Prognostic Significance of Human Papillomavirus Genotypes in Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVES: The prognostic significance of human papillomavirus (HPV) genotypes in oropharyngeal squamous cell carcinoma (OPSCC) has garnered considerable attention due to the increasing reliance on HPV status for clinical decision-making. This study aimed to compare the survival outcomes associated with different HPV genotypes in patients with OPSCC relative to HPV-negative tumors, providing insights into the potential implications for treatment de-intensification strategies. METHODS: Patients diagnosed with invasive OPSCC were included from the National Cancer Database (NCDB). Patients were stratified based on HPV status and genotype, with HPV-negative tumors serving as the reference group. Multivariable Cox regression analysis was performed to assess the independent prognostic value of different HPV genotypes. RESULTS: Th majority of patient were classified as HPV-positive (N = 17,358, 70.0%), with HPV 16 being the most common genotype (N = 15410/17358, 88.8%) compared with other high-risk (N = 1217/17,358, 7.0%) and low-risk (N = 731/17,358, 4.2%) HPV genotypes. A significantly lower risk of death was measured for all HPV-positive compared with HPV-negative tumors (HPV 16: adjusted HR 0.51; 95% CI: 0.49-0.54; other high-risk HPV: adjusted HR 0.56; 95% CI: 0.49-0.63; low-risk HPV: adjusted HR 0.59; 95% CI: 0.50-0.68; p < 0.001). CONCLUSION: This study highlights the significant prognostic value of HPV genotypes in OPSCC, underscoring the superior survival outcomes of HPV-positive tumors across all genotypes compared with HPV-negative tumors. Detailed HPV subtype analysis can inform better treatment decisions and support de-intensification strategies for patients with low-risk genotypes. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Neoadjuvant chemotherapy followed by transoral robotic surgery versus upfront surgery for locoregionally advanced oropharyngeal carcinoma: A propensity score matched analysis.

BACKGROUND: Transoral robotic surgery (TORS) performed after neoadjuvant chemotherapy (NAC) is a promising treatment for advanced-stage oropharyngeal carcinoma (OPSCC) able to reduce the adjuvant therapy administration rate. METHODS: A retrospective bi-centric study was conducted to analyze NAC + TORS versus upfront TORS patients. A 1:1 propensity score matching was used to compare the two groups. RESULTS: Among the 300 patients with stage III-IV OPSCC, 204 patients were matched for comparing NAC + TORS versus upfront TORS. Between the two groups, no significant difference was observed in recurrences and in survival for RFS, OS, and DSS. In the NAC + TORS p16-positive population, adjuvant therapy could be spared in 51% versus 16% in the upfront surgery cohort (p < 0.001) due to the lower frequency of pathological risk factors after NAC. CONCLUSIONS: NAC followed by TORS for locoregionally advanced OPSCC demonstrated to achieve non-inferior survival outcomes to upfront surgery, while in the p16-positive population allowed to significantly spare adjuvant therapy.

Development of machine learning models for fractional flow reserve prediction in angiographically intermediate coronary lesions.

BACKGROUND: Fractional flow reserve (FFR) represents the gold standard in guiding the decision to proceed or not with coronary revascularization of angiographically intermediate coronary lesion (AICL). Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. OBJECTIVES: We sought to develop machine learning (ML) models based on clinical, angiographic and OCT variables for predicting FFR. METHODS: Data from a multicenter, international, pooled analysis of individual patient's level data from published studies assessing FFR and OCT on the same target AICL were collected through a dedicated database to train (n = 351) and validate (n = 151) six two-class supervised ML models employing 25 clinical, angiographic and OCT variables. RESULTS: A total of 502 coronary lesions in 489 patients were included. The AUC of the six ML models ranged from 0.71 to 0.78, whereas the measured F1 score was from 0.70 to 0.75. The ML algorithms showed moderate sensitivity (range: 0.68-0.77) and specificity (range: 0.59-0.69) in detecting patients with a positive or negative FFR. In the sensitivity analysis, using 0.75 as FFR cut-off, we found a higher AUC (0.78-0.86) and a similar F1 score (range: 0.63-0.76). Specifically, the six ML models showed a higher specificity (0.71-0.84), with a similar sensitivity (0.58-0.80) with respect to 0.80 cut-off. CONCLUSIONS: ML algorithms derived from clinical, angiographic, and OCT parameters can identify patients with a positive or negative FFR.

Safety and Postoperative Outcomes of Transoral Surgery for Oropharyngeal Carcinoma in Older Adults.

