Caspr1 antibodies autoimmune paranodopathy with severe tetraparesis: Potential relevance of antibody titers in monitoring treatment response.

AIM: Nodopathies and paranodopathies are autoimmune neuropathies associated with antibodies to nodal-paranodal antigens (neurofascin 140/186 and 155, contactin-1, contactin-associated protein 1 [Caspr1]) characterized by peculiar clinical features, poor response to standard immunotherapies (e.g., intravenous immunoglobulins, IVIg). Improvement after anti-CD20 monoclonal antibody therapy has been reported. Data on Caspr1 antibodies pathogenicity are still preliminary, and longitudinal titers have been poorly described. METHODS: We report on a young woman who developed a disabling neuropathy with antibodies to the Caspr1/contactin-1 complex showing a dramatic improvement after rituximab therapy, mirrored by the decrease of antibody titers. RESULTS: A 26-year-old woman presented with ataxic-stepping gait, severe motor weakness at four limbs, and low frequency postural tremor. For neurophysiological evidence of demyelinating neuropathy, she was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy and treated with IVIg without benefit. MRI showed symmetrical hypertrophy and marked signal hyperintensity of brachial and lumbosacral plexi. Cerebrospinal fluid showed 710 mg/dL protein. Despite intravenous methylprednisolone, the patient progressively worsened, and became wheelchair-bound. Antibodies to nodal-paranodal antigens were searched for by ELISA and cell-based assay. Anticontactin/Caspr1 IgG4 antibodies resulted positive. The patient underwent rituximab therapy with slow progressive improvement that mirrored the antibodies titer, measured throughout the disease course. CONCLUSIONS: Our patient had a severe progressive course with early disability and axonal damage, and slow recovery starting only a few months after antibody-depleting therapy. The close correlation between titer, disability, and treatment, supports the pathogenicity of Caspr1 antibodies, and suggest that their longitudinal evaluation might provide a potential biomarker to evaluate treatment response.

Head and neck adult-type soft tissues sarcomas: survival analysis and comparison between the last two editions of the TNM staging system.

PURPOSE: Head and neck soft tissues sarcomas (HNSTS) are a heterogeneous group of rare tumours. The 8th edition of the TNM staging system (8TNM) considered these lesions separately for the first time. The aim of this study is to assess its effectiveness and identify the most significant prognostic factors for HNSTS. METHODS: A retrospective survival analysis on 101 HNSTS operated between 1995 and 2015 at the National Cancer Institute of Milan was carried out. The variables considered were pathological stage (according to both the 7TNM and 8TNM), site, histotype, depth, grading, surgical radicality, (neo)adjuvant radiotherapy and/or chemotherapy. RESULTS: According to the 7TNM, the T category distribution was 35 T1a, 23 T1b, 11 T2a, and 32 T2b. Applying the 8TNM, the distribution changed to 19 T1, 18 T2, 35 T3, and 29 T4. Five-year overall and disease-specific survivals were 74.3 and 76.2%, respectively. Univariate analysis demonstrated an increased hazard ratio (HR) for deep lesions invading adjacent structures, high-grade, surgery with close/microscopically positive margins, and chemotherapy. Multivariate analysis confirmed an increased HR for deep location and size > 5 cm, G2-G3 tumours, and marginal surgery. No significant difference was found among T categories of the 8TNM. CONCLUSION: The present study underlines the negative prognostic impact of depth, size > 5 cm, high grade, and marginal treatment for HNSTS. Our results did not allow to validate the 8TNM staging system since, apparently, it was not associated with meaningful prognostic stratification. Further studies with wider multicentric cohorts should, however, be performed to obtain more powerful statistical data.

Fascio-cutaneous-free flaps as primary reconstruction in salvage total laryngectomy.

