Changes in spike protein antibody titer over 90 days after the second dose of SARS-CoV-2 vaccine in Japanese dialysis patients.

OBJECTIVES: There is no report on antibody titers after vaccination against SARS-CoV-2 in Japanese dialysis patients. As dialysis is different between Japan and other countries, changes in antibody titers were examined. METHODS: Baseline characteristics and anti-spike protein antibody titers (Roche) over 90 days after administration of the BNT162b2 messenger RNA vaccine were investigated in dialysis patients. RESULTS: The maximum anti-spike protein antibody titer after the second dose was 738 (327 to 1143) U/mL and was reached at 19 (17 to 24) days after the second dose. Antibody titers decreased over time, with titers of 770 (316 to 1089) U/mL at 15 days, 385 (203 to 690) U/mL at 30 days, 254 (138 to 423) U/mL at 60 days, and 208 (107 to 375) U/mL at 90 days after the second dose. When an antibody titer of 137 U/mL was assumed to be a measure related to breakthrough infection, the proportion of subjects with antibody titers exceeding this level was 90.1% at 15 days, 85.3% at 30 days, 75.0% at 60 days, and 65.4% at 90 days after the second dose. When a decrease in antibody titers below the assumed breakthrough level was defined as an event, subjects with a pre-dialysis albumin ≥ 3.5 g/dL were significantly less likely to experience an event than subjects with a pre-dialysis albumin < 3.5 g/dL. CONCLUSIONS: The presence of anti-spike protein levels ≥ 313 U/mL at 30 days after the second vaccine dose might be a factor in maintaining enough antibody titers at 90 days after. Whether an additional vaccine dose is needed should be determined based on indicators serving as factors in maintaining antibody titers as well as the status of the spread of infection.

[A case of meningovascular syphilis presenting with bilateral oculomotor nerve palsy, cerebral aneurysm, and cerebral hemorrhage].

The patient was a 32-year-old man with no HIV infection and possible syphilis infection at the age of 22 years. At the age of 29 years, he visited an ophthalmologist for diplopia due to right oculomotor nerve palsy. He underwent diplopia strabismus surgery for unexplained oculomotor nerve palsy. At the age of 31 years, he had a left oculomotor nerve palsy and was referred to our department. He was diagnosed with neurosyphilis based on positive serum and cerebrospinal fluid syphilis antibodies. MRI showed aneurysm, asymptomatic cerebral hemorrhage, and contrast enhancement of the left oculomotor nerve, leading to the diagnosis of meningovascular syphilis. The patient's symptoms improved with penicillin and corticosteroids. The oculomotor nerve palsy may be due to microcirculatory disorder caused by syphilitic cerebral endarteritis.

Significant correlations between focal photopic negative response and focal visual sensitivity and ganglion cell complex thickness in glaucomatous eyes.

PURPOSE: To determine whether there are significant correlations between the focal photopic negative response (PhNR), the focal visual sensitivity and the ganglion cell complex (GCC) thickness in glaucomatous eyes. STUDY DESIGN: Single-center observational study. METHODS: Fifty-two eyes of 52 patients (71.4 ± 9.42 years) with clinically diagnosed open angle glaucoma were studied. Thirty-six age-matched normal subjects served as controls. The focal PhNR of the focal macular electroretinograms (fmERGs) were elicited by a 15° circular, a superior semicircular or an inferior semicircular stimulus centered on the fovea. The thickness of the GCC was measured in the corresponding retinal areas in the spectral-domain optical coherence tomographic images. The visual sensitivities (dB) were measured by microperimetry at the retinal area where the fmERGs were elicited and were converted to liner values (1/Lambert). RESULTS: The focal PhNR amplitudes were significantly correlated with the visual sensitivities of the full-circle (R = 0.532), the superior (R = 0.530) and inferior (R = 0.526) semicircular responses (P < 0.0001). The GCC thickness was correlated with the visual sensitivities in the same areas with stronger correlations (R = 0.700, 0.759 and 0.650, respectively; P < 0.0001). The focal PhNR amplitudes were proportionally reduced with the thinning of the GCC thickness (R = 0.494, 0.518 and 0.511, respectively; P < 0.0001). CONCLUSIONS: The significant correlations between the focal PhNR amplitudes, the focal visual sensitivities and the GCC thickness indicate that these may be good biomarkers to track the changes in the physiology and anatomy of the macular area in glaucomatous eyes.

