Association of circulating tumor DNA with patient prognosis in surgically resected renal cell carcinoma.

BACKGROUND: Despite complete resection, 20%-50% of patients with localized renal cell carcinoma (RCC) experience recurrence within 5 years. Accurate assessment of prognosis in high-risk patients would aid in improving outcomes. Here we evaluate the use of circulating tumor DNA (ctDNA) in RCC using banked samples and clinical data from a single institution. METHODS: The cohort consisted of 45 RCC patients (≥pT1b) who underwent complete resection. The presence of ctDNA in plasma was determined using a personalized, tumor-informed ctDNA assay (Signatera RUO, Natera, Inc.). Relationships with outcomes and other relevant clinical variables were assessed. The median follow-up was 62 months. RESULTS: Plasma ctDNA was detected in 18 out of 36 patients (50%) pre-operatively and was associated with increased tumor size (mean 9.3 cm vs. 7.0 cm, P < .05) and high Fuhrman grade (60% grades III-IV vs 27% grade II, P = .07). The presence of ctDNA, either pre-operatively or at any time post-operatively, was associated with inferior relapse-free survival (HR = 2.70, P = .046; HR = 3.23, P = .003, respectively). Among patients who were ctDNA positive at any time point, the sensitivity of relapse prediction was 84% with a PPV of 90%. Of note, ctDNA positivity at a post-surgical time point revealed a PPV of 100% and NPV of 64%. The lack of ctDNA detection at both time points yielded an NPV of 80%. CONCLUSIONS: Detection of plasma ctDNA using a personalized assay is prognostic of recurrence in patients with resected RCC. Herein, we describe a successful approach for its application and identify potential limitations to be addressed in future studies.

Complications Associated with Medical Tourism for Facial Rejuvenation: A Systematic Review.

BACKGROUND: Medical tourism for cosmetic surgery has become increasingly popular in recent years. The existing literature has identified poor outcomes associated with general cosmetic tourism; however, the complications associated with cosmetic tourism for facial rejuvenation remain poorly understood. The aims of this study are to delineate the risk profile associated with medical tourism for facial rejuvenation. METHODS: A systematic review of PubMed, MEDLINE, and Embase was performed through January 2019 using the PRISMA guidelines. Search terms included combinations of keywords including medical tourism and plastic surgery and other related nomenclature. Articles published in English relevant to medical tourism for facial rejuvenation and its associated complications were examined. RESULTS: We identified six retrospective studies including 31 patients who had obtained facial rejuvenation procedures abroad and experienced treatment-associated complications. Twenty-five of 26 listed patients (96%) were female (age range 33-62 years). Departure nations included the USA, Switzerland, England, Ireland, Australia, and Thailand. Destination nations included the Dominican Republic, Cyprus, the USA, Colombia, Thailand, India, and China. Procedures included blepharoplasty, facelift, rhinoplasty, chin lift, and injections with botulinum toxin and dermal fillers. Complications included abscess, poor cosmesis, facial nerve palsy, and death. CONCLUSIONS: We present the first study to systematically review the complications associated with medical tourism for facial rejuvenation. No definitive conclusions can be made given the paucity of relevant data, its clinical and statistical heterogeneity, and small sample size. Additional research is warranted to help inform patients who seek facial rejuvenation procedures abroad and to better understand the health system implications associated with cosmetic tourism for facial rejuvenation. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Mandibular rescue: Application of the ALT fascia free flap to arrest osteoradionecrosis of the mandible.

