Preoperative docetaxel, cisplatin, and 5-fluorouracil for resectable locally advanced esophageal and esophagogastric junctional adenocarcinoma.

BACKGROUND: Chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel is the standard perioperative treatment for resectable esophageal adenocarcinoma and esophagogastric junctional adenocarcinoma (EGJ-AC) in Western countries. Meanwhile, preoperative chemotherapy consisting of docetaxel, cisplatin, and 5-fluorouracil (DCF) has been developed for esophageal squamous cell carcinoma in Japan. However, there are few reports on the safety and efficacy of preoperative DCF for resectable EGJ-AC in the Japanese population. METHODS: Patients with histologically confirmed resectable EGJ-AC who received preoperative DCF (docetaxel 70 mg/m2 and cisplatin 70 mg/m2 on day 1 and continuous infusion of 5-fluorouracil 750 mg/m2/day on days 1-5 every 3 weeks with a maximum of three cycles) between January 2015 and April 2020 were retrospectively evaluated. We assessed the rates of completion of ≥ 2 courses of DCF and R0 resection, histopathological response, progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: Thirty-two patients were included. Median follow-up was 28.7 (range, 5.2-70.8) months and median age was 63 (range, 42-80) years. Twenty-one patients (66%) had a performance status of 0. The proportions of clinical stage IIA/IIB/III/IVA/IVB disease were 3%/0%/44%/44%/9%, respectively. The treatment completion rate was 84%. A histopathological response of grade 1a/1b/2/3 was obtained in 58%/26%/13%/3% of cases. Median PFS was 40.7 months (95% confidence interval 11.8-NA). Median OS was not reached (80.8% at 3 years). Grade ≥ 3 adverse events were observed in 63% of cases (neutropenia, 44%; febrile neutropenia, 13%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative DCF for resectable EGJ-AC was well tolerated and has promising efficacy.

Comparison of Survival Outcomes Between Larynx-Preserving Open Partial Pharyngectomy and Radiotherapy or Chemoradiotherapy in Patients with Hypopharyngeal Squamous Cell Carcinoma: A Single-Center Retrospective Analysis with Inverse Probability of Treatment Weighting Adjustments.

BACKGROUND: There is a group of hypopharyngeal squamous cell carcinoma (HPSCC) patients for whom larynx-preserving open partial pharyngectomy (PP) and radiotherapy/chemoradiotherapy (RT/CRT) are indicated. We aimed to retrospectively evaluate the survival difference as there is no evidence directly comparing the two therapies. METHODS: This study evaluated HPSCC patients who were initially treated by PP or RT/CRT at our institution between January 2007 and October 2019. Overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival (LFS), and local relapse-free survival (LRFS) were evaluated. The main analyses were performed with inverse probability of treatment weighting (IPTW) adjustments. Sensitivity analyses compared hazard ratios (HRs) obtained with three models: unadjusted, multivariate Cox regression, and propensity score-adjusted. RESULTS: Overall, 198 patients were enrolled; 63 and 135 underwent PP and RT/CRT, respectively. IPTW-adjusted 5-year OS, DSS, LFS, and LRFS rates in the PP and RT/CRT groups were 84.3% and 61.9% (p = 0.019), 84.9% and 75.8% (p = 0.168), 94.8% and 90.0% (p = 0.010), and 75.9% and 74.1% (p = 0.789), respectively. In the IPTW-adjusted regression analysis, PP was associated with a significant benefit regarding OS (HR 0.48, 95% confidence interval [CI] 0.26-0.90) and LFS (HR 0.17, 95% CI 0.04-0.77). The results obtained with the three models in the sensitivity analyses were qualitatively similar to those of the IPTW-adjusted models. CONCLUSION: Despite the risk of bias related to unadjusted factors, our results suggest that PP is associated with significantly better OS and LFS compared with RT/CRT for HPSCC.

[A Case of Robot-Assisted Laparoscopic Surgery for Stenotic Sigmoid Colon Cancer with Simultaneous Lateral Lymph Node Metastasis].

