Pain management after tonsil surgery in children and adults-A national survey related to pain outcome measures from the Swedish Quality Register for tonsil surgery.

OBJECTIVE: The primary aim of this study was to describe the current practice regarding pain management in relation to tonsil surgery among Ear Nose and Throat (ENT) clinics in Sweden. The secondary aim was to determine the impact of the provider's regime of rescue analgesics on the pain related Patient Reported Outcome Measures (pain-PROMs) from the Swedish Quality Register for Tonsil Surgery (SQTS). MATERIALS & METHODS: A descriptive cross-sectional study originating from a validated web-based questionnaire. The survey enrolled one respondent from each ENT clinic (47/48 participated) nationally. Pain-PROMs from the SQTS, recorded from October 2019 to October 2022, were included (8163 tonsil surgeries). RESULTS: Paracetamol was used by all enrolled ENT clinics as preemptive analgesia. The addition of COX inhibitors was used in 40% of the clinics. Betamethasone was usually administered, to prevent pain and nausea (92%). All clinics gave postdischarge instructions on multimodal analgesia with COX inhibitors and paracetamol. Rescue analgesics were prescribed after tonsillectomy for 77% of adults, 62% of older children, 43% of young children and less often after tonsillotomy. The most frequently prescribed rescue analgesic was clonidine in children (55%) and oxycodone in adults (72%). A high proportion of patients reported contact with health care services due to postoperative pain (pain-PROMs/ SQTS). Tonsillectomy procedures were associated with the highest rates of contacts (children/adolescents 13-15%; adults 26%), while tonsillotomy were associated with lower rates, (5-7% of children/adolescents). There was no significant difference in the frequency of health care contacts due to pain regarding whether clinics routinely prescribed rescue analgesics or not after tonsillectomy. CONCLUSION: The Swedish analgesic regimen after tonsil surgery is good overall. Nevertheless, there is a need for increased awareness and knowledge to achieve optimal patient recovery. Pain-PROM data demonstrate the call for improvement in pain management after tonsil surgery.

Extranodal follicular dendritic cell sarcoma of the tonsil: An extremely rare clinical entity.

Follicular dentritic cell sarcomatous neoplasms originate from dendritic cells contained within the lymph nodes. In extranodal location, these neoplasms, are rare clinical entities, and even more so, their location in the head-neck region is extremely rare. Only 17 cases of primary dendritic cell sarcoma of the tonsil are reported in the literature at present. Being such a rare entity, histopathological diagnosis can be complex and requires great expertise and proper immunohistochemical analysis [1]. We present a case of a 48-year-old young man diagnosed with follicular dendritic cell sarcoma of the tonsil who underwent, probably for the first time in the literature, transoral robotic surgical resection.

Bacterial colonisation of surface and core of palatine tonsils among Tanzanian children with recurrent chronic tonsillitis and obstructive sleep apnoea who underwent (adeno)tonsillectomy.

OBJECTIVE: Acute and chronic tonsillitis are frequently treated with antibiotics. This study aimed to understand the presence of pathogenic micro-organisms on the surface and core of chronically infected tonsils among Tanzanian children. METHODS: The study enrolled children undergoing adenotonsillectomy. Surface and core tonsillar swabs were taken. Quantitative polymerase chain reaction was performed for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Neisseria meningitidis and Pseudomonas aeruginosa. RESULTS: Surface and core combined, isolated N meningitidis (86.1 per cent) was found the most, followed by H influenzae (74.9 per cent), S pneumoniae (42.6 per cent) and S aureus (28.7 per cent). M catarrhalis and P aeruginosa were only found in a few patients, 5.6 per cent and 0.8 per cent respectively. CONCLUSION: Colonisation of the tonsillar surface and core has been found. Potentially pathogenic micro-organisms are likely to be missed based on a throat swab. Hence, the practice of surface tonsillar swabbing may be misleading or insufficient.

A validation study of the 30-day questionnaire in the national Norwegian Tonsil Surgery Register: can we trust the data reported by the patients?