Importance: Transoral surgery (TOS) has become the primary surgical treatment for oropharyngeal squamous cell carcinoma (OPSCC). However, despite the increasing incidence of OPSCC in older patients, data regarding the safety and postoperative outcomes of TOS in this subgroup are lacking. Objective: This study aimed to evaluate the safety and postoperative outcomes of TOS in patients with OPSCC aged 70 years or older compared with younger individuals. Design, Setting, and Participants: This retrospective cohort study included patients with microscopic diagnostic confirmation of invasive OPSCC diagnosed between 2010 and 2021. Data were obtained from the US National Cancer Database. Data were analyzed in March 2024. Exposure: Minimally invasive TOS not converted to an open approach. Main Outcomes and Measures: Multivariable logistic and linear regression models were constructed to compare postoperative outcomes, adjusting for baseline patient and tumor characteristics. The results are reported as odds ratios (ORs) or mean differences with corresponding 95% CI, as appropriate. Results: A total of 10 430 patients (mean [SD] age, 60.7 [9.6] years; 8744 [83.8%] male) were included, with 1808 patients (17.3%) aged at least 70 years. No clinically meaningful difference was observed in terms of postoperative mortality at 30 days (adjusted OR, 1.24; 95% CI, 0.65-2.33) or 90 days (adjusted OR, 1.11; 95% CI, 0.65-1.87). Patients aged 70 years or older were less likely to undergo adjuvant radiotherapy (adjusted OR, 0.69; 95% CI, 0.57-0.83) and chemotherapy (adjusted OR, 0.63; 95% CI, 0.51-0.77). In addition, the adjuvant treatment was more frequently not administered in the older population due to patient refusal or comorbidities, despite being clinically indicated (radiotherapy: adjusted OR, 1.36; 95% CI, 1.05-1.77; chemotherapy: adjusted OR, 1.70; 95% CI, 1.17-2.45). No meaningful differences were observed regarding the remaining study outcomes, apart from a slightly longer hospitalization time for older patients, with an adjusted mean difference of 0.39 (95% CI, 0.05-0.74) days. Conclusions and Relevance: Findings from this study suggest that age was not independently associated with postoperative mortality in older patients undergoing TOS for OPSCC. However, older patients less frequently received adjuvant radiotherapy and chemotherapy compared with younger patients, and future studies should be conducted to examine the impact on long-term survival.

Diffusion-Weighted MRI for Recurrent/Persistent Head and Neck Squamous-Cell Carcinoma After Radiotherapy: Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the accuracy of diffusion-weighted magnetic resonance imaging (DWI-MRI) in diagnosing persistent/recurrent head and neck squamous cell carcinomas (HNSCCs) after primary chemoradiotherapy (CRT). DATA SOURCES: Scopus, PubMed/MEDLINE, and Cochrane Library databases were searched for relevant publications until April 18, 2023. REVIEW METHODS: A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Test Accuracy statement. The search was conducted independently by 2 investigators. Methodological quality of included studies was assessed using the Quality Assessment of Diagnostic Studies-2 questionnaire. Extracted data were used to calculate the pooled DWI-MRI sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratio. RESULTS: A total of 618 patients from 10 studies were included for calculation of diagnostic accuracy parameters. At the level of the primary tumor, the pooled sensitivity and specificity were, respectively, 0.96 (95% confidence interval [CI]: 0.89-1.00) and 0.81 (95% CI: 0.54-0.98) in the case of qualitative analysis, and, respectively, 0.79 (95% CI: 0.66-0.89) and 0.88 (95% CI: 0.77-0.96) for quantitative analysis. At the level of the neck, the pooled sensitivity and specificity were, respectively, 0.87 (95% CI: 0.75-0.95) and 0.84 (95% CI: 0.74-0.93) when images were analyzed qualitatively, and 0.79 (95% CI: 0.60-0.94) and 0.90 (95% CI: 0.82-0.97) when analyzed quantitatively. CONCLUSION: DWI-MRI showed high diagnostic accuracy and should be considered if persistent/recurrent HNSCCs is suspected after primary CRT. No significant differences were found between qualitative and quantitative imaging assessment.

Functional Abdominal Bloating and Gut Microbiota: An Update.