The patient is a 63-year-old man. He visited his previous physician for abdominal pain. After close examinations, he was diagnosed with stenotic sigmoid colon cancer with left lateral lymph node metastasis. On the same day, colonic stenting was performed to relieve the symptoms of stenosis. After 1 month of stenting, a robot-assisted laparoscopic sigmoid colectomy and left lateral lymph node dissection were performed. Postoperative pathological examination revealed regional lymph node metastasis and left lateral lymph node metastasis(#283); the patient was diagnosed with pT4aN1bM1a(LYM), fStage Ⅳa. The patient was discharged on postoperative day 10, and is stable 5 months after surgery without recurrence. This case suggests that robot-assisted laparoscopic lateral lymph node dissection can be effective even in atypical cases of sigmoid colon cancer with lateral lymph node metastasis.

Safety and short-term efficacy of preoperative FOLFOX therapy in patients with resectable esophageal squamous cell carcinoma who are ineligible for cisplatin.

BACKGROUND: The standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (LAESCC) in Japan is docetaxel, cisplatin (CDDP), and 5-fluorouracil. However, patients with renal or cardiac dysfunction and elderly patients are ineligible for a CDDP-containing regimen because of toxicities. Oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) therapy has less renal toxicity than CDDP-containing regimens and does not require hydration. However, there are limited data on preoperative FOLFOX therapy in these patients. METHODS: This retrospective study analyzed patients with resectable LAESCC who were aged ≥ 75 years or had renal or cardiac dysfunction and received preoperative FOLFOX between 2019 and 2021. FOLFOX was administered every 2 weeks for 3 or 4 cycles and was followed by surgery. Adverse events associated with chemotherapy, the complete resection (R0) rate, relative dose intensity (RDI), and histopathological response were evaluated. RESULTS: Thirty-five patients were eligible. Median age was 77 (range 65-89) years; 68.6% were aged ≥ 75 years, 74.3% had renal dysfunction, and 17.1% had cardiac dysfunction. The RDI was 70.2% and 87.1% for bolus and continuous intravenous 5-fluorouracil, respectively and 85.2% for oxaliplatin. The most common grade ≥ 3 adverse events were neutropenia (60.0%) and leucopenia (28.6%). Two patients (5.7%) had febrile neutropenia and grade 3 pneumonia. Thirty-one patients underwent surgery. The R0 resection rate was 87.1%, and there was no histopathological evidence of residual tumor in 16.1%. There were no treatment-related deaths. CONCLUSIONS: Preoperative FOLFOX had a manageable safety profile and showed favorable short-term efficacy in patients with resectable LAESCC who were ineligible for CDDP-containing treatment.

Peer Support Formation and the Promotion of Recovery Among People Using Psychiatric Day Care in Japan.

The present study aimed to clarify the process of peer support formation and the promotion of recovery in people using psychiatric day care. From January to March 2014, semi-structured interviews were conducted with 18 participants with mental illness living in the community in Japan. The qualitative data were analyzed using a modified grounded theory approach. The results described a two-stage process: (1) awareness of peers with similar disability and distress and (2) formation and utilization of peer support. These results suggest that adjusting the environment and engaging in activities assisting others are useful for facilitating peer support and promoting the recovery of users in psychiatric day care.

[A Case of Metastatic Breast Cancer with BRCA1 Mutation after Breast Reconstruction and Pregnancy].

