Salvage surgery for patients with residual/persistent diseases after improper or insufficient treatment of oral squamous cell carcinoma: can we rectify these mistakes?

BACKGROUND: Patterns of failure after treatment of oral and squamous cell carcinomas (OSCC) are diversified, with recurrences being one of the common causes. A special group of patients are sometimes encountered in the outpatient clinic for improper or insufficient initial treatment with reports of positive margins, implying residual/persistent diseases. The question of whether these patients can be surgically salvaged remain unanswered. METHODS: A retrospective study was performed between January 2013 and December 2017 for patients with residual or rapid recurrent (within 3 months) OSCCs, who received salvage surgeries in our institution. The patients with residual/persistent OSCCs were those with microscopic or macroscopic positive surgical margins, while those with rapid recurrent OSCCs were those with close or negative margins, but unabated painful symptoms right after treatment. Both clinicopathological and prognostic variables were analyzed. The focus was also directed towards lessons for possible initial mistakes, resulting in these residual/persistent diseases. RESULTS: Of 103 patients, 68 (66%) were men, with mean age of 56.3 years. The overall survival reached 60.2%. Regarding the primary OSCC status, most of our patients (n = 75, 72.8%) were diagnosed with ycT2-3 stages. Besides, most patients were found with macroscopic residual diseases (52.4%) before our salvage surgery. The sizes of the residual/persistent OSCCs were generally under 4 cm (87.3%) with minimally residual in 21 (20.4%). Among all the variables, primary T stage (p = 0.003), and residual lesion size (p < 0.001) were significantly associated with the prognosis in multivariate analysis. Though the causes for the initial surgical failure were multifactorial, most were stemmed from poor planning and unstandardized execution. CONCLUSIONS: Cases with residual/persistent OSCCs were mostly due to mistakes which could have been avoided under well-round treatment plans and careful surgical practice. Salvage surgery for cases with smaller residual/persistent OSCCs is still feasible with acceptable outcomes.

Regional metastasis to anatomies beyond traditional neck dissection boundaries: a multi-institutional analysis focused on unconventional metastases in oral cancer patients.

BACKGROUND: Regional metastasis sometimes occurs in anatomies that are not included in traditional neck dissections. The purpose of this study was to evaluate the treatment outcomes of squamous cell carcinoma of oral cavity (SCCOC) patients with unconventional metastatic lymph nodes (UMLNs) in sublingual, buccinator, and parotid anatomies. METHODS: This retrospective multi-institutional analysis of squamous cell carcinoma of oral cavity patients with unconventional metastatic lymph nodes was performed from January 2008 to December 2015. All the included patients received surgical treatment for unconventional metastatic lymph nodes. The end point of the study was to determine the factors influencing these patients' survival and the corresponding solutions to improve survival. Pathological grade, contralateral metastasis, extranodal extension, and other factors were collected and analyzed by logistic regression and the Cox model. RESULTS: A total of 89 patients were identified. Among these patients, 25 (28.1%) received primary treatment, 28 (31.5%) received staged (therapeutic) neck dissections, and 36 (40.4%) had recurrent or residual diseases. Altogether, 45 patients (51%) had buccinator node metastases, 31 (35%) had sublingual metastases, 12 (14%) had parotid metastases, and 1 had both buccinator and parotid metastases. Regarding regional metastases, 31 patients (34.8%) had isolated unconventional metastatic lymph nodes. Adjuvant therapies were administered to 72 (80.9%) patients, 25 (28.1%) of whom were treated with radio-chemotherapies. The overall survival rate was 38.2%. Multivariate analysis found that the subsites of unconventional metastatic lymph nodes (P = 0.029), extranodal extension in both unconventional metastatic lymph nodes (P = 0.025) and cervical lymph nodes (P = 0.015), sites of primary or recurrent squamous cell carcinoma of oral cavity (P = 0.035), and types of neck dissections (P = 0.025) were significantly associated with overall survival. CONCLUSIONS: Unconventional metastatic lymph nodes are uncommon, yet awareness of potential unconventional metastatic lymph nodes should be heightened. Early surgical interventions are warranted in patients with sublingual or buccinator metastases, while caution should be given to those with parotid metastases. Aggressive en bloc (in-continuity) resections may be mandatory in advanced oral cancer cases for close anatomic locations with possible buccal or sublingual metastases.