(1) Background: Functional abdominal bloating and distension (FAB/FAD) are common disorders of the gut-brain interaction. Their physiopathology is complex and not completely clarified, although gut microbiota imbalances play a central role. The treatment of FAB/FAD still represents a clinical challenge for both patients and healthcare providers. Gut microbiota modulation strategies might play a crucial role in their management. The aim of this narrative review was to update the current evidence on FAB/FAD, with a focus on gut microbiota. (2) Methods: In October 2023, a review was conducted through the Medline, PubMed, and Embase databases. Selected literature included all available English-edited studies (randomized controlled trials and cross-sectional, cohort, and case-control studies). (3) Results: Twelve studies were selected, most of which investigated the relationship between IBS and microbiota, with bloating being one of its symptoms. The studies suggest that restoring a balanced microbiome appears to be the most promising solution for better management of FAB/FAD. Targeted approaches, such as the use of probiotics, prebiotics, antibiotics such as rifaximin or dietary modifications, may hold the key to alleviating symptoms. Other therapeutic options, such as diet, neuromodulators, and brain-gut behavioral therapies (i.e., cognitive-behavioral therapy) have shown promising outcomes, but strong data are still lacking. (4) Conclusions: Targeted approaches that focus on the gut microbiota, such as the use of probiotics, prebiotics, and antibiotics, are essential in managing FAB/FAD. Understanding the complex relationship between gut microbiota and FAB/FAD is crucial for developing effective treatments. Further studies are needed to explore the specific roles of different microbial populations in patients with FAB/FAD to enhance therapeutic strategies.

Surgical outcomes of profunda artery perforator flap in head and neck reconstruction: A systematic review and meta-analysis.

OBJECTIVE: This study aims to evaluate the efficacy of the profunda artery perforator (PAP) flap in head and neck reconstruction. METHODS: A single arm meta-analysis was performed for flap survival rate (primary outcome), reoperation for major complication, and overall complication rates (secondary outcomes). RESULTS: The search strategy yielded a total of 295 potentially relevant publications, of which 13 were included. A total of 305 patients (males: 80.8%, n = 232/281), with a median age of 56.1 years (n = 305/305; 95% CI 53.9-63), who underwent a total of 307 PAP flap reconstructions for head and neck defects were included. Flap survival rate was 100% (n = 306/307; 95% CI 99.6%-100%), with a reoperation rate for major complications of 3.7% (n = 15/307; 95% CI 1.85%-6.1%) and an overall complication rate of 26.5% (n = 92/307; 95% CI 15.7%-38.9%). Notable postoperative complications included wound dehiscence (n = 15/307, 4.9%), delayed healing (n = 14/307, 4.6%), and wound infection (n = 12/307, 3.9%). Partial flap necrosis and hematoma occurred in 2.6% of cases (n = 8/307), while arterial and venous thrombosis were documented in 0.7% (n = 2/307) and 1.3%, respectively (n = 4/307). CONCLUSION: The application of the PAP flap in head and neck reconstructions showed several favorable aspects, such as an exceptionally low flap failure rate, versatility in achieving variable dimensions, and a relatively low incidence of complications. PAP flap might be considered as a compelling alternative to the traditionally employed soft tissue free flaps in head and neck reconstruction.

Sinonasal squamous cell carcinoma in the United States: Temporal and geographic patterns associated with HPV testing and positivity.

OBJECTIVES: Human papillomavirus (HPV) has emerged as a potential etiological factor in sinonasal squamous cell carcinoma (SNSCC), but a clear understanding of HPV prevalence and its temporal patterns in SNSCC remains elusive. This study aimed to investigate temporal trends in HPV testing and positivity rates, and explore demographic and geographic factors associated with these trends. METHODS: A retrospective cohort study included patients diagnosed with invasive SNSCC between 2011 and 2017 from the US National Cancer Database (NCDB). Prevalence ratios (PR) of HPV positivity and testing rates were estimated with the corresponding 95% confidence interval (95% CI). RESULTS: The overall HPV testing rate was 45.4 % (N = 1762/3880), and the prevalence of HPV testing significantly decreased during the study period (adjusted PR: 0.97, 95 % CI: 0.95 - 0.99, p < 0.001). Overall HPV positivity frequency was 37.3 % (N = 650/1741), and the overall prevalence of HPV positive tumors significantly increased during the study period (adjusted PR: 1.04, 95 % CI: 1.02 - 1.05, p < 0.001). The increase in HPV positivity rate was observed solely in the white population (unadjusted PR: 1.10, 95 % CI: 1.06 - 1.14; p < 0.001). A significant geographical variation was observed for both HPV testing (range: 28.6 % - 61.7 %) and positivity (range: 28.3 % - 44.7 %). CONCLUSIONS: This study provides novel insights into the temporal trends and demographic factors associated with HPV testing and positivity in SNSCC. Despite increasing HPV positivity rates, disparities in testing rates persist, highlighting the need for standardized testing protocols and targeted interventions.

