Effect of oral intake initiation-establishment interval on hospital stay after oral cancer surgery.

OBJECTIVES: To clarify the effect of the period between initiation of oral intake (IOI) and establishment of oral intake (EOI) on length of hospital stay. METHODS: This retrospective study included postoperative oral cancer patients. The number of days from surgery to IOI and EOI and between IOI and EOI were recorded. We performed intergroup comparisons and Cox regression analysis using the number of days until discharge, representing hospital stay length as the dependent variable. RESULTS: The median number of days between IOI and EOI was 3 days for eligible patients and 4.5 and 1.5 for older and younger patients, respectively. The median number of days from surgery to IOI was 15 days. There was a significant correlation between the period between IOI and EOI and the length of hospital stay (r = 0.40, p < 0.01). The period between IOI and EOI was a significant independent variable for the length of hospital stay (HR [95% confidence interval] = 0.45 [0.28-0.72]). CONCLUSIONS: Shortening the IOI to EOI intervals was identified as an independently associated factor for shortening hospital stay, even in older postoperative patients with dysphagia who struggled with early oral intake initiation. Professional, step-by-step dysphagia rehabilitation tailored to the patient's condition yields beneficial outcomes.

Development and evaluation of a new intraoral voice assist device called the voice retriever.

Objective: Patients lose their voice after laryngectomy for laryngeal cancer or aspiration prevention surgery for severe dysphagia. To assist such patients, we developed and verified the utility of a novel vocalization method using a device termed the voice retriever (VR), in which the sound source is placed in the mouth. Methods: We investigated the effectiveness of the VR in patients. The VR consists of a mouthpiece with a built-in speaker and a dedicated application that serves as the sound source. We compared the speech intelligibility and naturalness in normal participants using VR and an electrolarynx (EL) for the first time as well as the voice-related quality of life (V-RQOL) in patients with dysphonia before and after using the VR. Results: The VR produced significantly higher 100-syllable test scores as well as fluency, amount of additional noise, intonation, intelligibility and overall long reading test ratings in the first-time VR and EL users. Furthermore, the VR use significantly improved the V-RQOL of participants with dysphonia. Conclusion: Compared to EL, VR allows more effective speech improvement in participants without experience using an alternative vocalization method and improves the V-RQOL in patients with dysphonia. Level of Evidence: Step 4.

Physical, oral, and swallowing functions of three patients with type a xeroderma pigmentosum: a report of three cases.

BACKGROUND: Xeroderma pigmentosum (XP) is an extremely rare and severe form of photosensitivity. It is classified into types A-G or V according to the gene responsible for the disease. The progression and severity of symptoms vary depending on the type. Although dysphagia caused by decreased swallowing function and dental malposition due to stenosis of the dentition in the facial and oral regions is common, it has not been reported in detail. We report three cases of type A XP, in which central and peripheral neurological symptoms appeared early on and progressed rapidly. We describe the oral function of these patients, focusing on the swallowing function and dentition malposition. CASE PRESENTATION: Two males (27 and 25 years old) and one female (28 years old) presented with diverse neurological symptoms. We focused on the relationship between the changes in swallowing and oral functions and conditions due to decline in physical function. Some effects were observed by addressing the decline in swallowing and oral functions. In particular, a dental approach to manage the narrowing of the dentition, which was observed in all three patients, improved the swallowing and oral functions and maintained the current status of these functions. CONCLUSIONS: In type A XP, early decline in oral and swallowing functions is caused by the early decline in physical function, and it is necessary to monitor the condition at an early stage.

Characteristic hysteroscopy appearance considerations for detecting uterine endometrial malignancies.

