Endoscopic Chemocauterization with Trichloroacetic Acid for Congenital or Recurrent Tracheoesophageal Fistula in Children with Esophageal Atresia: Experience from a Tertiary Center.

BACKGROUND: Recurrent tracheoesophageal fistula (rTEF) is a well-known complication after surgery of EA, occurring in roughly 3-10% of the patients. Recent studies have highlighted safety and efficacy of endoscopic management of recurrent TEF. The aim of this study was to evaluate the efficacy of chemocauterization with trichloroacetic acid (TCA) in rTEF and congenital tracheoesophageal fistula (cTEF). METHODS: Retrospective chart review of consecutive patients with recurrent or congenital TEF who underwent endoscopic chemo-cauterization between 2018 and 2022 at a tertiary center. Children diagnosed with TEF who underwent primary or secondary endoscopic treatment were included. Median follow up time was 19 months for rTEF and 33 months for cTEF. RESULTS: During the study period, 18 patients were treated endoscopically by chemocatuerization with TCA at our institution. Treatment of recurrent TEF was successful in 13 of 14 patients (93%) Treatment of congenital TEF was successful in 2 of 4 patients (50%). In 14 patients, closure was seen after 1-2 treatments. There were no serious adverse reactions or complications to the endoscopic treatment of TEF. CONCLUSION: Endoscopic chemocauterization is a minimal invasive technique with low morbidity and high success rate and may be considered as primary treatment for recurrent TEF. LEVEL OF EVIDENCE: III.

Distribution of sentinel nodes from parotid tumors-A feasibility study.

BACKGROUND: Optimum management of the N0 neck is unresolved in parotid salivary gland cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis and its´ clinical use is increasing for head and neck tumors. The object of this study was to establish whether the technique is applicable to detect distribution of sentinel nodes for parotid tumors. MATERIALS AND METHODS: Prosepective observational study in 30 patients with benign or low-grade T1-T2N0 malignant tumors in the parotid gland planned for surgical treatment. Distribution of SN was detected with a preoperative ultrasound-guided peritumoral injection with a technetium-99 (Tc-99 m) laballed tracer followed by a SPECT-CT and intraoperative measurement in the neck and parotidal tissue. In patients with cytologically suspected malignant tumor or highly unclerar cytology, SNB was also performed. RESULTS: Sentinel nodes (SNs) were detected in 26/30 cases. Out of these, 7 presented with only one SN, whereas multiple sentinel nodes where detected in 19 cases. No SNs were found in neck level 1. SN was detected in level 5 independent of tumor location within the parotid gland. An intraparotidal distribution of SNs was more frequent in larger tumors. CONCLUSIONS: The use of SN-technique in the planning of surgical treatment of parotid tumors seems feasible. It may be of clinical value for patients with parotid cancer to enable a more accurate staging and to detect occult metastasis in the SNs within the parotid as well as in the neck, enabaling the possibility to surgically remove all positive SNs at primary surgery and with reduced surgical morbidity.

Supraglottoplasty for severe laryngomalacia can be effective and safe also in children with high-risk comorbidities - Experience from a tertiary center.

OBJECTIVES: Supraglottoplasty (SGP) for severe laryngomalacia (LM) in children with medical comorbidities has been associated with high risk of surgical failure and increased need of postoperative pediatric intensive care unit (PICU) intervention, but evidence for this is ambiguous. The objective was to evaluate surgical outcome and risk of need for PICU-intervention following SGP for severe LM in comorbid patients. METHODS: Retrospective observational study of 116 patients treated with SGP for severe LM between 2000 and 2021 at a tertial referral pediatric airway surgery center Karolinska University Hospital. Medical records were reviewed and patient data regarding surgical timing, type of SGP procedure, PICU-intervention, complications, and outcomes were recorded. Patients were defined as non-comorbid vs high-risk comorbid (HRC) based on a coexisting comorbidity for risk of surgical failure and postoperative PICU-intervention. Surgical failure was defined as need of revision surgery, tracheostomy or assisted ventilation (continuous positive airway pressure and bilevel positive airway pressure). PICU intervention was defined as need of postoperative assisted ventilation or intubation. Statistical comparisons were performed with outcome of SGP on children with LM and no comorbidities. RESULTS: 41/116 patients included had a HRC associated with an increased risk of PICU-intervention and surgical failure. 75/116 patients were defined as non-comorbid. The overall surgical success in the study population was 89.7% (104/116), 94.7% in the non HRC group vs 80.5% in the HRC-group. 5/41 HRC patients and 1/75 non-comorbid patients needed SGP revision in which 5/6 was successful. There was no significantly increased need for postoperative PICU intervention in HRC patients. CONCLUSION: SGP for severe LM patients with high-risk comorbidities performed in a tertiary setting had an overall good result and low risk of PICU-intervention. Revision SGP was more common in HRC patients but had a good outcome. Multidisciplinary experience in perioperative care of comorbid patients may be of key importance for outcome and children with high-risk comorbidities should thus not be withheld the possible benefit of SGP without assessment at a tertiary pediatric airway center.

