Does Prehabilitation Reduce Postoperative Length of Hospital Stay after Esophageal Cancer Surgery?

Objectives: At our hospital, prehabilitation has been provided to patients undergoing esophageal cancer surgery since October 2019. This study explored the effects of prehabilitation based on the accumulated database of these patients. Methods: This retrospective cohort study included 621 patients who underwent thoracoscopic subtotal esophagectomy. Multiple linear regression analysis was performed using postoperative hospital stay as the objective variable and age, sex, body mass index (BMI), preoperative ventilatory impairment, left ventricular ejection fraction, preoperative hemoglobin A1c, clinical stage, histological type, operative time, surgical blood loss, postoperative complications, and prehabilitation as explanatory variables. We also performed a multivariate analysis in the subgroup of patients who developed postoperative complications and adjusted for possible confounding factors. Postoperative complications and postoperative hospital stay were compared between patients without (n=416) and with (n=205) prehabilitation. Results: Postoperative complications, age, blood loss, BMI, and ventilatory impairment influenced the overall length of hospital stay. When the analysis was restricted to patients with complications, prehabilitation was added to that list of factors as a substitute for BMI. The rate of postoperative complications was not affected by prehabilitation (P=0.1675). The number of hospital days did not change with or without prehabilitation in the overall population, but when restricted to patients with complications, the number of hospital days was significantly decreased in the prehabilitation group (P=0.0328). Conclusions: Prehabilitation as a perioperative approach has the potential to reduce the postoperative length of hospital stay in patients undergoing esophageal cancer surgery, and active intervention is recommended.

Butyricimonas is a key gut microbiome component for predicting postoperative recurrence of esophageal cancer.

BACKGROUND: Recently, intestinal bacteria have attracted attention as factors affecting the prognosis of patients with cancer. However, the intestinal microbiome is composed of several hundred types of bacteria, necessitating the development of an analytical method that can allow the use of this information as a highly accurate biomarker. In this study, we investigated whether the preoperative intestinal bacterial profile in patients with esophageal cancer who underwent surgery after preoperative chemotherapy could be used as a biomarker of postoperative recurrence of esophageal cancer. METHODS: We determined the gut microbiome of the patients using 16S rRNA metagenome sequencing, followed by statistical analysis. Simultaneously, we performed a machine learning analysis using a random forest model with hyperparameter tuning and compared the data obtained. RESULTS: Statistical and machine learning analyses revealed two common bacterial genera, Butyricimonas and Actinomyces, which were abundant in cases with recurrent esophageal cancer. Butyricimonas primarily produces butyrate, whereas Actinomyces are oral bacteria whose function in the gut is unknown. CONCLUSION: Our results indicate that Butyricimonas spp. may be a biomarker of postoperative recurrence of esophageal cancer. Although the extent of the involvement of these bacteria in immune regulation remains unknown, future research should investigate their presence in other pathological conditions. Such research could potentially lead to a better understanding of the immunological impact of these bacteria on patients with cancer and their application as biomarkers.

Diagnosis and Treatment of Metastatic Colon Cancer in Pregnancy First Presenting as Multiple Liver Masses: A Case Report.

Colorectal cancer (CRC) is the second most common cancer in women in Japan. However, it is uncommon during pregnancy. CRC diagnosis during pregnancy is often complicated and delayed due to the overlapping of symptoms, such as abdominal pain and nausea, with those of pregnancy and the limitations placed on potential diagnostic imaging and testing because of concerns for the fetus. A 39-year-old woman was referred from a local hospital at 32 weeks gestation after persistent right abdominal pain, which prompted an ultrasound that showed multiple liver lesions suggestive of malignancy. A combination of non-contrast computed tomography, non-contrast magnetic resonance imaging, contrast-enhanced ultrasound, and colonoscopy was utilized to make a definitive diagnosis; ultimately, colonoscopy confirmed the diagnosis of colon cancer with liver metastasis. A discussion within a multidisciplinary team led to the decision to deliver at 34 weeks by cesarean section and a left hemicolectomy was performed after delivery. The neonate was admitted to the neonatal intensive care unit due to prematurity but had no other complications. Chemotherapy was promptly initiated, and treatment was continued on an outpatient basis. Diagnostic algorithms for CRC during pregnancy are not yet well-established; however, the prognosis of CRC during pregnancy is poor, and clinicians should not hesitate to perform the necessary testing and consult experts in fields such as neonatology, medical oncology, internal medicine, and gastrointestinal surgery. Early diagnosis and intervention are essential for optimizing outcomes for both the mother and the fetus.

