FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?

Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors. We already investigated the role of the immune modulator FK506-binding protein 51 (FKBP51), a FK506-binding immunophilin, in cutaneous melanoma biology, and its expression in several human solid tumors. In the present study, we aimed to assess the value of FKBP51 expression in OSCC tumor cells as a marker of outcome. We collected clinical data from 72 patients who underwent surgery for Squamous Cell Carcinoma (SCC) of the tongue, floor, lips and palate. FKBP51 expression was assessed by immunohistochemistry on paraffin-embedded tumor tissues. In addition, we evaluated the human papillomavirus (HPV) status of primary tumors by immunohistochemistry, viral subtyping and In Situ Hybridization (ISH) assay. We found that high FKBP51-expressing tumors characterized the OSCCs with the worst prognosis: the high immunohistochemical expression of FKBP51 associated with death occurring within five years from the diagnosis with a sensitivity of 88.46% and a specificity of 91.67%. The estimated positive predictive value of the test was 88.45% and negative predictive value 91.67%. We tested FKBP51 mRNA presence, by RT-PCR assay, in a selected series of OSCC tumors, and we found that mRNA correlated well to the protein expression and to the clinical outcome. Applying the Bayes formula, we estimated an 88% probability of dying within five years from the diagnosis of OSCC patients with a high FKBP51 immunohistochemical (IHC) test result (>51% of FKBP51 positive tumor cells). On the basis of our analysis, we propose tumor tissue expression of FKBP51 protein as a reliable prognostic marker for OSCC tumors.

Sleep disturbance in patients with burning mouth syndrome: a case-control study.

AIM: To examine sleep complaints in patients with burning mouth syndrome (BMS) and the relationships between these disturbances, negative mood, and pain. METHODS: Fifty BMS patients were compared with an equal number of healthy controls matched for age, sex, and educational level. The Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) were administered. Descriptive statistics, including the Mann-Whitney U test and hierarchical multiple linear regression analyses were used. RESULTS: BMS patients had higher scores in all items of the PSQI and ESS than the healthy controls (P < .001). In the BMS patients, a depressed mood and anxiety correlated positively with sleep disturbances. The Pearson correlations were 0.68 for PSQI vs HAM-D (P < .001) and 0.63 for PSQI vs HAM-A (P < .001). CONCLUSION: BMS patients reported a greater degree of sleep disorders, anxiety, and depression as compared with controls. Sleep disorders could influence quality of life of BMS patients and could be a possible treatment target.

Detection of CAF-1/p60 in peripheral blood as a potential biomarker of HNSCC tumors.

To date, a very small number of serum biomarkers have been identified for clinical use in squamous carcinomas of the head and neck region. Chromatin Assembly Factor-1 (CAF-1) heterotrimeric complex subunit CAF1/p60 expression levels have been reported to be of prognostic value in Oral Squamous Cell Carcinoma (OSCC), as well as in other human solid tumors. Here our aim was to detect and quantify CAF1/p60 in the peripheral blood of Head and Neck Squamous Cell Carcinoma (HNSCC) patients, and to investigate the possible associations between serum concentration of CAF-1/p60 and HNSCC tumors. A total of 63 HNSCC patients (51 OSCC, 8 OPSCC, 3 laryngeal SCC, and 1 rhinopharynx SCC) and 30 healthy controls were enrolled. The serum levels of CAF-1/p60 were measured by ELISA assay before and after surgery. Serum CAF-1/p60 concentration resulted significantly higher in cancer patients, compared with healthy controls, in pre-surgery samples (P < 0.05). Serum levels of CAF-1/p60 significantly decreased in serum samples taken after surgery (P < 0.05). Our results demonstrated that CAF-1/p60 may be detected in serum, suggesting a role for CAF-1/p60 as potential soluble biomarkers in HNSCC tumors.

Accuracy of Fibula Reconstruction Using Patient-Specific Cad/Cam Plates: A Multicenter Study on 47 Patients.

OBJECTIVES: This prospective study evaluated the accuracy of mandibular reconstruction using free fibular flaps (by comparing virtual plans to the three-dimensional postoperative results), and the extent of bone-to-bone contact after computer-assisted surgery. METHODS: We included 65 patients who underwent partial-continuity mandibular resections from February 2013 to January 2017, and evaluated virtual planning, surgical techniques, and accuracy. RESULTS: Forty-seven patients were analysed. A total of 112 fibular segments received 54 implants. We measured 227 distances between landmarks to assess the accuracy of reconstruction. Postoperative reconstruction accuracy ranged from 0.5 to 3 mm. CONCLUSION: Virtual surgical planning very accurately translated simulation into reality, particularly in patients requiring large, complex mandibular reconstructions using multiple fibular segments. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2169-E2175, 2021.

A Machine-learning Approach for the Assessment of the Proliferative Compartment of Solid Tumors on Hematoxylin-Eosin-Stained Sections.

