). [ citation needed ]


Clinical trials  determine what type of therapy is generally most successful for treating any particular type of tumor. Panels of physicians, such as the  National Comprehensive Cancer Network , determine what therapies to recommend for a given tumor type based on the outcomes of these trials. Although in theory TACE can be applied to any tumor, currently TACE is used primarily for tumors of the liver. [ 2 ]


TACE of liver tumors derives its beneficial effect by two primary mechanisms. [ 3 ]  Most tumors within the liver are supplied by the  proper hepatic artery , so arterial embolization preferentially interrupts the tumor's blood supply and stalls growth until  neovascularization . Secondly, focused administration of chemotherapy allows for delivery of a higher dose to the tissue while simultaneously reducing systemic exposure, which is typically the dose-limiting factor. This effect is potentiated by the fact that the chemotherapeutic drug is not washed out from the tumor vascular bed by blood flow after embolization. Effectively, this results in a higher concentration of drug to be in contact with the tumor for a longer period of time. [ 4 ]


Park et al. conceptualized carcinogenesis of  hepatocellular carcinoma  (HCC) as a multistep process involving parenchymal arterialization, sinusoidal capillarization, and development of unpaired arteries (a vital component of tumor  angiogenesis ). All these events lead to a gradual shift in tumor blood supply from portal to arterial circulation. This concept has been validated using dynamic imaging modalities by various investigators. Sigurdson et al. demonstrated that, when an agent was infused via the hepatic artery, intratumoral concentrations were ten times greater compared to when agents were administered through the portal vein. Hence, arterial treatment targets the tumor while normal liver is relatively spared. Embolization induces ischemic necrosis of tumor causing a failure of the  transmembrane pump , resulting in a greater absorption of cytotoxic agents by the tumor cells. Tissue concentration of agents within the tumor is greater than 40 times that of the surrounding normal liver. [ citation needed ]


Transcatheter arterial chemoembolization has most widely been applied to hepatocellular carcinoma for patients who are not eligible for surgery. [ 5 ]  TACE has been shown to increase survival in patients with intermediate HCC by BCLC criteria. It has also been used as an alternative to surgery for resectable early stage HCC and in patients with regional recurrence of the tumor after previous resection. TACE may also be used to downstage HCC in patients who exceed the  Milan criteria  for  liver transplantation .


Other treated malignancies include  neuroendocrine tumors ,  ocular melanoma ,  cholangiocarcinoma , and  sarcoma . Transcatheter arterial chemoembolization plays a  palliative  role in patients with metastatic  colon carcinoma . There is a possible benefit for liver-dominant  metastases  from other primary malignancies. [ citation needed ]


TACE is an  interventional radiology  procedure performed in the  angiography  suite. The procedure involves gaining  percutaneous  transarterial access by the  Seldinger technique  to the  hepatic artery  with an arterial sheath, usually by puncturing the  common femoral artery  in the right groin and passing a  catheter  guided by a wire through the  abdominal aorta , through the  celiac trunk  and  common hepatic artery , and finally into the branch of the  proper hepatic artery  supplying the tumor.


The  interventional radiologist  then performs a selective angiogram of the  celiac trunk  and possibly the  superior mesenteric artery  to identify the branches of the hepatic artery supplying the tumor(s) and threads smaller, more selective catheters into these branches. This is done to maximize the amount of the chemotherapeutic dose that is directed to the tumor and minimize the amount of the chemotherapeutic agent that could damage the normal liver tissue. [ 6 ]


When a blood vessel supplying the tumor has been selected, alternating doses of the chemotherapy dose and of  embolic particles , or an infusion of embolic particles containing the chemotherapy agent, are injected through the catheter .


The physician removes the catheter and access sheath, applying pressure to the entry site to prevent bleeding. The patient must lie stationary for several hours after the procedure to allow the punctured artery to heal. The clinician can apply pressure using a Femostop or close the artery using a vascular sealing device. [ 7 ]  The patient will often be kept overnight for observation and will likely be discharged the following day. The procedure is normally followed up with a  CT scan  several weeks later to check the response of the tumor to the procedure. [ 8 ]


TACE may be either conventional TACE (cTACE) or TACE with  drug-eluting beads  (DEBs) (DEB-TACE). [ 1 ]


cTACE involves  intra-arterial injection  of  cytotoxic   chemotherapy  drugs  emulsified  in  Lipiodol , an  oily   radio-opaque  agent. [ 1 ]  Following this, an  embolic agent , for instance  gelatin sponge ,  polyvinyl alcohol particles , or  microspheres , is intra-arterially injected. [ 1 ]


DEB-TACE involves intra-arterial injection of DEBs, which are non-resorbable  embolic microspheres  that are loaded with chemotherapy drugs. [ 1 ]  DEBs allow for more sustained local chemotherapy drug release (e.g., 1   month) along with concomitant embolization. [ 1 ]  They are alternatively known as drug-eluting embolic (DEE) microspheres. [ 9 ]


Examples of specific types of DEBs include the following:


EmboCept S  is an embolic agent made up of  degradable starch microspheres  (DSM). It can be mixed with low-volume chemotherapeutic agents such as  doxorubicin  and  mitomycin  and high-volume chemotherapeutic agents such as  cisplatin  and  irinotecan  to be administered into a subject. It is a short-acting, thus will be degraded 2   hours after procedure, limiting the risk of ischemia to other healthy liver cells. [ 10 ]


The most commonly used chemotherapy agents in TACE for HCC are (in decreasing order of frequency):  doxorubicin ,  cisplatin ,  epirubicin ,  mitoxantrone , and  mitomycin C . [ 11 ]  Less frequently used drugs include  anthracyclines , like  pirarubicin ,  nemorubicin , and  idarubicin , and  platinum-based agents , like  miriplatin ,  carboplatin , and  lobaplatin . [ 11 ]  No evidence-based guidelines exist to guide choice of chemotherapy agents or their dosages and none of the preceding drugs are explicitly approved by regulatory authorities for loco-regional treatment of HCC. [ 11 ]  The choices of agents, doses, and procedures vary widely between centers and surgeons. [ 11 ]  There are few studies defining dose-limiting toxicity of these agents, which may explain the widely varying practices. [ 11 ]  Single-agent therapy (e.g., doxorubicin alone) is appropriate in most cases, but some centers use two- or three-drug combinations (e.g., doxorubicin plus mitomycin C, or doxurubicin plus mitomycin C plus  gemcitabine ). [ 11 ] [ 12 ]


TACE may be used in conjunction with  systemic  chemotherapy agents. [ 13 ]


TACE has also been used to treat people with:


As with any interventional procedure, there is a small risk of hemorrhage and/or damage to blood vessels.  Pseudoaneurysm  can develop at the site of puncture in the  femoral artery . During this procedure  contrast media  is utilized, to which patients may develop an  allergic reaction . Symptomatic  hypothyroidism  may result from the high retained iodine load of the contrast.


Off-target delivery of embolic agents such as reflux into healthy surrounding tissue is a potential side effect that may cause complications such as ulceration of the gut or  cholecystitis . Specialized techniques and devices may decrease the risk.


TACE induces tumor necrosis in more than 50% of patients; the resulting  necrosis  releases  cytokines  and other inflammatory mediators into the bloodstream. A self-limiting postembolization syndrome of pain, fever, and malaise may occur due to  hepatocyte  and tumor necrosis. [ 16 ]   Transaminases  may elevate 100-fold, and a  leukemoid reaction  is not uncommon. [ citation needed ]


Intrahepatic abscess (treated by  percutaneous drainage ) and gallbladder ischemia are extremely rare. Rising bilirubin is a warning sign of irreversible hepatic necrosis, generally occurring in the setting of cirrhosis. In an effort to reduce the likelihood of significant hepatic toxicity, chemoembolization should be restricted to a single lobe or major branch of the hepatic artery at one time. The patient may be brought back after 1 month, once toxicities and abnormal chemistries have resolved, to complete the procedure in the opposite lobe. Retreatment of new lesions may be necessary, if patients fulfill the original eligibility criteria. [ 17 ]


In 1972, surgical ligation of the hepatic artery was first used to treat recurrent hepatic tumors followed by infusion of  5-fluorouracil  into the portal vein. Due to the liver's dual blood supply from the  hepatic artery  and  portal vein , interruption of the flow through the  hepatic artery  was demonstrated to be safe in patients. Tumor embolization eventually developed, blocking the vascular supply to a tumor by primarily endovascular approaches. The application of angiography with embolization followed, and the administration of chemotherapeutic agents with embolic particles evolved into transcatheter arterial chemoembolization. [ 18 ]


Transjugular intrahepatic portosystemic shunt  ( TIPS  or  TIPSS ) is an artificial channel within the  liver  that establishes communication between the inflow  portal vein  and the outflow  hepatic vein . It is used to treat  portal hypertension  (which is often due to  liver cirrhosis ) which frequently leads to intestinal bleeding, life-threatening esophageal bleeding ( esophageal varices ) and the buildup of fluid within the abdomen ( ascites ).


An  interventional radiologist  creates the shunt using an image-guided  endovascular  (via the  blood vessels ) approach, with the  jugular vein  as the usual entry site.


The procedure was first described by  Josef Rösch  in 1969 at  Oregon Health and Science University . It was first used in a human patient by Dr. Ronald Colapinto, of the  University of Toronto , in 1982, but did not become reproducibly successful until the development of endovascular stents in 1985. In 1988 the first successful TIPS was realized by M. Rössle, G.M. Richter, G. Nöldge and J. Palmaz at the  University of Freiburg . [ 1 ]  The procedure has since become widely accepted as the preferred method for treating portal hypertension that is refractory to medical therapy, replacing the surgical  portacaval shunt  in that role.


TIPS is a life-saving procedure in bleeding from esophageal or gastric varices. A randomized study showed that the survival is better if the procedure is done within 72 hours after  bleeding . [ 2 ]  TIPS has shown some promise for people with  hepatorenal syndrome . [ 3 ]  It may also help with  ascites . [ 4 ]