Rapid and Highly Efficient Purification of Extracellular Vesicles Enabled by a TiO2 Hybridized Spongy-like Polymer.

We developed a novel purification medium of extracellular vesicles (EVs) by constructing a spongy-like monolithic polymer kneaded with TiO2 microparticles (TiO2-hybridized spongy monolith, TiO2-SPM). TiO2-SPM was applied in a solid-phase extraction format and enabled simple, rapid, and highly efficient purification of EVs. This is due to the high permeability caused by the continuous large flow-through pores of the monolithic skeleton (median pore size; 5.21 µm) and the specific interaction of embedded TiO2 with phospholipids of the lipid bilayers. Our method also excels in efficiency and comprehensiveness, collecting small EVs (SEVs) from the same volume of a cell culture medium 130.7 times more than typical ultracentrifugation and 4.3 times more than affinity purification targeting surface phosphatidylserine by magnetic beads. The purification method was completed within 1 h with simple operations and was directly applied to serum SEVs. Finally, we demonstrated flexibility toward the shape and size of our method by depleting EVs from fetal bovine serum (FBS), which is a necessary process to prevent contamination of culture cell-derived EVs with exogenous FBS-derived EVs. Our method will eliminate the tedious and difficult purification processes of EVs, providing a universal purification platform for EV-based drug discovery and pathological diagnosis.

Efficient Selective Adsorption of SARS-CoV-2 via the Recognition of Spike Proteins Using an Affinity Spongy Monolith.

Since the outbreak of COVID-19, SARS-CoV-2, the infection has been spreading to date. The rate of false-negative result on a polymerase chain reaction (PCR) test considered the gold standard is roughly 20%. Therefore, its accuracy poses a question as well as needs improvement in the test. This study reports fabrication of a substrate of an anti-spike protein (AS)-immobilized porous material having selective adsorption toward a spike protein protruding from the surface of SARS-CoV-2. We have employed an organic polymer substrate called spongy monolith (SPM). The SPM has through-pores of about 10 µm and is adequate for flowing liquid containing virus particles. It also involves an epoxy group on the surface, enabling arbitrary proteins such as antibodies to immobilize. When antibodies of the spike protein toward receptor binding domain were immobilized, selective adsorption of the spike protein was observed. At the same time, when mixed analytes of spike proteins, lysozymes and amylases, were flowed into an AS-SPM, selective adsorption toward the spike proteins was observed. Then, SARS-CoV-2 was flowed into the BSA-SPM or AS-SPM, amounts of SARS-CoV-2 adsorption toward the AS-SPM were much larger compared to the ones toward the BSA-SPM. Furthermore, rotavirus was not adsorbed to the AS-SPM at all. These results show that the AS-SPM recognizes selectively the spike proteins of SARS-CoV-2 and may be possible applications for the purification and concentration of SARS-CoV-2.

Thoracoscopic esophageal drainage for tracheal compression due to mucocele after esophagogastric bypass: a case report.

BACKGROUND: Esophagogastric bypass is performed for esophageal strictures. Mucus retention, known as mucocele, sometimes occurs at the stricture oral side of the remnant esophagus. It is often asymptomatic and is expected to be naturally decompressed, but it may cause respiratory failure depending on the case. Herein, we report a case in which we successfully performed thoracoscopic esophageal drainage as emergency airway management due to tracheal compression by a mucocele after esophagogastric bypass for unresectable esophageal cancer with esophagobronchial fistula. CASE PRESENTATION: A 56-year-old man underwent esophageal bypass surgery for an unresectable esophageal carcinoma with an esophagobronchial fistula following chemotherapy and radiation therapy. Nine months after bypass surgery, he experienced severe dyspnea due to tracheal compression caused by mucus retention on the oral side of the esophageal tumor. We planned thoracoscopic surgery for mucus retention drainage through the right thoracic cavity to secure the airway as an emergency procedure under general anesthesia. Intubation can be performed safely by guiding bronchoscopy in the semi-supine position. Upper esophageal dilation was observed on the cranial side of the azygos arch. We dissected the mediastinal pleura of the upper thoracic esophagus and exposed its wall. A 12-Fr silicone drain was placed in the esophagus through the right chest wall and 120 ml of white fluid was aspirated. He was discharged 9 days after surgery without complications and resumed treatment with an immune checkpoint inhibitor 23 days after surgery. Thereafter, he continued chemotherapy for esophageal cancer, but died of tumor progression and lung metastasis 35 months after bypass surgery and 25 months after thoracoscopic surgery. CONCLUSIONS: Thoracoscopic esophageal drainage could be performed safely as emergency airway management, shorten the period of discontinuance, and allow cancer treatment to be resumed promptly. We believe that this thoracoscopic procedure is an effective and less invasive method if the percutaneous approach is difficult.