OBJECTIVES: To evaluate the use of the anterolateral thigh fascia free flap for use in neovascularization of mandibular bone in moderate osteoradionecrosis (ORN). All patients had ORN secondary to prior radiation therapy that was not severe enough to warrant segmental resection and reconstruction. STUDY DESIGN: Case series. SETTING: Tertiary medical center. METHODS: IRB approval was obtained, and a retrospective chart review performed of all mandibular rescue procedures performed from 2011 to 2014. Patients with a minimum of two years of follow-up were included in the study. RESULTS: All surgeries were performed by the senior surgeon (MF). Eight patients underwent the mandibular rescue procedure with resolution of pain and return to oral feeding in all patients, and no evidence of ORN progression on follow-up imaging. A total of 9 ALT free flaps were performed (one patient had 2 surgeries). Gender was distributed evenly (4 female/4 male). The average age was 66 (58-78), average length of hospitalization was 2.8 days (1-7), and average follow-up was 46.5 months (25-63). CONCLUSIONS: The mandibular rescue procedure is a novel technique using the ALT fascia lata free flap to provide coverage and nutrient blood flow to mandible devascularized secondary to radiation therapy. The flap provides the advantages of low morbidity, ease of harvest, two-team approach to ablation and reconstruction, and quick recovery resulting in 'short-stay' free flap surgery. Although conclusions must be tempered in this small case series, our early clinical experience shows the ALT fascia lata flap holds promise in halting the destructive progression of ORN that is not yet advanced enough to require a segmental resection and reconstruction.

A novel technique for superior-based pharyngeal flaps: 10-year results with formal speech outcomes assessment.

PURPOSE: Describe a novel technique for superior-based pharyngeal flaps allowing restoration of bulk to the soft palate and intraoperative fine-tuning of lateral port size, while avoiding midline palate-splitting. Validated speech assessment tools are employed for quantitative analysis. METHODS: Retrospective review of all patients who underwent superior-based pharyngeal flap in a 10-year period by a single surgeon. Pittsburgh Weighted Values for Speech Symptoms Associated with VPI and the Goldman-Fristoe Test of Articulation were used for formal speech assessment. RESULTS: 78 patients met inclusion criteria with clinical data up to 10years postoperatively. 31 patients had congenital velopharyngeal insufficiency (VPI), and the remainder acquired VPI after cleft palate repair or adenoidectomy. 37 patients had a recognized syndrome. All patients noted subjective improvement in nasality, and evaluation with the validated speech assessment tools demonstrated statistically significant improvement in speech. Only one flap takedown was required in a patient with severe midface hypoplasia who developed sleep apnea several years postoperatively. CONCLUSIONS: This technique is successful in congenital and acquired VPI, and in patients with complex craniofacial syndromes. Customization of lateral ports based on preoperative nasopharyngoscopy, and avoidance of a midline palate splitting incision, make this an attractive option for superior-based flap surgery.

Management of Complications of Acute Otomastoiditis in Solid Organ Transplant Patients.

BACKGROUND: There are over 183,000 patients living with a functioning solid organ transplant in the United States, and almost no data exist discussing complications of acute otomastoiditis in this vulnerable population. Early recognition and treatment of acute otomastoiditis is essential in patients whose immune system is not normal, as progression can lead to sepsis, meningitis, brain abscess, Bezold's abscess, sigmoid sinus thrombosis, or other potentially fatal sequelae. METHODS: Case report with extensive literature review. RESULTS: A 63 year-old man presented 3 years after cadaveric renal transplant with otorrhea and altered mental status. His acute otitis media progressed to meningitis with sigmoid sinus thrombosis and sepsis, and management included IV and otic antibiotics, tympanostomy tube placement, and cortical mastoidectomy. The patient made a full recovery without residual neurologic deficit. CONCLUSION: Extrapolating data from patients immunosuppressed for other reasons, patients immunosuppressed after solid organ transplant should receive prompt recognition and aggressive treatment of acute otomastoiditis to prevent or address potentially devastating intracranial or systemic complications.

Intractable epistaxis and systemic lupus: high-dose intravenous pulse steroids.

IMPORTANCE: Epistaxis is most commonly an easily treated ENT entity with a relatively simple algorithm. Occasionally, however, it is encountered as a devastating disease process that can humble the otolaryngologist. In the setting of comorbidities that exacerbate bleeding, in this case vasculitis due to systemic lupus erythematosus (SLE), epistaxis can be life-threatening and refractory to conservative management. OBSERVATIONS: This case report describes the hospital course of a patient with severe SLE and intractable epistaxis. We discuss classic management options for epistaxis and offer a novel treatment option for patients with SLE-related vasculitides-goal-directed medical therapy with high-dose intravenous pulse steroid therapy. CONCLUSIONS AND RELEVANCE: To our knowledge, this report not only is the first description of targeted treatment options for intractable epistaxis in patients with SLE, but also serves to augment the traditional algorithm with the addition of a goal-directed medical therapy-control of epistaxis through high-dose intravenous pulse steroid therapy. We demonstrated that 6 mg of intravenous dexamethasone given every 6 hours can be highly effective in controlling epistaxis in patients with uncontrolled SLE. The presumed mechanism is through control of associated vasculitides.

