Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study.

BACKGROUND: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. METHODS: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. RESULTS: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81]). CONCLUSION: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification.

Fucoidan enhances the effect of chemotherapeutic drug against drug-resistant lung cancer cells.

Development of adjuvant chemotherapy drugs against drug-resistant lung cancer cells is necessary. The use of non-toxic adjuvant natural product combined with chemotherapy drugs will be an important treatment mode in the future. The purpose of the study investigates that fucoidan enhances chemotherapy drug poisoning drug-resistant lung cancer cell. Drug-resistant lung cancer cells are established in the study. Cell culture, MTT assay, wound healing assay, gelatin zymography assay, DNA fragmentation assay, apoptosis assay, reverse transcription polymerase chain reaction (RT-PCR) western blot analysis was adopted. The results showed that fucoidan synergized with doxorubicin increased efficacy of poisoning drug-resistant lung cancer cells and enhanced the ability of doxorubicin to inhibit the migration of drug-resistant lung cancer cells. It was observed that fucoidan synergized with doxorubicin induced the increase of apoptosis and inhibited expression of MMP-9, LC3, Beclin-1 and ß-catenin in drug-resistant lung cancer cells. Fucoidan synergized with doxorubicin significantly inhibited proliferation, migration and metastasis of drug-resistant lung cancer cells. Fucoidan strengthened doxorubicin to induce apoptosis and autophagy of drug-resistant lung cancer cells. This study confirms that the combined use of fucoidan and chemotherapeutic drugs can effectively poison drug-resistant lung cancer cells.

Factors affecting perforation of the esophagus in patients with deep neck infection.

BACKGROUND: Deep neck infection (DNI) is a serious disease that can lead to severe morbidity, including esophageal perforation, and mortality. However, no previous study has explored the risk factors associated with esophageal perforation in patients with DNI. This study investigated these factors. METHODS: Between September 2015 and September 2021, 521 patients with DNI were studied. Relevant clinical variables and deep neck spaces were assessed. RESULTS: In a multivariate analysis, involvement of the retropharyngeal space (OR 5.449, 95% CI 1.603-18.51, p = 0.006) and the presence of mediastinitis (OR 218.8, 95% CI 55.98-855.3, p < 0.001) were independent risk factors associated with esophageal perforation in patients with DNI. There were no differences in pathogens between 32 patients with and 489 patients without esophageal perforation (all p > 0.05). CONCLUSION: Involvement of the retropharyngeal space and the presence of mediastinitis were independent risk factors associated with esophageal perforation in patients with DNI. There were no differences in pathogens between the groups with and without esophageal perforation in DNI.

Factors affecting patients with concurrent deep neck infection and aspiration pneumonia.

BACKGROUND: Deep neck infection (DNI) is a life-threatening condition of the deep neck spaces with potential to obstruct the airway. Aspiration pneumonia (AP), which results from aspiration of colonized oropharyngeal or upper gastrointestinal contents, is a respiratory infection that affects the lungs, wherein the air sacs are filled with purulent fluid. The cooccurrence of these two diseases can cause severe damage to the respiratory system, leading to morbidity and mortality. However, the risk factors for concurrent DNI and AP have not yet been investigated. This study aimed to address this issue. METHODS: A total of 561 DNI patients were enrolled in this study between June 2016 and December 2021. Among these patients, 26 had concurrent DNI and AP at the time of diagnosis. Relevant clinical variables were assessed. RESULTS: In the univariate analysis, age > 60 years (OR = 3.593, 95% CI: 1.534-8.414, p = 0.002), C-reactive protein (OR = 1.005, 95% CI: 1.001-1.008, p = 0.003), involvement of ≥3 spaces (OR = 4.969, 95% CI: 2.051-12.03, p < 0.001), and retropharyngeal space involvement (OR = 4.546, 95% CI: 1.878-11.00, p < 0.001) were significant risk factors for concurrent DNI and AP. In the multivariate analysis, age > 60 years (OR = 2.766, 95% CI: 1.142-6.696, p = 0.024) and retropharyngeal space involvement (OR = 3.006, 95% CI: 1.175-7.693, p = 0.021) were independent risk factors for concurrent DNI and AP. The group with concurrent DNI and AP had longer hospital stays (p < 0.001) and lower rates of incision and drainage (I&D) open surgery (p = 0.020) than the group with DNI alone. There were no significant differences in pathogens (p > 0.05) between the groups. CONCLUSIONS: Both DNI and AP can independently compromise the airway, and the concurrence of these two conditions makes airway protection more difficult. Age > 60 years and retropharyngeal space involvement were independent risk factors for the concurrence of DNI and AP. The group with concurrent DNI and AP had longer hospital stays and lower rates of I&D open surgery than the group with DNI alone. There were no differences in DNI pathogens according to concurrent AP status.