Rational Strategy for Space-Confined Atomic Layer Deposition.

Atomic layer deposition (ALD) offers excellent controllability of spatial uniformity, film thickness at the Angstrom level, and film composition even for high-aspect-ratio nanostructured surfaces, which are rarely attainable by other conventional deposition methodologies. Although ALD has been successfully applied to various substrates under open-top circumstances, the applicability of ALD to confined spaces has been limited because of the inherent difficulty of supplying precursors into confined spaces. Here, we propose a rational methodology to apply ALD growths to confined spaces (meter-long microtubes with an aspect ratio of up to 10 000). The ALD system, which can generate differential pressures to confined spaces, was newly developed. By using this ALD system, it is possible to deposit TiOx layers onto the inner surface of capillary tubes with a length of 1000 mm and an inner diameter of 100 µm with spatial deposition uniformity. Furthermore, we show the superior thermal and chemical robustness of TiOx-coated capillary microtubes for molecular separations when compared to conventional molecule-coated capillary microtubes. Thus, the present rational strategy of space-confined ALD offers a useful approach to design the chemical and physical properties of the inner surfaces of various confined spaces.

Rational Supramolecular Strategy via Halogen Bonding for Effective Halogen Recognition in Molecular Imprinting.

Halogen bonding is a highly directional interaction and a potential tool in functional material design through self-assembly. Herein, we describe two fundamental supramolecular strategies to synthesize molecularly imprinted polymers (MIPs) with halogen bonding-based molecular recognition sites. In the first method, the size of the σ-hole was increased by aromatic fluorine substitution of the template molecule, enhancing the halogen bonding in the supramolecule. The second method involved sandwiching hydrogen atoms of a template molecule between iodo substituents, which suppressed competing hydrogen bonding and enabled multiple recognition patterns, improving the selectivity. The interaction mode between the functional monomer and the templates was elucidated by 1H NMR, 13C NMR, X-ray absorption spectroscopy, and computational simulation. Finally, we succeeded in the effective chromatographic separation of diiodobenzene isomers on the uniformly sized MIPs prepared by multi-step swelling and polymerization. The MIPs selectively recognized halogenated thyroid hormones via halogen bonding and could be applied to screening endocrine disruptors.

Comparison of Endotoxin Activity Assay and Various Biomarkers for Severity Assessment in Colorectal Perforation Patients.

Colorectal perforation is a serious disease with high mortality requiring emergency surgery. This study aimed to evaluate the role of the endotoxin activity assay (EAA) to assess the severity in patients admitted to the intensive care unit after emergency surgeries for colorectal perforations. Patients were divided into high (EAA ≥.4) and low (EAA <.4) groups based on the EAA levels, and the correlation between the EAA values and clinical variables related to the severity was evaluated. The SOFA scores were significantly higher in the high group than those in the low group. The high EAA value persisted even after 48 hours and extended the ICU length of stay. These results suggest that EAA may be a potential biomarker to assess severity and useful as one of the instrumental in predicting the outcomes for colorectal perforation patients.

Clinical Treatment of Perioperative Disseminated Intravascular Coagulation in Patients Who Underwent Gastrointestinal and Hepato-Biliary-Pancreatic Surgery.

