Magnets in Esophageal Atresia

Magnets in Esophageal Atresia (Bethany Slater)

The use of magnets is a non-surgical alternative for esophageal atresia (EA) anastomosis in selected patients. The United States Food and Drug Administration has approved a catheter-based magnetic device, the Flourish® Pediatric Esophageal Atresia Device (Cook Medical, Bloomington, IN), for use in lengthening atretic esophageal ends and creating an anastomosis in patients up to one year of age. It has been federally authorized as a humanitarian use device.

Flourish device

The device consists of an esophageal and gastric catheter each containing an inner catheter fitted with a bullet-shaped neodymium iron boron magnet. The proximal portion has a central opening for insertion of a guidewire as well as a port for suctioning saliva and for injection of contrast to confirm anastomosis. The distal catheter has a channel for enteral feeds and a five ml balloon. The magnets situated in the proximal and distal esophageal pouches have opposite polarity and thus once aligned attract one another which results in the lengthening of the ends. Once the magnets connect, or couple, the intervening tissue becomes ischemic and sloughs off while the outer rim heals establishing the anastomosis. The length of the gap must be within the magnetic field achievable by the two magnets to attain attraction and connection. The magnetic anastomosis procedure may be performed under anesthesia or sedation and is done under fluoroscopic guidance. After completion, daily chest radiographs are done to verify the proper alignment of the magnets. Successful anastomosis is confirmed by esophagram, saliva in the gastrostomy catheter or feeds in the esophageal catheter. After confirmation, the magnets may be removed and replaced with an oro- or nasogastric tube over a wire.

In addition, there is a magnetic device approved for compassionate use that has also been developed and is undergoing clinical testing. This device has disc shaped magnets in a convex / concave orientation. Once anastomosis is achieved it is spontaneously expelled.

Advantages

The main advantage of using magnets for the creation of esophageal continuity in esophageal atresia is to avoid an operation. The use of magnets for esophageal atresia may be particularly beneficial for patients with pure esophageal atresia without a long gap or patients that have undergone multiple operations or who have other comorbidities that increase the surgical risk.

Indications for use

The distance between the upper and lower pouches must be less than four cm in length to use the Flourish Device and within the specified gap distance of other magnetic devices. Magnets can be used in pure esophageal atresia cases or with a repaired fistula. For the catheter-based magnet device, a gastrostomy with a tract able to accommodate an 18 F catheter must be present. The magnets can be used as a primary procedure for anastomosis, as a staged procedure after surgical esophageal lengthening or for a recalcitrant stricture after tracheoesophageal fistula repair.

Review of evidence

Hendren and Hale first reported the use of electromagnetic bougienage to lengthen the esophageal ends in a patient with EA facilitating later surgical repair [1]. The catheter-based magnetic anastomosis was initially described in five infants with EA in Argentina [2]. The anastomosis was achieved in all of the patients in an average of 4.8 days. A later series was published describing the achievement of primary esophageal anastomosis in an additional four patients with EA using catheter-based bullet-shaped magnet pairs [3]. A recent study described a two-staged approach whereby young infants had an initial esophageal approximation without luminal continuity followed by magnamosis [4]. In addition, a retrospective study was recently published describing the use of the catheter-based magnet device in 13 patients. All achieved anastomosis with a 100% stricture rate and two patients required surgery for a refractory stricture [5]. Woo published a series of two patients that underwent magnetic compression stricturoplasty to treat refractory strictures after esophageal atresia repair [6].

Cryoablation

Cryoablation (Nicole Wilson and Edmund Yang)

Currently, there are two primary methods used to correct pectus excavatum: the open Ravitch procedure[10] and the minimally invasive Nuss procedure[11]. Traditionally, pain control after pectus excavatum repair has been challenging. In particular, the sudden remodeling of the chest wall inherent in the minimally invasive Nuss procedure is associated with significant postoperative pain. Pain after pectus excavatum repair is caused by several factors including incisional pain, interruption of cartilaginous, muscular, and ligamentous structures in the chest wall, and alteration of chest wall mechanics due to the presence of a bar and pain of pleural irritation from the bar. Inadequately controlled pain can result in the poor pulmonary toilet and result in sputum retention, atelectasis, pneumonia, lack of participation in physical therapy and other postoperative complications. Therefore, it is critical that pain be adequately addressed in the immediate postoperative period.

Historically, analgesia was achieved with opiates administered parenterally and transitioned to enteral administration after the first few postoperative days. More recently, multimodal therapies including thoracic epidural analgesia, patient-controlled parenteral opiate administration (PCA), anti-inflammatories, gabapentinoids, and muscle relaxants, have become the gold standard [12]. However, despite the development of extensive multimodal analgesic regimens, the mainstay of postoperative pain management remains opioid pain medications. Concerns regarding increased risk of long-term opioid use after postoperative opioid therapy [13] and management of the side effects of opioid administration (respiratory depression, itching, nausea, sedation, and constipation) continue to drive the search for alternative pain management strategies.

One of the first descriptions of the clinical application of cryotherapy to produce local blocking of peripheral nerves was in 1976 by Lloyd [14]. Cryotherapy techniques have since been applied to the treatment of various neuralgias [15][16] and chronic pain [17]. Cryoablation has been shown to improve respiratory mechanics and decrease opioid use when used for postoperative pain control after thoracotomy [18][19]. Given the success with cryoablation in adult patients after thoracic surgery, there has been recent interest in using cryoablation in pediatric patients undergoing repair of pectus excavatum [12][20][21][22][23].

Physiology

Cryoablation of intercostal nerves can offer both short and long-term analgesia. A cryoprobe makes use of the Joule-Thomson, or Joule-Kelvin, effect, which describes the cooling effect that occurs with the expansion of a gas that passes from an area of higher pressure to a lower pressure area [24]. The gas, typically carbon dioxide or nitrous oxide, is released at high pressure and allowed to rapidly expand within the bulb of the cryoprobe, resulting in cooling of the probe tip to approximately -50° to -70°C [19].

cryoprobe

adapted from Smiley [25]

The cryoprobe is applied directly or immediately adjacent to the peripheral nerve of interest and creates localized freezing which induces axonotmesis in which Wallerian degeneration of the axon and myelin sheath occurs distal, and to a lesser extent proximal, to the lesion [19]. This disrupts axonal continuity between the sensory nerve endings and the central nervous system (CNS). The perineurium and epineurium are relatively resistant to freezing so they remain intact, maintain continuity and provide a scaffold between the sensory nerve endings and the CNS. Recovery and restoration of sensation are accomplished via axonal regeneration through the perineurial canal which takes place at a rate of one to three mm/day.

Moorjani investigated the histologic changes after direct application of a cryoprobe to intercostal nerves for 60 seconds [19]. Immediate histologic changes included axonal degeneration, accumulation of edema fluid, capillary stasis, and the endoneurium remaining intact. They also showed that one week after cryoablation axonal swelling gradually resolved. Histologically, there were signs of Schwann cell proliferation and axonal segments had reappeared in some nerve fibers indicating partial recovery of the ablated nerve tissue. This partial recovery was progressive and complete by one month after cryoablation. Furthermore, they demonstrated that longer applications of the cryoprobe caused the same changes but the time taken for complete recovery was proportionally increased. After a standard 90 to 120 second application of a cryoprobe, complete axonal regeneration can be expected within four to six weeks [21].

Steps of the procedure

Since the use of cryoablation in the Nuss procedure is relatively novel, the surgical steps are somewhat variable and surgeon dependent. Many surgeons use the cryoICE cryoprobe (Cryo2 or 3, AtriCure, Inc., Mason, OH) which is a wand-shaped probe that can be placed into the chest under thoracoscopic guidance. It has an insulated shaft allowing minimal exposure of the cryoablation tip. The probe is used with a preprogrammed freeze/thaw cycle for 120 seconds. It cools to -60° C and effective ablation is visualized as ice crystal formation on the chest wall. The probe initially adheres to the tissues but releases from the area of ablation with warming in three to five seconds. The probe is commonly bent at the tip to facilitate longitudinal application along the inferior aspect of the rib.

