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Background: The clinical features of postoperative primary tracheobronchial necrosis (P‐TBN; the necrosis without anastomotic leakage or other cervical and mediastinal abscess) remains unclear. This nationwide multicenter retrospective study first investigated the clinical features of P‐TBN after esophagectomy for upper aerodigestive tract cancer with a large cohort. Methods: As a study of the Japan Broncho‐Esophagological Society, a nationwide questionnaire survey was conducted in 67 institutions. The clinical data of 6370 patients who underwent esophagectomy for laryngeal, pharyngeal, and esophageal cancer between 2010 and 2019 were collected. Grades of P‐TBN were defined as follows: Grade 1, mucosal necrosis; Grade 2, transmural bronchial wall necrosis without fistula or perforation; Grade 3, transmural bronchial wall necrosis with fistula or perforation. Results: P‐TBN was observed in 48 (0.75%) of 6370 patients. The incidences of P‐TBN for pharyngo‐laryngo‐cervical esophagectomy (PLCE; n = 1650), total pharyngo‐laryngo‐esophagectomy (TPLE; n = 205), and subtotal esophagectomy (SE; n = 4515) were 2.0%, 5.4%, and 0.1%, respectively. The upper mediastinal LN dissection (P = 0.016) and the higher level of the tracheal resection (P = 0.039) were significantly associated with a higher grade of necrosis in PLCE and TPLE. Overall survival rates were significantly lower in patients with Grade 2 (P = 0.009) and Grade 3 (P = 0.004) than in those with Grade 1. Conclusion: The incidence of TBN restricted to P‐TBN was lower than previously reported. Maintaining the tracheal blood flow is essential to prevent worsening P‐TBN, especially in PLCE and TPLE. Our new P‐TBN severity grade may predict the outcome of patients with P‐TBN. [ABSTRACT FROM AUTHOR]

We undertook genomic analyses of Japanese patients with stage I esophageal squamous cell carcinoma (ESCC) to investigate the frequency of genomic alterations and the association with survival outcomes. Biomarker analysis was carried out for patients with clinical stage T1bN0M0 ESCC enrolled in JCOG0502 (UMIN000000551). Whole‐exome sequencing (WES) was performed using DNA extracted from formalin‐fixed, paraffin‐embedded tissue of ESCC and normal tissue or blood sample. Single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) were identified. We then evaluated the associations between each gene alteration with a frequency of 10% or more and progression‐free survival (PFS) using a Cox regression model. We controlled for family‐wise errors at 0.05 using the Bonferroni method. Among the 379 patients who were enrolled in JCOG0502, 127 patients were successfully analyzed using WES. The median patient age was 63 years (interquartile range, 57‐67 years), and 78.0% of the patients ultimately underwent surgery. The 3‐year PFS probability was 76.3%. We detected 20 genes with SNVs, indels, or amplifications with a frequency of 10% or more. Genomic alterations in FGF19 showed the strongest association with PFS with a borderline level of statistical significance of P =.00252 (Bonferroni‐adjusted significance level is.0025). Genomic alterations in FGF4, MYEOV, CTTN, and ORAOV1 showed a marginal association with PFS (P <.05). These genomic alterations were all CNAs at chromosome 11q13.3. We have identified new genomic alterations associated with the poor efficacy of ESCC (T1bN0M0). These findings open avenues for the development of new potential treatments for patients with ESCC. [ABSTRACT FROM AUTHOR]

Aim: Digestive reconstruction after pharyngolaryngectomy with total esophagectomy (PLTE) remains challenging, with the optimal method remaining unclear. The current study aimed to clarify the short‐term outcomes after PLTE and determine the optimal digestive reconstruction method. Methods: Based on a nationwide survey of 151 patients who underwent PLTE, outcomes of digestive reconstruction methods are described. Results: Among digestive reconstruction methods, a simple gastric tube was most frequently used (37.1%), followed by gastric tube combined with free graft transfer (FGT) (35.1%), gastric tube with microvascular anastomosis (22.5%), and other procedures (5.3%). Intraoperative evaluation of microcirculation (IOEM) was utilized in 29 patients (19.2%). Among the included patients, 66.9% developed any‐grade complications, 41.0% developed severe complications, and 23.8% developed digestive reconstruction‐related complications (DRRCs; leakage or necrosis). Reoperation within 30 days for any complications and DRRCs was required in 13.9% and 8.6% of the patients, respectively. Mortality within 90 days was observed in 4.6%. Among the three major methods, gastric tube combined with FGT promoted the least DRRCs in the gastric tube (P =.005), although the overall incidence of DRRCs was comparable. The use of IOEM was significantly associated with a reduction of severe DRRCs (P =.005). Conclusions: Pharyngolaryngectomy with total esophagectomy is a high‐risk surgery significantly associated with the occurrence of postoperative morbidity and mortality. Nonetheless, the addition of FGT can help prevent gastric tip complications, while IOEM can be an effective method for improving outcomes. [ABSTRACT FROM AUTHOR]