Long-Term Observations of Thickness Changes of Each Retinal Layer following Macular Hole Surgery.

PURPOSE: To determine the long-term changes of the thickness of each retinal layer following macular hole (MH) surgery combined with internal limiting membrane (ILM) peeling. METHOD: The medical records of 42 eyes of 42 patients (41 to 86 years of age) who underwent MH surgery with ILM peeling between February 2016 and October 2018 were reviewed. A single surgeon operated on all patients, and all were followed for at least 24 months postoperatively. Spectral-domain optical coherence tomography (OCT) was performed to obtain retinal thickness maps of the parafoveal region corresponding approximately to the ILM peeled area. Each retinal layer was automatically segmented by the embedded software, and thickness maps were constructed for the total retinal layer (TRL), inner RL (IRL), middle RL (MRL), and outer RL (ORL). The averaged value of each retinal layer thickness was analyzed in the temporal/upper, temporal/lower, nasal/upper, and nasal lower quadrants. RESULTS: The TRL thickness was significantly decreased in the temporal areas postoperatively. The IRL thickness thinned progressively and significantly until 6 months without further thinning in the temporal quadrants. The MRL thickness of all areas was significantly thicker than the baseline values at 0.5 months and then gradually decreased in the temporal regions. However, the thickening in the nasal regions returned to the baseline values after 1.5 months. The ORL decreased transiently relative to the baseline values at 0.5 months in all areas. CONCLUSIONS: The ILM peeling does not affect only the thickness of the inner retina but also the middle and outer retinae in the parafoveal region. The chronological changes of the thickness after surgeries varied among the retinal layers and macular regions.

Relationships between the vascular structure and neural function of the macula in patients with diabetes mellitus.

PURPOSE: To determine the significance of the correlation between the vascular structure and neural function of the macula in patients with diabetes mellitus. STUDY DESIGN: Single-center observational study. PATIENTS AND METHODS: Ninety eyes of 90 diabetic patients with an average (SD) age of 63.5 (3.8) years were studied. Fifty of the eyes had no clinically apparent diabetic retinopathy (non-DR), and 40 eyes had mild-to-moderate nonproliferative DR (NPDR). Thirty age-matched healthy individuals were also studied in the same way. Swept-source optical coherence tomography angiography (OCTA) was performed to obtain 3 × 3-mm en face images of the posterior pole of the eye. The vascular densities (VDs) of the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) were determined. The focal macular electroretinograms (ERGs) elicited by a 15° circular stimulus centered on the fovea were recorded. The amplitudes of the a- and b-waves, sum of the oscillatory potentials (ΣOPs), photopic negative response (PhNR), and implicit times of the individual OPs (OP1-OP3) were measured. RESULTS: The VDs of the SCP and DCP were reduced in eyes with advanced DR (P < .01 for SCP). The implicit times of OP1-OP3 were significantly prolonged in eyes with a lower VD of the SCP and DCP in the non-DR group (P < .05). The amplitudes of the ΣOPs were significantly smaller in eyes with a reduced VD of the SCP and DCP in the NPDR group (P < .05). The correlation coefficients were higher for the OP implicit times than for the ΣOP amplitudes in the non-DR group. CONCLUSIONS: The OPs of the focal macular ERG are smaller with prolonged implicit times in association with capillary loss in the macula of diabetic patients. The implicit times are the most sensitive functional parameter that reflects the early changes of the microvasculature in the macula caused by diabetes.

Comparisons of photopic negative responses elicited by different conditions from glaucomatous eyes.