Cryoablation is performed posterolaterally at the same interspace in which the pectus bar is located - two intercostal spaces above and two below the bar [21][23][26]. This usually ends up being intercostal nerves four through eight although some authors extend ablation to include the ninth intercostal nerve. Care should be taken to count the interspaces, since Horner syndrome and abdominal wall laxity are potential complications from ablating the T1-2 and T11-12 intercostal nerves, respectively. Though initial publications described subcutaneous dissection using the cryoprobe to reach the intercostal nerves [12], recent studies describe intrathoracic use of the probe bilaterally with thoracoscopic guidance. Single-lung ventilation can assist by providing better exposure to the intercostal nerves. Some authors elevate and dissect the mediastinum, then extend the thoracoscope and cryoprobe across the mediastinum to ablate the contralateral nerves [20][21] whereas some insert the thoracoscope and probe into each side for ipsilateral cryoablation [27].

There is only a single study involving the use of cryoablation for analgesia in patients undergoing the modified Ravitch procedure [28]. The cryoablation was performed thoracoscopically in the pertinent intercostal spaces. This was done either before or after the Ravitch procedure.

A posterolateral thoracotomy incision may be used to gain access to the thorax for a number of operations. Either upon gaining access to the chest or before the closure of the thorax, the intercostal nerves (one at the level of the incision, one cranial, and two caudal) are identified and exposed by peeling off the parietal pleura [19]. The cryoprobe is then placed on each nerve to be ablated under direct vision and ablation proceeds according to steps similar to those outlined above. The same equipment used for thoracoscopic cryoablation can be used under direct vision with a thoracotomy incision.

The successful use of cryoablation in adolescent patients undergoing the Nuss procedure begs the question of use in younger pediatric patients during thoracotomy. Unfortunately, there have been no documented studies involving thoracotomy nerve cryoablation for analgesia in this age group. However, cryoablation has been used in younger patients for the ablation of tumors [29], vascular malformations [30] , and foci of cardiac arrhythmias [31].

Review of the evidence for safety and effectiveness

There have been a number of studies investigating the use of intercostal nerve cryoablation in patients undergoing thoracotomy and Nuss procedure. These studies show that the use of cryoablation, in conjunction with a multimodal approach to postoperative pain control, results in a decreased length of hospital stay and decreased usage of opioid analgesics both as an inpatient and after discharge.

The studies of cryoablation in pectus excavatum repair reviewed above are limited by their retrospective nature, rapidly evolving pain control protocols, and small sample sizes. Despite these limitations, the results are promising and suggest improved patient outcomes with cryoablation compared to other pain control modalities. While cryoablation is certainly promising as an additional therapy in our armamentarium, these studies demonstrate that cryoablation alone is not sufficient for postoperative pain control as it can take 24 to 36 hours to become fully effective [21][27]. In addition, its use is not without complications, side effects, and associated difficulties.

Complications and side effects

As would be expected, cryoablation increases operative times. A single nerve ablation takes two minutes and typically five nerves are ablated on each side - the minimum length of time for a full cryoablation procedure is 20 minutes. Longer operative times (range: 40 to 60 minutes, mean 30 minutes) have been reported in the most recent literature [12][13][21][27][32]. One study did not demonstrate an increase in operative time for the modified Ravitch procedure when comparing cryoablation to thoracic epidural anesthesia [28]. Potential long-term complications following cryoablation include chronic neuropathic pain and persistent chest wall numbness. A recent study which included 43 adult and pediatric patients, demonstrated neuropathic pain in 38.5% of adults (age older than 21 years) but an incidence of 0% in pediatric patients (age younger than 21 years) [33]. In this study, pediatric patients also had faster resolution of chest wall numbness (3.4 months versus 10.8 months) compared to adult patients. In addition, there have been previous reports of neuralgia (e.g. burning, electrical or tingling sensations) after cryoablation with an incidence reported between 20 and 30% in adult series using cryoablation after thoracotomy [34]. The Graves’ study included no reports of neuralgia in the group that underwent cryoablation. All patients had anterior chest wall numbness at initial follow-up and sensation returned to normal in all patients (6/10 at three months, 10/10 with one year) [21].

Cost

The cryoICE Probe (cryoICE Probe for Cryo Nerve Block, CRYO2, AtriCure, Inc., Mason, OH, USA) is the most common probe used for peripheral nerve ablation. The probe itself is a single-use piece and is designed to be used with the AtriCure Cryo Module (ACM; cryoICE BOX V6, AtriCure, Inc., Mason, OH, USA) and the AtriCure Cryo1 Accessory Kit (composed of a Nitrous Oxide tank heater, a pressure regulator unit, and a temperature display unit). The ACM and Accessory Kit represent capital investments. Pricing for all components is negotiated at the hospital level. There are video clips on the website demonstrating some uses of the cryoICE Probe and additional information.

Indocyanine Green (ICG)

Indocyanine Green (ICG) (Brian Gulack, Samir Pandya, Bradley Segura, Gustavo Villalona and Stefan Scholz)

Fluorescence-guided surgery (FGS) is a medical imaging technique used to detect fluorescent-labeled structures during surgery. Camera systems that detect near-infrared (NIR) light not visible to the human eye can provide information about anatomy or tissue viability to the surgeon through real-time visualization in the operating field.

Indocyanine green (ICG) is the only NIR fluorescent agent currently approved for human use. ICG is a safe, water-soluble compound that received FDA approval in the 1950s. Despite the bright green color of the reagent to the human eye, its use as a contrast agent is based on its robust fluorescence in the NIR range. Applications for ICG in the pediatric world are emerging.

Indocyanine green can be used for an arteriogram, venogram, or general perfusion assessment of tissues such as intestinal before anastomosis or soft tissue pedicles during plastic surgery. ICG gets exclusively cleared by the liver through the bile ducts and is applied in fluorescence cholangiography. When administered intradermally, ICG becomes protein-bound and confined to clearance via the lymphatic system which is used to facilitate sentinel lymph node detection and biopsy.

Scientific basis

ICG is one of the most frequently employed NIR fluorophores used for FGS. ICG is a water-soluble, anionic, amphiphilic tricarbocyanine probe with a molecular weight of 776 Da which rapidly binds to plasma proteins in the body. The excitation peak is 780 nm and the emission peak is at 820 nm which places outside the range of most tissue autofluorescence. ICG was first produced in 1955 by the Kodak Research Laboratories. It was approved by the FDA for retinal angiography in 1959. Historically, it has been used to measure cardiac output, hepatic function, and retinal angiography [35]. Throughout its history, ICG has maintained a high safety index as the number of allergic reactions is very low (1:10,000, as reported by the manufacturer). ICG also allows multiple repeated uses due to its short half-life of 150 to 180 seconds and is cleared exclusively by the liver.

After intravenous application, ICG remains largely protein-bound in the intravascular space and is cleared by the liver with an intravascular half-life of approximately three minutes. From the vasculature, ICG undergoes uptake by hepatocytes and hepatic clearance. This can be detected within minutes, peaks over the course of hours, and continues for over a day after typical dosing.

Clinical applications

Fluorescence-guided surgery utilizes cameras that can visualize the near-infrared wavelength of ICG. Specialized systems are available for open procedures, thoracoscopic/laparoscopic procedures, and robotic procedures. Numerous options are available including the Artemis (Quest Medical Imaging), IMAGE1 S™ Rubina NIR/ICG Technology (Storz), SPY, PINPOINT (Stryker, Novadaq), and Firefly (Intuitive) among others.