INTRODUCTION: Salvage total laryngectomy (STL) is the most common treatment for recurrent laryngeal cancer after (chemo)-radiotherapy [(C)RT]. In this scenario, a higher rate of local wound complications, such as pharyngo-cutaneous fistula (PCF) and pharyngo-esophageal stenosis (PES), is generally expected. The aim of the present study is to evaluate outcomes using a standardized reconstructive protocol. METHODS: Between 2009 and 2019, patients undergoing STL after (C)RT were collected at two referral hospitals with the objective of evaluating surgical outcomes using a standardized reconstructive policy based on the use of fascio-cutaneous free flaps as inlay patch grafts and a long-lasting salivary bypass stent. RESULTS: Fifty-five patients (mean age, 66 years; male-to-female ratio, 8:1) were included in the study. Previous treatments were RT in 22 (40%) patients, CRT in 21 (38.2%), and partial laryngeal surgery followed by adjuvant (C)RT in 12 (21.8%). Reconstruction was accomplished by radial forearm and anterolateral thigh free flaps in 16 (29.1%) and 39 (70.9%) patients, respectively. Flap success rate was 98.2%. Concerning postoperative complications, we encountered 3 PCFs (5.4%) and 1 PES (1.8%). CONCLUSION: The standardized reconstructive protocol analyzed herein granted significantly lower rates of PCF and PES after STL compared with data available in the literature.

Management of loco-regionally advanced squamous laryngeal cancer in elderly patients.

PURPOSE: To describe the management and outcomes of loco-regionally advanced (stages III-IV) laryngeal cancer (LRALC) in elderly patients. METHODS: Clinical records of 88 LRALC patients treated at our Institution from 2002 to 2017 were retrospectively reviewed. Patients were divided in 2 subgroups: age > 65 years (elderly) and age ≤ 65 years (controls). Survivals were estimated with Kaplan-Meier method and compared with log-rank test, multivariate analysis were performed with Cox proportional hazard methods. RESULTS: Eighty-eight LRALC patients were included: 45 elderly and 43 controls. Median follow-up was 55.3 months. Median age was 66 years (range 41-84) in the overall population, 72 years (range 66-84) in the elderly cohort. The majority (98%) of elderly patients had at least one comorbidity (ACE27 1-3), while ACE27 was 0 in 37% of controls (p = 0.0001). ECOG PS was 0 in 42% of elderly vs 79% of controls (p = 0.0029). Clinical stage (TNM eighth edition) was III in 67%, IVA in 22% and IVB in 11%. Treatment consisted in total laryngectomy (TL) in 55%, chemo-radiation in 29%, exclusive radiotherapy in 9%, and conservative surgery in 7%. In elderly patients 2-year disease-free and overall survivals were 58% and 74%, respectively. Multivariate analysis performed on the overall group of 88 patients showed that age (HR 1.07, p = 0.0006) and TNM (for both 7th and 8th Editions HR 0.27 for stage III vs IV, p = 0.0005) maintained an independent statistical significant association with OS. CONCLUSIONS: In this monocentric cohort, age and TNM confirmed their independent prognostic role in LRALC patients. Organ-preservation is still an unmet need in a significant portion of elderly patients.

Submandibular gland excision: From external surgery to robotic intraoral and extraoral approaches.

Submandibular gland excision is generally performed through a transcervical approach, a safe procedure that, however, carries few neurological, functional and aesthetic drawbacks. Intraoral approach to the submandibular gland has been described many years ago but it has been newly proposed in recent years thanks to endoscope-assisted and robot-assisted surgical procedures. The main purpose of intraoral approaches is to avoid cosmetic sequelae and to reduce the risk of marginal nerve injury although the recent introduction of retroauricular, postauricular, facelift and transhairline neck incisions has overcome the need for an alternative to traditional transcervical approach. Different surgical approaches (transoral versus transcervical) to the submandibular gland as well as different type of cutaneous incisions will be illustrated and discussed in the light of advancement of endoscope-assisted and robot-assisted procedures.

A novel integrated platform for the identification of surgical margins in oral squamous cell carcinoma: results from a prospective single-institution series.

BACKGROUND: The optimal surgical margins assessment is capital in oral squamous cell carcinoma (OSCC) management. We evaluated the clinical benefits of integrating intraoperative macroscopic margin (MM) assessment and narrow band imaging (NBI). METHODS: Sixteen OSCC patients eligible for surgery were prospectively enrolled. For each patient, 2 to 6 bioptic samples of MM and NBI margins were obtained and histologically analyzed for the presence of dysplasia and lymphocytes. Microvessel density was investigated by CD34 immunohistochemistry. RESULTS: Taken together, 104 specimens were analyzed, including 15% tumors, 33% MM, 33% NBI margins, and 19% MM-NBI overlapping margins. The NBI margins were closer to the lesion in 50% cases, while the same number of MM were more conservative than NBI, irrespective of the tumor site. The rate of histologically positive margins was similar among the two methods, akin to the microvessel density. CONCLUSIONS: MM assessment should be integrated but not replaced with the NBI technology to allow for more conservative surgery.