We present the case of a 31-year-old woman with a chief complaint of a left breast mass. The patient visited our department for an evaluation of this left breast mass. Left breast cancer(cT1cN0M0, cStage Ⅰ, triple negative type)was diagnosed, and left partial mastectomy and sentinel node biopsy were performed. Although the pStage was the same prior to surgery, a BRCA1 mutation was identified on genetic testing. After administration of postoperative adjuvant chemotherapy (epirubicin, cyclophosphamide, and paclitaxel), consorted mastectomy, tissue expander insertion, and breast reconstruction with silicone implant were performed. Spontaneous pregnancy occurred 1 year and 10 months after the first operation. She had an uneventful delivery with a normal course of labor 2 years and 6 months after the surgery. Two years and 11 months after the first operation, she visited our institution with complaints of headache, dizziness, and difficulty eating. Upon assessment, brain, lung, liver, and bone metastases were identified on contrast-enhanced computed tomography. Concentrated glycerin and fructose, steroid administration, and whole-brain irradiation improved the symptoms due to cerebral edema. Thereafter, olaparib was started, and treatment was continued while maintaining partial response(PR).

An autopsy case of pulmonary tumor thrombotic microangiopathy that developed during chemotherapy for salivary duct carcinoma of the parotid gland.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive cancer-related disease with a dismal clinical course. The patient in this report was a 43-year-old man with metastatic salivary duct carcinoma arising from the parotid gland. Combined androgen blockade therapy was administered started as first-line treatment, but failed after 5 months, followed by docetaxel plus carboplatin therapy as second-line treatment, which failed after 3 months. Genomic profiling revealed a BRAF V600E mutation, and combined BRAF and MEK inhibitor therapy was started as third-line treatment. The cancer remained stable during the first 10 months of third-line treatment, but treatment was subsequently discontinued due to the onset of symptoms of fatigue, myalgia and arthritis. Twenty days after the onset of these symptoms and interruption of third-line treatment, the patient was urgently admitted to hospital with respiratory distress and severe thrombocytopenia. CT images at the time of admission led our radiologist to the possibility of PTTM, but the patient died the day after admission and autopsy findings indicated that PTTM was the cause of death. This report describes a very informative case of PTTM with sequential imaging and detailed autopsy findings were available and provides a literature review.

Development of the Self-Assessment Self-Disclosure Questionnaire to Examine the Association between Self-Disclosure and Frailty among Community-Dwelling Older Adults in Japan.

Self-disclosure is the attitude of communicating one's experiences and condition to others and is an indicator of mental health and an open personality. Frailty, characterized by reduced physical and psychological resistance, predicts the incidence of dependency and mortality. Although low self-disclosure may be associated with frailty, there is no scale to measure older adults' self-disclosure. This cross-sectional study assessed the validity of a self-assessment self-disclosure questionnaire and examined the association between the content of self-disclosures to friends and acquaintances and frailty among community-dwelling older adults. A total of 237 adults aged ≥65 in Japan were surveyed using a mailed self-administered questionnaire in 2021. The self-disclosure scale consisted of 10 items and showed adequate validity. Participants were classified into a robust group (n = 117, women 57.3%) and a frailty group (n = 120, women 73.3%) using the Kihon Checklist. After adjusting for covariates, multivariate-adjusted logistic regression models revealed frailty was associated with lower self-disclosure of recent positive events, motivation and strengths (indicating strong points) in life, relationships with family and relatives, experiences of work and social activities, and financial status. The proposed questionnaire must still be further tested in other populations, but our initial results may contribute to preventing frailty and improving mental health among community-dwelling older adults.

Efficacy and Safety of Salvage-line Nivolumab Monotherapy for Advanced Esophageal Squamous Cell Carcinoma: Comparison of 240 mg Versus 480 mg Doses.