AIM: The effectiveness of hysteroscopy in diagnosing endometrial lesions has been demonstrated, showing high diagnostic accuracy for malignant endometrial lesions. Although the characteristic appearances of atypical and malignant endometria have been reported, they are not definitive and sometimes complicated. This study aimed to identify a small number of characteristic features to detect endometrial abnormalities using a simple judgment system and analyze the diagnostic characteristics and their accuracy in endometrial malignancy diagnosis. METHODS: We performed a retrospective analysis of hysteroscopy video data of 250 patients, of which we selected for analysis based on pathology examination 152 cases with benign changes, 16 with atypical endometrium, and 18 with carcinoma in situ or endometrial cancer. Endometrial characteristics assessed included protrusion, desquamation, extended vessel, atypical vessel, and white/yellow lesion. RESULTS: Multivariable analysis revealed that desquamation (p = 0.001, odds ratio [OR] 5.28), atypical vessels (p < 0.001, OR 8.50), and white/yellow lesions (p = 0.011, OR 1.37) were significant predictors for endometrial malignancy. From their contribution status, scoring points of 4, 6, and 1 were settled according to the odds ratio proportions. When scores ≥5 (at least both desquamation and white/yellow lesions or only atypical vessels) were used to define endometrial malignancy, sensitivity and specificity were 100% and 92%, respectively. When detecting cancer, atypical, and benign cases, sensitivity and specificity were 88% and 90%, respectively. CONCLUSION: Our characteristics hysteroscopic findings showed a higher predictive ability in detecting endometrial malignancies. However, further examination with more cases would be needed to accurately diagnose endometrial malignancy by hysteroscopy.

Kinematic analysis of chewing and swallowing function after cervical spine surgery.

PURPOSE: Although movement of the hyoid bone is different for masticatory swallowing and liquid swallowing in normal subjects, it has not been studied after cervical spine surgery. Therefore, we analyzed the swallowing dynamics of masticatory swallowing in anterior cervical spine disease surgery using foods that require chewing close to actual meals. METHODS: A day before and one week after the surgery, a videofluoroscopic swallow study (VFSS) was performed, and the distance of hyoid bone movement in the anterior and superior directions, amount of opening of the upper esophageal sphincter (UES), time of passage through the pharynx, number of swallows, and amount of pharyngeal residual were measured on the VFSS images during a masticatory swallow of corn flakes. The swallowing function was evaluated by DSS (dysphagia severity scale) and FOIS (functional oral intake scale). Imaging software was used for the measurements. RESULTS: Postoperative hyoid movement during masticatory swallowing was not significantly different for anterior movement but significantly limited in upward movement (p = 0.002); UES opening volume was significantly decreased (p < 0.001), and bolus residue was significantly worse (p < 0.001), compared to preoperative. The pharyngeal transit time was not significantly different; the number of swallows increased (p < 0.001), along with DSS (p < 0.001) and FOIS (p < 0.001), with significant differences before and after surgery, indicating worsened swallowing function. CONCLUSIONS: Swallowing function worsened in masticatory swallowing after surgery for cervical spine disease, mainly due to the restriction of upward movement of the hyoid bone and the resulting increase in pharyngeal residuals after swallowing.

Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma.

The purpose of this study is to clarify the metabolic dependence of ovarian clear cell carcinoma (CCC) by comparing normal tissues and to examine the applicability of fluorescence imaging probe to exploit these metabolic differences. Enhanced glutathione synthesis was supported by the increased uptake of related metabolites and elevated expression levels of genes. Accumulation of intracellular iron and lipid peroxide, induction of cell death by inhibition of the glutathione synthesis pathway indicated that ferroptosis was induced. The activation of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent imaging probe that recognizes γ-glutamyl transferase, which is essential for the synthesis of glutathione, was investigated in fresh-frozen surgical specimens. gGlu-HMRG detected extremely strong fluorescent signals in the tumor lesions of CCC patients, compared to normal ovaries or endometrium. These results revealed that CCC occurs in the stressful and unique environment of free radical-rich endometrioma, and that glutathione metabolism is enhanced as an adaptation to oxidative stress. Furthermore, a modality that exploits these metabolic differences would be useful for distinguishing between CCC and normal tissues.

