Ethanol Ablation of Ranulas and Risk Factor Analysis for Recurrence.

Importance: Ethanol ablation (EA) was shown to be safe and effective for treating ranula, but few studies have assessed long-term outcomes and recurrence of ranula after EA. Objective: To evaluate the long-term outcomes and the risk factors for recurrence and receipt of subsequent surgery in patients who underwent treatment with EA for ranula. Design, Setting, and Participants: This case-series study was conducted at a single tertiary hospital and assessed patients who were treated with EA between July 2009 and March 2021. Among 70 consecutive patients, those with follow-up loss or who were followed up for less than 24 months were excluded. Exposures: EA for ranula. Main Outcomes and Measures: The primary outcome was recurrence at last follow-up after single or multiple EA sessions. Secondary outcomes included receipt of subsequent surgery and the recurrence-free survival (RFS) rate after initial EA. Factors possibly associated with outcomes included patient age and sex; ranula site, type, diameter, volume, and echogenicity; the presentation-to-EA interval; parapharyngeal space extension; and sublingual gland herniation. Risk factors were identified on logistic regression analyses. Two-year RFS rates were analyzed for the initial cohort using the Kaplan-Meier method and compared by log-rank tests. Results: A total of 57 patients (mean [SD] age, 26.4 [12.1] years; 24 female individuals [42%]) who were followed up for a median of 57 months (range, 24-167 months) were included. The recurrence rate was 33% (n = 19), and 11 (19%) underwent subsequent surgery. Among patients with recurrence, 86% (31 of 36) experienced first recurrence within 12 months after initial EA. A presentation-to-EA interval of 12 months or longer was associated with an increased risk of recurrence (adjusted odds ratio [OR], 3.74; 95% CI, 1.01-13.82). No risk factors were significantly associated with subsequent surgery (highest OR in parapharyngeal space extension: adjusted OR, 4.96; 95% CI, 0.94-26.35). Among the initial cohort of 70 patients, 2-year RFS was lower in a maximum diameter of ranula of 5 cm or greater than less than 5 cm (24% [95% CI, 7%-41%] vs 50% [95% CI, 34%-66%]; difference, 26% [95% CI, -4% to 56%]; log-rank test, P = .02). Conclusions and Relevance: This case-series study found that the recurrence rate of ranula after EA was 33%. A presentation-to-EA interval of 12 months or longer may be a risk factor for recurrence, suggesting that early intervention with EA might minimize recurrence. Most first recurrences occurred within 12 months after EA, with a maximum diameter of ranula of 5 cm or greater being a possible risk factor.

Incidentally found parotid gland lesion in 18F-FDG PET/CT for staging evaluation of patients with hepatocellular carcinoma: remote possibility of metastatic tumor or second primary salivary gland malignancy.

OBJECTIVES: We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. METHODS: We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. RESULTS: A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001). CONCLUSIONS: Our study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.

Clinical implication of neck dissection for metastatic lymph nodes originating from non-head and neck regions.

BACKGROUND: Cervical lymph node metastasis (CLNM) from remote primary sites is rare in head and neck cancer. The efficacy of neck dissection is still being investigated for therapeutic benefits of local management in oligometastasis from non-head and neck cancer. OBJECTIVES: To evaluate the clinical efficacy of neck dissection (ND) in CLNM from distant primary cancers and identify factors contributing to improved survival. MATERIALS AND METHODS: This retrospective case-control study enrolled patients who underwent ND for CLNM from distant primary cancer at Asan Medical Centre between January 2010 and December 2020. We analysed overall survival and association between clinical covariate and survival. RESULTS: The study included 31 (14 males, 17 females) among 114 patients. Ovarian cancer was the most common primary malignancy (32.3%). Patients with fewer than three metastatic lymph nodes, without extranodal extension and with adjuvant therapy after surgery had better survival rates. CONCLUSION AND SIGNIFICANCE: In patients with CLNM from a distant primary cancer, ND is beneficial as local treatment. And adequate selection of patients for ND is pivotal to improve prognosis.

Enhancer of zeste homolog 2 (EZH2)-dependent sirtuin-3 determines sensitivity to glucose starvation in radioresistant head and neck cancer cells.