BACKGROUND: Nivolumab monotherapy is the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) after failure of platinum-based chemotherapy without anti-PD-1 antibody. Fixed dosing with 240 mg every 2 weeks was approved initially, followed by fixed dosing with 480 mg every 4 weeks based on pharmacokinetics data. However, information on the comparative efficacy and safety of the two doses remains limited. METHODS: We compared progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and the incidence of adverse events (AEs) between the two doses in 117 patients who received second-line (n = 85) or later-line (n = 32) nivolumab monotherapy at our institution between January 2016 and December 2021. RESULTS: In the second-line group, patient characteristics for the 240 mg and 480 mg groups were as follows (240 mg vs. 480 mg): performance status (PS) 0/1/2 was 34/61/5% vs. 54/42/4%, and prior fluoropyrimidine plus platinum therapy (FP) was 81.3% vs. 42.3%. In the later-line group, the characteristics were: PS 0/1/2 was 28/60/12% vs. 14/86/0%, and prior FP was 60.0% vs. 42.8%. ORR was 11.9 vs. 24.0% in the second-line group (p = 0.19) and 0 vs. 14.3% in the later-line group (p = 0.22). Median PFS was 1.7 vs. 4.1 months on second-line (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.35-1.01, p = 0.056) and 1.4 vs. 1.8 months on later-line (HR 0.58, 95% CI 0.23-1.46, p = 0.25); AEs of any grade were observed in 58.3 vs. 69.7%, respectively. CONCLUSIONS: The efficacy and safety of the two doses of nivolumab monotherapy were comparable in patients with advanced ESCC.

Transnasal photoimmunotherapy with cetuximab sarotalocan sodium: Outcomes on the local recurrence of nasopharyngeal squamous cell carcinoma.

Photoimmunotherapy for head and neck cancer (HNC-PIT) is a newly developed locoregional treatment targeting the epidermal growth factor. This treatment consists in administering cetuximab sarotalocan sodium that conjugates cetuximab with the dye IRdye700DX, which is activated by near-infrared ray illumination at 690 nm. HNC-PIT has been conditionally approved in Japan in September 2020 for the treatment of unresectable locally advanced or unresectable locoregionally recurrent HNC. However, its outcomes on the local recurrence of the nasopharyngeal squamous cell carcinoma (NPSCC) remain undetermined. In this report, we assessed the effects of HNC-PIT assisted by transnasal endoscopy on the local recurrence of NPSCC. A 77-year-old male presented with a local recurrence of NPSCC. The initial diagnosis revealed a squamous cell carcinoma, T2N2M0 stage III, positive for Epstein-Barr virus-encoded small RNA by in situ hybridization, which was treated with concurrent chemoradiotherapy (CRT). However, local recurrence was detected 14 months after CRT. We performed HNC-PIT under transnasal endoscopy. Seven months have passed since the HNC-PIT treatment, and the patient is alive without delayed adverse events and evidence of recurrence. Local recurrence of NPSCC, which is difficult to treat with minimally invasive surgery, is considered a potential candidate for HNC-PIT.

Clinical and pathological features of second primary neoplasms arising in head and neck reconstructive skin flaps.

The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is increasing because of the increase in head and neck flap reconstruction and cancer survival. Prognosis, optimal treatment, and their clinicopathological-genetic features are under debate and are difficult to diagnose. We retrospectively reviewed SNAFs based on a single center's experience over 20 years. Medical records and specimens of 21 patients with SNAF who underwent biopsies between April 2000 and April 2020 at our institute were retrospectively analyzed. Definite squamous cell carcinoma and the remaining neoplastic lesions were subclassified as flap cancer (FC) and precancerous lesions (PLs), respectively. Immunohistochemical studies focused on p53 and p16. TP53 sequencing was conducted using next-generation sequencing. Seven and 14 patients had definite FC and PL, respectively. The mean number of biopsies/latency intervals was 2.0 times/114 months and 2.5 times/108 months for FC and PL, respectively. All lesions were grossly exophytic and accompanied by inflamed stroma. In FC and PL, the incidences of altered p53 types were 43% and 29%, respectively, and those of positive p16 stains were 57% and 64%, respectively. Mutation of TP53 in FC and PL were 17% and 29%, respectively. All except one patient with FC under long-term immunosuppressive therapy survived in this study. SNAFs are grossly exophytic tumors with an inflammatory background and show a relatively low altered p53 and TP53 rate and a high p16 positivity rate. They are slow-growing neoplasms with good prognoses. Diagnosis is often difficult; therefore, repeated or excisional biopsy of the lesion may be desirable.