PURPOSE: To compare the clinical significance of the photopic negative response (PhNRs) elicited by different stimuli from glaucomatous eyes. STUDY DESIGN: Single-center observational study METHOD: Eighty-four eyes of 84 patients with open angle glaucoma (OAG) and 40 eyes of 40 normal subjects were studied. Cone electroretinograms (ERGs) were elicited by white stimuli on a white background (W/W) or red stimuli on a blue background (R/B). The luminance of the stimuli was 0.5, 1.0, 2.0 or 3.0 cd-s/m2, and of the background light was 10 cd/m2. The first and second troughs of the ERGs that appeared following the b-wave were designated as PhNR1 and PhNR2, respectively. The thickness of the circumpapillary retinal nerve fiber layer (cpRNFL) was measured by spectral-domain optical coherence tomography. The mean deviation (MD) was determined by standard automated perimetry. The area under the receiver operating characteristic curves (AUCs) was created to determine the diagnostic ability of the PhNRs elicited by the different stimulus conditions. RESULTS: The correlation coefficients of the amplitudes of the PhNR1 elicited by W/W stimuli to the MDs and cpRNFL thickness were generally stronger, and the regression lines steeper than for the amplitudes of the PhNR1 elicited by R/B stimuli. In contrast, the correlation coefficients of the amplitudes of the PhNR2 elicited by R/B stimuli to the MDs and cpRNFL thickness were generally stronger, and the regression lines were steeper than the amplitudes of the PhNR2 elicited by W/W stimuli. With both types of stimuli, the slopes of the regression lines became steeper when the ERG recorded with higher stimulus intensities. The AUCs were significantly larger for the PhNR2 elicited by the R/B stimuli at 3.0 cd-s/m2 than for PhNR1 and PhNR2 elicited by W/W stimuli at the same intensity when the PhNRs were used for diagnosing advanced glaucoma. CONCLUSION: The PhNR1 and PhNR2 elicited by the W/W and R/B stimuli are suitable measures to assess the function of the RGCs in eyes with OAG. The PhNR2 elicited by R/B stimuli at higher stimulus intensities is most effective in detecting functional and structural changes of the RGCs with the highest diagnostic capacity in discriminating advanced glaucoma.

Recent advances in reconstructive surgery: head and neck reconstruction.

Although advances in radiotherapy and chemotherapy for cancers of the head and neck have been remarkable, surgical resection followed by reconstructive surgery is still the mainstay of treatment. Of the reconstructive procedures, microsurgical tissue transfer has been considered the standard method for restoring postoperative functions and morphology. In this review article, we discuss the history of reconstructive surgery for treating cancers of the head and neck, current problems, and future challenges.

Narrow band imaging endoscopy for unknown primary tumor sites of the neck.

BACKGROUND: Examinations used to search for unknown primary tumors of squamous cell carcinomas of the neck include CT, MRI, laryngoscopy, gastrointestinal endoscopy, and positron-emission tomography (PET). Narrow band imaging (NBI) endoscopy in which an optical color-separation filter is used to narrow the bandwidth of spectral transmittance is also used. METHODS: Twenty-eight patients in whom primary squamous cell carcinomas could not be detected with conventional white light laryngoscopy underwent NBI endoscopy and PET. RESULTS: Primary lesions were detected with NBI endoscopy in 3 patients, but no primary lesions were detected with PET. However, PET was used to detect a lower gingival cancer and a palatine tonsillar cancer. CONCLUSION: Both PET and NBI endoscopy is effective for detecting unknown primary tumors of squamous cell carcinomas of the neck.

Usefulness of narrow-band imaging for detecting the primary tumor site in patients with primary unknown cervical lymph node metastasis.

OBJECTIVE: We sometimes experienced patients with primary unknown cervical lymph node metastasis. In such cases, if computed tomography, magnetic resonance imaging, laryngoscopy and gastrointestinal endoscopy cannot detect a primary site, there is no other effective method to identify a possible primary tumor. We investigated whether narrow-band imaging can detect a possible primary tumor in such. METHODS: Forty-six patients with primary unknown cervical lymph node metastasis were surveyed about primary tumors, from January 2003 to December 2006. All cervical lymph nodes were histologically proved to be squamous cell carcinoma by fine-needle aspiration cytology. Narrow-band imaging combined with magnifying endoscopy was used to identify the primary site in the head and neck region and cervical esophagus. Histological analysis was performed for all suspicious lesions by a biopsy specimen. RESULTS: Twenty-six lesions were suspected to be cancerous lesions by narrow-band imaging in the head and neck region. Sixteen lesions in 16 (35%, 16/46) patients were squamous cell carcinoma. Ten lesions were located in the hypopharynx and the remaining six lesions were located in the oropharynx. White light endoscopy could not point out any lesion. CONCLUSIONS: Narrow-band imaging endoscopy can detect possible primary cancer in patients with primary unknown cervical lymph node metastasis.