PURPOSE: The aim of this study was to validate the Patient Reported Outcome Measure (PROM) in the Norwegian Tonsil Surgery Register (NTSR) and to examine whether any improvements to the questionnaire could be useful. METHODS: This is a prospective, descriptive study. NTSR collects data from patients who undergo tonsil surgery and the intention of the register is to improve the quality of treatment and to contribute to research. The patients answers questions about admission due to postoperative haemorrhage, infection and pain 30 days after surgery. 305 patients were contacted on phone 1-2 weeks after answering the questionnaires electronically (ePROM) and asked the same questions. 180 of 305 patients we contacted had some kind of complications after surgery. They were asked additional questions to search for possible points for improvement of the questionnaire. RESULTS: When comparing the results on the ePROM with the answers on phone, we found that 12 out of 14 variables achieve almost perfect agreement (AC1 ≥ 0.81). Two variables are categorized to be substantial agreement (AC1 = 0.61-0.80). The additional questions showed us that the questionnaire can be improved with more detailed information regarding the severity of the postoperative haemorrhage and the need of better treatment against postoperative pain. CONCLUSION: This study shows that the information from the 30-day ePROM has high reliability. The questions were understood as they were intended, and the answers reflect what the patients had of complications. Some changes can be done to improve the questionnaire and to open up for more research around the tonsillectomy procedure.

Tonsil microbiome in pediatric patients with post tonsillectomy hemorrhage for tonsillar hypertrophy.

OBJECTIVE: This study aimed to compare the tonsillar microbiota between post tonsillectomy patients with bleeding and without bleeding, and to investigate the potential role of tonsillar microbiota in the development of post-tonsillectomy hemorrhage (PTH). METHODS: Nineteen tonsillar tissues from PTH patients and 21 tissues from control patients were collected. Metagenomic sequencing was used to compare the microbiota in PTH and control groups. Alpha diversity indices were used to compare the richness and evenness of the microbiota between the two groups. PCoA and NMDS analyses were used to evaluate beta diversity. LDA analysis was conducted to identify significantly abundant genera. RESULTS: No significant difference in alpha diversity indices was found between PTH and control patients. The dominant bacteria in the tonsillar microbiota were Haemophilus, Streptococcus, and Fusobacterium. PCoA and NMDS analyses showed significant differences in beta diversity between PTH and control patients. PTH patients had a significantly higher relative abundance of Neisseria, Capnocytophaga, and Veillonella. Capnocytophaga was also identified as a significantly abundant genus by LDA analysis. CONCLUSION: This study demonstrates that there is a difference in the tonsillar microbiota between PTH and control patients. The results suggest that Neisseria, Capnocytophaga, and Veillonella may be associated with the development of PTH. These findings provide new insights into the potential role of the tonsillar microbiota in the development of PTH, and may help to develop new strategies for preventing and treating this potentially life-threatening complication.

Postoperative Outcomes of Intracapsular Tonsillectomy With Coblation: A Systematic Review and Meta-Analysis.

OBJECTIVE: Following tonsillectomy, postoperative pain and hemorrhage from the tonsillar bed are causes of significant morbidity. Intracapsular tonsillectomy with Coblation is suggested to minimize such morbidity while remaining efficacious in long-term outcomes. This systematic review and meta-analysis assessed short-term morbidity and long-term outcomes from intracapsular tonsillectomy with Coblation, focusing primarily on posttonsillectomy hemorrhage. DATA SOURCES: Medline, Embase, and the Cochrane Library. REVIEW METHODS: Guided by PRISMA guidelines, studies on intracapsular tonsillectomy with Coblation published between December 2002 and July 2022 evaluating frequency of posttonsillectomy hemorrhage were screened. Studies without primary data were excluded. Meta-analysis was conducted using the random-effect model. The primary outcome was the proportion of patients who experienced posttonsillectomy hemorrhage. The secondary outcomes were posttonsillectomy pain, the proportion requiring revision tonsillectomy, and severity of sleep-disordered breathing measured by polysomnography outcomes. RESULTS: From 14 studies there were 9821 patients. The proportion of total posttonsillectomy hemorrhage was 1.0% (95% confidence interval [CI] 0.5%-1.6%, n = 9821). The proportion experiencing primary hemorrhage, secondary hemorrhage, and those requiring further tonsil surgery were 0.1% (95% CI 0.0%-0.1%; study n = 7), 0.8% (95% CI 0.2%-1.4%; study n = 7), and 1.4% (95% CI 0.6%-2.2%; study n = 6), respectively. Mean reduction in apnea-hypopnea index was -16.0 events per hour (95% CI -8.8 to -23.3, study n = 3) and mean increase in oxygen nadir was 5.9% (95% CI 2.6%-9.1%, study n = 3). CONCLUSION: Intracapsular tonsillectomy with Coblation has been demonstrated to have a low rate of posttonsillectomy hemorrhage. Data regarding long-term tonsil regrowth and need for reoperation were encouraging of the efficacy of this technique.