Upregulation of Plasminogen Activator Inhibitor-1 in Irradiated Recipient Arteries and Veins from Free Tissue Transfer Reconstruction in Cancer Patients.

BACKGROUND: Clinical studies have shown that radiotherapy can induce vascular disease at the site of exposure but is usually not clinically evident until years after treatment. We have studied irradiated human arteries and veins to better understand the underlying biology in search of future treatments. The aim was to investigate whether radiotherapy contributed to a sustained expression of plasminogen activator inhibitor-1 (PAI-1) in human arteries and veins. METHODS: Irradiated arteries and veins were harvested, together with unirradiated control vessels, from patients undergoing free tissue transfer reconstruction at a median time of 90 weeks [5-650] following radiation exposure. Differential gene expression of PAI-1 was analysed, together with immunohistochemistry (IHC) and immunofluorescence (IF). RESULTS: PAI-1 gene expression was increased in both arteries (p = 0.012) and veins (p < 0.001) in irradiated compared to unirradiated control vessels. IHC and IF indicated that cells expressing PAI-1 were located in the adventitia of both arteries and veins and colocalized with cells positive for CD68, CD45, and α-SMA in arteries and with CD45 and α-SMA in veins. CONCLUSION: The current study shows a sustained upregulation of PAI-1 in both arteries and veins after exposure to ionizing radiation, indicating a chronic inflammation mainly in the adventitia. We believe that the results contribute to further understanding of radiation-induced vascular disease, where targeting PAI-1 may be a potential treatment.

No evidence for human papillomavirus having a causal role in salivary gland tumors.

BACKGROUND: Salivary gland malignancies are a very heterogeneous group of cancers, with histologically > 20 different subtypes, and prognosis varies greatly. Their etiology is unknown, however, a few small studies show presence of human papillomavirus (HPV) in some subtypes, although the evidence for HPV having a causal role is weak. The aim of this study was to investigate if HPV plays a causal role in the development of different parotid salivary gland tumor subtypes. METHODS: DNA was extracted from 107 parotid salivary gland formalin fixed paraffin embedded tumors and 10 corresponding metastases, and tested for 27 different HPV types using a multiplex bead based assay. HPV DNA positive tumors were stained for p16INK4a overexpression by immunohistochemistry. RESULTS: One of the 107 malignant parotid salivary gland tumors (0.93%) and its corresponding metastasis on the neck were positive for HPV16 DNA, and both also overexpressed p16INK4a. The HPV positive primary tumor was a squamous cell carcinoma; neither mucoepidermoid nor adenoid cystic tumors were found HPV positive. CONCLUSIONS: In conclusion, HPV DNA analysis in a large number of malignant parotid salivary gland tumors, including 12 different subtypes, did not show any strong indications that tested HPV types have a causal role in the studied salivary gland tumor types.

Human Polyomaviruses Are Not Frequently Present in Cancer of the Salivary Glands.

BACKGROUND/AIM: Malignant tumors of the salivary glands are rare and heterogeneous, with more than 20 subtypes, and classified mainly by histopathology. Their diagnosis is often challenging and their etiology unknown. Here, the possible association between human polyomaviruses (PyVs) and one or more salivary gland tumor subtypes was examined. MATERIALS AND METHODS: Ninety-one primary tumors, including 12 subtypes and eight corresponding metastases, were analyzed for the presence of DNA of 10 different human PyV species by a bead-based multiplex assay using polymerase chain reaction and Luminex analyses. RESULTS: Three samples, one adenocarcinoma (not otherwise specified), one adenoid cystic carcinoma, and one mucoepidermoid carcinoma were found to be positive. However, the amount of MCPyV DNA in these tumors was estimated to be less than one genome per tumor cell. CONCLUSION: The analysis of DNA from 10 human PyVs in a large number of malignant salivary gland cancers did not implicate any of these human PyVs as an important causative agent in any of the 12 subtypes studied.

