Andrea Lovato

Indications for postoperative radiotherapy in laryngeal carcinoma: A panel of tumor tissue markers for predicting locoregional recurrence in surgically treated carcinoma. A pilot study

Combining primary surgery with postoperative radiotherapy (RT) significantly reduces locoregional recurrence rates in selected patients with laryngeal squamous cell carcinoma (SCC). A prognostic model was used to see if associating laryngeal SCC tissue markers (mammary serine protease inhibitor [MASPIN], CD105, angiogenin [ANG], and nm23‐H1) with conventional criteria could better discriminate higher‐risk patients warranting postoperative RT.

Multi-Dimensional Voice Program (MDVP) vs Praat for Assessing Euphonic Subjects: A Preliminary Study on the Gender-discriminating Power of Acoustic Analysis Software

OBJECTIVES The aim of this study was to compare the discriminatory power of the Multi-Dimensional Voice Program (MDVP) and Praat in distinguishing the gender of euphonic adults. STUDY DESIGN This is a cross-sectional study. METHODS The recordings of 100 euphonic volunteers (50 males and 50 females) producing a sustained vowel /a/ were analyzed with MDVP and Praat software. RESULTS Both computer programs identified significant differences between male and female volunteers in absolute jitter (MDVP P < 0.00001 and Praat P < 0.00001) and in shimmer in decibel (dB) (MDVP P = 0.006 and Praat P = 0.001). Using the scale proposed by Hosmer and Lemeshow, we found no gender discrimination for shimmer in dB with either the MDVP (area under the receiver operating characteristics curve [AUC] = 0.658) or Praat (AUC = 0.682). In our series, on the other hand, MDVP absolute jitter achieved an acceptable discrimination between males and females (AUC = 0.752), and Praat absolute jitter achieved an outstanding discrimination (AUC = 0.901). The discriminatory power of Praat absolute jitter was significantly higher than that of the MDVP (P = 0.003). Absolute jitter sensitivity and specificity were also higher for Praat (83% and 80%) than for the MDVP (74% and 49%). CONCLUSIONS Differences attributable to a subjects gender and to the software used to measure acoustic parameters should be carefully considered in both research and clinical settings. Further studies are needed to test the discriminatory power of different voice analysis programs when differentiating between normal and dysphonic voices.

A critical look at persistent problems in the diagnosis, staging and treatment of temporal bone carcinoma

Temporal bone squamous cell carcinoma (TBSCC) is an uncommon malignancy with a distinctly poor prognosis in advanced cases. There is still much controversy surrounding the rational diagnostic/therapeutic approach to TBSCC. Diagnostic differences are due mainly to: the small number of cases reported (even in the largest available series); the inappropriate histological heterogeneity of several case series; the lack of an internationally-accepted staging system for TBSCC; the frequent absence of adequate radiological imaging to enable a malignancys local, regional and distant extension to be studied in detail; and a non-standardized approach to final histological assessment of the surgical margins. As for the therapeutic approaches, several issues are still debated, including the choice between en bloc and piecemeal primary surgery for the tumors removal, and the role of elective neck dissection. Although radiotherapy seems to be an effective adjuvant therapy in advanced cases, its role in low-stage tumors or as a primary treatment has yet to be established. The value of chemotherapy is also still unclear. The treatment strategy for TBSCC is often based on the combined experience of a given surgeon and institution, bearing the results reportedly achieved by other oncology centers in mind. To date, the optimal management of TBSCC is still elusive. We aimed to critically review the ongoing crucial issues concerning the management of TBSCC, analyzing how it is diagnosed, staged and treated, the management of recurrences, rational follow-up schedules, and prognostic factors for this disease.

Nm23-H1 nuclear expression is associated with a more favourable prognosis in laryngeal carcinoma: univariate and multivariate analysis.