A combined analysis of maximum standardized uptake value on FDG-PET, genetic markers, and clinicopathological risk factors in the prognostic stratification of patients with resected oral cavity squamous cell carcinoma.

OBJECTIVE: Clinical outcomes of patients with resected oral cavity squamous cell carcinoma (OCSCC) chiefly depend on the presence of specific clinicopathological risk factors (RFs). Here, we performed a combined analysis of FDG-PET, genetic markers, and clinicopathological RFs in an effort to improve prognostic stratification. METHODS: We retrospectively reviewed the clinical records of 2036 consecutive patients with first primary OCSCC who underwent surgery between 1996 and 2016. Of them, 345 underwent ultra-deep targeted sequencing (UDTS, between 1996 and 2011) and 168 whole exome sequencing (WES, between 2007 and 2016). Preoperative FDG-PET imaging was performed in 1135 patients from 2001 to 2016. Complete data on FDG-PET, genetic markers, and clinicopathological RFs were available for 327 patients. RESULTS: Using log-ranked tests based on 5-year disease-free survival (DFS), the optimal cutoff points for maximum standardized uptake values (SUV-max) of the primary tumor and neck metastatic nodes were 22.8 and 9.7, respectively. The 5-year DFS rates were as follows: SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7 (n = 77) versus SUVtumor-max < 22.8 and SUVnodal-max < 9.7 (n = 250), 32%/62%, P < 0.001; positive UDTS or WES gene panel (n = 64) versus negative (n = 263), 25%/62%, P < 0.001; pN3b (n = 165) versus pN1-2 (n = 162), 42%/68%, P < 0.001. On multivariate analyses, SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7, a positive UDTS/WES gene panel, and pN3b disease were identified as independent prognosticators for 5-year outcomes. Based on these variables, we devised a scoring system that identified four distinct prognostic groups. The 5-year rates for patients with a score from 0 to 3 were as follows: loco-regional control, 80%/67%/47%/24% (P < 0.001); distant metastases, 13%/23%/55%/92% (P < 0.001); DFS, 74%/58%/28%/7% (P < 0.001); and disease-specific survival, 80%/64%/35%/7% (P < 0.001) respectively. CONCLUSIONS: The combined assessment of tumor and nodal SUV-max, genetic markers, and pathological node status may refine the prognostic stratification of OCSCC patients.

Tumor Depth of Invasion (Tumor > 4 cm/Depth > 10 mm and Depth > 20 mm) and Through Cortex/Skin Invasion are Both Valid Criteria for Classifying Tumors as pT4a in AJCC 2018 Oral Cavity Cancer Staging System.

BACKGROUND: According to the AJCC third to seventh edition staging manuals (1988-2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018) introduced a depth of invasion (DOI) > 20 mm as a criterion for pT4a. Subsequently, a revision maintained that tumors > 4 cm with a DOI > 10 mm should be classified as pT4a. We sought to analyze the prognostic impact of the three distinct criteria identifying pT4a disease. METHODS: We examined 667 consecutive patients with pT3-4 buccal/gum/hard palate/retromolar SCC who underwent surgery between 1996 and 2016. pT1/pT2 (n = 108/359) disease were included for comparison purposes. RESULTS: The 5-year outcomes of patients with pT1/pT2/without (n = 406)/with tumor > 4 cm/DOI > 10 mm (n = 261), pT1/pT2/DOI ≤ 20 mm (n = 510)/> 20 mm (n = 157), and pT1/pT2/without (n = 305)/with through cortex/skin invasion (n = 362) were as follows: disease-specific survival (DSS), 98%/89%/79%/65%, p < 0.001, 98%/89%/78%/59%, p < 0.001, and 98%/89%79%/69%, p < 0.001; overall survival (OS), 90%/79%/63%/51%, p < 0.001, 90%/79%/63%/42%, p < 0.001, and 90%/79%/65%/52%, p < 0.001. In pT3-4 disease, a tumor > 4 cm/DOI > 10 mm was an independent adverse prognosticator for 5-year DSS rate, DOI > 20 mm was an independent adverse prognosticator for 5-year DSS and OS rates, whereas through cortex/skin invasion independently predicted 5-year OS rates. CONCLUSIONS: All of the three criteria (tumor > 4 cm/DOI > 10 mm, DOI > 20 mm, and through cortex/skin invasion) identify high-risk patients, which should be reflected in further revisions of pT4a classification in OCSCC.