A two-centre experience of tonsil biopsies in the investigation of patients with tonsillar asymmetry.

INTRODUCTION: We aim to evaluate our experience of tonsil biopsies in the investigation of patients presenting with asymmetrical tonsils. METHODS: A two-centre retrospective analysis of all patients who underwent histology sampling of the palatine tonsils between 1 January 2013 and 31 December 2018 was completed. Data collected included patient demographics, method of obtaining tonsil tissue, histological diagnosis and need for repeat tissue sampling. A follow-up period of 36 months was allowed to establish whether any patients re-presented with missed diagnoses. RESULTS: In total, 937 patients were included for analysis: 375 (40.0%) had a biopsy, of which 191 (50.9%) were performed in clinic. The mean duration from initial appointment with the ear, nose and throat clinic to tissue sample collection was 17.6 days (range 0-327 days) for all biopsies, reducing to 0.2 days (range 0-17 days) for biopsies performed in clinic. This was significantly shorter than for tonsillectomies (mean 38.9 days, range 0-444 days; p<0.05). Of the patients who underwent tonsil biopsy, six (1.6%) had malignancy that was not unequivocally diagnosed on initial biopsy. In all six patients, prior clinical suspicion was high, and repeat tissue sampling was undertaken on receipt of negative histology results. CONCLUSIONS: Tonsil biopsy is a viable alternative to tonsillectomy for histology in the assessment of tonsil asymmetry. Tonsil biopsy in the outpatient setting has reduced surgical morbidity, significantly less delay in diagnosis, less inconvenience for patients and lower healthcare costs compared with formal tonsillectomy. Although tonsil biopsies should not be used in isolation, they can be useful in the investigation of patients presenting with tonsillar asymmetry.

Surgical anatomy of the cerebellar tonsils: A cadaveric study.

BACKGROUND: Knowledge of the normal anatomy of the cerebellar tonsils is a prerequisite in various surgeries of the posterior cranial fossa Clinical conditions, as the Chiari I malformations (CIM) alter the normal position of the cerebellar tonsils. OBJECTIVE: Therefore, we aim to better elucidate the surgical anatomy of and around the cerebellar tonsils in regard to the CIM. METHODS: Fifty formalin-fixed adult cadavers injected with colored latex through vertebral arteries underwent craniotomy and durotomy to expose the cerebellar tonsils and related structures. The tonsils and their surrounding anatomy were then studied. RESULTS: Forty cerebellar tonsils were at or above the foramen magnum. Five specimens presented with CIM with the tonsils below (3-5 mm) the FM with a mean tonsillar decent of 7.9 ± 2.3 mm. Of the cadavers without CIM, in forty-two cases, the thickness of the dura mater was within ±3SD ranges. In three cases, the dura mater was thinner at the CVJ and one case; the dura adhered tightly to the inner aspect of the occipital squama. In five CIM cadavers, the dura mater was markedly thicker at the CVJ. The PICA caudal loop was 5.9 ± 1.6 mm long. In CIM cases, the PICA loop was longer, nearer the dura, 1 mm below the superior border of the C1 posterior arch. The distances from the PICA loop were markedly reduced by 3 mm from the spinal accessory nerve and 2 mm from the first spinal nerve. The DN was significantly closer to the tonsillar peduncle in CIM cases. CONCLUSION: These data are important for better understanding the intrinsic and extrinsic anatomy of the cerebellar tonsils in patients with and without CIM. Importantly, tonsillectomy/tonsillar coagulation must consider the close relationship of the dentate nucleus to the base of the cerebellar tonsil to avoid iatrogenic injury.

Effect of the German tonsillitis guideline on indication for tonsil surgery in patients with recurrent acute tonsillitis: a population-based study.