Free-flap volume correlates with body mass index in patients with tongue squamous cell carcinoma.

Objectives: This study aimed to investigate the relationship between postoperative reconstructed tongue flap volume (RTFV) and body mass index (BMI) and identify factors affecting the flap volume in patients with tongue squamous cell carcinoma. Methods: Thirty-two patients were evaluated for RTFV from computed tomography images and BMI. The first and second evaluations were done at 6 months and 1.5 years after surgery respectively. RTFV rate changes and BMI differences from the first and second evaluations were calculated. The correlation between RTFV rate change and BMI difference was assessed using Spearman's rank correlation coefficient. Multiple regression analysis evaluated the relationship between the flap volume rate change and age, sex, flap type, and BMI difference to identify influencing factors. Results: The flap volume rate change and BMI difference correlated significantly (r = .594, p < .05). BMI difference and flap type were independent factors that affected reconstructed flap volume rate change in multiple regression analysis (p < .05). Conclusion: The flap volume of patients with tongue squamous cell carcinoma correlates with the BMI change in the chronic phase. Patients after tongue reconstruction need to be well nourished to maintain BMI and thus postoperative tongue volume to maintain the quality of life. Level of Evidence: Level 3.

Phase Ib/II Study of a Liposomal Formulation of Eribulin (E7389-LF) plus Nivolumab in Patients with Advanced Solid Tumors: Results from Phase Ib.

Purpose: To determine a recommended dose of liposomal eribulin (E7389-LF) in combination with nivolumab in patients with advanced solid tumors, and to evaluate the safety, efficacy, pharmacokinetics, and biomarker impact of this regimen. Experimental Design: Japanese patients with advanced, nonresectable, or recurrent solid tumors and no existing alternative standard/effective therapy (except nivolumab monotherapy) were assigned to either E7389-LF 1.7 mg/m2 plus nivolumab 360 mg every 3 weeks, E7389-LF 2.1 mg/m2 plus nivolumab 360 mg every 3 weeks, E7389-LF 1.1 mg/m2 plus nivolumab 240 mg every 2 weeks, or E7389-LF 1.4 mg/m2 plus nivolumab 240 mg every 2 weeks. Primary objectives were to evaluate the safety/tolerability of each dose cohort and to determine the recommended phase II dose (RP2D). Secondary/exploratory objectives, including safety [dose-limiting toxicities (DLT) and adverse events (AE)], pharmacokinetics, efficacy [including objective response rate (ORR)], and biomarker results were used in determining the RP2D. Results: Twenty-five patients were enrolled to treatment [E7389-LF 1.7 mg/mg2 every 3 weeks (n = 6), E7389-LF 2.1 mg/m2 every 3 weeks (n = 6), E7389-LF 1.1 mg/m2 every 2 weeks (n = 7), E7389-LF 1.4 mg/m2 every 2 weeks (n = 6)]. Twenty-four patients were evaluated for DLTs, of whom 3 had DLTs (1 at E7389-LF 1.7 mg/m2 every 3 weeks, 1 at 1.1 mg/m2 every 2 weeks, and 1 at 1.4 mg/m2 every 2 weeks). All patients had ≥1 treatment-related treatment-emergent AE (TEAE); 68.0% had ≥1 grade 3-4 treatment-related TEAE. Changes in vasculature and IFN-related biomarkers were seen in each cohort. The overall ORR was 16%. Conclusions: E7389-LF plus nivolumab was tolerable overall; the recommended dose for future study was 2.1 mg/m2 plus nivolumab 360 mg every 3 weeks. Significance: This phase Ib part of a phase Ib/II study assessed the tolerability and activity of a liposomal formulation of eribulin (E7389-LF) plus nivolumab in 25 patients with advanced solid tumors. The combination was tolerable overall; 4 patients had a partial response. Vasculature and immune-related biomarker levels increased, suggesting vascular remodeling.