Survival and complications after carotid resection for head and neck squamous cell carcinoma: A systematic review and pooled analysis.

OBJECTIVE: The aim of this study is to analyze oncologic outcomes and complications rate after common or internal carotid artery (CCA/ICA) resection for head and neck squamous cell carcinoma (HNSCC). METHODS: This study was conducted in conformity with the PRISMA statement. A systematic review and pooled analysis was performed for overall survival (OS), disease specific survival (DSS) (primary outcomes), and perioperative death rate (secondary outcome). RESULTS: A total of 276 patients (males: 76.7%, n = 191/249) with a median age of 59 years (n = 239/276; 95% CI 55.0-61.7) who underwent CCA/ICA resection for HNSCC were included. The median follow-up time was 11 months (n = 276). Estimated pooled OS rates (95% CI) at 1 and 2 years were 52.7% (46.9-59.2) and 29.8% (24.3-36.5), respectively. The median OS (95% CI) was 14 months (12-17). Estimated pooled DSS rates (95% CI) at 1 and 2 years were 58.6% (52.7-65.2) and 34.6% (28.5-41.9), respectively. The median DSS (95% CI) was 16 months (14-19). The perioperative death rate was 6.9% (n = 19/276). CONCLUSIONS: CCA/ICA resection should be considered as a treatment option for accurately selected patients. Multicentric prospective studies are recommended to develop a predictive score guiding the decision-making process.

Transoral robotic vertical partial laryngectomy (hemilaryngectomy) extended to the hypopharynx.

Locally advanced laryngeal cancers treatment often involves total laryngectomy, which some patients are unwilling to undergo, even if this choice reduces their survival probability. Therefore, the objective of laryngeal oncologic surgery is not only to remove the tumor, but also to preserve the organ and its functions. To overcome these concerns, several partial laryngectomy techniques have been developed. This article describes the surgical technique and a case study of a 64-year-old male patient with locally advanced laryngeal squamous cell carcinoma who underwent vertical partial laryngectomy extending to the subglottis and hypopharynx using transoral robotic surgery (TORS) with a da Vinci Single Port surgical robot. The video and article provide a detailed description of the surgical technique, which resulted in successful tumor removal with excellent oncological and functional outcomes.

Superior predictive value of transmural over endoscopic severity for colectomy risk in ulcerative colitis: a multicentre prospective cohort study.

BACKGROUND AND AIMS: Endoscopic activity is associated with an increased risk of surgery in patients with ulcerative colitis [UC]. Transmural activity, as defined by Milan Ultrasound Criteria [MUC] > 6.2, reliably detects endoscopic activity in patients with UC. The present study aimed to assess in UC patients whether transmural severity is a better predictor of colectomy as compared to endoscopy. METHODS: Consecutive adult UC patients were recruited in two IBD Referral Centres and underwent colonoscopy and intestinal ultrasound in a blinded fashion. The need for colectomy was assessed at follow-up. Univariable and multivariable logistic and Cox regression analyses were performed. Receiver operating characteristic [ROC] analysis was used to compare MUC baseline values and Mayo Endoscopic Scores [MES] in predicting colectomy risk. RESULTS: Overall, 141 patients were enrolled, and 13 underwent colectomy in the follow-up period. Both MES (hazard ratio [HR]: 3.15, 95% confidence interval [CI]: 1.18-8.37, p = 0.02) and MUC [HR: 1.48, 95% CI: 1.19-1.76, p < 0.001] were associated with colectomy risk, but only MUC was independently associated with this event on multivariable analysis [HR: 1.46, 95% CI: 1.06-2.02, p = 0.02]. MUC was the only independent variable associated with colectomy risk in patients with clinically active disease (odds ratio [OR]: 1.53 [1.03-2.27], p = 0.03). MUC demonstrated higher accuracy than MES (area under ROC curve [AUROC] 0.83, 95% CI: 0.75-0.92 vs 0.71, 95% CI: 0.62-0.80) and better performance for predicting colectomy [p = 0.02]. The optimal MUC score cut-off value for predicting colectomy, as assessed by the Youden index, was 7.7. CONCLUSIONS: A superior predictive value was found for transmural vs endoscopic severity for colectomy risk in UC patients.