Profunda Artery Perforator Flaps From the Posteromedial Region of the Thigh for Head and Neck Reconstruction.

OBJECTIVE: Profunda femoris artery perforator flaps (PAPFs) have not been widely used in head and neck reconstructions. The feasibility and outcomes of PAPFs for various head and neck reconstructions need to be investigated. STUDY DESIGN: Retrospective analysis. SETTING: A single-institution review. METHODS: PAPFs were utilized in head and neck reconstructions from 2019 to 2021. Local anatomy, surgical technique, and complications were discussed. Chimeric PAPF applications with muscle components were described for coverage of extensive multiunit defects. Additionally, aesthetic and functional outcomes were compared with anterolateral thigh perforator flaps. RESULTS: A total of 33 cases were included. The average age was 54.2 years (range, 30-74). The most common underlying pathology was oral squamous cell carcinoma (n = 26, 78.8%), while the mean ± SD body mass index was 25.4 ± 2.8 kg/m2 . Middle perforators (n = 14, 42.4%) were the most commonly utilized ones. The perforator-based chimeric/composite applications were used in 9 (27.3%), with the muscular components consisting of gracilis (n = 3, 9.1%), adductor magnus (n = 5, 15.2%), or semimembranosus muscles (n = 1, 3.0%). Venous thromboses of the PAPFs were found in 2 (6.1%), though salvaged. The occurrence of postoperative 90-day morbidity (complication) was related to mandibulectomy/maxillectomy (P = .020). Postoperative validated questionnaires showed a trend of intermediate to high scores, indicating noninferior outcomes in several categories, when compared with the anterolateral thigh perforator flap counterparts. CONCLUSION: PAPFs are a good reconstructive alternative for intermediate to large head and neck reconstructions. Besides, PAPFs can provide sufficient tissue volume and versatility of potentially incorporating adjacent muscle components.

Anteromedial thigh septocutaneous perforator flap as a first choice for head and neck reconstruction: A clinical algorithm based on perforator-pedicle relationship.

BACKGROUND: Anterolateral thigh perforator flaps (ALTPFs) have long been considered workhorse flaps for head and neck reconstructions. However, in some instances, anteromedial thigh septocutaneous perforator flaps (AMTPFs) are easier to harvest than ALTPFs. This study aimed to determine when and how the AMTPF should be considered the first choice as a reconstructive tool. METHODS: A retrospective cohort study was performed in the Department of Oral and Maxillofacial Surgery-Head & Neck Oncology, Shanghai Ninth People Hospital, from January 2014 to December 2018. Both the perforator-pedicle relationships and postoperative functional outcomes were compared. RESULTS: A total of 168 patients were included in this study, among whom 49 underwent AMTPF reconstructions. The AMTPF perforators in this study were mostly septocutaneous (n = 38, 77.5%). Notably, the AMTPF perforators mainly originated from the medial branch of the descending branches of the lateral circumflex femoral arteries (n = 44, 89.8%), while for the other 5 patients, the perforators were found to originate from the superficial femoral arteries. Additionally, the average pedicle length of the AMTPFs was 8.7 cm (range: 6.0 to 13.0 cm), which was comparable to that of the ALTPFs (8.9 cm) (p = 0.442). The postoperative complication rate and functional outcomes were comparable between the two groups. The algorithm and harvesting approaches are presented. CONCLUSIONS: The role of AMTPF should not be downplayed. After careful preoperative evaluation, we believe that AMTPF should not be considered a second choice in patients with sizable septocutaneous perforators.

A comparative study on using superior thyroid artery perforator flaps versus traditional sternocleidomastoid myocutaneous flaps for reconstructions after oral cancer ablation: "New tricks for old dogs"?