Influences of COVID-19 pandemic and the states of emergency on occupational therapy for physical disorders: A questionnaire survey in Hokkaido, Japan.

Objective: This study aimed to explore the influence of coronavirus disease-2019 (COVID-19) on occupational therapy (OT) for physical disorders, including changes in the assessment, treatment, other restrictions, and measures of OT. Methods: A questionnaire survey was conducted among occupational therapists working in Hokkaido, Japan, and 123 out of the 334 (36.8%) were from OT facilities that target physical disorders. The responses were classified the categories and codes by [ ] and < >, respectively. Results: The number of patients decreased in 47.1% of the OT facilities after the pandemic declaration. Only one facility reported . Therefore, [thoroughness of standard precautions] including , , and [changes in treatment structure] including were implemented. Additionally, there were not only [restrictions on participation of patients] and [restrictions on outpatient services], but also [restrictions on operations of OT], such as and so on. Furthermore, [changes in treatment structure] and [setting criteria for discontinuation of participation] were utilized in some facilities to prevent and to reduce the risk of infection. Conclusions: By revisiting the assessment and treatment guidelines on infection control, it is possible to provide continuous OT services and to tackle the challenges posed by the pandemic.

Association between Productive Roles and Frailty Factors among Community-Dwelling Older Adults: A Cross-Sectional Analysis.

The employment rate of older people in Japan is expected to increase in the future owing to the increase in the retirement age. Preventing frailty is imperative to maintaining productive roles of older adults. Therefore, this study aimed to examine the association between productive roles and frailty factors among community-dwelling older adults. A total of 135 older adults, enrolled in 2017, participated in the study. Productive roles and domains related to frailty were measured. We measured usual gait speed and grip strength for the physical domain; Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS-15) scores for the cognitive and mental domains; and social role and group activity for the social domain. Multivariate-adjusted logistic regression models revealed that having productive roles was associated with faster usual gait speed (odds ratios [OR] = 1.05; 95% confidence interval [CI], 1.01-1.08; p = 0.005) and lower GDS-15 score (OR = 0.79; 95% CI, 0.64-0.97; p = 0.023). These results suggest that health promotion to maintain gait speed and prevent depressive symptoms may contribute to maintaining productivity in community-dwelling older adults.

Effects of inspiratory rise time on triggering work load during pressure-support ventilation: a lung model study.

BACKGROUND: The rise in inspiratory flow is important during patient-triggered ventilation. Many ventilators incorporate a function to control the time to reach the targeted airway pressure (inspiratory rise time). However, it has not been clarified how inspiratory rise time affects inspiratory work load under various ventilator settings. In a bench study we investigated the effect of inspiratory rise time on inspiratory work load during pressure-support ventilation (PSV). METHODS: We studied 6 ICU ventilators. We measured flow and pressure at the airway opening (P(ao)) at PEEP of 5 cm H(2)O, pressure-support of 5 cm H(2)O and 10 cm H(2)O, 4 triggering sensitivities, and inspiratory drives 300 mL, 500 mL, and 700 mL. The inspiratory-rise-time setting was not consistent between the ventilators, and we chose 3 inspiratory-rise-time levels with each ventilator. The inspiratory delay time (DT) was defined as the time between the onset of inspiration and the return of P(ao) to baseline, and was divided into 2 parts at the point of the lowest P(ao): before the lowest P(ao) (DT(1)), and after the lowest P(ao) (DT(2)). As an indicator of inspiratory work load we calculated the pressure-time-product (PTP) of the P(ao) over the DT. PTP was also divided into PTP(1) and PTP(2), at the point of the lowest P(ao). RESULTS: Short inspiratory rise time reduced DT(2), PTP(1), and PTP(2), regardless of the pressure-support level, triggering sensitivity, or inspiratory drive. However, the inspiratory-rise-time setting did not affect DT(1). The PTP(1), PTP(2), and DT(2) values differed significantly among the ventilators. A combination of short inspiratory rise time, high PSV, and sharp triggering sensitivity resulted in the smallest PTP and DT values. CONCLUSIONS: Short inspiratory rise time decreased inspiratory work load, regardless of the pressure-support level, triggering sensitivity, or inspiratory drive. Inspiratory work load can be maximally lowered by a combination of a short inspiratory rise time, a sharp triggering sensitivity, and a high inspiratory pressure-support level for a given patient's inspiratory effort.