One of the most common utilizations of this technology is in biliary surgery - most notably cholecystectomy. Both laparoscopic and robotic utilization of this technology for cholecystectomy are widely reported in the adult literature - but much less frequently in the pediatric literature. In the adult literature, ICG has been found to be non-inferior to conventional plain radiographic intraoperative cholangiogram for identifying biliary structures. However, it cannot be used to identify distal common bile duct stones [36]. Although some reports have identified quicker cystic duct identification and a decrease in operative time, there is debate over whether its use has any benefit for uncomplicated cholecystectomy when compared to conventional intraoperative cholangiogram [37]. Use in children is much less frequently reported but those who have reported similar findings to the adult population. The Buffalo group reported its use in 31 cases at their institution with no associated complications [38]. They utilized 2.5 mg (2.5 mg/ml solution) of ICG injected just prior to trocar placement. The University of California San Francisco group has also reported good results from direct injection of ICG into the gallbladder at the time of surgery (1 ml of 0.25mg/ml solution) [39]. There have also been reports utilizing ICG technology during the Kasai procedure, both for diagnosis as well as intraoperative assistance. Utilizing 0.1 to 0.5 mg/kg injection twenty-four hours prior to laparotomy, multiple studies have found that ICG can improve the identification of bile excretion and the extent of the atresia [40][41]. Although still only utilized at a few select centers, this technology has the potential to revolutionize this procedure.

The other common use of near-infrared imaging with ICG in the adult population is the evaluation of bowel viability, especially for colorectal operations or other signs of tissue perfusion such as for flaps in plastic surgery. Reports are rare in the pediatric population and have demonstrated feasibility but not superiority over traditional procedures. In the adult population, it is often used to assess for bowel viability prior to an anastomosis and studies have found that it often leads to alterations in the site of the anastomosis (although no study has proven a reduced risk of anastomotic leaks to date). The dose in adults is 15 mg (5 mg/ml concentration) which is given immediately at the time of assessment. The dose in children is much smaller - from 0.05 to 0.1 mg/kg in infants to 5 mg in children. There is little to no data in children about its use regarding viability at the time of anastomosis. A few groups have reported experimental data utilizing ICG in the assessment of necrotizing enterocolitis, but again with no demonstrated benefit.

ICG uptake in hepatocellular carcinoma has been well studied in adults and it has also been found to work well with hepatoblastoma for evaluation of the primary neoplasm as well as the identification of thoracic metastases. While all liver and cancer cells uptake ICG, normal liver cells excrete it at a faster rate, which allows visualization of the malignant cells if the ICG is given well before surgery [42]. ICG injection for primary tumors should be four days prior to the procedure to allow normal hepatocytes enough time to excrete the fluorescent marker. Normal pulmonary parenchyma excretes ICG much faster, so an injection for a planned hepatoblastoma metastasectomy can be closer to 24 hours prior to the procedure [43][44].

While there are numerous utilizations of near-infrared fluoroscopy in adult thoracic surgery, many of these are rarely needed in children such as lymph node mapping. The most common utilization reported in children is the identification of pulmonary segments in order to aid in lobe sparing pulmonary resection for congenital pulmonary airway malformations (CPAM). By ligating the arterial supply of the target segment prior to ICG injection, the intersegmental plane is much more easily identified, theoretically reducing the risk of a prolonged postoperative air leak [45]. Others have utilized intrabronchial injection of ICG but this may be much more difficult in infants due to the small size of the airways [46]. Lastly, others have recommended the utilization of this technology to identify persistent air leaks although its efficacy has not been tested in vivo [47].

Side effects and complications

The side effect profile of ICG is favorable. It does contain sodium iodide and has been reported very rarely to cause anaphylaxis or urticarial reactions. Furthermore, iodine uptake studies should not be performed for a week following use. Lastly, there is no data to support or contraindicate use in pregnant or nursing mothers [48].

Capital investment and case cost estimates

ICG can be acquired from multiple vendors at a cost of about $50 to $85 per 25mg vial. Significant cost is associated with purchasing the technology and the tools needed for ICG fluorescent imaging ranging from $30k to $60k. Some older minimally invasive systems such as Stryker 1588 Advanced Imaging Modalities (AIM) Platforms already include SPY Fluorescence technology and may be readily available in your hospital. The technology could be used by multiple pediatric subspecialties such as general and thoracic surgery, plastic surgery, neurosurgery and transplant surgery. Pricing for all components are negotiated at each hospital system level and may differ significantly.

use of ICG

from the Practicing Surgeons Curriculum (Benjamin Zendejas and Jay Meisner)

Ultrasound in Pediatric Surgery

Ultrasound in Pediatric Surgery (Farokh Demehri and Marcus Jarboe)

Ultrasound (US) has become an increasingly important tool for the pediatric surgeon – both as a diagnostic and interventional instrument. As a radiation-free imaging modality, US is particularly well suited for the pediatric population, where other non-radiating modalities such as magnetic resonance imaging require sedation. In addition, the low-fat content of most pediatric patients provides excellent US images for diagnosis or procedures. The use of US guidance for various procedures has allowed the application of precision minimally invasive techniques for children. By allowing image-guided needle placement, US allows for increased patient safety via increased accuracy and reduced morbidity compared to landmark-based percutaneous or open techniques. Despite these benefits, US remains a skill-dependent imaging technique and it requires significant education and practice to allow the surgeon to appreciate the benefits of US-guided procedures. Rather than addressing the wide range of US capabilities – from vascular US to diagnostic abdominal imaging [49] - this guideline is aimed at the surgeon considering the adoption of US-guided techniques in her or his practice with tips on US equipment options and some considerations for a few US-guided procedures.

Selecting an Ultrasound Device

Cost is highly variable depending on systems and probe/transducer selections. Good, high image quality can be obtained for the $50 to 60,000 range as of 2020. Transducers and probes add significant costs at about $8 to 12,000 per probe. Specialty probes such as laparoscopic and endorectal probes can be much more. The relationship with hospital and ultrasound manufacturers also plays a role in the price.

Image quality is of great importance. Structures in children are small and poor image quality makes identifying and targeting these small structures very difficult. Good image quality can be found in the less expensive ultrasound machines but care must be taken to select the correct machines because not all manufacturers have the same image quality in their base models. The ultrasound you select also should be able to give the user good image quality without multiple adjustments.

Probes or transducers are important features of the ultrasound. Which probes to purchase is dependent on what the machine will be used for. For vascular access (which in children is usually very superficial - even for the central vessels) high-frequency linear probes are best. Linear probes can usually be recognized by the straight flat surface of the probe. “Hockey-stick” probes fall into this category, with an ergonomic advantage for needle placement in certain procedures. The high frequency of the probe gives very good image quality with excellent spatial resolution. However, the high-frequency ultrasound waves will not penetrate soft tissue very far so it is not suited for such work. For deeper structures (like abscess drainage) lower frequency curved probes work well. The lower frequency allows deeper tissue penetration (although in children there is rarely a need for large depth penetration-unlike fetal imaging for example). The curved surface of the probe also creates an image with a wider field of view as the imaging goes deeper into the body. Abdominal imaging such as Focused Assessment with Sonography for Trauma (FAST) usually requires a low-frequency probe. There are also several specialty probes such as laparoscopic and endorectal probes which can be used for specific purposes.

There is rarely as much room as is ideal in the operating room or on the wards. A small footprint is very useful in allowing the user to place the machine/screen in the appropriate position for optimal use. A large screen size also helps in circumstances where you cannot get the machine as close to the user as is optimal. In general, smaller footprints and larger screen size is best.