We introduce a machine learning-based analysis to predict the immunohistochemical (IHC) labeling index for the cell proliferation marker Ki67/MIB1 on cancer tissues based on morphometrical features extracted from hematoxylin and eosin (H&E)-stained formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples. We provided a proof-of-concept prediction of the Ki67/MIB1 IHC positivity of cancer cells through the definition and quantitation of single nuclear features. In the first instance, we set our digital framework on Ki67/MIB1-stained OSCC (oral squamous cell carcinoma) tissue sample whole slide images, using QuPath as a working platform and its integrated algorithms, and we built a classifier in order to distinguish tumor and stroma classes and, within them, Ki67-positive and Ki67-negative cells; then, we sorted the morphometric features of tumor cells related to their Ki67 IHC status. Among the evaluated features, nuclear hematoxylin mean optical density (NHMOD) presented as the best one to distinguish Ki67/MIB1 positive from negative cells. We confirmed our findings in a single-cell level analysis of H&E staining on Ki67-immunostained/H&E-decolored tissue samples. Finally, we tested our digital framework on a case series of oral squamous cell carcinomas (OSCC), arranged in tissue microarrays; we selected two consecutive sections of each OSCC FFPE TMA (tissue microarray) block, respectively stained with H&E and immuno-stained for Ki67/MIB1. We automatically detected tumor cells in H&E slides and generated a "false color map" (FCM) based on NHMOD through the QuPath measurements map tool. FCM nearly coincided with the actual immunohistochemical result, allowing the prediction of Ki67/MIB1 positive cells in a direct visual fashion. Our proposed approach provides the pathologist with a fast method of identifying the proliferating compartment of the tumor through a quantitative assessment of the nuclear features on H&E slides, readily appreciable by visual inspection. Although this technique needs to be fine-tuned and tested on larger series of tumors, the digital analysis approach appears to be a promising tool to quickly forecast the tumor's proliferation fraction directly on routinely H&E-stained digital sections.

Violence-related periorbital trauma with a retained foreign body: a case report.

BACKGROUND: Orbital fracture usually occurs as a result of blunt orbital and facial trauma and may involve ocular injuries. International studies on orbital floor fracture show several differences in epidemiology, diagnostic criteria, surgical treatment modalities, and complication rates; therefore, any comparison should be made with caution. Here we describe an unusual case involving a 19-year-old man with violence-related periorbital trauma, wherein a foreign body (a plastic pen cap) traversed the median wall of the maxillary sinus and penetrated the lower turbinate. CASE PRESENTATION: A 19-year-old Caucasian man was referred to our department with localized pain and swelling in the left suborbital region following a physical fight in May 2014. A clinical examination revealed no abnormalities in his eyeballs or eye movement, palpation of the orbital contour revealed no fractures, and ophthalmological evaluation showed no evidence of diplopia. A computed tomography scan revealed fractures in the left orbital floor, periorbital tissue herniation without muscular entrapment and left maxillary hemosinus were observed. A hypodense soft tissue mass was lodged in the left orbital floor, which extended to the median wall of the maxillary sinus and penetrated the left lower turbinate. Surgical exploration of the foreign body was conducted, revealing the foreign body to be a pen cap. CONCLUSIONS: History or clinical examination alone may be inadequate to raise the suspicion of a retained periorbital foreign body in a situation of orbital region trauma. Computed tomography is important for the evaluation of periorbital injuries, especially because it could reveal the presence of a foreign body. Periorbital foreign bodies can be observed distinctly on computed tomography, which remains the most sensitive study and should be the first imaging modality in such cases.

Rare case of isolated osteochondroma of the zygomatic bone: an endoscopic-assisted approach.

AIM: Osteochondroma is a benign neoplasia that in the craniofacial district unfrequently can occur in the coronoid process and in the zygomatic arch. We describe a rare case of isolated osteochondroma of the zygomatic bone, undergoing surgical treatment by means of intraoral approach and endoscopic assistance. MATERIAL OF STUDY: A Caucasian woman aged fifty-two, has been observed in our Department on March 2012 because of pain in the right zygomatic area. Computed tomography (CT) scans of the right zygomatic bone showed an undefined, sessile lesion with lobar bounds (Fig. 2). Suspected diagnosis was osteochondroma. Surgery was planned via intraoral approach under general narcosis. The procedure was endoscope-assisted. The lesion was removed by using an endoscopic rotating cutter. RESULTS: No edema, pain or fever occurred during the immediate recovery period. The patient has been followed up for 16 months and she is still actually lesion and symptoms free. DISCUSSION: The use of endoscopy in the surgical treatment of this pathology has allowed to obtain a higher accuracy and a greater respect of the anatomic structures CONCLUSIONS: In literature are not reported other cases of isolated zygomatic osteochondroma treated with endoscopicassisted procedures. Intraoral approach grants no scarring; endoscopic aid gives a better view of all anatomical structures of this district, a good management of the pathology and minimize the risk of pathological fractures during intraoperative procedures. KEY WORDS: Endoscopic-assisted surgery,Isolated osteochondroma, Zygomatic bone osteochondroma.

The "extended" endoscopic endonasal approach for the removal of a mixed intrasuprasellar germinoma: Technical case report.

BACKGROUND: Intracranial germ cell tumors (GCTs) represent less than 5% of pediatric brain tumors. Neurosurgical treatment remains essential in the management of patients with intracranial nongerminomatous GCT. CASE DESCRIPTION: A 12-year-old girl presented with clinical features of neurohypophyseal dysfunction and rapidly progressive visual worsening. Magnetic resonance imaging (MRI) showed a lesion arising from the sella with a significant suprasellar component, compressing the optic chiasm and extending into the third ventricle. The tumor was removed via an endoscopic endonasal transtuberculum-transplanum approach and the histology revealed a mixed germinoma. In the postoperative course, a conspicuous improvement of visual function was observed; an early postoperative MRI showed near-total removal of the lesion. The patient was referred to pediatric oncologist for the adjunctive chemotherapy and radiotherapy. CONCLUSIONS: The management of primary intracranial sellar and suprasellar germinomas still remains controversial. With this report we highlighted another possible surgical option among therapeutic strategies for these highly malignant tumors.