Evidence-based indication for tonsil surgery in patients with recurrent acute tonsillitis (RAT) is an ongoing matter of debate. Since introduction of the German tonsillitis guideline in 2015, the indication criteria for tonsil surgery have become much stricter. It is unclear, if this has changed the indication policy. A retrospective population-based study was performed including all 1398 patients with RAT admitted for tonsil surgery in all Thuringian hospitals in 2011, 2015, and 2019. Changes over the years concerning patients' characteristics, number of tonsillitis episodes in the last 12 months treated with antibiotics (T12), and decision for tonsillectomy or tonsillotomy were analyzed using univariable and multivariable statistics. The surgical rates decreased from 28.56/100,000 population in 2011 to 23.57 in 2015, and to 11.60 in 2019. The relative amount of patients with ≥ 6 T12 increased from 14.1% in 2011 over 13.3% in 2015 to 35.9% in 2019. Most patients received a tonsillectomy (98% of all surgeries). Decision for tonsillotomy was seldom (1.2%). Multinomial logistic regression analysis with the year 2011 as reference showed that compared to the year 2015, the age of the patients undergoing surgery increased in 2015 (Odds ratio [OR] = 1.024; 95% confidence interval [CI] = 1.014-1.034; p < 0.001), and also in 2019 (OR 1.030: CI 1.017-1.043; p < 0.001). Compared to 2011, the number T12 was not higher in 2015, but in 2019 (OR 1.273; CI 1.185-1.367; p < 0.001). Stricter rules led to lower tonsil surgery rates but to a higher proportion of patients with ≥ 6 T12 before surgery. Tonsillectomy remained the dominating technique.

Comparison of innate lymphoid cells from tissue and blood in chronic tonsillitis and tonsillar hypertrophy.

OBJECT: Recurrent tonsillitis and tonsillar hypertrophy are two common diseases in children for which tonsillectomy is the definitive solution. The underlying causes of both diseases are not fully known. The aim of this study was to identify the predominant innate lymphoid cells in both diseases of the palatine tonsils, which are known to play an important role in the immune system. METHODS: Children who underwent tonsillectomy were divided into two groups as recurrent tonsillitis and tonsillar hypertrophy according to the indication for surgery. The proportions of innate lymphoid cell (ILC) groups and IFN-gamma, IL-10 and IL-17 secreting T lymphocyte cells were determined in tonsil and blood samples obtained during surgery. Local and peripheral immune responses were evaluated. Innate immune responses and acquired immune responses were compared. RESULTS: The results of our study showed that the proportions of the innate lymphoid cell 1 group (ILC1) were similar in tonsil tissue in patients with recurrent tonsillitis and tonsil hypertrophy, with no statistically significant difference. It was observed that the innate lymphoid cell 2 group (ILC2) was the predominant group in tonsil hypertrophy, the innate lymphoid cell 3 group (ILC3) was the predominant innate lymphoid cell group in recurrent tonsillitis, and the proportion of IL-17 secreting T lymphocytes in blood and tonsillar mononuclear cells was higher in recurrent tonsillitis patients than in tonsil hypertrophy patients. CONCLUSION: With the results obtained, the predominant innate lymphoid cells in the pathogenesis of both diseases were identified and local and peripheral responses were compared. These findings may be a guide for possible medical treatments for both diseases in the future.

Expression of periostin in aeroallergen-sensitized children with adenotonsillar hypertrophy.

OBJECTIVES: The association between adenotonsillar hypertrophy (ATH) and allergies remains controversial. Periostin is an important player in allergic diseases. We aimed to investigate the expression of periostin in hypertrophic tonsils and adenoids in children. METHODS: We enrolled 24 children who underwent adenotonsillectomy due to sleep-disordered breathing. They were divided into atopic and control groups according to ImmunoCAP results. The presence and location of periostin in the tonsils and adenoids were determined by immunohistochemical staining. The mRNA expression and protein levels of periostin and inflammatory cytokines were measured. RESULTS: Immunoreactive periostin signals were observed in the subepithelial regions and germinal centers of both tonsils and adenoids. In the subepithelial regions and germinal center, periostin signals were more prominent in both tonsils and adenoids of the atopic group than in those of the control group. Significantly, the atopic group had higher periostin mRNA expression in tonsils and adenoids than the control group. The atopic group also had higher protein level of periostin in the adenoids than the control group. Atopic children had higher TGF-ß1 levels in the tonsils and adenoids than those in the controls. CONCLUSION: This study showed that periostin is present in both the tonsils and adenoids, and that its levels are increased in the adenoids of atopic children. Periostin and TGF- ß1 expressions in the adenoids may be associated with the atopic status in children. Further studies are required to investigate the association between ATH and periostin in a larger number of participants.