Outcomes of adult patients with early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) and non-ETP T-ALL.

Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) is generally considered to be a high-risk subtype. We retrospectively analyzed the clinical outcomes of adult patients diagnosed with ETP-ALL or other T-cell ALL (non-ETP T-ALL). The subjects were 82 patients (ETP-ALL: n = 18, non-ETP T-ALL: n = 64) for whom relevant immunophenotype data needed for classification were available. ETP-ALL patients were older (median age, 50.5 vs. 33.5 years, P = 0.042) and had less mediastinal involvement (27.8 vs. 73.4%, P < 0.001). The rate of complete remission (CR) with the first induction therapy was significantly lower in the ETP group (33.3 vs. 64.0%, P = 0.03), but the CR rate within 2 cycles of chemotherapy did not differ significantly (61.1 vs. 76.6%, P = 0.232). The 3-year overall survival (OS) rate was also similar in both groups (43.2 vs. 45.8%, P = 0.992). The ETP phenotype had no impact on survival in the transplant group or the non-transplant group. A multivariate analysis identified the male sex as a poor prognostic factor (HR: 4.43, P < 0.01), but not the immunophenotype of ETP. The prognosis for adult patients with ETP-ALL was comparable to that of non-ETP T-ALL patients. However, further studies aimed at improving the remission rate for ETP-ALL are needed.

Application of organoid culture from HPV18-positive small cell carcinoma of the uterine cervix for precision medicine.

BACKGROUND: Small cell carcinoma of the uterine cervix (SCCC) is a rare and highly malignant human papillomavirus (HPV)-associated cancer in which human genes related to the integration site can serve as a target for precision medicine. The aim of our study was to establish a workflow for precision medicine of HPV-associated cancer using patient-derived organoid. METHODS: Organoid was established from the biopsy of a patient diagnosed with HPV18-positive SCCC. Therapeutic targets were identified by whole exome sequencing (WES) and RNA-seq analysis. Drug sensitivity testing was performed using organoids and organoid-derived mouse xenograft model. RESULTS: WES revealed that both the original tumor and organoid had 19 somatic variants in common, including the KRAS p.G12D pathogenic variant. Meanwhile, RNA-seq revealed that HPV18 was integrated into chromosome 8 at 8q24.21 with increased expression of the proto-oncogene MYC. Drug sensitivity testing revealed that a KRAS pathway inhibitor exerted strong anti-cancer effects on the SCCC organoid compared to a MYC inhibitor, which were also confirmed in the xenograft model. CONCLUSION: In this study, we confirmed two strategies for identifying therapeutic targets of HPV-derived SCCC, WES for identifying pathogenic variants and RNA sequencing for identifying HPV integration sites. Organoid culture is an effective tool for unveiling the oncogenic process of rare tumors and can be a breakthrough for the development of precision medicine for patients with HPV-positive SCCC.

Analysis of swallowing function after anterior/posterior surgery for cervical degenerative disorders and factors related to the occurrence of postoperative dysphagia.