Is elective neck dissection justified in cT2N0M0 oral cavity cancer defined according to the AJCC eighth edition staging system?

BACKGROUND: The current NCCN guidelines recommend considering elective neck dissection (END) for early-stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. METHODS: We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). RESULTS: Patients who underwent END had better 5-year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease-specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate-to-poor tumor differentiation as independent risk factors for 5-year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low-risk subgroup (DOI <5 mm plus well-differentiated tumor), an intermediate-risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high-risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5-year survival outcomes (neck control/DSS/OS) for the low-risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%). CONCLUSIONS: By implementing risk stratification within the NO group, we found that 26% (251/979) of low-risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account.

Prognostic impact of elective tracheotomy in resected oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC. METHODS: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis. RESULTS: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001). CONCLUSIONS: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays.

Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.

Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

BACKGROUND: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. METHODS: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. RESULTS: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). CONCLUSIONS: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.

Assessment of Factors Associated With Long-Term Hospitalization in Patients With a Deep Neck Infection.

BACKGROUND: Deep neck infection (DNI) is a severe infectious disorder of deep neck spaces that can cause serious complications. Long-term hospitalization is when a patient spends more time in the hospital than originally expected for a disease. There are few studies assessing the risk factors associated with long-term hospitalization for a DNI. This study investigated the factors causing DNI patients to experience long-term hospitalization. METHODS: Long-term hospitalization is defined as a length of hospital stay exceeding 28 days (> 4 weeks) in this research. A total of 362 subjects with a DNI between October 2017 and November 2022 were recruited. Among these patients, 20 required long-term hospitalization. The relevant clinical variables were assessed. RESULTS: In a univariate analysis, C-reactive protein (odds ratio [OR] = 1.003, 95% CI: 1.000-1.007, P = .044), involvement of ≥3 deep neck spaces (OR = 2.836, 95% CI: 1.140-7.050, P = .024), and mediastinitis (OR = 8.102, 95% CI: 3.041-21.58, P < .001) were significant risk factors for long-term hospitalization in DNI patients. In a multivariate analysis, mediastinitis (OR = 6.018, 95% CI: 2.058-17.59, P = .001) was a significant independent risk factor for long-term hospitalization for a DNI. There were no significant differences in pathogens between the patients with and without long-term hospitalization (all P > .05). However, the rates of no growth of specific pathogens were significantly different between patients with and without long-term hospitalization, and those with long-term hospitalization had greater rates of growth of specific pathogens (P = .032). The rate of tracheostomy in patients with long-term hospitalization was higher than for those without (P < .001). Nevertheless, the rates of surgical incision and drainage between patients with and without long-term hospitalization did not achieve statistical significance (P = .069). CONCLUSIONS: Deep neck infection (DNI) is a critical, life-threatening disease that could lead to long-term hospitalization. The higher CRP and involvement of ≥3 deep neck spaces were significant risk factors in univariate analysis, while concurrent mediastinitis was an independent risk factor associated with long-term hospitalization. We suggest intensive care and prompt airway protection for DNI patients with concurrent mediastinitis.

Assessment of the Elderly Adult Patients with Deep Neck Infection: A Retrospective Study.

Background: Deep neck infection (DNI) is a potentially lethal infectious disease affecting middle-aged adults and can compromise the airway. There are limited data on the prognosis and outcomes of elderly (aged > 65 years) DNI patients, who tend to be immunocompromised. This study analyzed the clinical characteristics of elderly and adult (aged 18-65 years) DNI patients. Methods: Between November 2016 and November 2022, 398 patients with DNIs, including 113 elderly patients, were admitted to our hospital and enrolled in this study. The relevant clinical variables were investigated and compared. Results: The elderly DNI patients had longer hospital stays (P < .001), higher C-reactive protein levels (P = .021), higher blood sugar levels (P = .012), and a higher likelihood of diabetes mellitus (P = .025) than the adult patients. The higher blood sugar level is an independent risk factor for elderly (odds ratio = 1.005, 95% confidence intervals 1.002-1.008, P < .001). Moreover, the rates of intubation to protect the airway (P = .005) and surgical incision and drainage (I&D; P = .010) were higher in the elderly group. However, there were no group differences in pathogen distributions. Conclusion: The elderly DNI patients in this study had a more severe disease course, and poorer prognosis than the adult patients, as well as higher rates of intubation and I&D. However, the pathogen distributions did not differ significantly between the groups. Prompt intervention and treatment are important for elderly DNI patients.