Compartmental tongue surgery for intermediate-advanced squamous cell carcinoma: A multicentric study.

BACKGROUND: A multicentric study was conducted on technical reproducibility of compartmental tongue surgery (CTS) in advanced tongue cancers (OTSCC) and comparison to standard wide margin surgery (SWMS). METHODS: We studied 551 patients with OTSCC treated by CTS and 50 by SWMS. Oncological outcomes were analyzed. A propensity score was performed to compare survival endpoints for the two cohorts. RESULTS: In the CTS group, survival and prognosis were significantly associated with positive lymph-nodes, extranodal extension, depth of invasion and involvement of the soft tissue connecting the tongue primary tumor to neck lymph nodes (T-N tract), independently from the center performing the surgery. SWMS versus CTS showed a HR Cause-Specific Survival (CSS) of 3.24 (95% CI: 1.71-6.11; p < 0.001); HR Loco-Regional Recurrence Free Survival (LRRFS) of 2.54 (95% CI: 1.47-4.40; p < 0.001); HR Overall Survival (OS) of 0.11 (95% CI: 0.01-0.77; p = 0.03). CONCLUSION: Performing the CTS could provide better CSS and LRRFS than SWMS regardless of the center performing the surgery, in advanced OTSSC.

Case Report: Para-infectious cranial nerve palsy after bacterial meningitis.

A 27-year-old woman was admitted to our hospital for fever, associated with headache, nausea, and vomiting, and she rapidly developed mild left facial nerve palsy and diplopia. Neurological examination revealed mild meningitis associated with bilateral VI cranial nerve palsy and mild left facial palsy. As central nervous system (CNS) infection was suspected, a diagnostic lumbar puncture was performed, which revealed 1,677 cells/µl, 70% of which were polymorphonuclear leukocytes. Moreover, multiplex PCR immunoassay was positive for Neisseria meningitidis, supporting the diagnosis of bacterial meningitis. Finally, IgG oligoclonal bands (IgGOB) were absent in serum and cerebrospinal fluid (CSF). Therefore, ceftriaxone antibiotic therapy was started, and in the following days, the patient's signs and symptoms improved, with complete remission of diplopia and meningeal signs within a week. On the contrary, left facial nerve palsy progressively worsened into a severe bilateral deficit. A second lumbar puncture was therefore performed: the CSF analysis revealed a remarkable decrease of pleocytosis with a qualitative modification (only lymphocytes), and oligoclonal IgG bands were present. A new brain MRI was performed, showing a bilateral gadolinium enhancement of the intrameatal VII and VIII cranial nerves bilaterally. Due to suspicion of para-infectious etiology, the patient was treated with oral steroid (prednisolone 1 mg/kg/day), with a progressive and complete regression of the symptoms. We suggest that in this case, after a pathogen-driven immunological response (characterized by relevant CSF mixed pleocytosis and no evidence of IgGOB), a para-infectious adaptive immunity-driven reaction (with mild lymphocyte pleocytosis and pattern III IgGOB) against VII and VIII cranial nerves started. Indeed, steroid administration caused a rapid and complete restoration of cranial nerve function.

Oncological outcomes of compartmental surgery and wide local excision in oral tongue and floor of the mouth cancer.

OBJECTIVES: Oral tongue carcinomas represent more than half of the tumors arising in the oral cavity, a site with a high cancer specific mortality and impact on quality of life. Current guidelines are lacking for a standardized surgical approach of these tumors. The aim of this study is to compare two currently adopted surgical strategies, compartmental surgery (CTS) and wide local excision (WLE), with loco-regional control as the main oncological endpoint. MATERIALS AND METHODS: An observational retrospective multicentric study was carried out enrolling a cohort of patients affected by oral tongue or floor of the mouth squamous cell carcinoma and surgically treated in 4 international tertiary referral centers. Survival analysis was performed by propensity-score matching approach and multivariable Cox regression analysis. RESULTS: A cohort of 933 patients was enrolled. CTS was applied in 113 patients (12.1%) and WLE in 820 (87.9%). Analyzing a propensity-score matched cohort (98 CTS vs. 172 WLE) and applying a survival multivariable modeling strategy on the whole cohort, both confirmed that CTS and WLE are comparable and oncologically safe. Parameters such as number of positive lymph nodes, depth of invasion, and lymphovascular invasion still represent the key prognosticators. CONCLUSION: The main goals for surgical resection of oral cancer remain its three-dimensional circumferential clearance with adequate margins and en-bloc removal of the tumor-lymph node tract, independently of the technique adopted (CTS or WLE). Further prospective studies including quality of life evaluation are needed to better understand if one of these approaches can provide superior functional outcomes.