There are numerous different technologies and adjustments on ultrasounds that change image quality and character. Some machines make it easy to adjust their machines to optimal image quality while others require an extensive, deep understanding of ultrasound to obtain reasonable images. For the pediatric surgeon it is general best to have simple machines with superior image quality.

Equipment in the operating room tends to take a beating. All ultrasound systems are not equal in durability. Many of the specialty probes are more fragile and need more extensive decontamination and so it is important to have protective containers for these probes. The more frequently used probes need to be durable.

Technical principles

While many machines have numerous dials and knobs that allow fine-tuning of the image and detailed calculations, most of these adjustments are beyond the routine needs of the pediatric surgeon. The four core settings to be familiar with on a given machine are

• transducer selection - this selects the appropriate probe as described above
• gain - this increases the image signal or brightness. This may allow selective gain adjustment of the deep and shallow aspects of the image. For needle-guided procedures, setting the image to a high gain can make needle identification easier.
• depth - this allows adjustment of the depth of signal shown. This should be adjusted to the minimum depth necessary to include the relevant anatomy.
• color Doppler - This is helpful to identify vascular structures during an anatomic scan by adding a blue/red color to areas with flow. This often involves a reduction in image quality, so it is not recommended to leave this on while performing a procedure.

For longitudinal/inline needle guidance the ultrasound probe is oriented parallel to the needle axis. This enables visualization of the entire length of the needle. The needle can then be advanced with the tip’s location known relative to nearby major structures. This orientation is ideal for internal jugular access because inadvertent puncture of the carotid artery or lung can be avoided. A common mistake using this approach is to lose sight of the needle itself and to instead view the movement of the surrounding tissue. Losing clear visualization of the needle tip defeats the purpose of in-line orientation yet is easy to do with a subtle movement of the transducer. This approach requires patience because fine adjustments of the transducer head keep it aligned directly over the needle trajectory.

With transverse needle guidance, the transducer head is oriented perpendicular to the vessel and needle axis producing a cross-sectional view of both. The needle is inserted at a 45-degree angle at the midpoint of the transducer, producing excellent left-right resolution. Because the needle is seen in cross-section, however, it appears as only a small point on the display, with the location and depth of the needle tip unknown. This can be remedied by regularly sliding the transducer down the trajectory of the needle past the tip until it disappears and then back until it reappears so that the tip location is known as the needle is walked down into the vessel.

Developing and improving skill

Formalimage guidance courses - Image-guided techniques are a valuable set of tools for diagnosis, management, and therapy. To incorporate them into your armamentarium, learning the basics of the different imaging technologies is invaluable: how the technology works, how to optimize your image, and getting comfortable with the US, fluoroscopic, or MRI machines. Image-guided intervention courses are available through several critical care and surgical societies.

Repetition and practice to hone skills - Especially in the case of ultrasound, image guidance is a tool that should be utilized as much as possible and incorporated in as many cases as possible to maintain familiarity and comfort. Developing skills comes with repetition and practice, utilizing ultrasound/imaging for everyday cases such as central line placement or abscess drainage is an ideal way of keeping in practice.

Partnering with interventional radiology colleagues - Even after taking a course, learning from others is always encouraged. Interventional radiologists, other surgical colleagues familiar with image guidance techniques, and ultrasound technicians are all great resources. Having your colleagues available for assistance is an invaluable resource both early in developing image guidance skills and later when performing complex or challenging cases. In addition, developing the habit of reviewing all images you order followed by reading the report is an effective way of testing yourself to make sure you have seen what the experts saw.

Specific US guided procedures

Central venous catheter (CVCs) placement is among the most common procedures performed by pediatric surgeons. Over the last two decades, there has been a paradigm shift from the use of landmark techniques to US guidance in both children and adults largely due to its increased rate of success and improved safety profile. However, in a report by the American Pediatric Surgery Association in 2015, 38% of respondents believe US guidance for CVC placement is unnecessary, and only 66% of pediatric surgeons always use US when placing internal jugular CVCs [50].

Bruzoni studied 150 pediatric patients for whom central access was randomized to either US- or landmark-guided. Success within three attempts was achieved in 95% of the US group versus 74% of the landmark group (p=0.0001) [51]. There was no statistical difference in complication rate. In a randomized trial of US only versus US and fluoroscopy-guided subclavian CVC placement conducted by Pang US-guided venous puncture was more accurate for catheterization (p=0.002). There was no significant difference in the mean length of the operation (seven minutes in the US group versus six minutes in the fluoroscopy group) [52].

A meta-analysis looking at 1100 patients by Gurien found improved cannulation but no statistical difference in complication rate or arterial punctures between US-guided CVC insertion versus landmark technique [53]. A study of over 2000 patients by Criss looked at a complete shift in the practice of an entire group of pediatric surgeons at a single center from the traditional landmark approach to ultrasound guidance over a two-year transition period. By the end of the transition, pneumothorax complications went from one to zero percent [54].

Emergent extracorporeal membrane oxygenation (ECMO) can be difficult when performed under high-pressure situations. Failure or difficulties often result in patient death or serious morbidity. As with central access, ultrasound can be helpful in both catheter placement and optimizing flow. The exact placement of the cannulas offers multiple advantages inflow and safety [49]. Although fluoroscopy and plain radiographs are helpful, ultrasound or echocardiography can often ensure that cannula tip placement is optimal and quickly give the surgeon an idea of volume status and right atrial filling in times of flow problems. Using both fluoroscopy and echocardiography for placement of Avalon® bicaval venovenous ECMO cannulas has been shown to decrease flow-related problems requiring cannula repositioning [55]. Similarly, Kashiura found there was a statistically significant decrease in complication rate when US or fluoroscopy was used to place ECMO cannulas without delaying the ECMO circuit start time [56].

US is particularly effective in the subpopulation of pediatric patients whose central vasculature is inaccessible by traditional approaches. These patients typically have a prior history of ECMO cannulation, inflammatory bowel disease, prior central venous access or renal disease. In a study of 142 cannulations in low birth weight preterm infants, Breschan demonstrated the safety and feasibility of US-guided access to the brachiocephalic vein for CVC placement. The success rate was 94% within three attempts. Three patients had inadvertent arterial punctures [57]. In a series of 11 patients, Criss described a novel technique that allows for access to the superior vena cava from a supraclavicular approach in situations where the brachiocephalic vein itself is occluded or inaccessible [54]. These techniques provide a method of access in challenging vascular access situations and should remain a potential tool in the surgical armamentarium in difficult central lines.

Internal anal sphincter botox injection is used to treat chronic obstructive defecation when the internal anal sphincter is unable to relax as associated with Hirschsprung disease and internal anal sphincter (IAS) achalasia. Injection of botulinum into the IAS allows for relaxation of the sphincter without the risk of permanent sphincter damage or incontinence following myectomy or myotomy. Traditionally, these injections are done blindly in the operating room. However, the sphincters in children are very small and difficult to target with feeling alone. As one may expect, ultrasound guidance of the botulinum toxin injection has been shown to improve the durability of the initial injection thus decreasing the need for subsequent injections and more definitive operative management for functional obstructive defecation [58]. The US guidance helps improve the accuracy of the injection by showing precisely the location of the needle in relation to the small sphincter complex.