BACKGROUND CONTEXT: Dysphagia is one of the postoperative complications of cervical degenerative disorders. However, few studies have evaluated the pre- and postoperative swallowing function in detail. PURPOSE: To analyze pre- and postoperative swallowing dynamics kinetically and investigate factors associated with postoperative dysphagia in patients with cervical degenerative disorders. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: A total of 41 consecutive patients who underwent an anterior approach (anterior cervical discectomy/corpectomy and fusion (ACDF, ACCF), hybrid surgery (ACDF+ACCF) and total disc replacement) and 44 consecutive patients who underwent a posterior approach (laminoplasty and laminoplasty/laminectomy with fusion). OUTCOME MEASURES: We compared the pre- and postoperative functional oral intake scale (FOIS), dysphagia severity scale (DSS), esophageal dysphagia, anterior/superior hyoid movement, upper esophageal sphincter (UES) opening, pharyngeal transit time, bolus residue scale (BRS), and the number of swallows. METHODS: Videofluoroscopy was performed on the day before surgery and within two weeks after surgery. Data related to age, gender, disease, surgical procedure, surgical site, operative time, and blood loss were collected from the medical records. Pre- and postoperative data were compared for each item in the anterior and posterior approaches. The odds ratio of dysphagia after an anterior approach was also calculated. RESULTS: In the anterior approach, DSS, FOIS, the anterior and superior hyoid movements, maximum UES opening, BRS, and number of swallows worsened postoperatively (p<.05, respectively). In the posterior approach, DSS, FOIS, the anterior hyoid movement, and BRS worsened postoperatively (p<.05, respectively). The factors associated with dysphagia were a proximal surgical site above C3 (OR: 14.40, CI: 2.84-73.02), blood loss >100 mL (OR: 9.60, CI: 2.06-44.74), an operative time >200 minutes (OR: 8.18, CI: 1.51-44.49), and an extensive surgical field of more than three intervertebral levels (OR: 6.72, CI: 1.50-30.07). The decline in swallowing function after the posterior approach was related to aging (p=.045). CONCLUSIONS: Each approach may decrease swallowing function, especially because of the limitation on the anterior hyoid movement. Dysphagia after anterior approaches was associated with the operative site, operative time, and blood loss.

Predictors and outcomes of ischemia-driven target lesion revascularization in deferred lesion based on fractional flow reserve: a multi-center retrospective cohort study.

Background: Fractional flow reserve (FFR) has become the gold standard for diagnosing ischemia in angiographically intermediate epicardial coronary artery stenosis. This study investigated the clinical outcomes and predictors of revascularization deferral based on FFR. Methods: In this retrospective cohort study, we assessed 474 lesions (440 patients) where revascularization was deferred based on the FFR value. Minimum lumen diameter and %-diameter stenosis were measured. Calcification was graded as none, mild, moderate, or heavy. The synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score I was also determined. The primary outcome was ischemia-driven target lesion revascularization (TLR) in deferred lesions within 3 years. Patients were also assigned into two groups based on FFR value. Results: The average age of the patients was 69.7±10.4 years. The average FFR value was 0.86±0.05. Stable angina pectoris was noted in 298 (67.7%) cases, and in-stent restenosis (ISR) was present in 28 (5.9%). The average SYNTAX score was 7.2±4.2. The 3-year ischemia-driven TLR was 18 lesions (3.8%). Cox proportional hazard model revealed that the SYNTAX score and ISR were independent predictors for TLR in deferred lesions [hazard ratio (HR) =1.10, 95% confidential interval (CI): 1.01-1.19, P=0.03; HR =6.33; 95% CI: 2.25-17.8, P<0.01, respectively]. The deferral group, with a low FFR value, tended to have higher TLR rates than other groups. Conclusions: Lesions with lower FFR values were associated with a higher incidence of ischemia-driven TLR than those with higher FFR values. SYNTAX score and ISR were predictors for ischemia-driven TLR at 3 years in the deferred lesions.

Design, Synthesis, and Anticancer Activity of Triptycene-Peptide Hybrids that Induce Paraptotic Cell Death in Cancer Cells.

We report on the design and synthesis of triptycene-peptide hybrids (TPHs), 5, syn-6, and anti-6, which are conjugates of a triptycene core unit with two or three cationic KKKGG peptides (K: lysine and G: glycine) through a C8 alkyl chain. It was discovered that syn-6 and anti-6 induce paraptosis, a type of programmed cell death (PCD), in Jurkat cells (leukemia T-lymphocytes). Mechanistic studies indicate that these TPHs induce the transfer of Ca2+ from the endoplasmic reticulum (ER) to mitochondria, a loss of mitochondrial membrane potential (ΔΨm), tethering of the ER and mitochondria, and cytoplasmic vacuolization in the paraptosis processes.

