Clinical outcomes of Taiwanese patients with cT4 oral cavity squamous cell carcinoma: Toward the identification of the optimal initial treatment approach for cT4b patients

[[abstract]]BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) >/=45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes

Additional file 1: of Efficient undergraduate learning of liver transplant: building a framework for teaching subspecialties to medical students

Table S1. Feedback questionnaire form after class of liver transplantation. (DOCX 17 kb

Additional file 3: of Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma: a nationwide high-risk cohort study

Table S1. Anatomical Therapeutic Chemical codes and generic names of the chemoprevention drugs available in Taiwan during the study period. (DOCX 16 kb

Additional file 2: of Efficient undergraduate learning of liver transplant: building a framework for teaching subspecialties to medical students

Table S2. Descriptive details of qualitative feedback of students’ comments. (DOCX 28 kb

Additional file 5: of Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma: a nationwide high-risk cohort study

Table S3. Duration and amount of HBV medications and interferons in patients who received them in the study period, as grouped according to the use of ACEIs or ARBs within 6 months after the index date. (DOCX 17 kb

C1GALT1 modifies O-glycans on integrin β1.

<p>(<i>a</i>) Integrin β1 carried O-glycans in HCC cells. Lysates of HA22T cells (0.5 mg) were treated with neuraminidase (Neu) and/or PNGaseF and then pulled down (PD) by PNA agarose beads. The pulled down proteins were separated by 6% SDS-PAGE and analyzed by immunoblotting (IB) with anti-integrin β1 antibody. (<i>b</i>) C1GALT1 enhanced PNA binding to integrin β1 in HCC36 cells. (<i>c</i>) Knockdown of C1GALT1 suppressed PNA binding to integrin β1 in HA22T cells. Cell lysates (1.2 mg) were immunoprecipitated (IP) by anti-integrin β1 antibody, and were treated with (+) or without (−) neuraminidase. Proteins were separated by 8% SDS-PAGE, and then blotted with PNA or anti-integrin β1 antibody. Non-specific mouse IgG was used as control.</p

Morphological changes in peritoneal mesothelial cells (PMCs) after fibrin application.

<p>The morphology of the PMCs changed from a polygonal cobblestone-like appearance (A) to a spindle-shaped form (B) after fibrin overlay for 24 h. (C) Morphological changes were attenuated by treatment with 0.3 mg/ml of pentoxifylline.</p

Protocol for the animal study.

<p>Thirty male Wistar rats were randomly divided into 5 groups of 6 rats per group. Rats received intraperitoneal injections of PBS (Group 1), <i>S. aureus</i> (6×10⁸ colony forming units (CFU); Group 2), 15 ml fibrinogen (10 mg/ml; Group 3), or both <i>S. aureus</i> and fibrinogen (Group 4). Group 5 animals received intraperitoneal injections of <i>S. aureus</i> and fibrinogen and also received daily intravenous injections of PTX (100 mg/kg) for 7 days. Animals were then subjected to the peritoneal equilibration test (PET) and sacrificed. The details of procedures are shown in the figure. ▾: Catheter placement in the internal jugular vein. ○: PBS intraperitoneally. •: 1 ml <i>S. aureu</i>s (6×10⁸ CFU/ml) intraperitoneally. ◊: 15 ml PBS intraperitoneally. ⧫: 15 ml fibrinogen (10 mg/ml) intraperitoneally. ▪ ▪ ▪ ▪ ▪: 1.5 ml intravenous PBS daily for 7 days. ▪▪▪▪▪▪: 100 mg/kg intravenous pentoxifylline (20 mg/ml; approximately 1.5 ml) daily for 7 days. ×: Performed PET and then sacrificed.</p

Western blots of cell markers in fibrin-covered peritoneal mesothelial cells (PMCs).

<p>Equal amounts of protein (20 µg per lane) from untreated or fibrin-covered PMCs were resolved, transferred, and blotted for α-SMA, fibronectin, FSP-1, α_vβ₃ integrin, cytokeratin 18, E-cadherin, and GAPDH (A). The relative levels of α-SMA/GAPDH (B), α_vβ₃ integrin/GAPDH (C and D), fibronectin/GAPDH (E), FSP-1/GAPDH (F), cytokeratin 18/GAPDH (G), and E-cadherin/GAPDH (H) were measured by densitometry. C, PMCs without fibrin; F1, fibrin covered for 1 h; P1, fibrin covered and treated with pentoxifylline (PTX) 0.3 mg/ml for 1 h; F4, fibrin covered for 4 h, P4, fibrin covered and treated with PTX 0.3 mg/ml for 4 h; A4, fibrin covered and treated with α_vβ₃ integrin antibody for 4 h. *P<0.05 vs. C, # P<0.05 between groups, n = 3.</p

Histological analysis of the submesothelial compact zones.

<p>The compact zones were thicker in Group 4 than in Group 1 on both the parietal peritoneum (A) and liver surface (B). Rats treated with PTX (Group 5) had significantly less submesothelial matrix formation than Group 4 on both the parietal peritoneum and liver surface. *p<0.05 vs. Group 1 (Control), #p<0.05 vs. Group 4.</p