Sirtuin 3 (SIRT3) regulates mitochondrial function as a mitochondrial deacetylase during oxidative stress. However, the specific regulatory mechanism and function of SIRT3 in radioresistant cancer cells are unclear. In this study, we aim to investigate how SIRT3 determines the susceptibility to glucose deprivation and its regulation in p53-based radioresistant head and neck cancer cells. We observed mitochondrial function using two established isogenic radioresistant subclones (HN3R-A [p53 null] and HN3R-B [p53 R282W]) with intratumoral p53 heterogeneity. Cell counting analysis was performed to evaluate cell proliferation and cell death. The correlation between the regulation of SIRT3 and enhancer of zeste homolog 2 (EZH2) was confirmed by immunoblotting and chromatin immunoprecipitation assay. p53-deficient radioresistant cells (HN3R-A) expression reduced SIRT3 levels and increased sensitivity to glucose deprivation due to mitochondrial dysfunction compared to other cells. In these cells, activation of SIRT3 significantly prevented glucose deprivation-induced cell death, whereas the loss of SIRT3 increased the susceptibility to glucose deficiency. We discovered that radiation-induced EZH2 directly binds to the SIRT3 promoter and represses the expression. Conversely, inhibiting EZH2 increased the expression of SIRT3 through epigenetic changes. Our findings indicate that p53-deficient radioresistant cells with enhanced EZH2 exhibit increased sensitivity to glucose deprivation due to SIRT3 suppression. The regulation of SIRT3 by EZH2 plays a critical role in determining the cell response to glucose deficiency in radioresistant cancer cells. Therefore, EZH2-dependent SIRT3 could be used as a predictive biomarker to select treatment options for patients with radiation-resistance.

Assessment of vocal fold movement through anterior-posterior view of videofluoroscopic swallowing study.

Objective: The aim of this study is to assess the value of using videofluoroscopic swallowing study (VFSS) for assessing vocal fold paralysis. Methods: This was a retrospective study of patients who underwent VFSS with a vocal fold testing maneuver from June 2020 to February 2022, and who had undergone laryngoscopy within 2 weeks before or after VFSS. The vocal fold testing maneuver consisted of making an 'e' sound for about 2-3 seconds during VFSS anterior-posterior (AP) view. The diagnostic value of the VFSS was evaluated by a trained reviewer, who assessed the presence and laterality of vocal fold paralysis by examining videos of the patients performing the vocal fold testing maneuver. Intra-rater reliability was determined by evaluation of the videos by the same reviewer 2 weeks later, and inter-rater reliability was determined by evaluation by a second reviewer. Results: Seventy patients were enrolled in the study. The positive predictive value was 91.43% and the intra-rater and inter-rater reliabilities, as determined by Cohen's kappa value, were 0.746 and 0.824 respectively. Conclusions: The presence and laterality of vocal fold paralysis were identified accurately and reliably by the reviewers, showing that VFSS can be used to assess vocal fold paralysis. Level of evidence: 2.

Surgical outcomes of 500 robot-assisted minimally invasive esophagectomies for esophageal carcinoma.

Background: In 2003, robot-assisted minimally invasive esophagectomy (RAMIE) was first reported to overcome the technical limitations of minimally invasive esophagectomy. RAMIE requires repeated modifications to set up the robotic system, and sufficient experience is required to gain technical proficiency. This study aimed to identify the learning periods and the outcomes of RAMIE for esophageal carcinoma. Methods: We retrospectively reviewed 500 consecutive RAMIE cases for esophageal cancer from December 2008 to February 2021. The learning curve for RAMIE was identified using cumulative sum analysis. Results: In a total of 500 RAMIE patients, the Ivor Lewis and McKeown operation were performed in 267 patients (53.4%) and 192 patients (38.4%), respectively. We classified learning periods into the learning phase (first 50 cases), the developing phase (51-150 case), and the stable phase (151-500 case). The rates of vocal cord palsy (42.0% vs. 28.4%) and anastomotic leakage (10.0% vs. 6.4%) were reduced after the learning phase. The mean total operative time (420 vs. 373 min), the mean length of stay (21.6 vs. 16.7 days), and the rate of anastomotic stricture (27.0% vs. 12.4%) were significantly reduced after reaching stable phase. In the stable phase, the proportion of the Ivor Lewis operation (26.0% vs. 67.1%), neoadjuvant chemoradiation therapy (14.0% vs. 25.7%), and bilateral cervical node dissection cases (12.0% vs. 22.0%) were significantly increased. Conclusions: Fifty procedures might be needed to achieve early proficiency, and extensive experience of more than 150 procedures is needed for quality stabilization.