Induction of Paraptosis by Cyclometalated Iridium Complex-Peptide Hybrids and CGP37157 via a Mitochondrial Ca2+ Overload Triggered by Membrane Fusion between Mitochondria and the Endoplasmic Reticulum.

We previously reported that a cyclometalated iridium (Ir) complex-peptide hybrid (IPH) 4 functionalized with a cationic KKKGG peptide unit on the 2-phenylpyridine ligand induces paraptosis, a relatively newly found programmed cell death, in cancer cells (Jurkat cells) via the direct transport of calcium (Ca2+) from the endoplasmic reticulum (ER) to mitochondria. Here, we describe that CGP37157, an inhibitor of a mitochondrial sodium (Na+)/Ca2+ exchanger, induces paraptosis in Jurkat cells via intracellular pathways similar to those induced by 4. The findings allow us to suggest that the induction of paraptosis by 4 and CGP37157 is associated with membrane fusion between mitochondria and the ER, subsequent Ca2+ influx from the ER to mitochondria, and a decrease in the mitochondrial membrane potential (ΔΨm). On the contrary, celastrol, a naturally occurring triterpenoid that had been reported as a paraptosis inducer in cancer cells, negligibly induces mitochondria-ER membrane fusion. Consequently, we conclude that the paraptosis induced by 4 and CGP37157 (termed paraptosis II herein) proceeds via a signaling pathway different from that of the previously known paraptosis induced by celastrol, a process that negligibly involves membrane fusion between mitochondria and the ER (termed paraptosis I herein).

Hemoptysis due to progressive scoliosis associated with congenital heart disease: a case report.

BACKGROUND: Patients with congenital heart disease (CHD) are associated with an increased incidence of scoliosis, often with severe progression. We report a case of hemoptysis caused by rapid scoliosis progression subsequent to surgery for CHD that was successfully managed by surgical curve correction following coil embolization. CASE PRESENTATION: A 14-year-old girl with scoliosis had undergone open heart surgery for CHD at the age of 1 year. She was first noted to have scoliosis at 12 years of age, which began to progress rapidly. At age 13, her main thoracic curve Cobb angle was 46°, and hemoptysis with high pulmonary vein pressure due to vertebral rotation was detected. Nine months after coil embolization, she received posterior spinal fusion from T5 to L2 for scoliosis correction. Postoperatively, her pulmonary vein diameter was enlarged, with no detectable signs of hemoptysis. CONCLUSIONS: We encountered a case of hemoptysis caused by advanced scoliosis after cardiac surgery that was successfully treated by correction of the scoliotic curve following coil embolization. Patients with secondary scoliosis after surgery for CHD should be carefully monitored for the possibility of cardiovascular system deterioration.

Dose Escalation Data from the Phase 1 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Japanese Patients with Advanced Solid Tumors.