Comparison of Different Staging Systems Applied to a Cohort of Patients With Oral Tongue and Floor of the Mouth Cancer.

Purpose: The present work compares the effects produced by the application of the 7th edition of the tumor node metastasis (TNM) staging system (TNM7), 8th Edition (TNM8) with its two subsequent revisions, and pN-N+ classification on a cohort of patients with oral tongue and floor of the mouth cancer. Methods: A monocentric cohort of 148 patients was retrospectively analyzed. Patients were staged according to the TNM7, TNM8 and revisions, and pN-N+ classification. Stage migration was assessed and overall survival (OS) analyzed with the Kaplan-Meier method. The pT, pN, and stage stratification was evaluated with univariate and multivariate Cox regression and comparing adjacent categories with the log-rank method. Results: pT3-T4a categories showed significant differences in comparison to pT1-T2 for each staging metric employed in both uni- and multivariate analysis. When comparing adjacent pT categories, OS was significantly different only between pT2 and pT3 categories of the TNM8. Disproportionate patient distribution among pN categories was observed in the TNM8, and stratification was scarce. Conversely, in the pN-N+ classification the difference between pN2 and pN3a categories was significant. Only stage IVa reached statistical significance in TNM7, whereas stage III and above were significant in TNM8 and revisions in both uni- and multivariate analysis. However, no significant difference was noted comparing adjacent stages. Conclusion: The TNM8 pT classification differentiated low- from high-risk diseases. Nonetheless, it failed to separate pT1 from pT2 and pT3 from pT4a categories. Conversely, although TNM8 nodal staging was inaccurate, the number of metastatic lymph nodes was more valuable.

Neonatal Respiratory Distress and Airway Emergency: Report of Two Cases.

We discuss two cases of congenital airway malformations seen in our neonatal intensive care unit (NICU). The aim is to report extremely rare events characterized by immediate respiratory distress after delivery and the impossibility to ventilate and intubate the airway. The first case is a male twin born at 34 weeks by emergency caesarean section. Immediately after delivery, the newborn was cyanotic and showed severe respiratory distress. Bag-valve-mask ventilation did not relieve the respiratory distress but allowed for temporary oxygenation during subsequent unsuccessful oral-tracheal intubation (OTI) attempts. Flexible laryngoscopy revealed complete subglottic obstruction. Postmortem analysis revealed a poly-malformative syndrome, unilateral multicystic renal dysplasia with a complete subglottic diaphragm, and a tracheo-esophageal fistula (TEF). The second case is a male patient that was vaginally born at 35 weeks. Antenatally, an ultrasound (US) arose suspicion for a VACTERL association (vertebral defects, anal atresia, TEF with esophageal atresia and radial or renal dysplasia, plus cardiovascular and limb defects) and a TEF, and thus, fetal magnetic resonance (MRI) was scheduled. Spontaneous labor started shortly thereafter, before imaging could be performed. Respiratory distress, cyanosis, and absence of an audible cry was observed immediately at delivery. Attempts at OTI were unsuccessful, whereas bag-valve-mask ventilation and esophageal intubation allowed for sufficient oxygenation. An emergency tracheostomy was attempted, although no trachea could be found on cervical exploration. Postmortem analysis revealed tracheal agenesis (TA), renal dysplasia, anal atresia, and a single umbilical artery. Clinicians need to be aware of congenital airway malformations and subsequent difficulties upon endotracheal intubation and must plan for multidisciplinary management of the airway at delivery, including emergency esophageal intubation and tracheostomy.

Predictive nomograms for oral tongue squamous cell carcinoma applying the American Joint Committee on Cancer/Union Internationale Contre le Cancer 8th edition staging system.