Predictive modelling for the diagnosis of oral and laryngeal premalignant and malignant lesions using p53 and Ki-67 expression.

Oral and laryngeal epithelial lesions are currently diagnosed using histological criteria based on the World Health Organization (WHO) classification, which can cause interobserver variability. An integrated diagnostic approach based on immunohistochemistry (IHC) would aid in the interpretation of ambiguous histological findings of epithelial lesions. In the present study, IHC was used to evaluate the expression of p53 and Ki-67 in 114 cases of oral and laryngeal epithelial lesions in 104 patients. Logistic regression analysis and decision tree algorithm were employed to develop a scoring system and predictive model for differentiating the epithelial lesions. Cohen's kappa coefficient was used to evaluate interobserver variability, and next-generation sequencing (NGS) and IHC were used to compare TP53 mutation and p53 expression patterns. Two expression patterns for p53, namely, diffuse expression type (pattern HI) and null type (pattern LS), and the pattern HI for Ki-67 were significantly associated with high-grade dysplasia (HGD) or squamous cell carcinoma (SqCC). With an accuracy and area under the receiver operating characteristic curve (AUC) of 84.6% and 0.85, respectively, the scoring system based on p53 and Ki-67 expression patterns classified epithelial lesions into two types: non-dysplasia (ND) or low-grade dysplasia (LGD) and SqCC or HGD. The decision tree model constructed using the p53 and Ki-67 expression patterns classified epithelial lesions into ND, LGD, and group 2, including HGD or SqCC, with an accuracy and AUC of 75% and 0.87, respectively. The integrated diagnosis had a better correlation with near perfect agreement (weighted kappa 0.92, unweighted kappa 0.88). The patterns HI and LS for p53 were confirmed to be correlated with missense mutations and nonsense/frameshift mutations, respectively. A predictive model for diagnosis was developed based on the correlation between TP53 mutation and p53 expression patterns. These results indicate that the scoring system based on p53 and Ki-67 expression patterns can differentiate epithelial lesions, especially in cases when the morphological features are ambiguous.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

OBJECTIVE: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. METHODS: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. RESULTS: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. CONCLUSION: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Concurrent Killian-Jamieson and Zenker's Diverticula.

Pharyngoesophageal diverticula are rare causes of dysphagia. Zenker's diverticulum is the most common type, followed by Killian-Jamieson diverticulum. A 44-year-old male presented to our clinic with a longstanding history of dysphagia and globus sensation. Bilateral pharyngoesophageal diverticula were confirmed by imaging CT and esophagogastroscopy. He underwent transcervical resection, and a right Killian-Jamieson diverticulum was observed during surgery. The left diverticulum was found to originate above the cricopharyngeus muscle and was labeled as Zenker's diverticulum. Bilateral pharyngoesophageal diverticula are rare, and physicians should be aware of the variable clinical presentations and management options for pharyngoesophageal diverticula.

Frequent apocrine changes in pleomorphic adenoma with malignant transformation: a possible pre-malignant step in ductal carcinoma ex pleomorphic adenoma.

BACKGROUND: The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA). METHODS: Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody. RESULTS: Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression. CONCLUSIONS: Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.

Exosome-guided direct reprogramming of tumor-associated macrophages from protumorigenic to antitumorigenic to fight cancer.

Highly immunosuppressive tumor microenvironment containing various protumoral immune cells accelerates malignant transformation and treatment resistance. In particular, tumor-associated macrophages (TAMs), as the predominant infiltrated immune cells in a tumor, play a pivotal role in regulating the immunosuppressive tumor microenvironment. As a potential therapeutic strategy to counteract TAMs, here we explore an exosome-guided in situ direct reprogramming of tumor-supportive M2-polarized TAMs into tumor-attacking M1-type macrophages. Exosomes derived from M1-type macrophages (M1-Exo) promote a phenotypic switch from anti-inflammatory M2-like TAMs toward pro-inflammatory M1-type macrophages with high conversion efficiency. Reprogrammed M1 macrophages possessing protein-expression profiles similar to those of classically activated M1 macrophages display significantly increased phagocytic function and robust cross-presentation ability, potentiating antitumor immunity surrounding the tumor. Strikingly, these M1-Exo also lead to the conversion of human patient-derived TAMs into M1-like macrophages that highly express MHC class II, offering the clinical potential of autologous and allogeneic exosome-guided direct TAM reprogramming for arming macrophages to join the fight against cancer.

