MicroRNA-196 (miR-196), which is highly up-regulated in oral cancer cells, has been reported to be aberrantly expressed in several cancers; however, the significance of miR-196 in oral cancer has not ...yet been addressed.
Cellular functions in response to miR-196 modulation were examined, including cell growth, migration, invasion and radio/chemosensitivity. Algorithm-based studies were used to identify the regulatory target of miR-196. The miR-196 target gene and downstream molecular mechanisms were confirmed by RT-qPCR, western blot, luciferase reporter and confocal microscopy analyses. miR-196 expression was determined in paired cancer and adjacent normal tissues from oral cancer patients.
Both miR-196a and miR-196b were highly over-expressed in the cancer tissue and correlated with lymph node metastasis (P = 0.001 and P = 0.006, respectively). Functionally, miR-196 actively promoted cell migration and invasion without affecting cell growth. Mechanistically, miR-196 performed it's their function by inhibiting NME4 expression and further activating p-JNK, suppressing TIMP1, and augmenting MMP1/9.
miR-196 contributes to oral cancer by promoting cell migration and invasion. Clinically, miR-196a/b was significantly over-expressed in the cancer tissues and correlated with lymph node metastasis. Thus, our findings provide new knowledge of the underlying mechanism of cancer metastasis. miR-196 may serve as a promising marker for better oral cancer management.
Functional and aesthetic mandibular reconstruction can be achieved in a single operation by means of a double-barreled fibula osteoseptocutaneous free flap with dental implants loaded simultaneously ...into the upper barrel. The aim of this study was to evaluate the quality and result of such reconstruction.
From 2005 to 2007, 10 patients underwent segmental mandibular defect reconstructions with double-barreled fibula osteoseptocutaneous flaps and simultaneous dental implantations. Implant marginal bone loss, clinical mucosal changes, marginal plaque indices, bleeding on probing, and pocket probe depth were evaluated at an average of 22.2 months after implant functional loading.
Ten patients with a total of 25 osseointegrated implants were evaluated. The mean implant marginal bone loss was 0.18 ± 0.18 mm (range, 0 to 0.6 mm) at the mesial surfaces and 0.25 ± 0.2 mm (range, 0 to 0.6 mm) at the distal surfaces. Probing pocket depth was shallower for implants protected by palatal mucosal grafts (2.56 ± 0.54 mm) than by skin flaps (3.50 ± 0.90 mm) (p < 0.05). There was a significant difference in marginal bone loss between palatal mucosal grafts (0.11 ± 0.09 mm) and skin flaps (0.29 ± 0.23 mm) (p < 0.05). Bleeding on probing was more prominent when pocket depth exceeded 5 mm and occurred more frequently in skin flap-protected than in keratinized mucosa graft-protected implants.
The one-stage combined surgical method is safe and reliable. Both oral function and mandible contour were good. Firmly attached gingiva-like palatal mucosal grafts prevent periimplant soft-tissue inflammation and facilitate maintenance of oral hygiene.
Therapeutic, V.
•The prognosis of pN3b oral squamous cell carcinoma (OCSCC) remains heterogeneous.•SUV-nodal-max, LNR, and level IV/V metastases were independent prognosticators.•A scoring system based on these ...three factors improves prognostic stratification.Our results are expected to inform treatment and follow-up of this patient group.
The prognosis of pN3b oral cavity squamous cell carcinoma (OCSCC) remains heterogeneous. We sought to improve the prognostic stratification of patients with pN3b OCSCC through a combined analysis of FDG-PET parameters and clinicopathological risk factors (RFs).
From 2001 to 2019, complete data on maximum standardized uptake values derived from FDG-PET of neck metastatic nodes (SUV-nodal-max) and clinicopathological RFs were available for 257 patients with pN3b disease.