Larynx-preserving esophagectomy and jejunal transfer for cervical esophageal carcinoma.

OBJECTIVES/HYPOTHESIS: To examine the efficacy and safety of free jejunal transfer after larynx-preserving esophagectomy in patients with cervical esophageal carcinoma, especially with a high tumor involving the hypopharynx. STUDY DESIGN: A retrospective analysis of patients with cervical esophageal carcinoma who underwent free jejunal transfer after larynx-preserving esophagectomy. METHODS: The subjects were 32 patients who underwent larynx-preserving cervical esophagectomy and microvascular jejunal transfer. Fifteen patients had a high cervical esophageal carcinoma that involved the hypopharynx (high-tumor group), and 17 patients had a low cervical esophageal carcinoma that did not involve the hypopharynx (low-tumor group). For each group, mortality, morbidity (anastomotic leakage, wound infection, stricture, and recurrent laryngeal nerve palsy), functional outcomes (time to start oral intake, achieve complete oral intake, decannulation, and rate of larynx preservation), and oncologic outcomes (survival and local control rate) were reviewed and compared. RESULTS: No perioperative deaths occurred in either group. The incidence of postoperative complications did not differ between the groups. Oral intake started significantly later in the high-tumor group (14.9 days) than in the low-tumor group (10.4 days), but all patients in the high-tumor group could finally achieve oral intake without aspiration. Decannulation was possible in patients who underwent tracheostomy, and laryngeal function was completely preserved in the high-tumor group. Both survival and local control rate did not differ between the groups. CONCLUSIONS: Free jejunal grafts in larynx-preserving surgery can be performed safely and reliably in patients with low cervical esophageal carcinomas and in selected patients with high tumors involving the hypopharynx.

Functional outcomes and reevaluation of esophageal speech after free jejunal transfer in two hundred thirty-six cases.

Swallowing and communication are occasionally impaired after free jejunal transfer. Here, the relationship between surgical procedure and functional outcome was analyzed in 236 patients undergoing free jejunal transfer after total laryngopharyngectomy from 1992 through 2003. Swallowing and communication functions were also investigated with a questionnaire in 40 long-surviving patients. Although oral feeding could be resumed after surgery in most patients, anastomotic stricture and nasal regurgitation occurred in 12.7% and 29.7% of patients, respectively. Use of our standardized procedure, the tensed jejunal method, significantly reduced the incidence of stricture (P < 0.01) but increased the rate of nasal regurgitation; however, in most cases regurgitation gradually resolved. Of the 40 long-surviving patients, 17 attended a speech rehabilitation program at which 12 learned to perform esophageal speech without voice restoration procedures (11 of the 12 had received a tensed jejunal graft). Our standardized procedure helps prevent strictures and encourages esophageal speech.

Simultaneous squamous cell carcinoma with leiomyosarcoma of the larynx.

OBJECTIVE: To present the first reported case of a simultaneous squamous cell carcinoma with a leiomyosarcoma of the larynx, our treatment of the patient, and the 9-month follow-up results. STUDY DESIGN: Case study. METHODS: Review of diagnostic studies, the operative technique, and the patient's chart for the 9-month period after treatment. RESULTS: A case with double laryngeal tumors with simultaneous evolution but different histological patterns is described. The squamous cell carcinoma and leiomyosarcoma involved both the vocal cords and the anterior commissure. A partial laryngectomy was performed, and the patient has been free of disease for 9 months. CONCLUSIONS: Multiple laryngeal tumors are exceedingly rare. To our knowledge, no previous reports of a simultaneous squamous cell carcinoma and a leiomyosarcoma of the larynx have been reported. Both tumors were not invasive in this case, so conservation surgery was feasible.

Three-dimensional reconstruction of supraglottic structures after partial pharyngolaryngectomy for hypopharyngeal cancer.