Swallowing analysis in hemi-tongue reconstruction using motor-innervated free flaps: A cine-magnetic resonance imaging study.

BACKGROUND: This study aimed to explore the outcomes of motor-innervated free flaps in hemi-tongue reconstruction by assessing the tongue mobility through midsagittal images from cine-magnetic resonance imaging. METHODS: In this retrospective study, 47 patients who underwent tongue reconstruction following hemi-glossectomy and 10 control subjects without any surgical history were included. Patients were classified into two groups: the motor and no-motor innervation group. Various spatial parameters related to tongue mobility that were acquired from midsagittal sections were compared during consecutive swallowing phases. RESULTS: Overall, the motor group showed improved functional swallowing scale compared with the no-motor group. In case of tongue base resection, the motor group showed improved mobility of the tongue base during pharyngeal phase, whereas the no-motor group showed increased laryngeal elevation for compensatory movement. CONCLUSION: The tongue reconstruction with motor-innervated free flaps may facilitate swallowing capacity in patients with a hemi-tongue defect combined with tongue base resection.

Surgical outcomes of oro-intestinal continuity reconstruction after total esophagectomy in patients with cervicothoracic malignancy: a thoracic surgeon's perspective.

Background: Oro-intestinal continuity reconstruction following total esophagectomy in patients with head-neck or esophageal cancer is rare and results in high operative morbidity and mortality. This case series aimed to investigate the perioperative surgical outcomes of oro-intestinal continuity reconstruction after total esophagectomy in selected patients with advanced head/neck or esophageal cancer. Methods: From 2011 to 2018, 14 patients who underwent oro-intestinal reconstruction after total esophagectomy were assessed. We analyzed perioperative mortality, postoperative complications, oncologic outcomes, and recovery of dietary function. Results: The median age of the patients was 61 (range, 42-72) years old and median follow-up time was 18.6 (range, 0-52.9) months. For conduit selection, 11 cases of oro-gastrostomy (78.6%), 2 of oro-colo-gastrostomy (14.3%), and 1 of oro-jejuno-gastrostomy (7.1%) were performed. Complete resection was pathologically confirmed in 10 patients (71.4%). Anastomosis site leakage was observed in three patients (21.4%) and conduit necrosis in two (14.3%). Postoperative mortality within 30 days, 90 days, and 1 year was 7.1%, 28.6%, and 42.8%, respectively. Conclusions: Oro-intestinal continuity reconstruction following total esophagectomy showed acceptable morbidity and mortality in selected patients with advanced head/neck cancer or esophageal cancer. Careful selection of surgical candidates and multidisciplinary collaboration of experienced surgical teams are essential to minimize the surgical risk.

Risk Stratification of Dysphagia After Surgical Treatment of Hypopharyngeal Cancer.