Juvenile ossifying fibroma of the middle turbinate.

Juvenile ossifying fibroma is a rare, benign tumor that may present in the sinonasal area but has never been described arising from the middle turbinate. The lesion's locally aggressive behavior and close proximity to orbit and anterior skull base create a significant challenge for the patient and practitioner. This is a case presentation of a 7-year-old female with an invasive recurrent juvenile ossifying fibroma arising from the middle turbinate.

Managing massive palatial defect secondary to palatoplasty failures: an in-depth analysis.

PURPOSE OF REVIEW: Massive palatal defects resulting from palatoplasty failures arising from cleft palate repair complications present ongoing challenges in clinical practice. The purpose of this review is to provide up-to-date insights into aetiology, risk factors, surgical techniques, and adjunctive therapies, aiming to enhance the understanding of such complex cases, and optimize patient outcomes. RECENT FINDINGS: Primary palatoplasty has fistula recurrence rates ranging from 2.4% to 55%. Factors such as cleft width, surgical repair method, and patient characteristics, influence the likelihood of failure. Classifications such as the Pakistan Comprehensive Classification and Richardson's criteria aid in assessing defects. Surgical options range from local flaps and revision palatoplasty to regional flaps (e.g., buccinator myomucosal, facial artery-based flaps, tongue flaps, nasal septal flaps) to free microvascular flaps. Alternative approaches include obturator prostheses, and acellular dermal matrix has been used as an adjuvant to multiple repair techniques. Hyperbaric oxygen therapy has emerged as an adjunctive therapy to enhance tissue healing. SUMMARY: This comprehensive review underscores the intricate challenges associated with massive palatal defects resulting from palatoplasty failures. The diverse range of surgical and nonsurgical options emphasizes the importance of patient-centric, individualized approaches. Practitioners, armed with evidence-based insights, can navigate these complexities, offering tailored interventions for improved patient outcomes.

Prospective Outcomes of Noma Facial Reconstructive Surgery in Sokoto, Nigeria.

Background: Noma is a gangrenous infection of the face that results in severe facial deformity, occurring primarily in malnourished and impoverished populations. Objective: To assess clinician- and patient-reported outcomes (PROs) before and after reconstructive surgery for patients with noma in northwest Nigeria. Methods: Objective outcomes were recorded using the noma-specific NOITULP (nose, outer cheek, inner cheek, trismus, upper/lower lip, particularities) classification system. PROs were recorded using a locally developed tool. Postsurgical changes were assessed by Wilcoxon signed-rank testing. Linear regression was used to look for associated risk factors. The inter-rater reliability (IRR) of the NOITULP score was assessed using the weighted kappa statistic. Results: Forty-nine patients (median age 25 years, 71% male) underwent local/regional flap reconstruction and/or trismus release. Twelve complications were reported. Univariate analysis showed a 3.20 change in PRO score (95% confidence interval 0.59 to 5.81, p = 0.018) per kilogram the patient underwent at time of surgery. The NOITULP score improved from a presurgery median of 3.5 to 2.3 (p < 0.0001), however, the IRR was poor (kappa = 0.0894, p < 0.0001). The PRO score also improved from a median of 7.0 to 12.0 (p < 0.0001). Conclusions: Facial reconstructive surgery improves the NOITULP score and PROs in patients with noma in northwest Nigeria. Clinical Trial Registration: OCA017-63.

Fibula Free Flap Reconstruction of Cervical Spine Defects: A Multi-Institutional Study.