Quantitative Measurement of Perineural Invasion for Prognosis Analysis of Oral Cavity Cancer Treated by Radical Surgery With or Without Adjuvant Therapy.

Objectives: Perineural invasion (PNI) was quantitatively analyzed in oral squamous cell carcinoma (OSCC) specimens obtained by radical surgery to correlate with survival outcomes. Methods: This is a retrospective study that reviewed the Cancer registry data between 2009 and 2015. Inclusion criteria were oral cavity cancer, treatment by radical surgery, presence of PNI, and available pathologic samples for S100 staining. Patients with M1 disease and those with synchronous or metachronous cancer during staging work-up were excluded. All pathologic samples were reviewed to confirm PNI status and processed by immunohistochemical staining for S100 to quantify PNI. Pathologic information and staging results were also reviewed, and clinical outcomes were analyzed. Results: The retrospective study included 92 patients; 63 had intratumoral PNI (IPNI) and 29 had extratumoral PNI (EPNI). The average number of PNI foci (APNI) was higher in the EPNI group than in the IPNI group (6.7 vs 3.8, t-test 2-tail significance = 0.021). The 3-year overall survival (OS) and time-to-recurrence (TTR) rates of all patients were 82.5% and 81.2%, respectively. Univariate analysis showed that pathological T4 or N2-3 stage correlated with poor OS, whereas APNI ≥4 correlated with poor TTR. In multivariate analysis, only the pathological N2-3 stage was significantly correlated with poor OS, whereas only APNI ≥ 4 was an independent factor of poor TTR. The 3-year TTR rates were 92.4% and 65.6% for diseases with APNI < 4 and ≥ 4, respectively (P = .008). Conclusions: In patients with OSCC with PNI, a greater amount of PNI identified by S100 staining indicated a poorer TTR regardless of stage and other prognostic factors. Quantification of PNI by S100 immunohistochemistry is a potential method for prognosis prediction.

Indications for elective neck dissection in cT1N0M0 oral cavity cancer according to the AJCC eight edition: A nationwide study.

OBJECTIVES: According to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition. METHODS: Of the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation. RESULTS: The 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively. CONCLUSION: Because all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes.

Recurrent sudden sensorineural hearing loss-A literature review.

Objective: Sudden sensorineural hearing loss (SSNHL) is one of the few emergent otologic conditions. Although more than half of all patients would benefit from timely treatment, recurrence occasionally develops unexpectedly. The aim of our study is to evaluate the recurrence rate after SSNHL, and present the prognosis after first-episode and recurrent SSNHL. Methods: A literature search was conducted of the PubMed and Embase electronic databases. Results: Seven studies with a total of 3781 patients were included, and 96 patients experienced recurrence. The recurrence rate ranged between 1.4% and 17%. The average time to recurrence was about 2 years in most studies. The majority of the studies reported using systemic steroids for treating first-episode SSNHL, and one study used a plasma expander in patients with recurrent SSNHL. The recovery rate for first-episode patients was 58%-79%, while that for recurrent SSNHL ranged widely, from 21% to 86%. There were no common risk factors for SSNHL recurrence among the studies, although low-frequency hearing loss, the presence of tinnitus during follow-up, and an increased neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio have been proposed. Conclusion: Understanding the recurrence rate, risk factors, and prognosis after recurrence of SSHNL is crucial for comprehensive medical care; in this respect, further prospective studies with long-term follow-up may be instructive. Level of Evidence: 4.

Factors Affecting Patients with Concurrent Deep Neck Infection and Lemierre's Syndrome.