PURPOSE: We report the dose-escalation part of a phase I study of liposomal eribulin (E7389-LF) in Japanese patients with advanced solid tumors and no alternative standard therapy. PATIENTS AND METHODS: Patients ≥20 years old were enrolled. E7389-LF doses of 1.0 to 1.5 mg/m2 once every two weeks (Q2W) or 1.0 to 2.5 mg/m2 once every three weeks (Q3W) were planned. The primary objective was to determine the MTD by evaluating dose-limiting toxicities (DLT). Secondary objectives included safety/tolerability assessments, objective response rate (ORR), and progression-free survival; serum biomarker assessment was an exploratory objective. RESULTS: Twenty-one patients were enrolled and treated; 12 in the Q3W group (1.0 mg/m2, n = 3; 1.5 mg/m2, n = 3; 2.0 mg/m2, n = 6) and 9 in the Q2W group (1.0 mg/m2, n=3; 1.5 mg/m2, n = 6). The Q3W and Q2W MTDs were 2.0 mg/m2 and 1.5 mg/m2, respectively. One patient receiving 2.0 mg/m2 Q3W had a DLT of grade 3 febrile neutropenia. The most common grade 3 treatment-emergent adverse events were neutropenia (66.7% in Q3W and Q2W) and leukopenia (Q3W, 58.3%; Q2W, 33.3%). One patient in the Q3W group (2.0 mg/m2) and 3 in the Q2W group (1.0 mg/m2, n = 1; 1.5 mg/m2, n = 2) achieved a partial response [overall ORR, 19.0%; 95% confidence interval (CI), 5.4-41.9]. Endothelial [TEK receptor tyrosine kinase (TEK), intercellular adhesion molecule 1 (ICAM1), vascular endothelial growth factor receptor 3 (VEGFR3), platelet/endothelial cell adhesion molecule 1 (PECAM1)], vasculature (collagen IV), and immune-related [interferon gamma (IFNγ), C-X-C motif chemokine ligand 11 (CXCL11), C-X-C motif chemokine ligand 10 (CXCL10)] biomarker levels were increased. CONCLUSIONS: E7389-LF was well tolerated at 2.0 mg/m2 Q3W and 1.5 mg/m2 Q2W. Considering the toxicity profile of both regimens, the recommended dose was 2.0 mg/m2 Q3W. Expansion cohorts are ongoing.

Can Videofluoroscopic Swallowing Kinematic Analysis Predict Recovery of Oral Intake in Postoperative Oral Cancer Patients Requiring Nasogastric Tube Feeding?

This retrospective study determined the significant predictive factors for the number of days required to remove nasogastric tubes (NGTs) after surgery in patients with oral cancer (OC). In this study, patients underwent a videofluoroscopic swallowing study (VFSS) approximately 2 weeks after surgery. Videofluoroscopic images were analyzed, and variables such as swallowing and swallowing kinematics were measured. Patient characteristics, swallowing kinematics, and swallowing results were assessed using a Cox proportional hazards model. This study assessed 129 participants (66 men, 63 women, mean age: 69.0 ± 14.1 years) with nine types of cancer. The Cox proportional hazard ratio revealed that sex, body mass index before surgery, radiotherapy and/or chemotherapy, dysphagia before surgery, normalized pharyngeal constriction ratio, upper esophageal sphincter (UES) opening, and laryngeal vestibule disclosure (LVC) disorder were predictive factors for the removal of NGTs when adjusted for age. The study identified several predictive factors for the removal of NGTs and oral intake recovery in patients with OC. Regarding swallowing kinematics, UES opening is the most significant predictive factor. After surgery for OC, VFSS should be performed to assess safe eating methods and predict the recovery of oral intake and removal of the NGT.

Intraperitoneal Administration of a Cisplatin-Loaded Nanogel through a Hybrid System Containing an Alginic Acid-Based Nanogel and an In Situ Cross-Linkable Hydrogel for Peritoneal Dissemination of Ovarian Cancer.

Intraperitoneal chemotherapy demonstrates potential applicability in the treatment of peritoneally disseminated ovarian cancer because the disseminated tumors can directly receive exposure to high concentrations of anticancer drugs. However, a considerable proportion of drugs, particularly micromolecular and hydrophilic drugs, such as cisplatin (CDDP), are often excreted through glomerular filtration for a short period. To effectively deliver CDDP into peritoneally disseminated ovarian cancer tissues, we developed an alginate (AL)-based hybrid system in which a CDDP-loaded AL nanogel (AL/CDDP-nanogel) was encapsulated in an injectable AL-hydrogel cross-linked with calcium ions. This system enabled the sustained release of CDDP from the AL/CDDP-nanogel/AL-hydrogel hybrid for over a week. Herein, we constructed a peritoneally disseminated ovarian cancer mouse model using ovarian cancer cell lines with KRAS mutations (ID8-KRAS: KRASG12V). The AL/CDDP-nanogel/AL-hydrogel hybrid system showed significant antitumor activity in vivo. This therapy may be considered a novel strategy for the treatment of advanced-stage ovarian cancer with KRAS mutations.

