Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer.

BACKGROUND/AIM: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). PATIENTS AND METHODS: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. RESULTS: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. CONCLUSION: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.

Treatment Efficacy of PD-1 Inhibitor Therapy in Patients With Recurrent and/or Metastatic Salivary Gland Carcinoma.

BACKGROUND/AIM: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. RESULTS: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. CONCLUSION: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.

Infrahyoid myofascial flap transfer for the prevention of concave deformity and gustatory sweating after parotidectomy.

OBJECTIVE: Concave deformities and gustatory sweating are the most common complications that cause substantial patient dissatisfaction after parotidectomy. Various surgical methods to prevent these complications have been described. However, effective techniques have not been established, especially in patients with medium- to large-sized parotidectomy defects. We evaluated the utility of infrahyoid myofascial flap reconstruction of parotidectomy defects for the prevention of these complications. METHODS: We conducted a retrospective case series study in patients with a benign or malignant parotid tumor measuring over 4 cm who underwent immediate pedicle infrahyoid myofascial flap reconstruction after total or subtotal parotidectomy or total resection of either the superficial or deep parotid gland at our hospital. Subjective analyses of facial symmetry, postoperative concave deformities of the anterior neck, gustatory sweating, voice disorders, odynophagia, neck scarring in the parotid and anterior neck areas, sensory disorders, pain, and neck stiffness were performed using patient interview data. Objective evaluations of facial symmetry were made by the first or second author. Both analyses were performed after a follow-up of more than six months. Additionally, patient demographic data, clinicopathological factors, parotidectomy and skin incision types, flap survival, and postoperative complications were evaluated. RESULTS: We included eight patients (male, n=5; mean age, 69.3 years [range, 37-93 years]). Procedures included total or subtotal parotidectomy (n=4), superficial lobe parotidectomy (n=2), and deep lobe parotidectomy with partial superficial lobe parotidectomy (n=2). Infrahyoid myofascial flaps reached the cranial tip of the parotid defect without tension, and their volume sufficiently filled the parotidectomy defect in all patients. There were no local signs of insufficient blood flow within the transferred flaps. Objective and subjective assessments were made after a mean duration of 1.2 years (range, 0.6-1.8). Postoperatively, no patient subjectively reported facial asymmetry. Objectively, facial symmetry was "good" in four patients and "fair" in four patients. No distinctly visible concave deformity in the parotid or anterior neck area occurred in any patient. Gustatory sweating occurred in one patient; this individual had the largest parotidectomy defect. Only one patient experienced donor site morbidity (mild anterior neck stiffness) related to infrahyoid myofascial flap elevation. CONCLUSION: Although complete prevention of gustatory sweating was unsuccessful, infrahyoid myofascial flap reconstruction of medium- to large-sized parotidectomy defects led to postoperative facial symmetry with minimal donor site morbidity.

Diagnosis and following up of Ménière's disease using multifrequency tympanometry-Cutoff values and temporal changes in measurements.

OBJECTIVE: This study aimed to verify cutoff values for G width (the width of bimodal peaks for the waveform obtained when measuring conductance at 2000Hz) in Japanese individuals diagnosed with Ménière's disease (MD) using multifrequency tympanometry (MFT) and to determine the relationship between the G width and ability to hear low-pitched sounds using measurements over time. METHODS: The study included 51 patients with clinically diagnosed MD, who had not undergone endolymphatic sac surgery, but had no other known ear disease (57 ears in patients aged 22-80 years were affected, and 45 ears in patients aged 18-83 years were unaffected; mean age: 53.3±16.9 years). We also enlisted 80 healthy controls with no prior history of ear disease (160 ears, aged 22-76 years, mean age: 40.8±15.7 years). MFT was used to measure the bimodal peak width of the waveform obtained when measuring conductance at resonance frequency of 2000Hz. For patients who had G width measured several times over multiple outpatient visits, we used initial test data to analyze cutoff values. In nine cases with four or more measurements over time, we evaluated a possible correlation between G width and the sum of the hearing threshold for three low-pitched frequencies (125Hz, 250Hz, and 500Hz). We used Student's t-test to determine significance. RESULTS: The both ears in the MD patients had a G width wider than the distribution in the control group. There was a significant difference between G width in the control group and in affected ears with MD (p=0.00026) and there was also a significant difference between G width in the control group and in unaffected ears of MD patients (p=0.0056). The cutoff value set with a specificity of 95% was 200daPa, with a sensitivity of 35.1% and specificity of 95.6%. The cutoff value set with a sensitivity of 50% was 140daPa, with sensitivity of 50.9% and specificity of 78.8%. There was no significant difference between resonance frequency of ears in the control group and ears with MD (p=0.41). In nine cases with four or more measurements over time, a case showed a statistically significant positive correlation between the G width and hearing ability threshold for low-pitched sounds (125Hz, 250Hz, and 500Hz) (p=0.03), while an another case showed a tendency toward a positive correlation, which was not statistically significant (p=0.08). Further, there were cases that did not show significant differences in the present study, but might have shown a negative correlation if the number of measurements had been increased. CONCLUSION: Measurement of G width using MFT may have accuracy as the traditional endolymphatic hydrops test. MFT is non-invasive, causes little discomfort for patients, requires little time to perform, and can be performed by paramedics. MFT was shown to be useful in screening for MD and it is effective in diagnosing MD to measure the change over time of G width using MFT.