OBJECTIVE: Larynx-preserving surgery is frequently performed for advanced hypopharyngeal cancer involving the larynx. However, reconstruction after partial pharyngolaryngectomy (PPL) remains a challenging problem because of the high risk of postoperative aspiration. In this report, we describe our new three-dimensional method for reconstructing supraglottic structures with a radial forearm flap. This is a retrospective analysis of 20 patients who underwent PPL for having hypopharyngeal cancer involving the larynx at our institution from 1996 to 2005. METHODS: The resulting pharyngolaryngeal defects were reconstructed with radial forearm flaps in all patients. Three-dimensional structures were reconstructed with a single nylon suture, which was used to hoist the flap and ensures that the arytenoids and the aryepiglottic fold were of appropriate height. RESULTS: Radial forearm flaps were transferred successfully in all but one case. Swallowing function was satisfactory in all patients, and decannulation could be performed in all but one patient. Postoperative conversational function in all patients was rated as excellent with Hirose's scoring system. CONCLUSIONS: Free jejunum transfer is the method of first choice for reconstruction of a defect after partial hypopharyngectomy. However, the complex supraglottic structures of the larynx are difficult to reconstruct with a free jejunal graft after PPL. In such cases, we perform three-dimensional reconstruction of the pharyngolaryngeal defect with a radial forearm flap and have achieved satisfactory postoperative function. We believe that our new procedure is a useful method for functional reconstruction after PPL.

Spontaneous regression of cervical lymph node metastasis in a patient with mesopharyngeal squamous cell carcinoma of the tongue: possible association between apoptosis and tumor regression.

BACKGROUND: We report a case of mesopharyngeal squamous cell carcinoma with spontaneous regression of lymph node metastasis. Spontaneous regression of lymph node metastasis of head and neck carcinoma has not been reported previously. Possible causes of the regression of lymph node metastasis include regression of lymphocytic division transiently inflated by an immunological stimulus, and en-bloc tumor necrosis due to degradation of vascularity, such as thromboembolism and intranodal hemorrhage. However, the patient's history and repeated imaging analyses suggested that these factors were not responsible for the regression. To clarify the etiology of this rare phenomenon, we investigated the cause of spontaneous regression with analyses of paraffin-embedded sections. METHODS: The frequency of cystic lesions, en-bloc necrotic lesions, and apoptosis of carcinoma were investigated with immunohistochemical analysis, and these features were compared with those in specimens from five other patients with head and neck squamous cell carcinoma. RESULTS: The present case revealed no tendency towards microscopically confirmed cystic formation or necrosis, but the frequency of apoptosis was significantly higher than that in the other five cases. The apoptotic tendency was not restricted to the lymph node in which spontaneous regression was confirmed clinically, but was also consistently observed in other lymph nodes and in the primary lesion that was detected and radically ablated 2 months after complete neck regional dissection had been done. CONCLUSION: Our case may be the first case of squamous cell carcinoma undergoing spontaneous regression in which enhanced apoptosis was demonstrated quantitatively. The findings were considered to contribute to evidence of spontaneous regression in squamous cell carcinoma of the head and neck resulting from enhanced apoptosis.

Palliative total pharyngo-laryngo-esophagectomy.

OBJECTIVE: To evaluate the outcomes of total pharyngo-laryngo-esophagectomy (TPLE) as a palliative procedure for achieving oral intake without tube placement. BACKGROUND: Patients with head and neck cancers require airway maintenance achieved by the placement of a tracheostomy tube and nutrition provided through a gastric fistula or a central vein, which may markedly decrease the quality of life (QOL) of the patients. CASES: Two patients with cervical esophageal cancer are described. The first patient was a 69-year-old male with cervical esophageal cancer with vertebral invasion, for which complete resection was not possible. Following TPLE, oral intake was initiated on post-operative day 9 and was maintained for 138 days. The second patient was a 73-year-old male with recurrent cervical esophageal cancer and unresectable lymph node metastasis for which lymph node dissection was not applicable. Following TPLE, oral intake was initiated on post-operative day 7 and was maintained for 199 days. Both patients were satisfied with the outcome. CONCLUSIONS: The QOL of the two patients was improved following the restoration of oral intake ability. Palliative TPLE may be appropriate for patients with advanced head and neck cancers.

Surgical management of carcinoma of the cervical esophagus.