Marioni G, Ottaviano G, Lionello M, Lora L, Lovato A, Staffieri C, Favaretto N, Giacomelli L, Stellini E, Staffieri A & Blandamura S 
(2012) Histopathology
Nm23‐H1 nuclear expression is associated with a more favourable prognosis in laryngeal carcinoma: univariate and multivariate analysis

Recurrent squamous cell carcinoma of the temporal bone: critical analysis of cases with a poor prognosis ☆,☆☆

PURPOSE Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive malignancy with a significant recurrence rate. We reviewed our experience with recurrent TBSCCs. MATERIALS AND METHODS Clinicopathological and therapeutic variables potentially associated with disease-free survival (DFS) and disease-specific survival (DSS) were assessed in 17 TBSCC patients who died of their disease after treatment. RESULTS TBSCC recurrences were treated with surgery in 12 cases (palliative in 11, with curative intent in 1) and palliative chemotherapy in 5; the median DFS and DSS were 6 and 16 months, respectively. The mean DFS and DSS were longer in patients who had primary lateral temporal bone resection (LTBR) rather than subtotal temporal bone resection (STBR) (p=0.0173 and p=0.03, respectively). Patients given non-surgical palliative treatment for recurrences had a longer mean DSS than those who underwent surgery (trend toward significance, p=0.09). CONCLUSIONS Our results reflect the aggressive nature of TBSCC recurrences. Our findings seem to support the use of non-surgical treatments (chemotherapy, radiotherapy, or specialist palliative care) in patients with loco-regionally advanced recurrent TBSCC. Salvage surgery might be considered for early recurrences when radicality is still achievable. Precise guidelines for the rational follow-up of surgically-treated TBSCCs need to be shared between tertiary centers.

Sudden hearing loss followed by deep vein thrombosis and pulmonary embolism in a patient with factor V Leiden mutation

Abstract Objective: Factor V Leiden (FVL) is by far the most prevalent inherited thrombophilic abnormality in Western countries, and this genetic condition has been associated with sudden sensorineural hearing loss (SSHL). Audiologists should be aware that SSHL may be the precursor of life-threatening thromboembolic events, especially in Caucasians who are more likely to be FVL carriers. Design: Case report. Study sample: A 41-year-old male patient. Results: Although this is not the first report of SSHL in a FVL carrier, it is the first to describe SSHL occurring in a heterozygous FVL carrier who — within a month — was also diagnosed with deep vein thrombosis of the left common femoral, saphenous, and popliteal veins, and pulmonary embolism of the left pulmonary artery branch serving the posterior basal segment of the inferior lobe. Conclusions: SSHL is an emergency condition that warrants prompt medical examination and treatment. Hematological investigations should be considered in SSHL patients at least for those with a family history of thrombotic events, and for women on estrogen-progestin therapy or during pregnancy, with a view to providing adequate antithrombotic prophylaxis and reducing the risk of other thromboembolic events.

Relaxin-2 expression in temporal bone carcinoma

Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive malignancy with a significant local recurrence rate even in patients with postoperative pathology reports of free surgical margins. This raises the question of how “free” negative margins should be to be oncologically safe, especially in bone tissue. A potential role for relaxin-2 hormone in tumor-driven osteolysis has recently been reported. The aim of this study was to assess the prognostic role of relaxin-2 expression in TBSCC tissue specimens and pathologically negative bone margins. Relaxin-2 immunohistochemical expression was assessed in 25 consecutively operated TBSCC patients. Several pathological variables correlated with recurrence rate (pT stage, dura mater involvement), disease-free survival (DFS) (pT stage, pN status, grade, and dura mater involvement), and disease-specific survival (DSS) (pT stage, pN status, grade, and dura mater involvement). The recurrence rate, DFS, and DSS did not correlate with relaxin-2 expression in TBSCC specimens or pathologically negative bone margins. Although local recurrence in TBSCC could relate to neoplastic bone invasion not apparent on conventional pathological investigations, the present preliminary findings seem to rule out any role of relaxin-2 in mediating this local aggressiveness. Molecular mechanisms of TBSCC recurrence after curative treatment should be further investigated.