Gastrostomy tube (GT) placement for enteral access is one of the most common procedures performed by pediatric surgeons. Originally developed as an open (i.e. Stamm) procedure, there are a variety of techniques to place gastrostomy tubes that have developed over the decades including laparoscopic, percutaneous endoscopic gastrostomy (PEG), and fluoroscopically guided. The PEG has been used both as a routine technique for GT placement, but also in circumstances where entering the abdomen may be difficult such as in a patient with multiple past abdominal operations. Unfortunately, major complications with PEG occur with variable incidence (five to 17%) and include colonic perforation, small bowel injury, solid organ injury, bleeding, and infection [59]. This has prompted surgeons to develop adjuncts to PEG to allow for safer placement. Real-time US-guided GT placement is a new technique that appears safe, efficient, and effective [60]. It relies on the transabdominal US for direct visualization while inserting a small gauge needle into a stomach filled with saline. The ultrasound guidance also provides a means of visualizing the stomach while pushing away other structures (e.g. bowel) and identifying organs that may be inadvertently injured (e.g. liver, bowel) with other percutaneous methods. The benefit of US-guided GT is especially useful in those patients whose adhesive disease may otherwise preclude a safe entry laparoscopically.

Replacement of a tube that inadvertently falls out or is malfunctioning is a common occurrence. These are frequently replaced at the bedside. However, improper placement can result in a number of complications including perforation, fistula creation, peritonitis, and sepsis. The standard approach to ensure the proper placement is the use of contrast fluoroscopy. US guidance can also be useful for quick and safe replacement of gastrostomy tubes in the emergency department or clinic.

Pediatric inguinal hernia repair has gone through an evolution from an open to minimally invasive approach using laparoscopy and needle ligation of the internal ring. Reino-Pires and colleagues recently published a study looking at the feasibility, reliability, and safety of US-guided percutaneous ligation of the internal inguinal ring in rabbits as a surrogate for indirect inguinal hernia repair in the female pediatric patient [61]. They performed the procedure using a 20-gauge peripheral intravenous catheter and a 2-0 monofilament nonabsorbable suture on 28 rabbits that were divided into two groups – one that simulated the human female inguinal hernia and the second that simulated the male’s morphology. The procedure was followed by laparoscopic exploration to evaluate the quality of the repair. During laparoscopy, they found complete and reliable suture repair 66.7% of the time and inappropriate suturing 16.7% of the time in the simulated female hernia group. Inappropriate suturing included a large gap or distal ligation. In the male group, there was a 76.9% complete but unreliable ligation meaning no gap in the closure but the spermatic cord was entrapped. Currently, the senior author offers this approach to female patients which was recently presented at the 2019 American Pediatric Surgical Association conference. This approach is an example of the continued evolution of surgical procedures due to ongoing advances in imaging technology.

Traditionally, open biopsy for soft tissue lesions has been the standard for diagnosis and tissue analysis. However, the use of image guidance percutaneous biopsy is increasingly being used for the diagnosis and characterization of malignant benign soft-tissue masses. In a study of 180 pediatric soft tissue lesions undergoing computerized tomography or US-guided percutaneous core needle biopsies, Metz found image-guided percutaneous biopsies to be safe with a high diagnostic rate (97%) with sufficient tissue for necessary ancillary testing. The study also showed a relatively large number of core needle specimens could be obtained (mean 8.9 core needle biopsies) with a very low complication rate (one percent) [62].

Skin and soft tissue infections such as cellulitis and abscesses are common in the pediatric population. US has long been the modality of choice for evaluating and diagnosing abscesses although there is less literature regarding drainage. US guidance allows for direct visualization of the needle or scalpel while avoiding surrounding structures. Gaspari retrospectively reviewed 377 patients who presented for potential skin abscesses. 137 of the patients undergoing US-guided drainage were compared to those who underwent abscess drainage without US guidance. The failure rate was statistically lower when US guidance was used (4.4% versus 15.6%; p < 0.005) [63]. Given the relative safety, efficacy, and ease of use, US should be used in all cases of suspected abscess.

Fluoroscopy has been invaluable in the localization of radiopaque foreign bodies (FB). However, with radiolucent FBs, pediatric surgeons are forced to rely on palpation and exploration making the operation difficult and often requiring larger incisions and soft tissue destruction to gain access to the FB. Ultrasound guidance is excellent in this situation where the FB will typically have a different echogenicity than the surrounding tissue thereby making the FB easily visible. Mosquito or crocodile forceps are ideal instruments for the removal of the FB while using needle localization in combination with ultrasound guidance. This reduces the required incision length and surrounding tissue damage during the extraction.

Image guidance can also be used for tube thoracostomy placement when compared to an open approach. Computerized tomography, fluoroscopy, US, or any combination of these techniques may accurately guide chest tube placement. Image guidance is selected based on which modality will best image the pleural lesion (pneumothorax versus effusion) and best guide placement of the drain. US guidance allows visualization of the needle in real-time as it enters the pleural cavity without inadvertent insertion into other structures (e.g. diaphragm, lung, liver, or heart and subcostal vessels). A study by Miraglia retrospectively looked at 25 patients who had pigtail chest tubes placed with a real-time US and report no major complications. They noted that when using direct US visualization there is no need for a follow-up chest radiograph [64]. A 16-year retrospective study by Lewis looked at 285 children who had 303 pigtail catheters placed using US guidance for parapneumonic effusions and empyema. The investigators placed 7-F drains or 8.5-F for children older than years. The treatment was successful in 93% of patients after a single drain (98.2% success after a 2nd or 3rd drain was placed). There was a 7.8% complication rate which included five periprocedural complications, 14 bronchopleural fistulae, and four patients whose drains fell out prematurely. Five patients required surgery for treatment failure but in the last five years of the study, no patient required surgical intervention.

Crohn disease is challenging in the pediatric population. Perirectal fistulizing Crohn disease with recurrent abscesses and fistulae is particularly difficult to treat. The principal in managing perirectal Crohn disease is abscess drainage and Seton placement while avoiding any fistulotomies or surgical procedure that would jeopardize continence. To this end, endorectal US (ERUS) has been utilized both as a diagnostic and therapeutic modality in the management of fistulizing Crohn disease. In a retrospective study of 25 children who underwent 42 ERUS procedures, Rosen used ERUS to evaluate suspected perianal disease, guide precise Seton placement through the fistulae, and evaluate for persistent periSeton inflammation. The purpose of this postSeton placement surveillance with ERUS was to determine the best time for seton removal. When there was resolution of periSeton inflammation on ERUS the Setons were removed. Although not powered for statistical significance, those that had ERUS surveillance were noted to have experienced a longer perianal symptom-free disease course [65].

Lymphatic (LMs) and venous malformations (VMs) are specific forms of vascular malformations commonly seen in children. US is routinely used to diagnose lesions. The most common treatment for these lesions is sclerotherapy which is nearly always performed with image guidance (ultrasound with or without fluoroscopy). Access to the lesion is performed with US guidance and the injection is performed with ultrasound or fluoroscopic guidance to avoid extravasation. To this end, Blaise demonstrated safe and effective results using US guidance to inject VM’s with polidocanol microfoam with 95.8% of patients having improvement in their symptoms with an average of 2.3 sessions [66]. Scorletti demonstrated similar results with the use of sodium tetradecyl sulfate [67]. LMs, on the other hand, are typically injected with doxycycline. For both lesions, once the procedure is completed a compression stocking is placed over the area and left in place for two to three days. This procedure may be repeated in eight to 10 weeks until there is no longer recanalization, swelling, or pain.

With increasing comfort using the procedural US, one may consider an endless array of new ways to use US for surgical purposes. In theory, many things that can be diagnosed with US may be intervened upon with US guidance. New areas that are being explored include the use of contrast-enhanced ultrasound to detect solid organ injury or for distal colostogram / cloacagram in anorectal malformations [68].

Complications

While there are no known risks or complications associated with the use of diagnostic US when used as a tool to enable a procedure the risks inherent to that procedure remain. For example, US-guided CVC placement may still result in any of the usual CVC-related complications such as pneumothorax, hemothorax, arterial injury, or catheter malposition. When used effectively in experienced hands, however, US decreases the risks of these complications compared to landmark-based approaches while reducing operative time.