Deep neck infection (DNI) is a severe disease affecting the deep neck spaces, and is associated with an increased risk of airway obstruction. Lemierre's syndrome (LS) refers to septic thrombophlebitis of the internal jugular vein after pharyngeal infection, and is linked with high morbidity and mortality. Both diseases begin with an oropharyngeal infection, and concurrence is possible. However, no studies have examined the risk factors associated with co-existence of LS and DNI. Accordingly, this study examined a patient population to investigate the risk factors associated with concurrent DNI and LS. We examined data from a total of 592 patients with DNI who were hospitalized between May 2016 and January 2022. Among these patients, 14 had concurrent DNI and LS. The relevant clinical variables were assessed. In a univariate analysis, C-reactive protein (odds ratio (OR) = 1.004, 95% CI: 1.000−1.009, p = 0.045), involvement of multiple spaces (OR = 23.12, 95% CI: 3.003−178.7, p = 0.002), involvement of the carotid space (OR = 179.6, 95% CI: 22.90−1409, p < 0.001), involvement of the posterior cervical space (OR = 42.60, 95% CI: 12.45−145.6, p < 0.001) and Fusobacterium necrophorum (F. necrophorum, OR = 288.0, 95% CI: 50.58−1639, p < 0.001) were significant risk factors for concurrent DNI and LS. In a multivariate analysis, involvement of the carotid space (OR = 94.37, 95% CI: 9.578−929.9, p < 0.001), that of the posterior cervical space (OR = 24.99, 95% CI: 2.888−216.3, p = 0.003), and F. necrophorum (OR = 156.6, 95% CI: 7.072−3469, p = 0.001) were significant independent risk factors for concurrent LS in patients with DNI. The length of hospitalization in patients with concurrent LS and DNI (27.57 ± 14.94 days) was significantly longer than that in patients with DNI alone (10.01 ± 8.26 days; p < 0.001), and the only pathogen found in significantly different levels between the two groups was F. necrophorum (p < 0.001). Involvement of the carotid space, that of the posterior cervical space and F. necrophorum were independent risk factors for the concurrence of DNI and LS. Patients with concurrent LS and DNI had longer hospitalization periods than patients with DNI alone. Furthermore, F. necrophorum was the only pathogen found in significantly different levels in DNI patients with versus those without LS.

Factors Creating a Need for Repeated Drainage of Deep Neck Infections.

Deep neck infection (DNI) is associated with morbidity and mortality. Surgical incision and drainage (I&D) of DNI abscesses are essential. Refractory abscesses require repeat I&D. Few studies have assessed the risk factors associated with repeat I&D; here, we investigated such factors. In total, 605 patients with DNI were enrolled between July 2016 and February 2022. Of these patients, 107 underwent repeat I&D. Clinical variables were assessed. On univariate analysis, a high blood sugar level (odds ratio (OR) = 1.006, p < 0.001), the involvement of at least four neck spaces (OR = 15.44, p < 0.001), and mediastinitis (OR = 1.787, p = 0.040) were significant risk factors for repeat I&D. On multivariate analysis, a high blood sugar level (OR = 1.005, p < 0.001) and the involvement of at least four neck spaces (OR = 14.79, p < 0.001) were significant independent risk factors for repeat I&D. Patients who required repeat I&D had longer hospital stays and a higher tracheostomy rate than did other patients (both p < 0.05). The pathogens did not differ between patients who did and did not require repeat surgical I&D (all p > 0.05), but the rates of pathogen non-growth from blood cultures were 19.47% (97/498) in the group without a need for repeat I&D and 0.93% (1/107) in the group with such a need (p < 0.001). DNI can be fatal; a higher blood sugar level and the involvement of at least four neck spaces were independent risk factors for repeat surgical I&D. If at least four neck spaces are involved, we recommend controlling the blood sugar level after admission. We found significant differences in the length of hospital stay and the need for tracheostomy between groups who did and did not require repeat surgical I&D. Although the pathogens did not differ between the groups, pathogen non-growth from blood cultures was less common in the group with for repeat surgical I&D than in the group without such a need.

Factors Affecting Patients with Concurrent Deep Neck Infection and Cervical Necrotizing Fasciitis.