Enhanced antitumor activity of combined lipid bubble ultrasound and anticancer drugs in gynecological cervical cancers.

Chemotherapy plays an important role in the treatment of patients with gynecological cancers. Delivering anticancer drugs effectively to tumor cells with just few side effects is key in cancer treatment. Lipid bubbles (LB) are compounds that increase the vascular permeability of the tumor under diagnostic ultrasound (US) exposure and enable the effective transport of drugs to tumor cells. The aim of our study was to establish a novel drug delivery technique for chemotherapy and to identify the most effective anticancer drugs for the bubble US-mediated drug delivery system (BUS-DDS) in gynecological cancer treatments. We constructed xenograft models using cervical cancer (HeLa) and uterine endometrial cancer (HEC1B) cell lines. Lipid bubbles were injected i.v., combined with either cisplatin (CDDP), pegylated liposomal doxorubicin (PLD), or bevacizumab, and US was applied to the tumor. We compared the enhanced chemotherapeutic effects of these drugs and determined the optimal drugs for BUS-DDS. Tumor volume reduction of HeLa and HEC1B xenografts following cisplatin treatment was significantly enhanced by BUS-DDS. Both CDDP and PLD significantly enhanced the antitumor effects of BUS-DDS in HeLa tumors; however, volume reduction by BUS-DDS was insignificant when combined with bevacizumab, a humanized anti-vascular endothelial growth factor mAb. The BUS-DDS did not cause any severe adverse events and significantly enhanced the antitumor effects of cytotoxic drugs. The effects of bevacizumab, which were not as dose-dependent as those of the two drugs used prior, were minimal. Our data suggest that BUS-DDS technology might help achieve "reinforced targeting" in the treatment of gynecological cancers.

Tongue-pressure resistance training improves tongue and suprahyoid muscle functions simultaneously.

PURPOSE: Producing tongue pressure (TP) by pushing the tongue against the palate consists of lifting the tongue muscles and elevating the floor of the mouth via suprahyoid muscle contraction. Though studies have shown that tongue-pressure resistance training (TPRT) increases tongue function, none have focused on suprahyoid muscle function enhancements. Our study aimed to verify whether TPRT improves both tongue function and hyoid movement during swallowing. MATERIALS AND METHODS: Eighteen patients (mean age: 76.8±6.2 years) with presbyphagia presenting with symptoms such as coughing and choking were enrolled. All patients performed daily living activities independently. None of the participants had diseases causing dysphagia or previous oral or pharyngeal surgery. Participants were instructed to push their tongues against the palate as hard as possible with their mouths closed for 10 seconds, and then resting for 10 seconds. A set consisted of five consecutive exercise and resting periods; two sets per day were performed for a month. TP and the oral diadochokinetic rate (ODKR), measured by repetitions of the syllables /ta/ and /ka/, assessed tongue function. The extent of anterior and superior hyoid movement and parameters related to swallowing, including the penetration aspiration scale (PAS) and the normalized residue ratio scale (NRRS) in the valleculae (NRRSv) and piriform sinus (NRRSp), were evaluated based on videofluoroscopic data. RESULTS: The anterior (P=0.031) and superior hyoid movement (P=0.012), TP (P=0.002), ODKR/ta/ (P=0.034), ODKR/ka/ (P=0.009), and the width of the upper esophageal sphincter (P=0.001) were larger at follow-up than at baseline. NRRSp (P=0.022), PAS (P=0.016), and pharyngeal transit times (P=0.004) were smaller at follow-up than at baseline. CONCLUSION: TPRT improved tongue strength, dexterity, both anterior and superior hyoid elevation, and swallowing functions. Therefore, TPRT could improve tongue function and suprahyoid muscle function simultaneously and contribute to prevention of sarcopenic dysphagia.