Capital Investment and cost estimates

The cost of a portable US machine for procedures varies widely - roughly from $10,000 to over $150,000. Newer handheld US devices are at a lower price point but have generally been designed for bedside point of care diagnostic purposes rather than for surgical procedures. For practical purposes, a surgical US allows the use of a sterile cover, provides high enough image quality for needle placement, and can be positioned in an operation without difficulty. Commonly used US brands include: Sonosite , BK Ultrasound, GE, and Mindray – among others. In general, a US machine represents a capital investment, and pricing for all components is negotiated at the hospital level.

3D Modeling and Printing

3D Modeling and Printing for Abnormalities of the Chest Wall

3D Modeling and Printing for Abnormalities of the Chest Wall

Nicole A. Wilson, Ph.D., MD

Introduction: Deformities and abnormalities of the chest wall, both congenital and acquired, are commonly encountered in a pediatric surgical practice. These conditions range from pectus excavatum and pectus carinatum to acquired deformities following prior chest surgery. Regardless of the etiology, the wide range of presentation types and severity mean that the treatment and correction of each chest wall deformity requires a patient-specific approach. The increasing use of three-dimensional (3D) scanning, modeling, and printing has led to the accessibility of these technologies in the clinical setting. These technologies have been used to help in the assessment and treatment of the various abnormalities of the chest wall. Pectus excavatum is the most common malformation of the anterior chest wall and comprises 87–90% of malformations[87], while pectus carinatum accounts for 5%–7% of all chest wall malformations[88]. Three-dimensional scanning, modeling, and printing have all been used in the assessment and treatment of pectus excavatum and carinatum. However, all of the applications for this technology remain experimental.

Assessment of Severity: The current gold standard for assessment of the extent or severity of pectus excavatum and carinatum is computed tomography (CT) of the chest. The Haller index, or the ratio of the transverse diameter of the chest to the anteroposterior diameter (the shortest distance between the anterior vertebral body and the sternum) is used for surgical decision making in pectus excavatum (Figure 1, blue).

Figure 1

Illustration of chest computed tomography (CT). Blue lines demonstrate the traditional Haller index. Red lines demonstrate an external Haller index or optical index based on the topography of the external chest wall.

No similar index or standard exists for evaluating the extent of deformity in pectus carinatum. In order to avoid exposure to ionizing radiation, various other scanning methods (e.g., optical and white-light scanning) have been explored for quantification of deformity and to follow the results of non-operative management in these conditions. Szafer et al.[89] reported 3D optical imaging of patients with pectus excavatum and pectus carinatum. They proposed an alternative to the Haller index, the optical index (the skin-to-skin transverse distance across the chest divided by the skin-to-skin posterior-anterior distance at the point of deepest deformity), as a method for measurement of chest wall deformities.[89] While they demonstrated the ability to quickly obtain reproducible results with scans and measurements performed by a variety of clinical and non-clinical staff, no direct comparisons were made to the Haller indices of patients in this study.[89] Daemen et al.[90] performed a systematic review that identified five studies comparing the use of 3D optical imaging to CT scans in the quantification of pectus severity. They determined that external Haller indices are highly correlated with the traditional Haller index, but demonstrated the need to determine new threshold values for external Haller indices as the Haller index criteria are not directly applicable to external 3D scanning.[90] They concluded that 3D optical scanning is an attractive, feasible, and promising imaging technique to determine the severity of pectus excavatum without exposure to ionizing radiation, but no evidence was found that supports nor discards the use of 3D scans to determine pectus carinatum severity.[90]

Non-operative management: Several non-operative treatments have been proposed for pectus excavatum and carinatum. Thoracic compression bracing has extensively been used as an effective alternative to surgical correction in pectus carinatum.[91] In pectus excavatum, the use of the vacuum bell as an alternative to operative management has been shown to be effective in select patients.[92] However, these therapies slowly change the shape of the chest over a relatively long period of time. Many studies have shown that the lack of obvious changes can lead to patient frustration and subsequent poor adherence to treatment protocols or abandonment of treatment altogether.[92][93] Similarly, Port et al.[94] used white light scanning to measure the impact of bracing interventions on patients with pectus carinatum. They concluded that white light Scanning is quick, non-invasive, and safe, making it an ideal option for the frequent measurements necessary for progress monitoring and evaluation of patients with pectus carinatum.[94] Kelly et al.[93] described the use of a non-invasive optical scanning system to monitor the progress of nonoperative treatments for chest wall deformities. They demonstrated that the positive feedback of an objective demonstration of improvement is especially valuable for patients treated with nonoperative therapies that result in slow changes to the chest shape over a relatively long period of time.[93] 3D scanning technology is a promising adjunctive technology that can easily be incorporated into the clinical environment for the severity assessment of pectus defects and for monitoring of nonoperative therapies (Table 1). However, in pectus excavatum, the Haller index is still considered the reference standard for research purposes and reimbursement decisions and reference standards for these newer technologies have not yet been established. The fast, non-invasive, and safe nature of 3D scanning makes it an ideal tool for personalized medicine, but further research is needed before it can replace the role of CT scans, particularly with respect to surgical decision-making.

Table 1: Advantages and disadvantages of 3D scanning technology for the assessment and monitoring of patients with pectus excavatum and pectus carinatum.

Disadvantages	Advantages
Requires purchase / training on specialized equipment	Scanning is fast, non-invasive, and safe
No established standardized / reference / threshold values	No ionizing radiation
Unable to obtain intrathoracic anatomic information (e.g., sternal torsion, cardiopulmonary impression)	Ability to generate patient-specific reports
Relies on body constitution (i.e., difficult/less reliable in obese and female patients)	Improved patient experience (positive reinforcement)

Operative management: Pectus excavatum is most frequently treated with the Minimally Invasive Repair of Pectus Excavatum (MIRPE) since it was described by Nuss et al. in 1998.[11][92] The MIRPE procedure is performed by introducing curved metal bars into the thoracic cavity. The curvature, length, and planned intercostal space for the bar(s) are critical issues, which traditionally have relied on the experience of the surgeon and the use of intraoperative template bars.[95] This may result in an inexact, handmade, and time-consuming procedure that may further lead to incorrect selection of the length and configuration of the implants.[80] Common difficulties include requiring extensive rebending, removal, and repetitive flipping of the bars intraoperatively. Also, this strategy of bending the implant during surgery prompts the creation of multiple scratches and notches on the implant surface, which may favor adhesion formation to adjacent tissues and may exacerbate allergies to the standard stainless surgical steel bar.[80] Park et al.[96] suggested a patient-specific approach based on anthropometric/morphologic assessments of the patient’s chest wall, but ultimately this technique still relied on surgeon experience. Lin et al.[97] proposed a role for 3D printing personalized pectus bars. They used 3D printing to determine the optimal curvature of the pectus bar based on chest CT images, and 3D printed template bars, and then pre-bend the pectus bar to match the 3D-printed template. Their prospective study included 10 patients treated with this modification of the MIRPE procedure and demonstrated decreased need for multiple bar insertions and flipping of the bar intraoperatively and shorter operative times.[97] Since that time, other groups have published similar, experiences using 3D printed bars based on CT scan images to pre-operatively plan the number of bars, bar length, bar shape, and insertion site.[80][81][95] Similar morphologic outcomes have been reported (compared to hand-bent bars), but there have been improvements in operative time[95], and the number of times the bar needs to be reinserted and flipped intraoperatively.[80][81][95][97] Pre-bent Lorenz pectus bars based on preoperative CT scans are now available via large manufacturers (e,g., Zimmer Biomet, Jacksonville, FL, USA).[98] An additional advantage of custom pre-bent bars is that they are generally manufactured out of titanium, which can be laser-printed based on 3D models, thereby further limiting concerns related to bar allergies (Table 2).