Deep neck infection (DNI) is a severe disease of the deep neck spaces, which has the potential for airway obstruction. Cervical necrotizing fasciitis (CNF) is a fatal infection of the diffuse soft tissues and fascia with a high mortality rate. This study investigated risk factors in patients with concurrent DNI and CNF. A total of 556 patients with DNI were included in this study between August 2016 and December 2021. Among these patients, 31 had concurrent DNI and CNF. The relevant clinical variables were assessed. In univariate analysis, age (> 60 years, odds ratio (OR) = 2.491, p = 0.014), C-reactive protein (CRP, OR = 1.007, p < 0.001), blood sugar (OR = 1.007, p < 0.001), and diabetes mellitus (DM, OR = 4.017, p < 0.001) were significant risk factors for concurrent DNI and CNF. In multivariate analysis, CRP (OR = 1.006, p < 0.001) and blood sugar (OR = 1.006, p = 0.002) were independent risk factors in patients with concurrent DNI and CNF. There were significant differences in the length of hospital stay and therapeutic management (intubation, tracheostomy, incision and drainage) between DNI patients with and without CNF (all p < 0.05). While there were no differences in pathogens between the DNI alone and concurrent DNI and CNF groups (all p > 0.05), the rate of specific pathogen non-growth from blood cultures was 16.95% (89/525) in the DNI alone group, in contrast to 0% (0/31) in the concurrent DNI and CNF group (p = 0.008). Higher CRP and blood sugar levels were independent risk factors for the concurrence of DNI and CNF. With regard to prognosis, there were significant differences in the length of hospital stay and therapeutic management between the groups with and without CNF. While there were no significant differences in pathogens (all p > 0.05), no cases in the concurrent DNI and CNF group showed specific pathogen non-growth, in contrast to 89/525 patients in the group with DNI alone.

Towards an Improved Pathological Node Classification for Prognostic Stratification of Patients With Oral Cavity Squamous Cell Carcinoma: Results From a Nationwide Registry Study.

Background: To assess the prognostic significance of different nodal parameters [i.e., number of pathologically positive nodes, log odds of positive lymph nodes, lymph node ratio (LNR), and extra-nodal extension (ENE)] in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC), and to devise an optimized pN classification system for predicting survival in OCSCC. Methods: A total of 4287 Taiwanese patients with first primary OCSCC and nodal metastases were enrolled. Cox proportional hazards regression analysis with the spline method was applied to identify the optimal cut-off values for LNR, log odds of positive lymph nodes, and number of pathologically positive nodes. Results: On multivariable analysis, we identified a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE as independent prognosticators for 5-year disease-specific survival (DSS) and overall survival (OS) rates. We therefore devised a four-point prognostic scoring system according to the presence or absence of each variable. The 5-year DSS and OS rates of patients with scores of 0-3 were 70%/62%/50%/36% (p <0.0001) and 61%/52%/40%25%, respectively (p <0.0001). On analyzing the AJCC 2017 pN classification, patients with pN3a displayed better survival rates than those with pN2 disease. The 5-year DSS and OS rates of patients with pN1/pN2/pN3a/pN3b disease were 72%/60%/67%/43% (p <0.0001) and 63%/51%/67%/33%, respectively (p <0.0001). Conclusions: Three nodal parameters (i.e., a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE) assessed in combination provided a better prognostic stratification than the traditional AJCC pN classification.

Clinical outcomes of patients with pT4a and pT4b oral cavity squamous cell carcinoma who had undergone surgery: Results from a Taiwanese registry-based, nationwide cohort study.

OBJECTIVES: While the NCCN guidelines maintain that T4b oral cavity squamous cell carcinoma (OCSCC) should undergo either non-surgical treatments or clinical trials, promising outcomes of T4b OCSCC having surgical excision have been reported. We analyzed and compared the clinical outcomes of Taiwanese patients with pT4a and pT4b OCSCC who had undergone surgical treatment. METHODS: From 2011 to 2017, a total of 4031 and 355 patients with first primary pT4a and pT4b OCSCC were identified. A propensity score (PS)-matched analysis of patients (n = 351 each) for pT4a and pT4b tumors was also performed. RESULTS: The 5-year disease-specific and overall survival (DSS/OS) rates were more favorable in patients with pT4a than in those with pT4b OCSCC (64%/55%, p < 0.0001; 55%/43%, p < 0.0001, respectively). Compared with pT4a, those with pT4b tumors had a higher burden of the following risk factors: buccal/retromolar/hard palate subsite, male sex, depth ≥ 10 mm, and positive margins. Before PS matching, multivariable analyses revealed that pT4b tumors (versus pT4a) were an adverse prognosticator for both 5-year DSS and OS (hazard ratios: 1.32 and 1.39, respectively). However, in the PS-matched cohort, no significant differences in 5-year DSS and OS rates were observed between pT4a and pT4b OCSCC (57%/56%, p = 0.4024; 48%/44%, p = 0.1807, respectively) CONCLUSIONS: No significant outcome differences were evident between pT4b and pT4a OCSCC after PS matching. The most plausible hypothesis for the observed survival difference between T4a and T4b tumors is that it was driven by positive margins. We suggest that T4b OCSCC should undergo initial surgical excision if adequate resection is possible.