INTRODUCTION: Cervical spine defects result in spinal instability, putting the spinal cord and vertebral arteries at risk of damage and possibly devastating neurological injuries. The fibula free flap can span the spinal defects for stability. There is a paucity of literature on this technique. METHOD: Multi-institutional retrospective case series reviewing patients who underwent cervical spine reconstruction with a fibula free flap. Patient demographic information, comorbidities, characteristics of cervical spine defects, and free flap complications were collected. RESULTS: A total of 1187 fibula free flaps across 10 different institutions were reviewed. Thirteen patients (1.09%) underwent cervical spine reconstruction with a fibula free flap. Average age was 52.3 years old with an age range of 12-79 years. There were six males (46.1%) and seven females (53.8%). The most common defect etiology was infection (n = 6, 46.1%). Most commonly involved cervical spine level of the defect was C5 (n = 10) followed by C6 (n = 9) and C4 (n = 8). The majority of reconstructed defects spanned three or more cervical levels, (n = 9, 69.2%). Facial artery was the most common arterial anastomosis (n = 8). Eight patients (61.5%) required a tracheostomy during their postoperative course. None of the patients had symptomatic or radiographic nonunion. CONCLUSION: This case series demonstrates that a vascularized fibula flap is a potential reconstructive option for cervical spine defects, especially in defects greater than three cervical levels, in the setting of infection, and previously radiated patients. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Intraoral flaps for oral cavity and oropharyngeal reconstruction.

PURPOSE OF REVIEW: Oral cavity reconstruction using local flaps is an area of head and neck surgery that has been overshadowed since the introduction of free flaps. Here, we discuss new developments, predominantly modifications to existing techniques for intraoral reconstruction, the utility of different local flaps and a review of functional outcomes. RECENT FINDINGS: The facial artery musculomucosal (FAMM) flap has seen the greatest number of modifications to technique, most notably the extended double-pedicled, kite-shaped tunnelized and osseous myomucosal approaches. The tunnelled buccal fat pad flap has gained popularity as well as the use of combining two flaps such as the buccal fat pad and palatal island flap to reconstruct oral cavity defects with good effect. There is still a paucity of literature surrounding functional outcomes post reconstruction. Despite this, the complication rate for local flaps remains low. SUMMARY: The value of intraoral flaps for oral cavity reconstruction is undisputed. However, they are potentially underutilised in the modern era of expanding availability and indications for free tissue transfer. As many practices see greater numbers of aging patients, often with multisystem comorbidities, local flaps are an important tool that can provide the surgeon with a greater number of reconstructive options.

Comparison of postoperative complications in early versus delayed tracheostomy decannulation in patients undergoing oral cancer surgery with microvascular reconstruction.

The purpose of this study was to determine the relationship of early and delayed tracheostomy decannulation protocols on the length of stay, time to oral feeding and incidence of postoperative complications in patients undergoing microvascular reconstruction for oral cancer. A review of all patients who underwent surgical management of oral squamous cell carcinoma (OSCC) over the study period from 01/07/2017 to 31/06/2021 was performed. Patients who underwent elective tracheostomy as part of their microvascular reconstruction were included. Two cohorts were identified based on distinct postoperative tracheostomy decannulation protocols; early (Within 7 days) and delayed (≥7 days). Time to oral feeding, length of stay and complication rates was determined for both groups for statistical analysis. A total of 103 patients with OSCC were included in the study. The overall complication rate was 35.9% and were more likely in node positive patients (53.7% vs 23.2%; p = 0.003) and in cases where the geniohyoid muscle complex was disrupted during tumour resection (66.7% vs 31.9%; p = 0.026). Early decannulation was significantly associated with shorter length of hospital stay (10 days vs 15 days) and earlier removal of nasogastric feeding tubes (7 vs 10 days). There was no difference in the overall complication rate between the two groups (33.3% vs 37.5%; p = 0.833). Early decannulation in appropriately selected patients is recommended as it significantly reduces the length of hospital stay and aids in early resumption of oral intake. Furthermore, this approach is not associated with increased rates of complications.

Systematic Review and Meta-Analysis on the Incidence of Level-Specific Cervical Nodal Metastasis in Primary Parotid Malignancies.