Tonsillectomy as Prevention of Tonsil and Base of Tongue Cancer: Systematic Review and Meta-analysis on the Immuno-Oncological Effect of One Among the Most Common Surgeries in the World.

Otorhinolaryngology tradition is that tonsillectomy (TE) is conducted among children and adolescents for obstructive sleep apnea secondary to adenotonsillar hypertrophy and in adults for chronic disease of the tonsils and adenoids (recurrent tonsillitis). Nevertheless, over the last 50 years, we have observed a decline in TE worldwide. As a result, there is an emerging concern of a correlated possible increased risk of tonsil cancer (TC) and other subtypes of oropharyngeal squamous cell carcinoma. Since the available data on such topics are limited and controversial, our aim was to elucidate the impact of TE on the incidence mainly of TC through a systematic review of the literature and a meta-analysis of the studies. After a thorough search, 7 retrospective studies were considered eligible for review and meta-analysis (MA). At MA, patients with a history of TE seem to show a reduced risk of TC but a higher predisposition for base of tongue (BOT) cancer (p<0.001): however, the elevated heterogeneity of the studies hampers drawing firm and convincing conclusions (statistical inconsistency >95%). In future, randomized control trials will be welcome to elucidate the prophylactic role of TE against TC and its real impact on BOT cancer.

Spontaneous Unilateral Chiari I Secondary to Acquired Tonsillar Hypertrophy/Pseudomass With Syringomyelia in a Juvenile With Progressive Scoliosis.

Chiari type 1 malformation (CM-1) is a structural defect of the central nervous system in which part of the cerebellar tonsils descend below the level of the foramen magnum, sometimes with associated syringomyelia. Although Chiari malformations were traditionally believed to be congenital, several cases of acquired CM-1 with syringomyelia have been reported. Usually associated with repeat lumbar puncture, increased intracranial pressure, and craniocephalic disproportion, CM-1 in the absence of an underlying etiology is rare. We report a rare case of spontaneous idiopathic tonsillar hypertrophy causing unilateral CM-1 with syringomyelia associated with progressive scoliosis in a juvenile with a previously normal neonatal MRI brain and no known underlying pathology. A 9-year-old boy was found to have scoliosis at a routine well-child visit with progression indicated on radiographs 4 months later. Whole spine MRI was performed and showed a new CM-1 with globular, mass-like configuration of the descended right tonsil with otherwise normal tonsillar characteristics. Surgical decompression via suboccipital craniectomy and C1 laminectomy with duraplasty was performed with improvement illustrated on repeat MRI 3 months postoperatively. This rare case emphasizes the importance of routine MRI spine early in select patients with idiopathic scoliosis and illustrates the favorable outcomes noted after decompressive craniectomy.

Oropharyngeal microbiome in children with adenotonsillar hypertrophy and after adenotonsillectomy.

BACKGROUND: The microbiome of tonsils and adenoid in adenotonsillar hypertrophy (ATH) has been profiled. Adenotonsillectomy (AT) is widely used for ATH in children. The variation of the oropharyngeal microecology in children with ATH or after AT have never been studied. OBJECTIVES: Here we aimed to evaluate the change in oropharyngeal microbiome in ATH Children after AT. MATERIALS AND METHODS: In this cross-sectional study, throat swabs for microbiome analysis were collected from ATH, AT and control groups. Using 16s rDNA sequencing, this study investigated the characteristics of oropharyngeal microbiome. RESULTS: The α-diversity showed a statistical difference in richness and the ß-diversity was significantly different among the three groups. The relative abundance of Haemophilus (member of Proteobacteria) increased but that of Actinomyces (member of Actinobacteriota) decreased in the ATH group compared to those in the AT and control groups, but their abundances showed no statistical difference between the AT and control groups. CONCLUSIONS: The oropharyngeal microbial diversity and composition are disrupted in children with ATH and can be restored after AT. This microbiome analysis provides a new understanding about the pathogenesis of ATH in children.SummaryIn this study, we aimed to evaluate the change in oropharyngeal microbiome in ATH Children after AT. The oropharyngeal microbial diversity and composition are disrupted in children with ATH and can be restored after AT.

