Combination therapy with BRAF and MEK inhibitors for anaplastic thyroid cancer: A report of two cases.

Anaplastic thyroid cancer (ATC) is an aggressive malignancy with a poor prognosis and limited treatment options. Herein, we report two cases of unresectable ATC treated with a combination of BRAF and MEK inhibitors. The patients were initially treated with other therapies but were switched to BRAF and MEK inhibitors after testing positive for BRAF mutations. This resulted in a partial response, tumor shrinkage, and conversion to resectability in one case. The patient experienced manageable adverse events. BRAF mutations are common in thyroid cancers, and studies have demonstrated the efficacy of combining BRAF and MEK inhibitors for treating advanced or recurrent differentiated thyroid cancer or ATC with BRAF mutations. These cases emphasize the importance of BRAF gene testing at the initial diagnosis and the potential of BRAF and MEK inhibitors as treatment options for unresectable ATC with BRAF mutations. The oral administration and manageable adverse event profiles of these medications make them suitable for outpatient treatment. In conclusion, BRAF gene testing should be performed at the initial diagnosis, and the use of BRAF and MEK inhibitors should be considered in patients with ATC.

Combined Positive Score and Cisplatin Sensitivity Are Prognostic Factors for Response to Nivolumab Therapy for Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck.

Background: Recurrent or metastatic squamous cell carcinoma of the head and neck (R/MHNSCC) is a challenging malignancy with a poor prognosis and limited treatment options. Nivolumab, an immune checkpoint inhibitor (ICI) targeting the programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) pathway, has emerged as a promising therapy for these patients. However, identifying biomarkers predictive of response to nivolumab remains critical for optimizing treatment strategies. Previous studies have suggested that PD-L1 expression, as determined by the Combined Positive Score (CPS) and other clinical factors, may influence treatment outcome. This study aims to retrospectively examine whether CPS can be a biomarker by staining PD-L1 with 22 C3 antibody in R/MHNSCC patients treated with nivolumab. Methods: This retrospective study reviewed the medical records of R/MHNSCC patients treated with ICIs at Tokai University Hospital from April 2017 to December 2022. We examined the relationship between response rate to ICI therapy, PD-L1 staining, biomarkers, and survival. Statistical analyses included t-test, chi-square test, and Cox regression. Results: This study included 92 nivolumab-treated patients. Combined Positive Score was evaluable in 53 of these patients. Patients with a CPS of 15 or higher had better progression-free survival (PFS) (P = .0171), with a median PFS) of 13 months. In the Various Definitions analysis, cisplatin-sensitive patients also had good PFS (P = .0295). The cisplatin-sensitive patient population with a CPS of 15 or higher had the best PFS, with a median of 14 months (P = .006). There was no significant difference in overall survival (OS) by CPS value. Immune-related adverse events did not affect OS or PFS. Conclusions: CPS ⩾ 15 and cisplatin sensitivity are promising prognostic markers for nivolumab therapy in R/MHNSCC. Considering these biomarkers in patient selection could maximize the therapeutic benefits of nivolumab. This finding may help to optimize ICI therapy strategies.

Safety and outcome of three-dimensional transoral videolaryngoscopic surgery.

BACKGROUND: Transoral videolaryngoscopic surgery (TOVS) is widely used in Japan, and conventional two-dimensional (2D) endoscopic methods have been established. Three-dimensional (3D) endoscopic surgery offers superior distance perception because it provides stereoscopic views. Recently, we have developed 3D endoscopy for TOVS (3D TOVS). METHODS: This study included 46 patients with pharyngeal cancer who underwent 3D TOVS. The perioperative complications and survival curves were retrospectively analyzed. RESULTS: One patient with oropharyngeal cancer who underwent neck dissection and transoral resection simultaneously experienced postoperative hemorrhage of the neck. Another patient with oropharyngeal cancer underwent hemostasis for postoperative pharyngeal hemorrhage. There was one case of aspiration pneumonia. One patient developed cervical lymph node recurrence; however, there was no local recurrence or primary mortality. The 2-year overall survival, disease-specific survival, local control rates, locoregional control rate, and invasive disease-free survival were 90.9%, 100%, 100%, 97.4%, and 79.9%, respectively. CONCLUSIONS: Three-dimensional endoscopy can be safely applied to TOVS.

Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan.

Background/purpose: The incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ. Materials and methods: After excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose. Results: Low doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy. Conclusion: To the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses.

Immunoglobulin A vasculitis without purpura in an elderly female patient: a case report.

Immunoglobulin A (IgA) vasculitis mainly affects the joints, skin, kidneys, and gastrointestinal tract; however, purpura is an essential diagnostic criterion. Here, we report an unusual case of IgA vasculitis without purpura in an elderly woman. A 76-year-old woman was admitted to our hospital complaining of diarrhea and abdominal pain. No skin rash, purpura, jaundice, or peripheral lymphadenopathy was observed. Endoscopy of the small intestine revealed severe mucosal sloughing in the duodenum, and a biopsy specimen showed severe erosive duodenitis. A decrease in coagulation factor XIII (FXIII) activity was also observed during laboratory blood tests. IgA immunostaining revealed granular IgA deposition on the walls of the interstitial small blood vessels. Although the patient showed no purpura or renal involvement, a diagnosis of IgA vasculitis was made based on the histopathology findings from biopsies. The administration of purified FXIII concentrate improved her symptoms immediately and facilitated regeneration of the duodenal villi. When gastroenterologists encounter severe erosive duodenitis or inflammation of the small intestine, IgA vasculitis should be listed as part of the differential diagnosis even without purpura and/or renal involvement. For a definitive diagnosis, measurement of FXIII and IgA immunostaining using duodenal biopsy specimens should be performed actively.