OBJECTIVE: In primary parotid gland malignancies, the incidence of level-specific cervical lymph node metastasis in clinically node-positive necks remains unclear. This study aimed to determine the incidence of level-specific cervical node metastasis in clinically node-negative (cN0) and node-positive (cN+) patients who presented with primary parotid malignancies. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, PubMed, Cochrane). REVIEW METHODS: Random-effects meta-analysis was used to calculate pooled estimate incidence of level-specific nodal metastasis for parotid malignancies with 95% confidence intervals (CIs). Subgroup analyses of cN0 and cN+ were performed. RESULTS: Thirteen publications consisting of 818 patients were included. The overall incidence of cervical nodal involvement in all neck dissections was 47% (95% CI, 31%-63%). Among those who were cN+, the incidence of nodal positivity was 89% (95% CI, 75%-98%). Those who were cN0 had an incidence of 32% (95% CI, 14%-53%). In cN+ patients, the incidence of nodal metastasis was high at all levels (level I 33%, level II 73%, level III 48%, level IV 39%, and level V 37%). In cN0 patients, the incidence of nodal metastasis was highest at levels II (28%) and III (11%). CONCLUSION: For primary parotid malignancies, the incidence of occult metastases was 32% compared to 89% in a clinically positive neck. It is recommended that individuals with a primary parotid malignancy requiring elective treatment of the neck have a selective neck dissection which involves levels II to III, with the inclusion of level IV based on clinical judgment. Those undergoing a therapeutic neck dissection should undergo a comprehensive neck dissection (levels I-V).

Total autogenous mandibular reconstruction using virtual surgical planning.

Free fibula transfer has become the workhorse in mandibular reconstruction. Total mandibular reconstruction is an uncommon procedure with added complexity. Numerous techniques have been described for such reconstruction, many requiring a temporomandibular joint prosthesis. We present a novel method where simultaneous bilateral free fibula transfer utilizing preoperative virtual surgical planning was used to produce a total autogenous reconstruction. The virtual surgical planning allows to effectively quantify the bone stock required preoperatively and facilitates intraoperative modeling of the fibula. Therefore, a more anatomically correct reconstruction is obtained resulting in improved functional and aesthetic outcomes.

Transaxillary gasless robotic thyroid surgery with nerve monitoring: initial two experince in a North American center.

Minimally invasive thyroid surgery using various techniques is well described. The present study reviews our initial experience with the technique with added intraoperative monitoring to assess its safety and feasibility. The study group consisted of ten consecutive patients with suspicious thyroid nodules who were candidates for thyroid lobectomy from September to December 2009. All patients underwent intraoperative nerve integrity monitoring and postoperative direct laryngoscopy. The patients' demographic information, operative times, learning curve, complications, and postoperative hospital stay were evaluated. All procedures were successfully completed with intraoperative nerve monitoring. No cases were converted to an open procedure. The median age was 38.5 years (σ = 13.5) and nine of the ten patients were females. The mean operating time was 131 minutes (range 101-203 minutes) and the mean operating time with the da Vinci system was 55 minutes. All patients were discharged home after an overnight stay. One patient developed transient radial nerve neuropathy that resolved spontaneously. There were no other postoperative complications. None of the patients complained of postoperative neck pain. Postoperative laryngoscopy showed intact and mobile vocal cords in all patients. Robotic endoscopic thyroid surgery with gasless transaxillary approach is feasible and safe in the treatment of suspicious thyroid nodules. Monitoring of the RLN during this approach is feasible.

Laryngeal trauma: a review of current diagnostic and management strategies.

PURPOSE OF REVIEW: The purpose of this review is to provide the most up to date information on evaluation and management of laryngeal trauma. RECENT FINDINGS: Timely diagnosis and proper treatment of laryngeal fractures are imperative for preserving a functional larynx. This review will focus on evaluation and management strategies. SUMMARY: The larynx provides significant functions including respiration, phonation, and airway protection. Algorithms have been developed in order to standardize the evaluation and management of these injuries to preserve a functional larynx. Physicians must diagnose and treat these laryngeal traumas in a timely fashion in order to prevent morbidity and, rarely, mortality.

Postoperative pain management in pediatric cleft lip and palate repair.