Tonsillectomy and risk of post-tonsillectomy haemorrhage - a protocol for a randomised clinical trial.

INTRODUCTION: Tonsillectomy is one of the most common procedures in the ear, nose and throat field, and 7.7% of the Danish population had undergone a tonsillectomy by the age 20 years in 2012. One feared complication is post-tonsillectomy haemorrhage (PTH), which in a Danish register-based study was found to increase from 3% in 1991 to 13% in 2012. PTH represents a significant risk and deaths are reported in the literature. The aim of the trial is to compare hot and cold haemostasis during tonsillectomy and assess, firstly, the risk of PTH and, secondly, the reported pain perception. METHODS: This is a single-centre, two-arm, interventional randomised controlled trial. The study targets patients > 12 years of age referred for tonsillectomy. Participants will have both tonsils removed; on one side cold haemostasis will be performed and on the other hot diathermia will secure haemostasis. The participants will subsequently receive three questionnaires in the course of a month concerning bleeding episodes and pain perception. Owing to the study design, patients and surgeons act as their own controls. CONCLUSIONS: The results of the study may guide future research and practice of tonsillectomy to reduce the risk of PTH. FUNDING: Lizzi and Mogens Staal Fonden and Nordsjællands Hospital. The funding sources had no influence on trial design, data collection, analysis or publication. CLINICALTRIALS: gov Identifier: NCT05161754. Registration date: 20042021; version 2: 20042021.

Hamartomatous polyp of the palatine tonsil: histological considerations and review of the literature.

The hamartomatous polyp is a rare benign hamartoma of the palatine tonsil, usually encountered during the second decade of life. It may be reported under various terms in the literature, like lymphangioma of the tonsil, angiofibrolipoma, lymphangiomatous tonsillar polyp and lymphangiectatic fibrous polyp. Macroscopically, it appears as a large, pale, pedunculated mass. Typically, a hamartomatous polyp is asymptomatic or manifests mild symptoms, like foreign body sensation. It is not related to a generalised lymphatic malformation process. Despite its typical appearance, an excisional biopsy is necessary to rule out a malignancy. Histological findings are consistent with a squamous epithelial covering, a core of loose fibrous and adipose tissue with sparse lymphoid aggregations and dilated lymphatic channels filled with lymph and lymphocytes. Several embryologically based theories suggested its pathogenesis; however, recurrent tonsillitis does not play an established role. A typical tonsillectomy is suggested as a sufficient therapeutical approach with no tendency for recurrence.

Cancer risk following surgical removal of tonsils and adenoids - a population-based, sibling-controlled cohort study in Sweden.

BACKGROUND: Removal of tonsils and adenoids is among the most common surgical procedures worldwide. Evidence of increased risk of cancer following such surgery is, however, inconclusive. METHODS: We conducted a population-based, sibling-controlled cohort study of 4,953,583 individuals in Sweden with a follow-up during 1980-2016. History of tonsillectomy, adenotonsillectomy, and adenoidectomy was identified from the Swedish Patient Register whereas incident cases of cancer during follow-up were identified from the Swedish Cancer Register. We used Cox models to calculate hazard ratios (HR) with 95% confidence intervals (CI) of cancer in both a population and a sibling comparison. The sibling comparison was used to assess the potential impact of familial confounding, due to shared genetic or non-genetic factors within a family. RESULTS: We found a modestly increased risk for any cancer following tonsillectomy, adenoidectomy, or adenotonsillectomy in both the population (HR 1.10; 95%CI 1.07-1.12) and sibling (HR 1.15; 95%CI 1.10-1.20) comparisons. The association did not differ greatly by type of surgery, age at surgery, or potential indication for surgery, and persisted more than two decades after surgery. An excess risk was consistently observed for cancer of the breast, prostate, thyroid, and for lymphoma in both population and sibling comparisons. A positive association was observed for pancreatic cancer, kidney cancer, and leukemia in the population comparison whereas a positive association was observed for esophageal cancer in the sibling comparison. CONCLUSIONS: Surgical removal of tonsils and adenoids is associated with a modestly increased risk of cancer during the decades following the surgery. The association is unlikely attributed to confounding due to shared genetic or non-genetic factors with a family.