OBJECTIVES: The aim of the present study was to clarify the clinicopathological characteristics, reconstruction methods after resection, and prognosis of cervical esophageal squamous cell carcinoma. METHODS: Seventy-four with squamous cell carcinomas of the cervical esophagus not previously treated who underwent cervical esophagectomy or total esophagectomy with or without laryngectomy were retrospectively analyzed. RESULTS: The operative morbidity and in-hospital mortality rates were 34% (25 patients) and 4% (3 patients), respectively. Alimentary continuity was achieved with free jejunal transfer (50 patients), gastric pull-up (19 patients), and other procedures (5 patients). The frequencies of postoperative complications and death did not differ between free jejunal transfer and gastric pull-up. The overall 3- and 5-year survival rates were 42% and 33%, respectively. The significant clinicopathological factors affecting survival were patient gender, high T factor, lymph node involvement, palpable cervical lymph nodes, vocal cord paralysis, lymphatic invasion, and extracapsular invasion. The pattern of first failure was most often locoregional (82%, 36 patients). CONCLUSION: The choice of free jejunal transfer or gastric pull-up for reconstruction after surgical resection of cervical esophageal carcinoma depends on the degree of tumor extension. Adverse factors affecting survival should be considered when candidates for the surgery are selected.

Standardization of free jejunum transfer after total pharyngolaryngoesophagectomy.

OBJECTIVE: Our latest free jejunum transfer procedure was reviewed and compared with previous procedures to standardize the operation. METHODS: This was a retrospective study of 269 patients who had undergone total pharyngolaryngoesophagectomy and free jejunum transfer from 1992 through 2004. The patients were divided into two groups: a late group, in which surgery was performed with our latest standard procedure from 2000 through 2004, and an early group, in which various procedures had been used from 1992 through 1999. Surgical times, postoperative progress, and complications were evaluated. RESULTS: The mean surgical time was shortened from 3 hours 25 minutes in the early group to 3 hours 9 minutes in the late group, and ischemic time was shortened from 2 hours 44 minutes to 2 hours 20 minutes. For recipient vessels, branches of the external carotid artery and the internal jugular vein were more often used in the late group. Length of hospitalization decreased from 31.7 days in the early group to 24.4 days in the late group, although the start of drinking was similar (15.4 days versus 12.1 days). The rates of complications were significantly reduced in the late group, particularly those associated with the enteric anastomosis such as minor leakage (18.2-5.2%) and stenosis (17.6-3.0%). CONCLUSION: Our latest method of free jejunum transfer reconstruction has become reliable and expeditious through simple and stable minor revisions of procedures.

[Contralateral cervical lymph node metastasis in piriform sinus carcinoma].

OBJECTIVE: To evaluate relative factors affecting contralateral cervical lymph node metastasis in piriform sinus carcinoma. METHODS: Ninety-six cases of piriform sinus carcinoma with no preoperative treatments were selected. The contralateral cervical lymph node metastasis and relative factors were analyzed during operation or postoperative follow-up. The contralateral cervical metastasis was defined as followed: 1 contralateral cervical metastasis was confirmed pathologically after bilateral neck dissection (pN2c) or 2 contralateral cervical metastasis was found firstly during postoperative follow-up and the recurrence of primary lesion was excluded. RESULTS: The incidence of contralateral cervical metastasis was 32% (31/96). According to the T stage, the incidence of contralateral cervical metastasis was T1: 0% ,T2: 18%, T3: 37%, T4: 32% and to the N stage N0: 12%, N1: 13%, N2a: 17%, N2b: 39%, N2c: 100%, and N3: 75%. For primary lesions beyond midline the incidence of contralateral cervical metastasis was 52% but for those remaining on ipsilateral side it was 18%. CONCLUSIONS: Contralateral cervical lymph node showed higher metastatic incidence with higher T and N stage. When the primary lesions invaded beyond midline, the contralateral cervical metastasis increased greatly and neck dissection should be selected positively.

Functional reconstruction with free flaps following ablation of oropharyngeal cancer.

With the development of various reconstructive procedures, most patients who have undergone ablative surgery for oropharyngeal cancer have obtained satisfactory functional results and good quality of life. However, many questions remain concerning methods of obtaining optimal postoperative oral and pharyngeal functions, especially after glossectomy. This review focuses on reconstructive methods after partial glossectomy, hemiglossectomy, and subtotal or total glossectomy and discusses current problems and the possibility of sensory and dynamic reconstruction.