Improved Head and Neck Free Flap Outcome-Effects of a Treatment Protocol Adjustment from Pre- to Postoperative Radiotherapy.

BACKGROUND: The impact of preoperative radiotherapy on microvascular reconstructive surgery outcome has been a subject of debate. However, data are conflicting and often dependent on local treatment protocols. We have studied the effects of radiotherapy in a unique, single-center setting where a treatment protocol change was undertaken from pre- to postoperative radiotherapy administration for microsurgical head and neck reconstructions. METHODS: A cohort study was conducted for 200 consecutive head and neck free flap cases, where 100 were operated on before and 100 after the treatment protocol adjustment in 2006. Only direct cancer reconstructions were included. Complication rates of anastomosis-related (flap necrosis) and flap bed-related (infection, fistula, and wound dehiscence) complications were compared between irradiated and nonirradiated patients. A multivariate analysis was performed to correct for treatment period. RESULTS: One hundred twenty-six patients had received radiotherapy before reconstruction due to cases of cancer recurrence. There were no significant differences in demographic data or risk factors between irradiated and nonirradiated cases. Irradiated cases had a higher rate of both flap loss (9.5% versus 1.4%; P = 0.034) and flap bed-related complications (29% versus 13%; P = 0.014). However, after multivariate analysis, there was only a significant relationship between preoperative irradiation and infection (odds ratio = 2.51; P = 0.033) and fistula formation (odds ratio = 3.13; P = 0.034). CONCLUSIONS: The current single-center study clearly indicates that preoperative radiotherapy is a risk factor for both infection and fistula formation, most likely related to an impaired flap bed. We suggest postoperative radiotherapy administration whenever possible for oncological reasons, otherwise proper antibiotic cover and meticulous flap insetting to prevent radiation-related infection and fistula formation.

Regional recurrence in early stage I-II oral tongue cancer: a single institutional study and review of the literature.

CONCLUSIONS: There is a high propensity for locoregional and isolated regional failure in stage II patients, even though treated with combined therapy. In stage I patients the risk of isolated regional failure was moderate, at levels below 10%. BACKGROUND: The neck treatment of early stages of oral tongue squamous cell carcinoma (OTSCC) are still debatable, considering that previous studies have produced diverting results. The purpose of this study is to report on the outcome of patients with stages I-II, with special respect to regional outcome. MATERIALS AND METHODS: All patients treated for OTSCC at Karolinska University Hospital between 2008-2014 were included. Patient demographics, intention of treatment, treatment modality, time of follow-up and status at follow-up, recurrence, and place of recurrence were recorded. RESULTS: Of 230 patients, 149 presented within stages I and II. Of those, 105 were electively treated to the neck. In stage I, the risk of presence of disease in the neck specimen was four out of 63 (6%), whereas 17 out of 41 (41%) were positive in stage II patients. The overall risk of isolated regional failure at any time in stage I patients was six out of 89 and in stage II 25 out of 60.

Shock wave trauma leads to inflammatory response and morphological activation in macrophage cell lines, but does not induce iNOS or NO synthesis.

BACKGROUND: Experimental CNS trauma results in post-traumatic inflammation for which microglia and macrophages are vital. Experimental brain contusion entails iNOS synthesis and formation of free radicals, NO and peroxynitrite. Shock wave trauma can be used as a model of high-energy trauma in cell culture. It is known that shock wave trauma causes sub-lytic injury and inflammatory activation in endothelial cells. Mechanical disruption of red blood cells can induce iNOS synthesis in experimental systems. However, it is not known whether trauma can induce activation and iNOS synthesis in inflammatory cell lines with microglial or macrophage lineage. We studied the response and activation in two macrophage cell lines and the consequence for iNOS and NO formation after shock wave trauma. METHODS: Two macrophage cell lines from rat (NR8383) and mouse (RAW264.7) were exposed to shock wave trauma by the Flyer Plate method. The cellular response was investigated by Affymetrix gene arrays. Cell survival and morphological activation was monitored for 24 h in a Cell-IQ live cell imaging system. iNOS induction and NO synthesis were analyzed by Western blot, in cell Western IR-immunofluorescence, and Griess nitrite assay. RESULTS: Morphological signs of activation were detected in both macrophage cell lines. The activation of RAW264.7 was statistically significant (p < 0.05), but activation of NR8383 did not pass the threshold of statistical significance alpha (p > 0.05). The growth rate of idle cells was unaffected and growth arrest was not seen. Trauma did not result in iNOS synthesis or NO induction. Gene array analyses showed high enrichment for inflammatory response, G-protein coupled signaling, detection of stimulus and chemotaxis. Shock wave trauma combined with low LPS stimulation instead led to high enrichment in apoptosis, IL-8 signaling, mitosis and DNA-related activities. LPS/IFN-É£ stimulation caused iNOS and NO induction and morphological activation in both cell lines. CONCLUSIONS: Shock wave trauma by the Flyer Plate method caused an inflammatory response and morphological signs of activation in two macrophage cell lines, while iNOS induction appeared to require humoral signaling by LPS/IFN-É£. Our findings indicated that direct energy transfer by trauma can activate macrophages directly without humoral mediators, which comprises a novel activation mechanism of macrophages.