Relationship between self-disclosure to first acquaintances and subjective well-being in people with schizophrenia spectrum disorders living in the community.

OBJECTIVE: Focusing on people with schizophrenia spectrum disorders living in the community, the present study aims to examine the characteristics of and gender differences in self-disclosure to first acquaintances, and to clarify the relationship between self-disclosure and subjective well-being. METHODS: Participants (32 men and 30 women with schizophrenia spectrum disorders) were examined using the subjective well-being inventory, an original self-disclosure scale for people with mental illness, as well as the Rosenberg self-esteem scale, the Link devaluation-discrimination scale, and the affiliation scale. RESULTS: The self-disclosure content domains in descending order were as follows: "living conditions," "own strengths," "experiences of distress," and "mental illness and psychiatric disability." There were no significant gender differences in self-disclosure in the total and domain scores. Multiple regression analyses by gender revealed that: (1) in men, decreasing feelings of ill-being were significantly predicted by self-disclosure about "living conditions," self-esteem, and perceived stigma; (2) in women, increasing feelings of well-being were significantly predicted by self-disclosure about "own strengths," self-esteem, and sensitivity to rejection. CONCLUSIONS: Self-disclosure to first acquaintances was related to subjective well-being in people with schizophrenia spectrum disorders living in the community. This result supports the recovery model and the strengths model. It suggests the importance of interventions targeting self-disclosure to first acquaintances about experiences as human beings, such as "living conditions" and "own strengths," as it relates to subjective well-being in community-based mental health rehabilitation.

Increasing cellular level of phosphatidic acid enhances FGF-1 production in long term-cultured rat astrocytes.

We found in a previous study that both mRNA expression and release of fibroblast growth factor 1 (FGF-1) are greater in rat astrocytes that are long term-cultured for one month (W/M cells) than in the cells cultured for one week (W/W cells). However, FGF-1 does not enhance phosphorylation of Akt, MEK, and ERK in W/M cells, while it does in W/W cells. In this work we studied the mechanism to cause these differences between W/W and W/M cells in culture. As it is known that long term culture generates oxidative stress, we characterized the stresses which W/M cells undergo in comparison with W/W cells. The levels of superoxide dismutase 1 (SOD1) and mitochondrial Bax were higher in W/M cells than in W/W cells. W/M cells recovered their ability to respond to FGF-1 to enhance phosphorylation of Akt, MEK, and ERK in the presence of antioxidants. Oxidative stress induced by hydrogen peroxide (H2O2) had no effect on mRNA expression of FGF-1 in W/W cells, although H2O2 enhances release of FGF-1 from W/W cells without inducing apoptosis. The influence of cell density was studied on mRNA expression of FGF-1 and cellular response to FGF-1, as an increasing cell density is observed in W/M cells. The increasing cell density enhanced mRNA expression of FGF-1 in W/W cells without suppression of responses to FGF-1. The decrease in cell density lowered the FGF-1 mRNA expression in W/M cells without recovery of the response to FGF-1 to enhance phosphorylation of Akt, MEK, and ERK. These findings suggest that oxidative stress attenuate sensitivity to FGF-1 and higher cell density may enhance FGF-1 expression in W/M cells. In addition, we found that the cellular level of phosphatidic acid (PA) increased in H2O2-treated W/W and W/M cells and decreased by the treatment with antioxidants, and that PA enhances the mRNA expression of FGF-1 in the W/W cells. These findings suggest that the increasing PA production may enhance FGF-1 expression to protect astrocytes against oxidative stress induced by long-term culture.