Objective: Hypopharyngeal cancer is managed by either surgical resection or radiation therapy-based treatment. In choosing the treatment modality, the patient's swallowing function should be considered to achieve optimal treatment outcomes. This study aimed to stratify the risk factors predictive of postoperative dysphagia in hypopharyngeal cancer. Study Design: Retrospective study. Setting: Tertiary referral center. Methods: We enrolled 100 patients who were diagnosed with hypopharyngeal cancer and underwent curative surgery between January 2010 and December 2019, and retrospectively reviewed their medical records. Results: Postoperative dysphagia occurred in 29 patients (29%) who required a tracheostomy tube or percutaneous gastrostomy tube for feeding or preventing aspiration; additionally, the overall survival rate was lower in those patients than in those without dysphagia. The univariate analysis revealed that postoperative dysphagia was associated with clinical T stage (p = 0.016), N stage (p = 0.002), and surgical resection extent of the larynx and pharynx (p < 0.001). Patients who underwent total laryngectomy with total/partial pharyngectomy were more likely to have dysphagia than those in the larynx-preserving pharyngectomy groups (odds ratio [OR] = 3.208, 95% confidence interval [CI] 1.283-8.024, p = 0.011). Concerning the posterior pharyngeal wall (PPW), which has an important role in swallowing, patients who underwent resection of ≥1/2 of the PPW were more likely to have dysphagia (OR = 7.467, 95% CI 1.799-30.994, p = 0.003). Conclusions: Surgical resection extent was proportionally associated with dysphagia in hypopharyngeal cancer patients. Patients with smaller lesions but no laryngeal invasion had better postoperative swallowing function than patients with larger lesions or laryngeal involved lesions. Preserving the larynx and hypopharyngeal mucosa (especially the PPW) as much as possible can help preserve postoperative swallowing function.

Feedback amplification of senolysis using caspase-3-cleavable peptide-doxorubicin conjugate and 2DG.

Therapy-induced senescence (TIS), a common outcome of current cancer therapy, is a known cause of late recurrence and metastasis and thus its eradication is crucial for therapy success. In this study, we introduced a conceptually novel strategy combining radiation-induced apoptosis-targeted chemotherapy (RIATC) with an effective glycolysis inhibitor, 2-deoxy-d-glucose (2DG) to target TIS. RIATC releases cytotoxic payload by amplification, continually increasing TIS, and this can be targeted by 2DG that stimulates an intrinsic apoptotic pathway in senescent cells, the senolysis; the senolytic 2DG also sensitizes cancer cells to chemo/radiation treatment. Anti-tumor efficacy of RIATC was investigated in numerous tumor models, and various cancer types were screened for TIS. Furthermore, in vitro evaluations of molecular markers of senescence, such as senescence-associated ß-galactosidase (SA-ß-Gal) assay, were performed to confirm that TIS was induced by RIATC therapy in MCF-7 cells. The combination therapy with 2DG proved to be effective in MCF-7 tumor-bearing mice that demonstrated feedback amplification of senolysis and successful inhibition of tumor growth. Our findings suggest that RIATC, when given together with 2DG, can overcome therapy-induced senescence and this combination is a promising strategy that enhances the therapeutic benefit of anti-cancer cytotoxic therapy.

Early Ambulation to Prevent Delirium After Long-Time Head and Neck Cancer Surgery.

Objective: Postoperative delirium is known to have various adverse effects on head and neck surgery patients. This study was designed to identify possible risk factors of delirium following long periods of head and neck cancer surgery and to help prevent postoperative delirium. Methods: We enrolled 197 patients who underwent long-time (>6 h) head and neck surgery at the Asan Medical Center from January 2017 to December 2018 in this study. Clinical covariates that may be associated with delirium were analyzed retrospectively using univariate and multivariate analyses. Results: Delirium occurred in 18 patients (9.1%). Within the first 7 days, 16 patients (88.9%) experienced delirium. Upon univariate analysis, delirium was associated with old age (≥75, p = 0.001), past neurological history (p = 0.019), time to ambulation (p = 0.014), and postoperative hospital day (p = 0.048). In multivariate analysis, old age (≥75, odds ratios (OR) 6.16, CI 2.00-19.00, p = 0.002), time to ambulation (OR 1.04, CI 1.01-1.07, p = 0.017), and past neurological history (OR 5.26, CI 1.09-25.37, p = 0.039) were significant risk factors associated with postoperative delirium. Conclusions: Older patients or patients with neurologic history must be attended with care, especially early after surgery. Encouraging early ambulation might lower the incidence of postoperative delirium and, subsequently, reduce adverse effects. This result could benefit patients by helping them avoid undesirable outcomes.

Preoperative Magnetic Resonance Image and Computerized Tomography Findings Predictive of Facial Nerve Invasion in Patients with Parotid Cancer without Preoperative Facial Weakness-A Retrospective Observational Study.