BACKGROUND: It is unclear how effective recombinant thrombomodulin (rTM) treatment is in disseminated intravascular coagulation (DIC) during the perioperative period of gastrointestinal and hepato-biliary-pancreatic surgery. The current study aimed to evaluate the therapeutic outcomes of rTM for perioperative DIC. METHODS: We enrolled 100 consecutive patients diagnosed with perioperative DIC after gastrointestinal surgery, and hepato-biliary-pancreatic including emergency procedures, between January 2012 and May 2021. Patients received routine rTM treatment immediately after DIC diagnosis. Then, the DIC, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated and used for evaluation. The outcomes of rTM treatment and the predictors of survival were evaluated. RESULTS: The causative diseases of DIC were as follows: perforated peritonitis, n = 38; intestinal ischemia, n = 23; intra-abdominal abscess, n = 13; anastomotic leakage, n = 7; pneumonia, n = 7; cholangitis, n = 4; and others, n = 6. The 30-day mortality rate was 18.0%. There were significant differences in the platelet count (13.78 vs 10.41, P = .032) and the SOFA score (5.22 vs 9.89, P<.0001) at the start of DIC treatment between the survivor and non-survivor groups (day 0). The survivor group had a significantly lower DIC score (3.13 vs 4.93, P = .0006) and SOFA score (4.94 vs 12.14, P < .0001) and a higher platelet count (13.50 vs 4.34, P < .0001) than the non-survivor group on day 3. CONCLUSIONS: Comprehensive and systemic treatment is fundamentally essential for DIC, in which rTM may play an important role in the treatment of perioperative DIC.

Classification of Extracellular Vesicles Based on Surface Glycan Structures by Spongy-like Separation Media.

Extracellular vesicles (EVs) are lipid bilayer vesicles that enclose various biomolecules. EVs hold promise as sensitive biomarkers to detect and monitor various diseases. However, they have heterogeneous molecular compositions. The compositions of EVs from identical donor cells obtained using the same purification methods may differ, which is a significant obstacle for elucidating objective biological functions. Herein, the potential of a novel lectin-based affinity chromatography (LAC) method to classify EVs based on their glycan structures is demonstrated. The proposed method utilizes a spongy-like monolithic polymer (spongy monolith, SPM), which consists of poly(ethylene-co-glycidyl methacrylate) with continuous micropores and allows an efficient in situ protein reaction with epoxy groups. Two distinct lectins with different specificities, Sambucus sieboldiana agglutinin and concanavalin A, are effectively immobilized on SPM without impacting the binding activity. Moreover, high recovery rates of liposomal nanoparticles as a model of EVs are achieved due to the large flow-through pores (>10 µm) of SPM compared to a typical agarose gel. Finally, lectin-immobilized SPMs are employed to classify EVs based on the surface glycan structures and demonstrate different subpopulations by proteome profiling. This is the first approach to clarify the variation of protein contents in EVs by the difference of surface glycans via lectin immobilized media.

Predictive Factors of Febrile Neutropenia After Primary Prophylactic Pegfilgrastim With DCF Chemotherapy for Esophageal Cancer.

BACKGROUND/AIM: We investigated the predictive factors of febrile neutropenia (FN) after the administration of pegfilgrastim as primary prophylaxis in patients with esophageal cancer who received neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) to support the appropriate management of FN. We evaluated changes in neutrophil counts and relative dose intensity (RDI) after the incidence of FN. PATIENTS AND METHODS: This retrospective study involved 122 patients with esophageal cancer who were treated with DCF and pegfilgrastim at Showa University Hospital, Japan, between April 2016 and August 2021. The primary outcome was FN incidence after cycle 1 of DCF chemotherapy. The significant independent factors associated with FN incidence were selected using the multivariate analysis. Changes in neutrophil counts and RDI were compared between the FN and non-FN groups. RESULTS: One-hundred patients were included in the analysis. The incidence of FN in cycle 1 was 21%. In the multivariate analysis, geriatric nutritional risk index (GNRI) <92 [odds ratio (OR)=13.162, p<0.001] and combination of platelet and neutrophil-to-lymphocyte ratio (COP-NLR) score of 0 (OR=4.619, p=0.012) were independent predictors of FN. The neutrophil count on day 7-10 and RDI in the FN group were lower than those in the non-FN group (all p<0.05). CONCLUSION: GNRI <92 and COP-NLR score of 0 are important indicators to predict patients at high risk of DCF chemotherapy-induced FN. Furthermore, FN incidence after pegfilgrastim administration had a strong effect on delayed neutrophil recovery and reduced RDI.

Selective Separation of Thyroid-Hormone-Receptor-Binding Substances Using Molecularly Imprinted Polymers.