OBJECTIVES: To introduce new superior thyroid artery perforator flaps (STAPF), and to compare the clinical outcomes with sternocleidomastoid myocutaneous flaps (SCMMF) for their intraoral applications. MATERIALS AND METHODS: Between January 2013 and December 2020, forty-three oral cancer patients who received post-oncologic reconstructions with one of these two regional flaps were retrospectively collected. Their techniques and outcomes were compared. All the STAPFs were preprepared with radiologic evaluations. RESULTS: Despite the common arterial origins, the compositions and harvesting procedures of STAPF and SCMMF were different. Though SCMMFs (n = 23) were designed in rotational styles, most STAPFs (n = 20) were septocutaneous perforator flaps, with 2 chimeric ones. In addition, the sizes of STAPFs were generally larger than those of SCMMFs (p = 0.006). Success rate for STAPFs was much higher, with only three partial cutaneous necroses. Radiotherapy delay was more frequently found in those reconstructed with SCMMFs (P = 0.046), mostly due to fistula formations. Besides, incomplete level IIB dissections were also reported in 9 (20.9%) patients in SCMMF group. In our study, the overall survival was affected by both flap conditions (p = 0.014, 1.333-12.881) and postoperative surgical complications (except fistula) (P = 0.005, 2.240-84.134). Functionally speaking, post-reconstructive speech and neck mobility (p < 0.001) were better in the STAPF group. CONCLUSIONS: With accumulated experiences on the use of locoregional flaps in the neck, STAPF, when well-prepared, can provide superior reconstructive outcomes for various intraoral defects. As a comparison with SCMMF in the same middle region, STAPF is a viable option with higher success rates and oncological safety for oral cancer patients.

Radiation-Induced Soft Tissue Injuries in Patients With Advanced Mandibular Osteoradionecrosis: A Preliminary Evaluation and Management of Various Soft Tissue Problems Around Radiation-Induced Osteonecrosis Lesions.

OBJECTIVES: Radiation-induced soft-tissue injuries (STIs) in mandibular osteoradionecrosis (ORN) are not well studied regarding their correlations with nearby bone lesions. The aim of this study is to investigate the severity of radiation-induced STIs in advanced mandibular ORN and its relationship with hard-tissue damage and postoperative outcomes. METHODS: A retrospective study was performed in our institution from January 2017 to December 2019. Aside from demographic factors, the associations between the triad ORN variables (irradiation doses, ORN stages, ORN sizes) and radiation-related STI factors, vascular characteristics, and postoperative functional recovery were assessed. In addition, the severity of STI was also compared with treatment outcomes. Such correlations were established via both univariate and multivariable analyses. RESULTS: A total number of 47 patients were included. The median follow-up reached 27 months. Nasopharyngeal cancer was the histology type among most patients (n = 21, 44.7%). The median irradiation doses reached 62 Gy (range, 40-110 Gy). For STI, the symptom scoring equaled an average of 5.4 (range from 1 to 12), indicative of the severity of STI problems. During preoperative MRI examinations, signs of hypertrophy or edema (n = 41, 87.2%) were frequently discerned. Most patients (n = 23, 48.9%) also had extensive muscular fibrosis and infection, which required further debridement and scar release. Surprisingly, most STI factors, except cervical fibrosis (p = 0.02), were not in parallel with the ORN levels. Even the intraoperative soft-tissue defect changes could not be extrapolated by the extent of ORN damage (p = 0.096). Regarding the outcomes, a low recurrence rate (n = 3, 6.9%) was reported. In terms of soft tissue-related factors, we found a strong correlation (p = 0.004) between symptom scores and recurrence. In addition, when taking trismus into consideration, both improvements in mouth-opening distance (p < 0.001) and facial contour changes (p = 0.004) were adversely affected. Correlations were also observed between the intraoperative soft-tissue defect changes and complications (p = 0.024), indicative of the importance of STI evaluation and management. CONCLUSIONS: The coexistence of hard- and soft-tissue damage in radiation-induced advanced mandibular ORN patients reminds surgeons of the significance in assessing both aspects. It is necessary to take the same active measures to evaluate and repair both severe STIs and ORN bone lesions.

Extranodal Extension in Bilateral Cervical Metastases: A predictor of Undesirable Survival Outcomes despite Aggressive Salvage Treatment in Oral Cancer Patients.