A microsensing system for the in vivo real-time detection of local drug kinetics.

Real-time recording of the kinetics of systemically administered drugs in in vivo microenvironments may accelerate the development of effective medical therapies. However, conventional methods require considerable analyte quantities, have low sampling rates and do not address how drug kinetics correlate with target function over time. Here, we describe the development and application of a drug-sensing system consisting of a glass microelectrode and a microsensor composed of boron-doped diamond with a tip of around 40 µm in diameter. We show that, in the guinea pig cochlea, the system can measure-simultaneously and in real time-changes in the concentration of bumetanide (a diuretic that is ototoxic but applicable to epilepsy treatment) and the endocochlear potential underlying hearing. In the rat brain, we tracked the kinetics of the drug and the local field potentials representing neuronal activity. We also show that the actions of the antiepileptic drug lamotrigine and the anticancer reagent doxorubicin can be monitored in vivo. Our microsensing system offers the potential to detect pharmacological and physiological responses that might otherwise remain undetected.

Patterns of lymphatic spread and the management of eyelid carcinomas.

OBJECTIVE: Eyelid carcinomas are rare, and the management strategy of regional lymph node metastasis linked to eyelid carcinomas has not been standardized to date. The aim of the present study was to analyze the patterns of regional metastasis and to assess the optimal extent of surgical treatment for lymph node metastasis of eyelid carcinoma. METHODS: This study was a retrospective review of patient data from a single institution. From a series of 268 eyelid carcinomas, we selected the 21 patients with lymph node metastasis, and we analyzed the patterns of lymphatic spread, approach to treatment and outcomes. RESULTS: The most common histological type of eyelid carcinoma with regional metastasis was sebaceous carcinoma (17/21, 81.0%). Submandibular area metastases were seen only in the patients with the primary tumor originating in the medial half of the eyelid, but parotid area metastases were seen in both the patients whose tumors had a medial-half origin and those with a lateral-half origin. Although 11 of the 16 patients with parotid-area metastases underwent a tumorectomy or superficial parotidectomy (which resulted in four cases of recurrence in the parotid area), none of the five patients who underwent a total parotidectomy developed parotid-area recurrence. The incidence of regional recurrence of the patients who received adjuvant radiotherapy (14.3%) was lower than that of the patients without adjuvant radiotherapy (57.1%). CONCLUSION: Continued surveillance and optimal management of regional lymph node metastases are important for the control and survival of eyelid carcinomas.

NKCCs in the fibrocytes of the spiral ligament are silent on the unidirectional K⁺ transport that controls the electrochemical properties in the mammalian cochlea.

Unidirectional K(+) transport across the lateral cochlear wall contributes to the endocochlear potential (EP) of +80 mV in the endolymph, a property essential for hearing. The wall comprises two epithelial layers, the syncytium and the marginal cells. The basolateral surface of the former and the apical membranes of the latter face the perilymph and the endolymph, respectively. Intrastrial space (IS), an extracellular compartment between the two layers, exhibits low [K(+)] and a potential similar to the EP. This IS potential (ISP) dominates the EP and represents a K(+) diffusion potential elicited by a large K(+) gradient across the syncytial apical surface. The K(+) gradient depends on the unidirectional K(+) transport driven by Na(+),K(+)-ATPases on the basolateral surface of each layer and the concomitant Na(+),K(+),2Cl(-)-cotransporters (NKCCs) in the marginal cell layer. The NKCCs coexpressed with the Na(+),K(+)-ATPases in the syncytial layer also seem to participate in the K(+) transport. To test this hypothesis, we examined the electrochemical properties of the lateral wall with electrodes measuring [K(+)] and potential. Blocking NKCCs by perilymphatic perfusion of bumetanide suppressed the ISP. Unexpectedly and unlike the inhibition of the syncytial Na(+),K(+)-ATPases, the perfusion barely altered the electrochemical properties of the syncytium but markedly augmented [K(+)] of the IS. Consequently, the K(+) gradient decreased and the ISP declined. These observations resembled those when the marginal cells' Na(+),K(+)-ATPases or NKCCs were blocked with vascularly applied inhibitors. It is plausible that NKCCs in the marginal cells are affected by the perilymphatically perfused bumetanide, and these transporters, but not those in the syncytium, mediate the unidirectional K(+) transport.