To date, an identification protocol for endocrine disruptors that bind to the thyroid hormone receptor (TR) has not been established. A method for screening and identifying TR-binding substances is highly required due to the existence of unknown TR-binding substances from the environment. Here, we conceived a chromatographic method using a molecularly imprinted polymer (MIP) to create a novel screening protocol for the endocrine disruptors. A receptor-imitating MIP was prepared using N-acetylthyroxine (AcetylT4) and 4-vinylpyridine as a pseudo-template and a functional monomer, respectively, based on the existing molecular recognition mechanism of the TR. The receptor-imitating MIP provided molecular recognition ability for all the TR-binding substances that were employed in this study. The prepared MIPs were packed into a high-performance liquid chromatography column for the simultaneous analysis of TR-binding and non-binding substances. The former was strongly retained, while the latter was not. The presence or absence of TR-binding/non-binding activity resulted in successful dichotomous separation. Additionally, the surface imprinting technique was applied to improve the separation performance of the MIP packing material. MIP-coated uniformly sized silica-based particles of 5 µm were successfully prepared, and the MIP-coated silica column enabled more efficient dichotomous separation of TR-binding and non-binding substances.

Moderate molecular recognitions on ZnO m-plane and their selective capture/release of bio-related phosphoric acids.

Herein, we explore the hidden molecular recognition abilities of ZnO nanowires uniformly grown on the inner surface of an open tubular fused silica capillary via liquid chromatography. Chromatographic evaluation revealed that ZnO nanowires showed a stronger intermolecular interaction with phenylphosphoric acid than any other monosubstituted benzene. Furthermore, ZnO nanowires specifically recognized the phosphate groups present in nucleotides even in the aqueous mobile phase, and the intermolecular interaction increased with the number of phosphate groups. This discrimination of phosphate groups in nucleotides was unique to the rich (101̄0) m-plane of ZnO nanowires with a moderate hydrophilicity and negative charge. The discrimination could be evidenced by the changes in the infrared bands of the phosphate groups on nucleotides on ZnO nanowires. Finally, as an application of the molecular recognition, nucleotides were separated by the number of phosphate groups, utilizing optimized gradient elution on ZnO nanowire column. Thus, the present results elucidate the unique and versatile molecular selectivity of well-known ZnO nanostructures for the capture and separation of biomolecules.

Development of a microfluidic dispensing device for multivariate data acquisition and application in molecularly imprinting hydrogel preparation.

Molecularly imprinted polymers (MIPs) are superior materials with a molecular recognition ability that apply to various applications. In order to get high specificity recognition for target molecules, selecting polymerization conditions, which provide high interaction with the target template, is crucial. However, it requires time and labor to find the optimal polymerization composition, especially for large biomolecules. The advance in the microfluidic field enables researchers to control the flow rate and divide solutions based on the design of microfluidic devices for acquiring multivariate data by simultaneously preparing samples with different conditions. In this work, we fabricated microfluidic dispensing devices with different flow path widths that can give the solution of different flow rates. The accuracy of the flow rate was compared with the simulation value. As a result, the flow rate data showed almost the same data as the simulation value, and the dispensing volume ratio showed high reproducibility. Besides, the multivariate data from mixing the fluorescent molecule and protein solutions prepared by the dispensing device and a micropipette showed no significant difference with existing laboratory equipment. Finally, the dispensing device was used for preparing MIP hydrogels for lysozyme as a template protein. We successfully acquired multivariate data on the adsorption capacity of proteins, as a result, the hydrogels provided a high imprinting factor and adsorption specificity toward lysozymes.

Specific recognition of a target protein, cytochrome c, using molecularly imprinted hydrogels.

Protein imprinted hydrogel, which is one form of protein imprinted molecularly imprinted polymer (MIP), is an important material for enzyme-linked immunosorbent assay, drug delivery materials, sensors, separation materials, etc. To obtain a high protein recognition performance, it is essential to optimize the involved compositions. This work studies a copoly(poly(ethylene glycol) diacrylate/poly(ethylene glycol) acrylate), in short copoly(PEGDA/PEGA), based MIP hydrogel targeting cytochrome c recognition. The presented MIP hydrogel employs water-soluble PEGDA as the crosslinker, PEGA as the side chain, and sodium allylsulfonate as the functional monomer. The fabricated MIP hydrogels and non-imprinted polymer (NIP) hydrogels were treated as adsorbents for protein adsorption. Efforts were made targeting an optimized recognition performance. Factors including the template to functional monomer ratio, crosslinker length, crosslinker ratio of PEGDA/PEGA, ionic strength in the adsorption test, and presence of acidic modifier in the adsorption test were investigated. The results showed that a higher template to functional monomer ratio, a shorter crosslinker, and additional NaCl (20 mM) in the adsorption solvent provided a higher imprinting factor. A lower crosslinker ratio of no less than 6/4 offered a faster template removal; at the same time, the imprinting factor remained at a quite high level. Highly specific recognition of cytochrome c was realized with the presence of an optimized amount of HCl (10 mM) as an acidic modifier.