Using the 5-year disease-free survival (DFS) as the outcome of interest, the optimal cutoff points for SUV-nodal-max and lymph node ratio (LNR) were 15.9 and 0.17, respectively. The 5-year DFS rates/(number of cases) for patients with pN3b disease were as follows: SUV-nodal-max < 15.9 versus ≥ 15.9, 49%(226)/21%(31), p = 0.000003; LNR < 0.17 versus ≥ 0.17, 49%(230)/17%(27), p = 0.000117; absence versus presence of neck level IV/V metastases, 49%(230)/15%(27), p = 0.000004. Multivariable analyses revealed that SUV-nodal-max ≥ 15.9, LNR ≥ 0.17, and level IV/V metastases were independent prognosticators for 5-year distant metastases (DM), DFS, disease-specific survival (DSS), and overall survival (OS) rates. Based on these variables, we devised a scoring system that identified three distinct prognostic subgroups at low (score 0, n = 190), intermediate (score 1, n = 51), and high (scores 2–3, n = 16) risk. The 5-year rates of patients with pN3b disease deemed to be at low/intermediate/high risk were as follows: DM, 31%/52%/89%; DFS, 54%/26%/0%; DSS, 59%/36%/8%; OS, 42%/31%/6%, respectively; all p < 0.001.
A scoring system based on SUV-nodal-max, LNR, and level IV/V metastases improves the prognostic stratification of OCSCC patients with pN3b disease.
Aesthetic and functional mandibular reconstruction can be achieved in 1-stage. It involves simultaneous dental implant placement in a free vascularized fibula transfer with a low-profile ...reconstruction plate. The aim of this study was to assess the postoperative aesthetic profile and oral functional result.
Ten patients with a mean age of 31.6 years and an average follow-up time of 83.7 months underwent 1-staged mandibular reconstructions after segmental mandibulectomies. Simultaneous dental implantation was placed at the fibular segment according to the maxillary dentition. The fibula-implant construct was stabilized superiorly with miniplates and an additional low-profile reconstruction plate recreated the inferior mandibular contour. Any remaining vascularized soft tissue was used for augmentation. Palatal mucosa grafts were placed around the dental implant healing abutment at the uncovering stage surface. Aesthetic profile and oral function were evaluated postoperatively for 5 years.
All microsurgical transplantations were successful. None of the patients required subsequent revisions. All patients completed prosthodontic rehabilitation. All patients had palatal mucosal grafts placed around the dental implants. The mean probing pocket depths were shallower around the implants, 3.09 ± 0.82 mm at mesial, 3.33 ± 1.05 mm at distal, 3.02 ± 1.13 mm at buccal, and 3.23 ± 1.17 mm at lingual surfaces. Radiographs revealed no statistical differences in mean of the mesial 0.27 ± 0.26 mm and distal 0.33 ± 0.25 mm of peri-implant bone loss. The prosthetic load mean follow-up time was 71.7 months with a satisfactory implant-supported prosthesis. Two slender female patients palpated the reconstruction plate beneath the soft tissue envelope.
This approach is selectively fashioned for patients with benign disease when the overlying soft tissue drape is adequate. The technique described results in improved appearance and function through definition of the lower third of the face and simultaneous dental implant replacement.
•NCCN guidelines maintain that T4b OCSCC should be treated with non-surgical approach.•The 5-year survival rates were more favorable in patients with pT4a than pT4b OCSCC.•Compared with pT4a, pT4b ...tumors had a higher burden of pathological risk factors.•After PS matching, no outcome difference between pT4b and pT4a OCSCC was observed.•T4b OCSCC should undergo initial surgical excision if adequate resection is possible.
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.
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.
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)
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.
Thirty patients with trismus resulting from betel nut chewing-induced oral submucous fibrosis were treated with either fibrotic tissue release only (group I) or fibrotic tissue release in combination ...with masticatory muscle myotomy and coronoidotomy (group II). The latter procedures were only performed in patients whose intraoperative interincisal distance remained less than 35 mm immediately after submucous fibrous tissue release. There were eight and 22 patients in groups I and II, respectively. In group I patients, the average intraoperative interincisal distance improved from 19.5 mm to 42 mm. In group II patients, the average intraoperative interincisal distance improved from 13.5 mm to 27 mm after fibrotic tissue release and further improved to 40 mm after masticatory muscle myotomy and coronoidotomy. At an average follow-up of 22.1 months (range, 7 to 70 months), the group I and II patients had an average interincisal distance of 41.5 mm (range, 35 to 50 mm) and 32.9 mm (range, 20 to 42 mm), respectively. These results demonstrate the efficacy of submucous fibrotic tissue release in treating trismus resulting from betel nut chewing-induced submucous fibrosis and confirm the role of additional masticatory muscle and coronoidotomy in treating its severe forms.