Table 2. Other causes of chest wall insufficiency

Cause	Congenital or Acquired
Jarcho-Levin Syndrome (spondylocostal dysostosis)	Congenital
Jeune Syndrome (asphyxiating thoracic dystrophy)	Congenital or Acquired
Poland Syndrome	Congenital
Sternal cleft	Congenital
Chest wall tumor excision	Acquired
Sequelae of chest wall radiation therapy	Acquired
Chest wall trauma	Acquired

Other chest wall anomalies: While pectus excavatum and carinatum are the two most common chest wall anomalies, many other forms of thoracic insufficiency are encountered in a pediatric surgical practice. A variety of etiologies may result in thoracic insufficiency, ranging from congenital or acquired conditions (Table 2). Commonly these conditions consist of large defects with missing or distorted bones and soft tissue, making reconstruction a difficult technical challenge for the surgeon. Many authors have proposed custom 3D-printed prostheses for the correction of these deformities.[99][100][101] For example, Anderson et al.[102] reported two cases using 3-D printed prostheses for correction of large chest wall deformities in a patient with Poland syndrome and after resection of a chest wall osteosarcoma. The techniques of CT segmentation, computer-aided design of the implant, and fabrication of custom-made anatomical titanium prostheses for reconstruction are feasible, safe and provide satisfactory results. Hence, a patient-specific 3-D printed titanium chest wall implant is another useful adjunct to the surgical approach for reconstructing large chest wall defects whilst preserving the anatomical shape, structure and function of the thorax.

3D Printed Tracheal External Splints

3D-printed tracheal external splints

Anthony Tsai, MD

Introduction: The use of 3D-printed tracheal splints is one of the first successful uses of 3-D printing technology in surgical implants. This was first reported in the treatments of severe tracheobronchomalacia, or dynamic collapse of the trachea and mainstem bronchi. Severe forms of congenital or acquired airway flaccidity are troublesome pathologies that are difficult to treat with a mortality as high as 80%.[103] Supportive care with a tracheostomy or positive airway pressure may be insufficient and there may not be good surgical options, including anterior or posterior pexying of the airway.[104][105][106] Internal airway stenting carries a significant risk of device migration and airway obstruction or formation of granulation tissue.[107][108] Resorbable internal stents require careful surveillance due to short resorption time and possible device migration.[109][110][111] External splints using polytetrafluorethylene (PTFE) prostheses have significant risks of death, restenosis, and airway perforation.[99][100] 3D-printed tracheal splints using resorbable polycaprolactone (PCL) have had good success in patients with severe tracheobronchomalacia at high risk of death or permanent disability. Resorbable PCL splints have been successfully implanted with a comparable mortality rate and no reoperations in a more severe clinical population, compared to PTFE external splints.[101] Tracheal agenesis is another airway pathology where a supportive airway substitute is required with few viable solutions. In this rare, congenital airway malformation that occurs in less than 1 in 50,000 live births, the outcome is nearly universal lethality.[112] This is commonly classified into anatomical variations defined by Floyd (Figure 2).

Figure 2

Floyd classification of tracheal agenesis

There are fewer than 10 survivors reported in the literature and all of them, after temporizing with distal esophageal division with gastrostomy and proximal esophageal division with airway esophagostomy and spit fistula, required airway support with either internal or external splint.[101][112][113][114][115] Similar to tracheobronchomalacia, the choice of airway support faces the same potential complications. The use of a 3-D printed resorbable PCL external splint has the potential benefit of minimal migration and erosion risk, decreased infection rate, and opportunity for future airway growth. In addition, it can be customized to each patient’s specific anatomy which has significant advantages in congenital anomalies.[101] This has been successfully applied in a case of tracheal agenesis reported by Tsai et al (Figure 3).[116]

Figure 3

Repair of tracheal agenesis with esophagotracheoplasty and placement of a 3-dimensional–printed bioresorbable external splint. A, Following tracheoesophageal fistula resection and anastomosis of the esophagus to the trachea, rows of partial-thickness sutures are placed in the esophageal airway and brought through the splint interstices. B, The splint is parachuted onto the esophageal airway and sutures tied. C, Completed anastomosis of the esophagus to the trachea showing anterior sutures (arrow). D, Splint positioned around esophageal airway before suture

This project aimed to provide a successful protocol for institutions treating rare cases of severe tracheobronchomalacia or tracheal agenesis that may benefit from the placement of 3D-printed airway splints.

Protocol: 3-D printed Airway Splint design protocol Regulatory Approvals 1. Food and Drug Administration (FDA) under Expanded Access pathway (“compassionate use”) a. Contact Andrea Les (fasles@med.umich.edu) from the University of Michigan for prior examples 2. State Department of Health 3. Respective Institutional Review Board (IRB) 4. Informed consent for Expanded Access of the splint The sterilization of the 3-D printed splints will also need to be done at a FDA certified facility

Surgical Technique Guideline for 3-D Printed External Airway Splint Pre-operative bronchoscopy is performed to evaluate the airway. A median sternotomy with or without a cervical incision is performed. The anterior and lateral aspects of the trachea/airway and/or mainstem bronchi were isolated and the area(s) of malacia are confirmed. After choosing the splint(s) of best fit, a series of partial-thickness polypropylene sutures are placed circumferentially around the malacic segment(s). The sutures were then passed through the interstices of the splint, and the splints are parachuted down onto the airways. The sutures were then tied, suspending the trachea/bronchi within the splint. Surgical clips denoted proximal and distal ends of the splints for radiographic studies. If the child required concomitant cardiac repair, this can be completed before or after splint implantation. Intra-operative bronchoscopy confirmed patency of the splinted regions.

Stakeholders: Patients, patient families, hospital professionals, pediatric surgeons, anesthesiologists, perioperative staff, multidisciplinary medical teams (otolaryngology, gastroenterology, speech therapy, pulmonology, cardiology, pediatric cardiothoracic surgery, social work), children’s hospitals, children’s surgical centers, tertiary referral centers for tracheal agenesis.

Challenges and solutions: The care of these patients requires tertiary referral centers where Level IV neonatal intensive care unit (NICU) and Level I pediatric intensive care unit (PICU) with ECMO capabilities are available. In addition, care should take place in centers where pediatric anesthesiologists, pediatric cardiothoracic surgeons, and pediatric otolaryngologists trained in airway reconstruction are available.

3D Bioprinting of Hollow Organs/Esophagus

3D Bioprinting of hollow organs/esophagus

Christine Finck, MD; Heather Wancyzk

Introduction: The development and commercialization of affordable desktop 3D bioprinters has led to an explosion of technological advancements in the field of tissue engineering over the past few years. Previously, the fabrication of hollow tube-like scaffolds for tissue engineering purposes has been facilitated by a nanofiber production process known as electrospinning.[117] This technique uses electrostatic forces to produce biomimetic scaffolds from polymers such as polyurethane (PU) and poly-lactic acid (PLA).[118] These scaffolds consist of fibers with varying degrees of porosity that facilitate cell growth and adhesion.[119] In 2022, the paper published in NPJ Regenerative Medicine, demonstrated the utility of an electro-spun biodegradable scaffold composed of polyurethane and seeded with autologous adipose-derived mesenchymal stem cells (AD-MSCs), in the regeneration of an esophageal gap in a porcine model of esophageal atresia.[120] Twenty-one days after implantation, the scaffold was removed endoscopically, and in its place was tissue consisting of newly regenerated mucosal and epithelial cell layers (Figure 4C + D).