Longitudinal study of risk for facial nerve injury in mandibular condyle fracture surgery: marginal mandibular branch-traversing classification of percutaneous approaches.

OBJECTIVE: This study aimed to longitudinally assess the risk of facial nerve injury (FNI) in the surgical repair of mandibular condylar neck and subcondylar fractures (CN/SCFs) and to explore its predictors. MATERIALS AND METHODS: In a retrospective cohort study, the outcome was defined as FNI at 1 week and 1, 3, and 6 months postoperatively. Potential predictors included age, sex, etiology, fracture site and pattern (dislocation/non-dislocation), concomitant facial fractures, interval to surgery, surgeons' experience, plate types, and the marginal mandibular branch-traversing approach (deep/superficial group). We employed generalized estimating equations (GEEs) for repeated measurements throughout the 6-month follow-up period. RESULTS: Among 102 patients with 114 fractures, 27 patients (26.5%) developed FNI within 1 week. Prolonged FNI (≥ 1 month) occurred in 19 (19.2%) of 99 patients. Multivariate GEE analyses revealed that deep surgical approaches (i.e., traditional submandibular and retroparotid approaches; odds ratio [OR], 18.90; p = 0.011), fractures with dislocation (OR, 3.60; p = 0.025), and female gender (OR, 2.71; p = 0.040) were independently associated with the overall FNI risk. Additionally, the deep approaches (OR, 15.91; p = 0.014) and female gender (OR, 3.41; p = 0.035) were correlated with a prolonged FNI risk. Sensitivity analyses for the outcomes identified the same predictors. CONCLUSION: The predictors longitudinally associated with FNI in CN/SCF surgeries included a deep MMB-traversing approach, dislocated fracture, and female gender. CLINICAL RELEVANCE: The superficial surgical approaches (i.e., transparotid, transmasseteric anteroparotid, and high perimandibular approaches) should be adopted for CN/SCF treatment to minimize postoperative morbidity, especially for female patients with dislocated condyles.

[Clinicopathological Evaluation of Preoperative Chemotherapy Containing S-1 as a Treatment for Patients with Oral Squamous Cell Carcinoma during Waiting Time for Surgery].

BACKGROUND: In our department, patients with oral squamous cell carcinoma(OSCC)received preoperative chemotherapy containing S-1 to prevent the growth and dissemination of tumors during the waiting time before definitive surgery. We retrospectively evaluated the usefulness of this treatment. PATIENTS AND METHODS: One hundred and five patients comprising stages T1(26), T2(64), T3(7), and T4(8 cases)were enrolled in this study from July 2001 to June 2013. In principle, patients were administered S-1(80mg/m / 2/day, days 1-14)and followed by a drug holiday(days 15-21), continuing until 1 week before surgery. RESULTS: The median administration period was 14 days(256 days). Ninety-eight patients underwent definitive surgery, but 7 patients who revealed clinical CR underwent only biopsy and showed histological CR. The histological responses of all patients were CR(24), PR(22), and NC(59), and the response rate was 43.8%. Almost all adverse effects were Grade 1 or 2, except 1 case of neutropenia(Grade 3)and 1 case of urticaria(Grade 3). The 5-year overall survival rates were 86.7% in all cases, 95.3% in CR/PR cases, and 79.7% in NC cases. CONCLUSION: Preoperative S-1 administration during the waiting time was a safe and very effective method and was considered beneficial for patients with OSCC.

Isolation, structural identification and biological characterization of two conopeptides from the Conus pennaceus venom.

A novel anti-mollusk conopeptide pn4c was isolated from the Conus pennaceus venom by repeated HPLC fractionation based on the activity against freshwater snails. The primary structure of pn4c was determined by the mass spectrometric de novo sequencing analysis. In addition, pn3a was isolated from the same fraction containing pn4c, as a peptide with unknown functions.

C-arm-guided reduction of zygomatic fractures revisited.

BACKGROUND: Anatomic reduction of the zygomatic arch, a key surgical landmark for midfacial width and projection, is essential for the treatment of combined fractures of the zygomaticomaxillary complex and zygomatic arch. Reduction control in surgery for this common facial fracture would be facilitated by intraoperative real-time assessment using widely available and reliable equipment. Although C-arm fluoroscopy is routinely used in the repair of orthopedic fractures, its use in the maxillofacial region, particularly for combined zygomatic fractures, has been scarcely reported. METHODS: We prospectively evaluated C-arm-guided reduction in 38 patients of combined zygomatic fracture without concurrent craniofacial fractures. Patients were classified according to the presence or absence of bone contact in the displaced zygomatic arch, namely as conserved (C) and loss (L) types, respectively. Reduction status was determined by the degree of recovery of the malar prominence and arch shape. RESULTS: In all cases, C-arm imaging clearly displayed the displaced zygomatic arch and body in a single image. Cumulative fluoroscopic time was a few minutes in all cases. Total reduction status was excellent in 21 patients and good in 17. No case was classified as fair or poor. Repair was significantly more favorable in type C than in type L cases (p = 0.0016). CONCLUSIONS: In combined zygomatic fractures, the C-arm technique provides easy, flexible, and time-efficient adjustment. Its comprehensive imaging for zygomatic arch shape and body contour markedly facilitates the control of fracture reduction and protects against unexpected, unsatisfactory outcomes.

Calcifying epithelial odontogenic tumor of the maxilla with ulcerative stomatitis: a case report.

Calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic tumor, known as Pindborg tumor. Although ulcer formation was reported in one previously involving the peripheral maxilla, such change of the overlying mucosa has been reported in intraosseous CEOT. We report maxillary CEOT in a patient who complained of spontaneous pain due to extensive ulcer formation of the oral mucosa.