A Higher Angiogenin Expression is Associated With a Nonnuclear Maspin Location in Laryngeal Carcinoma.

Objectives In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC). Methods Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes. Results On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P<0.001), and shorter DFS (P=0.01) than those with a nuclear Maspin pattern. The mean ANG expression was significantly higher in cases with loco-regional recurrent disease (P=0.007); and patients with an ANG expression ≥5.0% had a significantly shorter DFS than those with an ANG expression <5.0% (P=0.007). On multivariate analysis, ANG expression ≥5.0% was a significant, independent, negative prognostic factor in terms of DFS (P=0.041). Conclusion Our results support the hypothesis that a higher ANG expression is associated with a nonnuclear Maspin expression pattern in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC.

Immunohistochemical and HPV-related features of laryngeal adenosquamous carcinoma.

BACKGROUND Adenosquamous carcinoma (ASC) of the head and neck is a rare malignancy characterized by loco-regional and distant aggressiveness. At histology, ASC reveals two distinct, juxtaposed components, squamous cell carcinoma (SCC), and true adenocarcinoma. METHODS The immunohistochemical expression of AE3, CK19 and CAM5.2, and HPV infection was tested in a case of laryngeal ASC. RESULTS The patient had no regional lymph node metastases, but developed a recurrence in neck soft tissues shortly after primary radical surgery. The laryngeal surgical specimen had the typical morphological features of ASC. The tumors squamous and glandular components were both strongly and diffusely immunoreactive for AE3 and CK19, whereas CAM5.2 selectively stained only the gland-like part. We found no high- or low-risk HPV DNA (28 genotypes) in the specimens. The patient underwent salvage extended radical neck dissection and received postoperative radio-chemotherapy. At 4-month follow-up control, neck recurrence was found. Palliative chemotherapy was instituted. CONCLUSIONS An accurate histological and immunohistochemical diagnosis is mandatory to differentiate ASC from conventional SCC. Radical surgical excision is recommended for laryngeal ASC. Adjuvant postoperative therapy is administered in most cases, but there are no widely accepted indications for these treatments.

In reference to Laboratory assessment of sudden sensorineural hearing loss: A case-control study

We read with interest the recent case-control study by Fasano and colleagues describing the laboratory assessment of 131 patients with sudden sensorineural hearing loss (SSHL). The authors found elevated blood glucose, glycated hemoglobin, lipoprotein (a), and factor VIII in SSHL patients and concluded that glucometabolic, lipidic, and coagulative laboratory data supported the vascular hypothesis for SSHL. Steroids are commonly suggested as a treatment for SSHL. Unfortunately, Fasano et al. did not report the treatment regimen in their case series and its temporal relationship with the laboratory assessment, but it is rational to assume that most of patients underwent steroid therapy. Blood samples were collected from the SSHL patients within 20 days from the onset of symptoms, and that could hypothetically be before, during, or shortly after the steroid treatment. This is an important matter, as corticosteroids are known to elevate blood glucose levels, and more interestingly, may stimulate factor VIII secretion. Factor VIII is a glycoprotein cofactor that serves as a critical component in the intrinsic blood coagulation pathway. High factor VIII levels are considered to be a predisposing factor for venous thromboembolism. However, factor VIII levels can vary due to a multitude of physiological and disease factors. Body mass index (positively correlated with factor VIII levels) and higher levels of glucose (diabetes mellitus), insulin, fibrinogen, and triglycerides are associated with increased factor VIII. Furthermore, a transient elevation in factor VIII levels could be the result of adrenalin and b2-adrenergic receptor stimulation. Corticosteroids play a well-documented regulation on badrenergic receptors, and thus they may have a relevant role on factor VIII elevation. If laboratory assessment is considered in SSHL patients, it is our opinion that blood samples should be collected either before starting the steroid therapy or at least 1 month after the conclusion of such a treatment. This is due to the relevant influence played by steroids on glucose metabolism and on the secretion of other plasmatic proteins such as factor VIII.