Figure 4

Schematic of preclinical model. (A) Harvest of adipose cells, culture and expand cells, seed onto a scaffold in a sterile bioreactor, implant the scaffold (B). At day 21 endoscopy shows a complete fibro vascular core of tissue bridging the gap in the esophagus. The stent and scaffold are removed (D). Gross picture of the regenerated esophagus at 1 year demonstrating intact epithelium and muscular layers (E).

All animals were able to feed normally and maintained a consistent weight over the length of the study. After one year, harvest of regenerated tissue revealed the presence of epithelial and muscular layers, however, the muscular regions were disorganized compared to normal controls. Another study performed by Grikscheit et al.[121] has also demonstrated the feasibility of using polyglycolic acid/poly-L-lactic acid scaffolds seeded with human intestinal organoids (HIOs) to regenerate portions of the small intestine. These HIOs, derived from human embryonic stem cells, were seeded on scaffolds within the omentum of mice to generate tissue-engineered small intestine (TESI). After 4 weeks, the presence of mature villus and crypt-like structures were evident in explanted tissues. These findings are important because they show that tissue engineered scaffolds can promote the development of mature tissue that is functional, which is a prerequisite for organ replacement. Based on these exciting preliminary results, the use of implantable biomimetic scaffolds for whole organ replacement may soon be a new reality.

Benefits of 3D printing for hollow organ replacement: Although electro-spun scaffolds have shown promising results in tissue replacement studies, reproducibility of fiber size and porosity is limited. Additionally, it is difficult to mimic complex 3D tissues of the body such as the heart and lungs. Another disadvantage is that the solvents used during the production process may be toxic, which can further limit translational applications. One way to build and improve upon this method is through the use of 3D bioprinting technologies to create anatomically precise hollow organs that incorporate biomimetic “inks’’ with patient-derived cells (Figure 5).

Figure 5

Extrusion based 3D Bioprinter from CellInk

Additionally, fused-deposition modeling (FDM) based printers can also be used to efficiently fabricate synthetic polymers exhibiting excellent structural properties that can be used as scaffolds for cell seeding (Figure 6).

Figure 6

FDM-based 3D printer from PRUSA

FDM printers are similar to extrusion-based bio printers in that they are an additive manufacturing technology that involves the deposition of thermo-plastic materials in a layer-by-layer fashion. These technologies differ in that cells cannot be incorporated into materials during the FDM printing process due to the use of high temperatures. Due to debilitating conditions such as esophageal atresia (EA), whereby a congenital defect results in the abnormal development of the esophagus, there is a tremendous need for tailorable organ replacement options that will “grow” with the patient over time. The fabrication of patient-specific hollow organs such as the esophagus, can be achieved with increased efficiency using magnetic resonance imaging (MRI) and programs such as 3D Slicer, which converts anatomical images into STL files recognized by the printer. Following extrusion-based printing, highly accurate and reproducible models can be made for organ replacement or tissue engineering purposes. A benefit of this approach is that the porosity of printed constructs can be fine-tuned by adjusting nozzle and infill sizes. Additionally, several different biomimetic inks can be utilized based on the shore hardness of the tissue being replaced to create constructs that more closely resemble native structures. These can range from natural inks (collagen, decellularized tissue, gelatin, alginate, silk fibroin) to synthetic polymers (PLA, PU, PCL and silicone) (Table 3).

Table 3: Commonly used Bioinks for 3D printing Types of Bioinks Natural 1. Collagen 2. Gelatin 3. Silk 4. Decellularized tissue 5. Alginate 6. Fibrin Synthetic 1. Ploylactic acid (PLA) 2. Polycaprolactone (PCL) 3. Silicone 4. Polyethylene glycol (PEG) 5. Polvinylpyrrolidone (PVP) 6. Poly(Lactic-Co-Glycolic) Acid (PLGA)

Natural bioinks have been shown to support cell viability and adhesion, and closely mimic components of the extracellular matrix (ECM) found within a cell’s normal microenvironment.[122] Synthetic bioinks are useful as support structures upon which cells can be seeded. Some can even impart flexibility to printed constructs, which initiates mechanical cues within seeded cells to facilitate their growth and differentiation.[123]

Our work in 3D printing of the esophagus: Building off our previous work, we are currently fabricating a 3D printed esophageal construct for implantation into pediatric patients suffering from congenital defects of the esophagus.

Initial designs: See Figure 7 for a CAD-rendered depiction of the esophagus in 3D.

Figure 7

Computer-Aided Design (CAD) of the Esophagus

We are currently testing different synthetic polymer combinations to determine which is suitable for the fabrication of a pediatric-sized esophageal construct. Ideally, the material should be flexible, yet strong enough to prevent esophageal collapse after implantation into a patient (See Figure 8).

Figure 8

3D printed cylinder composed of material exhibiting flexible properties

Additionally, adequate porosity is essential to promote seeded cell growth and proliferation, as well as cell adhesion and extracellular matrix production (See Figure 9).

Figure 9

Live (green)/Dead (red) staining of epithelial cell line on porous scaffolding.

When comparing scanning electron micrograph images between electrospun scaffolds and 3D printed scaffolds, fiber sizes are smaller in the electrospun scaffolds and more variable between scaffolds. In 3D printed scaffolds, the pore sizes can be adjusted and reliably reproduced. (See Figure 10)

Figure 10

Scanning electron micrograph comparison of elctrospun scaffold (A,B) and 3D bioprinted scaffold (C-F)

Future: Personalized surgical tools to augment or repair absent or damaged tissue is the ultimate goal of tissue engineering. 3D printers enable scientists to reliably produce hollow scaffolds designed from the specific measurements of a patient. These patient-specific scaffolds combined with autologous stem cells can revolutionize the surgical approach in esophageal diseases.

3D Bioprinting for Preoperative Planning: Conjoined Twins

3D Bioprinting for preoperative planning: Conjoined Twins

Matias Bruzoni, MD

Surgical separation of conjoined twins requires the delicate joint efforts of a multidisciplinary medical and surgical team. Standard 2D radiological methods are usually insufficient for accurate pre-surgical planning. 3D technology provides a better understanding of the anatomy in these cases.[124][125][126][127][128] More complex conjoined twins’ cases may require even more planning, which includes diagnostic endoscopy and laparoscopy before the final separation and reconstruction. In addition to standard radiology images (chest and abdominal x-rays), computed tomography (CT) with both oral and IV contrast is usually performed under general anesthesia to begin the pre-operative planning. Even though CT will give a good approximation of what kind of systems are being shared, it is difficult to understand the vascular supply/drainage in standard 2D imaging. 3D technology is then used to complement the CT data, by the creation of 3D virtual rendering (VR) reconstructions to better represent the anatomical structures involved in the congenital fusion (Figure 11-14).

Figure 11

3D virtual reconstruction of skeletal anatomy in omphalo-ischiopagus conjoined twins.

Figure 12

3D-printed model of the pelvic skeletal anatomy in omphalo-ischiopagus conjoined twins.

[127][128]Specific computer software packages are used to translate these images into 3D printing and reconstruction, rendering models that can be used for planning and simulation of the operation, improving the clinical decision-making process (Figure 13a, 13b). 3D-printed models are also used to communicate with the rest of the medical team as well as with the parents in order to set up expectations and prognosis.

Figure 13a

3D virtual reconstruction of CT images in omphalo-ischiopagus conjoined twins.

[125][127]There is still a lot of room for improvement with these technologies. Printing models with materials that have tactile and tensile features closer to human tissues, or having 3D-printed models with flexible materials and structures that can be assembled or disassembled to simulate the separation and reconstruction, could make it more useful during preoperative planning.

Figure 13b

3D virtual reconstruction of CT images in omphalo-ischiopagus conjoined twins.

Figure 14

3D-printed skeletal and vascular anatomy model in omphalo-ischiopagus conjoined twins.