BACKGROUND: Nomograms applying the 8th edition of the TNM staging system aimed at predicting overall (OS), disease-specific (DSS), locoregional recurrence-free (LRRFS) and distant recurrence-free survivals (DRFS) for oral tongue squamous cell carcinoma (OTSCC) are still lacking. METHODS: A training cohort of 438 patients with OTSCC was retrospectively enrolled from a single institution. An external validation set of 287 patients was retrieved from two independent institutions. RESULTS: Internal validation of the multivariable models for OS, DSS, DRFS and LRRFS showed a good calibration and discrimination results with optimism-corrected c-indices of 0.74, 0.75, 0.77 and 0.70, respectively. The external validation confirmed the good performance of OS, DSS and DRFS models (c-index 0.73 and 0.77, and 0.73, respectively) and a fair performance of the LRRFS model (c-index 0.58). CONCLUSIONS: The nomograms herein presented can be implemented as useful tools for prediction of OS, DSS, DRFS and LRRFS in OTSCC.

Transoral robotic submandibular sialadenectomy: how and when.

Traditional removal of the submandibular gland is done through a transcervical approach; new proposals have come into the scientific limelight such as endoscopy-assisted transcervical sialadenectomy or (robot-assisted) submandibular sialadenectomy through a postauricular facelift transcervical approach. Transoral submandibular sialadenectomy has been described in the past, but with the advent of transoral robotic surgery, the proposal of removing the submandibular gland from the oral floor is gaining strength. A transoral robotic submandibular sialadenectomy by the Si Da Vinci Surgical Robot was performed in a 68-years-old female patient under general anaesthesia. The transoral robotic procedure was successful with no major postoperative complications. A mild tingling of the tip of the tongue was described by the patient 3 months after. The surgical time took 110 minutes. No residual gland was observed at ultrasonography. The transoral robotic submandibular sialadenectomy seems to be, with selective indication based on clinical and radiological assessment, a viable and safe alternative to traditional management in patients who refuse a cervical scar and the risk of paralysis of the facial nerve.

Radiation-induced papillary thyroid cancer: is it a distinct clinical entity?

PURPOSE OF REVIEW: To present the current status of knowledge regarding radiation-induced papillary thyroid cancer (RIPTC), defining its epidemiologic, pathologic, and clinical characteristics, with ensuing possible therapeutic and prognostic consequences. RECENT FINDINGS: Cumulative evidence shows that RIPTC resembles sporadic papillary thyroid cancer (PTC) of comparable age, both in terms of clinical-pathological features and prognosis. Therefore, more aggressive treatment does not seem to be required when managing RIPTC as its prognosis is comparable to that of never-irradiated patients. SUMMARY: Radiation exposure in childhood is a well-documented risk factor for development of PTC. Therefore, increased exposure to medical or environmental radiation may be in part responsible, along with increased screening, of the recent burgeoning incidence of PTC. A specific morphological and molecular portrait of RIPTC is unlikely to exist. The more aggressive histologic and clinical features initially reported in radiation-induced cases are consistent with the expectations in nonradiation-related PTC of a comparable age. Aggressive histology, nodal, and distant metastases correlate with early age at onset rather than with radiation exposure. Although relapses are frequent in children, long-term cancer-specific mortality is approximately 1%, lower than that observed for adults and comparable between irradiated and nonirradiated cohorts. RIPTC does not require more aggressive surgery or more adjuvant treatments, as prognosis is as good as that of sporadic PTC when matched for stage and treatment received.

Microvascular head and neck reconstruction after (chemo)radiation: facts and prejudices.

PURPOSE OF REVIEW: This article critically analyzes the recent literature on microvascular head and neck reconstruction after (chemo)radiation [(C)RT], taking into consideration both the underlying pathogenetic mechanisms and their clinical consequences. RECENT FINDINGS: Microvascular reconstruction has gradually become a mainstay in the management of head and neck cancer both in primary and salvage scenarios. However, limited data are available concerning the influence of previous radiotherapy/chemoradiation therapy (CRT) on free flap survival and surgical complications. Molecular studies show that the effects of radiotherapy/CRT may be essentially reduced to three components: inflammation, a prothrombotic state and fibrosis. From a clinical point of view, this is reflected in a moderate increase in free flaps failure and surgical complications. Nevertheless, free flaps continue to offer clear advantages even in such an unfavorable condition. SUMMARY: Radiotherapy/CRT induce a less favorable tissue environment, potentially leading to a higher risk of complications. In this scenario, however, free tissue transfer still plays the role of favoring wound healing bringing well vascularized tissue to less vascularized microenvironments.