Increased long-term expression of pentraxin 3 in irradiated human arteries and veins compared to internal controls from free tissue transfers.

BACKGROUND: Clinical studies have shown that radiotherapy increases the risk of cardiovascular disease at irradiated sites years after exposure. However, there is a lack of biological explanations in humans. We therefore examined human blood vessels exposed to radiotherapy and studied C-reactive protein (CRP) and pentraxin 3 (PTX3), a new marker for adverse cardiovascular outcome dependent on TNF- alpha (TNFα) or interleukin-1beta (IL-1ß) expression. METHODS: Pairs of irradiated and non-irradiated human conduit arteries and veins were harvested from the same patient during autologous free tissue transfer for cancer-reconstruction at a median time of 48 weeks after radiotherapy. Differential gene expression was studied using qRT-PCR, confirmed by immunohistochemistry and cellular origins determined by immunofluorescence. RESULTS: Gene expression in irradiated arteries compared to non-irradiated showed a consistent up-regulation of PTX3 in all patients and in a majority of veins (p < 0.001). Both TNFα and IL-1ß were increased in irradiated compared to non-irradiated arteries (p < 0.01) and IL-1ß correlated to the PTX3 expression (p = 0.017). Immunohistochemical and immunofluorescence staining confirmed an increased expression of PTX3 in endothelial cells, macrophages and smooth muscle cells. CONCLUSIONS: The sustained expression of PTX3 in arteries and veins tie biological evidence in humans to clinical studies and encourage further exploration of innate immunity in the pathogenesis of a radiation-induced vasculopathy.

Sustained inflammation due to nuclear factor-kappa B activation in irradiated human arteries.

OBJECTIVES: The aim of this study was to investigate gene expression networks related to cardiovascular disease in radiated human arteries. BACKGROUND: Recent epidemiological studies have shown that radiotherapy is associated with cardiovascular disease years after treatment. However, the molecular mechanisms underlying late effects of radiation are poorly described. METHODS: Arterial biopsies from radiated and nonradiated human conduit arteries, from the same patient, were simultaneously harvested during microvascular free tissue transfer for cancer-reconstruction in 13 patients, 4 to 500 weeks from radiation treatment. Radiated and nonradiated arteries were compared, with Affymetrix (Santa Clara, California) microarrays on a subset of the material to generate candidate genes. A Taqman (Applied Biosystems, Foster City, California) low-density array of 45 selected genes was designed for analysis of the whole material. RESULTS: Thirteen genes were synchronously expressed in all patients (p = 0.0015), including CCL8, CCL3, CXCL2, DUSP5, FGFR2, HMOX1, HOXA9, IL-6, MMP-1, PTX3, RDH10, SOD2, and TNFAIP3. A majority of differentially regulated genes related to the nuclear factor-kappa B (NF-kappaB) signaling pathway and were dysregulated even years after radiation. The NF-kappaB activation was confirmed by immunohistochemistry and immunofluorescence. CONCLUSIONS: In the present study, we found sustained inflammation due to NF-kappaB activation in human radiated arteries. The results are supported by previous in vitro findings suggesting that deoxyribonucleic acid injury, after radiation, activates NF-kappaB. We also suggest that HOXA9 might be involved in the regulation of NF-kappaB activation. The observed sustained inflammatory response can explain cardiovascular disease years after radiation.

Popliteal pterygium syndrome (PPS) with intra-alveolar syngnathia: a discussion of anesthetic and surgical considerations.

Popliteal pterygium syndrome (PPS) is a rare genetic disorder that involves the association of a popliteal web with a combination of craniofacial, genitourinary and extremity malformations. In this article, we describe a patient with PPS complicated with multiple intra-alveolar syngnathia. We discuss the anesthetic and the surgical management of this case and review the literature regarding PPS and intra-alveolar syngnathia.