Transoral robotic surgery in oropharyngeal squamous cell carcinoma: A comparative study between da Vinci Single-Port and da Vinci Xi systems.

BACKGROUND: The recently developed da Vinci single-port (SP) system offers potential advantages in maneuverability within narrower surgical spaces. This study aims to compare intra- and post-operative outcomes, technical advantages, and limitations of transoral resections using the da Vinci SP and da Vinci Xi systems for oropharyngeal squamous cell carcinoma (OPSCC). METHODS: A single-center retrospective cohort study included patients with OPSCC who underwent transoral robotic surgery (TORS) after neoadjuvant chemotherapy (NCT). Data on pre-operative variables, intraoperative data, postoperative complications, and functional outcomes were collected. RESULTS: A total of 209 patients (males: 175; mean age: 59.0 ± 9.3) were included (SP: n = 136; Xi: n = 73). A significantly lower docking time was measured for the SP group (5.7 ± 2.5 min vs. 10.0 ± 4.4 min; p <.001). Similarly, the console time was reduced for the SP group though not reaching statistical significance (76.3 ± 30.7 min vs. 88.1 ± 36.9 min; p =.06). A greater proportion of patients showed wide negative resection margins in the SP group (71 % vs. 56 %; p =.10), although not statistically significant. No significant differences were observed in complication rates or postoperative functional outcomes. DISCUSSION: This study demonstrates the safety and efficacy of the da Vinci SP system in oropharyngeal surgery, with potential advantages in terms of reduced docking and console times. The findings suggest that the SP system offers improved maneuverability and instrument placement compared to the da Vinci Xi system.

Impact of Adjuvant Radiotherapy in Squamous Cell Carcinoma of the Oral Cavity with Perineural Invasion.

OBJECTIVE: Current guidelines indicate postoperative radiotherapy (PORT) in oral squamous cell carcinoma (OSCC) with perineural invasion (PNI), however, its real benefit has never been proven. The aim of our study is to investigate the benefit of PORT in OSCC patients with PNI in terms of survival and disease control. DATA SOURCES: The Pubmed/MEDLINE, Cochrane Library, and Scopus databases. REVIEW METHODS: Patients with PNI + OSCC treated with primary surgery were extracted from the included studies. The pooled logHR was calculated by comparing patients who underwent PORT to those who underwent only observation for overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional control (LRC). RESULTS: About 690 patients with primary OSCC and PNI were included from nine studies. 374 (54.2%) patients underwent PORT, while 316 (45.8%) underwent observation. Analyses showed non-significant difference between the two groups for OS (HR: 1.01; 95% CI: 0.38-2.69), DSS (HR: 2.03; 95% CI: 0.54-7.56), and LRC (HR: 0.89; 95% CI: 0.53-1.50). They showed a significant difference in terms of DFS (HR: 0.86; 95% CI: 0.77-0.97). CONCLUSION: The real benefit of PORT in OSCC patients with PNI is still unclear, although it may have a positive impact on DFS. Clinicians should consider individual patient's characteristics, tumor factors, and treatment goals when deciding whether to recommend PORT. Further studies are needed to clarify which entity of PNI really benefits from PORT. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2019-2027, 2024.

Postoperative Morbidity of Different Tonsillectomy Techniques: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To compare different tonsillectomy techniques in terms of postoperative bleeding incidence and postoperative pain. METHODS: An arm-based network analysis was conducted using a Bayesian hierarchical model. The primary and secondary outcomes were postoperative bleeding incidence and mean postoperative pain score. RESULTS: A total of 6464 patients were included for five different interventions (cold dissection tonsillectomy; extracapsular coblation tonsillectomy; intracapsular coblation tonsillectomy [ICT]; bipolar diathermy tonsillectomy [BDT]; monopolar diathermy tonsillectomy). ICT showed the lowest absolute risk (4.44%) of postoperative bleeding incidence (73.31% chance of ranking first) and the lowest mean postoperative pain score (1.74 ± 0.68) with a 94.0% chance of ranking first, whereas BDT showed both the highest absolute risk of bleeding incidence (10.75%) and the highest mean postoperative pain score (5.67 ± 1.43). CONCLUSIONS: ICT seems to offer better postoperative outcomes, in terms of reduced risk of bleeding and reduced pain. Further prospective studies are advised to confirm these findings. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1696-1704, 2024.