The mechanism underlying maintenance of the endocochlear potential by the K+ transport system in fibrocytes of the inner ear.

The endocochlear potential (EP) of +80 mV in the scala media, which is indispensable for audition, is controlled by K+ transport across the lateral cochlear wall. This wall includes two epithelial barriers, the syncytium and the marginal cells. The former contains multiple cell types, such as fibrocytes, which are exposed to perilymph on their basolateral surfaces. The apical surfaces of the marginal cells face endolymph. Between the two barriers lies the intrastrial space (IS), an extracellular space with a low K+ concentration ([K+]) and a potential similar to the EP. This intrastrial potential (ISP) dominates the EP and represents the sum of the diffusion potential elicited by a large K+ gradient across the apical surface of the syncytium and the syncytium's potential, which is slightly positive relative to perilymph. Although a K+ transport system in fibrocytes seems to contribute to the EP, the mechanism remains uncertain. We examined the electrochemical properties of the lateral wall of guinea pigs with electrodes sensitive to potential and K+ while perfusing into the perilymph of the scala tympani blockers of Na+,K+-ATPase, the K+ pump thought to be essential to the system. Inhibiting Na+,K+-ATPase barely affected [K+] in the IS but greatly decreased [K+] within the syncytium, reducing the K+ gradient across its apical surface. The treatment hyperpolarized the syncytium only moderately. Consequently, both the ISP and the EP declined. Fibrocytes evidently use the Na+,K+-ATPase to achieve local K+ transport, maintaining the syncytium's high [K+] that is crucial for the K+ diffusion underlying the positive ISP.

A minimally invasive method to prevent postlaryngectomy major pharyngocutaneous fistula using infrahyoid myofascial flap.

INTRODUCTION: To prevent postoperative pharyngocutaneous fistula (PCF) after total (pharyngo)laryngectomy, simultaneous coverage of pharyngeal anastomosis with vascularised flaps such as pectoralis major muscle, anterolateral thigh or radial forearm, has been reported to be effective. As an alternative to the invasive methods using distant flaps, we used the infrahyoid myofascial flap (IHMFF), which was harvested from the same operation field of (pharyngo)laryngectomy, for covering the site of pharyngeal anastomosis. Herein, we describe the safety and effectiveness of our minimally invasive method for preventing PCF. METHODS: Eleven patients who were at a high risk of developing PCF due to previous chemoradiotherapy underwent simultaneous coverage of pharyngeal anastomosis with IHMFF after total (pharyngo)laryngectomy. The incidence of PCF and the rate of major fistula requiring surgical closure were determined, and the results were compared with the control group (23 patients without IHMFF cover after laryngectomy). RESULTS: PCF developed in 2 of the 11 patients (18.2%). The fistulae of these two patients were closed conservatively and did not require additional surgery. PCF developed in 6 of 23 patients (26.1%) in patients without IHMFF cover. All the six patients with fistula required additional closure surgery. The incidence of PCF did not differ in patients with or without IHMFF cover (Fisher's exact probability test; p=0.939, NS). However, the rate of major PCF requiring surgical closure was significantly lower in patients with IHMFF cover (Fisher's exact probability test; p=0.036<0.05). CONCLUSIONS: For (pharyngo)laryngectomy patients, IHMFF cover is a minimally invasive method that can prevent major PCF.

Management of chylous fistula after neck dissection using negative-pressure wound therapy: A preliminary report.

Chylous fistula is a distressing complication resulting from thoracic duct injury during neck dissections. We have successfully managed chylous fistula using negative-pressure wound therapy (NPWT) in a case where all conservative treatments failed. A 60-year-old man with tongue cancer underwent subtotal glossectomy and bilateral neck dissections. On postoperative day 4, a chylous fistula with large drainage developed in the right neck. Conservative treatments were not effective, therefore, NPWT was started from postoperative day 9. The drainage volume then began to decrease, and the chylous fistula was closed 6 days after starting NPWT. In our case, the effects of wound shrinkage and fluid removal by NPWT were considered to contribute to early closure. Although preliminary, NPWT can be an important treatment choice for the management of a chylous fistula after neck dissections.