Objectives: Despite the inclusion of extranodal extension (ENE) in the recent staging system, the presence of ENE alone is not sufficient to depict all clinical situations, as ENE is frequently found in multiple nodes. Thus, the purpose of this study was to evaluate the surgery-based treatment outcomes and clinicopathological features of oral cavity squamous cell carcinoma (OCSCC) patients with ENE found in bilateral multiple cervical metastases. Materials and methods: A retrospective single-institutional study of OCSCC patients with bilateral ENE nodes was performed from January 2011 to December 2018. OCSCC patients of different admission statuses (with primary lesions (PL), recurrent lesions (RL) and isolated neck metastases (INM)) were included for subgroup comparisons. All patients received surgical treatment with/without adjuvant therapies and had complete follow-up data. Disease-free survival (DFS) was regarded as the main outcome. Time-to-relapse data were also collected for comparison. Results: A total of 128 patients were included, of whom 97 (75.8%) were male. The mean follow-up period reached 15 months. Among the patients, 85 (66.4%) were treated for PLs, followed by 26 (20.3%) treated for RLs after failed prior therapy and 17 (13.3%) treated for INMs (concurrent or sequential). The DFS rate was merely 35.2%. Treatment-related factors such as surgical margin (p=0.003), postoperative adjuvant therapy (p=0.014) and perioperative complications (p=0.036) were significantly associated with patient outcomes. In addition, oral lesion-related variables such as oral subsites (p=0.037), T classification (p=0.026) and skull base involvement (p=0.040) were indicators of a worse prognosis. For bilateral ENE features, ENE subclassification (p=0.036), maximum size of ENE nodes (p=0.039) and arterial nodal encasement (p=0.025) tended to predict the surgery-based treatment outcomes of these patients. Conclusions: Bilateral cervical metastases with ENE features, though uncommon, are a serious regional burden, and these patients have lower-than-expected treatment outcomes, especially those with RLs or INMs. A fairly large number of OCSCC patients with advanced oral lesions gain little benefit from intensified salvage surgical treatment. Such treatment should instead be offered to select patients with smaller bilateral ENE nodes (<3 cm) and those with lower ENE subclassifications and no arterial nodal encasement.

Proximal-type epithelioid sarcoma in the maxillary sinus: an unusual presentation.

Epithelioid sarcoma (ES) is a rare histological type of soft tissue sarcoma presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Recently, a more aggressive, so called 'proximal-type' ES has been described. The literature is limited on the clinical features and management of ES originating in the head and neck area. We here report a case of 16-year-old female who initially presented with progressive swelling and pain in the left cheek. On physical and radiographic examination, a malignant neoplasm was found in the left maxillary sinus with bony invasion. The definite diagnosis of proximal-type ES was based on the pathological and immunohistochemical characteristics. A subtotal maxillectomy with wide margins was performed on this patient. The patient survived uneventfully for three years. This is the first report of a proximal-type ES found in the maxillary sinus.

Surface modification of titanium with collagen/hyaluronic acid and bone morphogenetic protein 2/7 heterodimer promotes osteoblastic differentiation.

The aim of this study was to evaluate the effects of a collagen/hyaluronic acid coating without or with incorporated heterodimeric bone morphogenetic protein 2/7 (BMP2/7) on in-vitro osteoblastic differentiation on titanium discs. The multilayer collagen/hyaluronic acid coatings without or without incorporated BMP2/7 were deposited on titanium discs via a layer-by-layer technique. The effects of the coatings were evaluated by assessing the alkaline phosphatase (ALP) activity (an early osteoblastic differentiation marker) and the osteocalcin expression (a late osteoblastic differentiation marker). The expression levels of the osteoblastic genes, such as alkaline phosphatase 2 (AKP2) and osteocalcin (OC) were detected using real-time RT-PCR. ALP activity and OC expression were significantly increased when cells were cultured with collagen/hyaluronic acid+BMP2/7 heterodimer (p<0.05). The same result was found in cells with the expression of a BMP2/7 fusion gene, OC and AKP2. These results indicated that collagen/hyaluronic acid+BMP2/7 heterodimer-coated discs might have the potential to greatly enhance osseointegration than a either BMP2 or BMP7 solution or a mixture of BMP2 and BMP7 BMP2/7.