•Stage IVB OCSCC is defined as either pT4b or pN3 disease.•The 5-year outcomes of pT4a and pT4b tumors are similar.•The prognosis of pT3-4N3b is less favorable than that of pT1-2N3b disease.•pT4bN0-2 ...and pT1-2N3b should be downstaged from pStage IVB to IVA.•The newly proposed pStage IV improves prognostic stratification.
pStage IVB oral cavity squamous cell carcinoma (OCSCC) is defined as either pT4b or pN3 disease. We sought to devise an improved prognostic stratification of this patient group.
Between December 2003 and January 2018, we retrospectively reviewed the clinical records of 1331 consecutive patients with OCSCC who received tumor excision and neck dissection. The number of patients with pT4a/pT4b, pT1N3b/pT2N3b/pT3N3b/pT4N3b, and pStage IVA/IVB was 370/83, 3/49/42/142, and 332/295, respectively.
The 5-year rates of disease-free survival (DFS) and disease-specific survival (DSS) for patients with pT4a/pT4b disease were 64%/63% (p = 0.973) and 72%/69% (p = 0.672), respectively. The 5-year DFS and DSS rates for patients with pT1N3b/pT2N3b/pT3N3b/pT4N3b disease were 67%/65%/40%/42% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002) and 100%/68%/45%/49% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002), respectively. We devised a new definition for pStage IV by considering patients with pT4bN0-2 and pT1-2N3b diseases as pStage-IVA. The number of patients with pStage IVA/IVB (pT3-4N3b) was 443/184. The 5-year rates of AJCC pStage IVA/IVB and the newly proposed pStage IVA/IVB (pT3-4N3b) were as follows: DFS, 74%/52% and 72%/42%; DSS, 83%/58% and 81%/47%; respectively, all p value < 0.001.
The clinical outcomes of pT4b and pT4a OCSCC are similar. However, patients with pT3-4N3b disease have a less favorable 5-year prognosis compared with cases with pT1-2N3b. In light of the unfavorable outcomes, pT3-4N3b disease should continue to be classified as pStage IVB. Conversely, pT4bN0-2 and pT1-2N3b diseases portend a less adverse prognosis and should therefore be downstaged to pStage IVA.
•Compared to lower gum SCC, upper gum SCC had less favorable 5-year DSS and OS rates.•Upper gum SCC had higher frequencies of aged ≥ 65 years and margin status ≤ 4 mm.•Wide resection margins are ...recommended to improve outcomes of upper gum SCC.
This large-scale cohort study was designed to compare the clinical outcomes of Taiwanese patients with squamous cell carcinoma (SCC) of the upper versus lower gum.
Between 2004 and 2017, we identified 4244 patients with first primary SCC of the gum (694 upper gum; 3550 lower gum) who were treated with surgery either with or without adjuvant therapy. Of them, 1990 patients (329 upper gum; 1661 lower gum) enrolled from 2011 to 2017 had a higher number of histopathological variables and entered subgroup analyses. Five-year disease-specific survival (DSS) and overall survival (OS) rates served as outcome measures.
The 5-year DSS and OS rates of patients with upper gum SCC were lower than those of cases with lower gum SCC (65%/74%, p < 0.0001; and 55%/65%, respectively, p < 0.0001). Compared with lower gum SCC, upper gum SCC had a higher prevalence of the following variables: female sex, age ≥ 65 years, pNx (without neck dissection), no-betel chewing (2011–2017), no-smoking (2011–2017), and margin status ≤ 4 mm (positive and close margins, 2011–2017). On multivariable analysis, gum subsite (upper versus lower), age (≥65 versus < 65 years), pT (T3 − 4 versus T1 − 2), pN (N1 − 3 versus N0/Nx), depth (≥10 mm versus < 10 mm, 2011–2017), ENE (present versus absent, 2011–2017), and margins (≤4 mm versus > 4 mm 2011–2017, only DSS) were identified as independent adverse prognostic factors for 5-year DSS and OS.
Compared to lower gum SCC, upper gum SCC had less favorable 5-year outcomes. Wide resection margins are recommended to improve prognosis of upper gum SCC.
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.
Patients with cT1−2N0M0 oral cavity cancer who underwent initial surgery demonstrated significantly improved disease‐specific and overall survival rates compared to those who received primary definitive radiotherapy (≥6600 cGy), even after propensity score matching. Subgroup analyses further revealed that survival outcomes remained significantly better for the positive margin subgroup compared to the radiotherapy group, irrespective of whether they received concurrent chemotherapy.
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