(1) Background: Facial nerve resection with reconstruction helps achieve optimal outcomes in the treatment of facial nerve invasion (FNI) of parotid cancer. Preoperative imaging is crucial to predict facial nerve reconstruction. The radiological findings of CT or MRI may predict FNI in the parotid cancer even without facial paralysis. Methods: We retrospectively reviewed the records of 151 patients without facial nerve paralysis before surgery who had undergone tumor resection. Previously untreated parotid cancers were included. (2) Results: The median follow-up duration was 62 months (range: 24-120 months). The FNI (+) group (n = 30) showed a significantly worse 5-year overall survival compared with the FNI (-) group (75.5 vs. 93.9%; hazard ratio = 4.19; 95% confidence interval: 1.74-10.08; p = 0.001). The tumor margin, tumor size, presence in the anterolateral parotid region (area 3), retromandibular vein involvement, distance from the stylomastoid foramen to the upper tumor margin, and a high tumor grade were significant factors related to FNI in the univariate analysis. A spiculated tumor margin, the tumor size (2.2 cm), and presence in area 3 were factors predicting FNI in the logistic regression model (p = 0.020, 0.005, and 0.050, respectively; odds ratio: 4.02, 6.40, and 8.16, respectively). (3) Conclusions: The tumor size (≥2.2 cm), spiculated margin, and presence in area 3 as presented in CT and MRI may help clinicians preoperatively predict FNI in patients with parotid cancer and establish an appropriate surgical plan.

Albumin metabolism targeted peptide-drug conjugate strategy for targeting pan-KRAS mutant cancer.

Despite recent breakthroughs in the development of direct KRAS inhibitors and modulators, no drugs targeting pan-KRAS mutant cancers are clinically available. Here, we report a novel strategy to treat pan-KRAS cancers using a caspase-3 cleavable peptide-drug conjugate that exploits enhanced albumin metabolism in KRAS altered cancers to deliver a cytotoxic agent that can induce a widespread bystander killing effect in tumor cells. Increased albumin metabolism in KRAS mutant cancer cells induced apoptosis via the intracellular uptake of albumin-bound MPD1. This allowed caspase-3 upregulation activated MPD1 to release the payload and exert the non-selective killing of neighboring cancer cells. MPD1 exhibited potent and durable antitumor efficacy in mouse xenograft models with different KRAS genotypes. An augmentation of anti-cancer efficacy was achieved by the bystander killing effect derived from the caspase-3 mediated activation of MPD1. In summary, albumin metabolism-induced apoptosis, together with the bystander killing effect of MPD1 boosted by caspase-3 mediated activation, intensified the efficacy of MPD1 in KRAS mutant cancers. These findings suggest that this novel peptide-drug conjugate could be a promising breakthrough for the treatment in the targeting of pan-KRAS mutant cancers.

Suture Ligation of Pyriform Sinus Fistulas Following Cauterization to Treat Branchial Cleft Anomalies.

OBJECTIVES: Obliteration with cauterization of the internal opening of pyriform sinus fistulas, with or without marsupialization, has been a mainstay for preventing recurrence. However, this procedure predisposes patients to recurrence caused by the reopening of the cauterized orifice. We applied suture ligation to secure the closure of the internal orifice following cauterization and evaluated treatment. METHODS: A total of 42 patients were diagnosed with third or fourth branchial cleft anomaly with internal pyriform sinus fistula and treated either with cauterization or with cauterization and suture ligation, between January 2008 and December 2020. The medical records were reviewed to assess demographic characteristics, clinical presentations, diagnoses, surgical treatment, and outcomes. Treatment flow characteristics for intractable patients were analyzed. RESULTS: The median age of onset was 9 years (range, 0-57 years). Neck swelling (n = 32, 76.2%) was commonly encountered symptom, and a history of neck infection was found in 27 patients (64.3%). After initial treatment, 11 cases (56.2%) recurred. Younger age (≤9 years) and thyroid involvement were associated with recurrence (P = .034 and P = .046, respectively). Cauterization with suture ligation presented lower recurrence rate (19.2%) than cauterization only (37.5%, P = .037). Cauterization with suture ligation for recurrent cases (n = 11) showed 81.8% (9/11) of cure rate. Intractable fistulas (n = 2) from both groups were also salvaged by suture ligation. CONCLUSIONS: Suture ligation with cauterization for an internal orifice of branchial anomaly showed lower recurrence rate than cauterization only. This method was beneficial for refractory cases.