Development of transient trapping micellar electrokinetic chromatography coupled with mass spectrometry for steroids analysis.

An on-line sample preconcentration technique based on transient trapping (tr-trapping) in micellar electrokinetic chromatography (MEKC) was applied for steroid detection with UV (tr-trapping-UV) and electrospray ionization mass spectrometry detection (tr-trapping-ESI-MS). ESI-MS was used to improve the sensitivity in MEKC. The MEKC separation was carried out using volatile ammonium formate as a background solution to facilitate the coupling with ESI-MS. The partial introduction of a sodium dodecyl sulfate (SDS) micellar solution before the introduction of a sample solution to the capillary provided the effective preconcentration of analytes. At the same time, the SDS micelle would not enter the ESI-MS system, so its interference in ESI-MS detection was suppressed under the optimal condition, then five steroids can be separated by the developed method. In tr-trapping-ESI-MS, an acidic condition of pH 3.5 was employed to suppress the electroosmotic flow, which can avoid micellar solution migrating to the MS instrument. The developed method showed that the micellar solution requires a twofold slower time than the sample to migrate along the column, which can prohibit the cause of the problem with the MS instrument and interference signal of SDS in the steroid's detection. The tr-trapping-ESI-MS protocol showed up to 540-fold enhancements of the peak intensity and 50-fold improvement of the limit of detection compared with capillary zone electrophoresis using androsterone as a model sample.

Open Surgery including Lymphadenectomy without Adjuvant Therapy for Uterine-Confined Intermediate- and High-Risk Endometrioid Endometrial Carcinoma.

Minimally invasive surgery may not be an appropriate surgical approach in intermediate- and high-risk endometrial carcinoma, even though adjuvant therapy is given. The objective of this study was to evaluate the results of open surgery including lymphadenectomy without adjuvant therapy in patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma. Two hundred fifty-six patients with uterine-confined endometrioid endometrial carcinoma were treated with open surgery, including pelvic with or without para-aortic lymphadenectomy. Of the 81 patients with uterine-confined intermediate- or high-risk disease, 77 were treated with systematic lymphadenectomy without adjuvant therapy. Seven patients developed recurrence, comprising 5.5% (3/55) and 18.2% (4/22) of the intermediate- and high-risk patients, respectively. The time to recurrence was 1-66 months. The sites of recurrence were the vaginal apex (n = 2), lung (n = 2), vaginal sidewall (n = 1), pelvic lymph nodes (n = 1), and para-aortic to supraclavicular nodes (n = 1). Of these, five patients were alive without disease after salvage treatment, but two understaged high-risk patients died of disease. The five-year disease-specific survival rates of intermediate- and high-risk patients were 100% and 90%, respectively. The present study indicated that patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma had excellent survival when treated with open surgery, including lymphadenectomy alone. The safety of omitting adjuvant therapy should be evaluated in prospective randomized trials comparing open surgery with minimally invasive surgery.

The clinical outcome of the patients with horizontal semicircular canal variants of benign paroxysmal positional vertigo.

BACKGROUND: Gufoni maneuver is known to be effective for horizontal canal benign positional vertigo (HC-BPPV), but there are some intractable patients that the treatment procedure does not work. OBJECTIVE: The clinical outcomes of patients with HC-BPPV were investigated. We also investigated the characteristics of intractable patients which needed long time to the remission. METHODS: Sixty-six patients with HC-BPPV receiving Gufoni maneuver at Tokyo Medical University Hachioji Medical Center were investigated. The patients were classified into geotropic DCPN group and apogeotropic DCPN group. The clinical outcomes in 2 groups were examined. RESULTS: There were 48 patients with geotropic DCPN and 18 patients with apogeotropic DCPN. There were significant differences between the geotropic HC-BPPV and apogeotropic HC BPPV in the period to remission. There were 7 intractable patients and the average ages of these intractable patients were higher than other patients. CONCLUSION: The patients with geotropic DCPN and the patients with the nystagmus conversion from apogeotropic to geotropic DCPN have tendency to easy to resolve, but in patients with apogeotropic type without nystagmus transformation have long time to resolve. The elderly patients whose nystagmus remains apogeotropic without nystagmus conversion have tendencies to become intractable.

Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.