PURPOSE OF REVIEW: There has been an increased interest in the literature on methods to improve perioperative outcomes in surgical patients while minimizing opioid use. Pediatric cleft palate repair can be a painful procedure, and this postoperative pain can lead to longer hospital stays and worse surgical outcomes. RECENT FINDINGS: Recent literature has explored four key areas surrounding analgesia after cleft lip and palate repair. These areas are management of postoperative pain with nonopioid oral analgesics, peripheral nerve blockade, liposomal bupivacaine for donor-site analgesia in bone grafting, and enhanced recovery after surgery (ERAS) protocols. SUMMARY: The included studies indicate that patients undergoing palatoplasty may have a decreased opioid requirement if nonopioid analgesics such as acetaminophen and ibuprofen are started early in the postoperative setting. Peripheral nerve blockade is an important adjunct to analgesia in these patients. Suprazygomatic maxillary nerve blockade may improve pain management over traditional infraorbital nerve blockade. In patients undergoing alveolar bone grafting, injection of liposomal bupivacaine into the donor site can significantly decrease oral opioid requirements. Finally, ERAS protocols are emerging ways to decrease postoperative pain in cleft palate patients.

Reflux Disease and Laryngeal Neoplasia in Nonsmokers and Nondrinkers.

Gastroesophageal reflux disease (GERD) has been hypothesized as a risk factor for development of laryngeal cancer. A case-control study was performed to assess the association of laryngeal neoplasia with GERD. Cases consisted of patients with a history of laryngeal cancer or carcinoma in situ. Controls were patients without neoplasia who matched cases 2:1 on age, sex, race, and smoking history. Univariate and multivariate analyses were performed to assess risk of laryngeal neoplasia and GERD. In total, 2094 patients were included. Cases had higher rates of GERD. Univariate analysis demonstrated a positive association between GERD and laryngeal neoplasia (odds ratio, 1.33; 95% CI, 1.07-1.64). Multivariate analysis controlling for alcohol use history also demonstrated a positive association between GERD and laryngeal neoplasia (adjusted odds ratio, 1.29; 95% CI, 1.04-1.59). These results suggest increased odds of laryngeal carcinoma and carcinoma in situ in patients with GERD when controlling for smoking and drinking history.

Outcomes at 18 mo of 37 noma (cancrum oris) cases surgically treated at the Noma Children's Hospital, Sokoto, Nigeria.

BACKGROUND: Noma is a rapidly progressing infection of the oral cavity frequently resulting in severe facial disfigurement. We present a case series of noma patients surgically treated in northwest Nigeria. METHODS: A retrospective analysis of routinely collected data (demographics, diagnosis and surgical procedures undergone) and in-person follow-up assessments (anthropometry, mouth opening and quality of life measurements) were conducted with patients who had surgery >6 mo prior to data collection. RESULTS: Of the 37 patients included, 21 (56.8%) were male and 22 (62.9%) were aged >6 y. The median number of months between last surgery and follow-up was 18 (IQR 13, 25) mo. At admission, the most severely affected anatomical area was the outer cheek (n = 9; 36.0% of patients had lost between 26% and 50%). The most frequent surgical procedures were the deltopectoral flap (n = 16; 43.2%) and trismus release (n = 12; 32.4%). For the eight trismus-release patients where mouth opening was documented at admission, all had a mouth opening of 0-20 mm at follow-up. All patients reported that the surgery had improved their quality of life. CONCLUSIONS: Following their last surgical intervention, noma patients do experience some improvements in their quality of life, but debilitating long-term sequelae persist.

Functional proteomics interrogation of the kinome identifies MRCKA as a therapeutic target in high-grade serous ovarian carcinoma.

High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological cancer with few effective, targeted therapies. HGSOC tumors exhibit genomic instability with frequent alterations in the protein kinome; however, only a small fraction of the kinome has been therapeutically targeted in HGSOC. Using multiplexed inhibitor beads and mass spectrometry, we mapped the kinome landscape of HGSOC tumors from patients and patient-derived xenograft models. The data revealed a prevalent signature consisting of established HGSOC driver kinases, as well as several kinases previously unexplored in HGSOC. Loss-of-function analysis of these kinases in HGSOC cells indicated MRCKA (also known as CDC42BPA) as a putative therapeutic target. Characterization of the effects of MRCKA knockdown in established HGSOC cell lines demonstrated that MRCKA was integral to signaling that regulated the cell cycle checkpoint, focal adhesion, and actin remodeling, as well as cell migration, proliferation, and survival. Moreover, inhibition of MRCKA using the small-molecule BDP9066 decreased cell proliferation and spheroid formation and induced apoptosis in HGSOC cells, suggesting that MRCKA may be a promising therapeutic target for the treatment of HGSOC.