Background: A frailty index (FI) based on domain‐level deficits identified through a comprehensive geriatric assessment (CGA) has been previously developed and validated in general geriatric patients. Our objectives were to construct an FI‐CGA and to assess its construct validity in the geriatric oncology setting. Methods: Five hundred forty consecutive Japanese patients with cancer who underwent a CGA on a geriatric oncology service were included (median age 80 years, range 66–96 years). We developed a 10‐item frailty index based on deficits in 10 domains (FI‐CGA‐10): cognition, mood, communication, mobility, balance, nutrition, basic and instrumental activities of daily living, social support, and comorbidity. Deficits in each domain were scored as 0 (no problem), 0.5 (minor problem), and 1.0 (major problem). Scores were calculated by dividing the sum of the scores for each domain by 10 and then categorized as fit (<0.2), pre‐frail (0.2–0.35), and frail (>0.35). Construct validity was tested by correlating the FI‐CGA‐10 with other established frailty measures. Results: FI‐CGA‐10 was well approximated by the gamma distribution. Overall, 20% of patients were fit, 41% were pre‐frail, and 39% were frail. FI‐CGA‐10 was correlated with Canadian Study of Health and Aging (CSHA) Clinical Frailty Scale (r = 0.83), CSHA rules‐based frailty definition (r = 0.67), and CSHA Function Score (r = 0.77). Increasing levels of frailty were significantly associated with functional and cognitive impairments, high comorbidity burden, poor self‐rated health, and low estimated survival probabilities. Conclusion: The FI‐CGA‐10 is a user‐friendly and construct‐validated measure for quantifying frailty from a CGA. Implications for Practice: This article describes the construction of a user‐friendly 10‐item frailty index based on a comprehensive geriatric assessment (FI‐CGA‐10) for older adults with cancer: cognition, mood, communication, mobility, balance, nutrition, basic and instrumental activities of daily living, social support, and comorbidity. The FI‐CGA‐10 simplifies the original FI‐CGA used in the general geriatric setting while maintaining its content validity. The index's construct validity was demonstrated in a cohort of older adults with various cancer types. The advantage of the FI‐CGA‐10 is that a frailty score can be calculated more readily and interpreted in a more clinically sensible manner than the original FI‐CGA. Frailty is associated with chemotherapy intolerance, postoperative complications, and death. This study aimed to construct an easy‐to‐use frailty index based on a comprehensive geriatric assessment that would be applicable in the geriatric oncology setting. [ABSTRACT FROM AUTHOR]

Background: The clinical features of postoperative primary tracheobronchial necrosis (P-TBN; the necrosis without anastomotic leakage or other cervical and mediastinal abscess) remains unclear. This nationwide multicenter retrospective study first investigated the clinical features of P-TBN after esophagectomy for upper aerodigestive tract cancer with a large cohort., Methods: As a study of the Japan Broncho-Esophagological Society, a nationwide questionnaire survey was conducted in 67 institutions. The clinical data of 6370 patients who underwent esophagectomy for laryngeal, pharyngeal, and esophageal cancer between 2010 and 2019 were collected. Grades of P-TBN were defined as follows: Grade 1, mucosal necrosis; Grade 2, transmural bronchial wall necrosis without fistula or perforation; Grade 3, transmural bronchial wall necrosis with fistula or perforation., Results: P-TBN was observed in 48 (0.75%) of 6370 patients. The incidences of P-TBN for pharyngo-laryngo-cervical esophagectomy (PLCE; n = 1650), total pharyngo-laryngo-esophagectomy (TPLE; n = 205), and subtotal esophagectomy (SE; n = 4515) were 2.0%, 5.4%, and 0.1%, respectively. The upper mediastinal LN dissection ( P  = 0.016) and the higher level of the tracheal resection ( P  = 0.039) were significantly associated with a higher grade of necrosis in PLCE and TPLE. Overall survival rates were significantly lower in patients with Grade 2 ( P  = 0.009) and Grade 3 ( P  = 0.004) than in those with Grade 1., Conclusion: The incidence of TBN restricted to P-TBN was lower than previously reported. Maintaining the tracheal blood flow is essential to prevent worsening P-TBN, especially in PLCE and TPLE. Our new P-TBN severity grade may predict the outcome of patients with P-TBN., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum. In multiregion analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under chemoradiotherapy selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of chemoradiotherapy. Single-region analysis of 28 pretreatment tumors indicated that focal copy-number gain at the MYC locus was significantly associated with poor progression-free survival and overall survival after chemoradiotherapy. MYC gain remained throughout the chemoradiotherapy course and potentially contributes to intrinsic resistance to chemoradiotherapy. Consistent with these findings, MYC copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and MYC knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by chemoradiotherapy and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision chemoradiotherapy. SIGNIFICANCE: Whole-exome sequencing reveals the genetic evolution of ESCC during chemoradiotherapy, highlighting MYC gain in pretreatment tumors as a potential marker of therapy resistance., (©2021 American Association for Cancer Research.)

Aim: Digestive reconstruction after pharyngolaryngectomy with total esophagectomy (PLTE) remains challenging, with the optimal method remaining unclear. The current study aimed to clarify the short-term outcomes after PLTE and determine the optimal digestive reconstruction method., Methods: Based on a nationwide survey of 151 patients who underwent PLTE, outcomes of digestive reconstruction methods are described., Results: Among digestive reconstruction methods, a simple gastric tube was most frequently used (37.1%), followed by gastric tube combined with free graft transfer (FGT) (35.1%), gastric tube with microvascular anastomosis (22.5%), and other procedures (5.3%). Intraoperative evaluation of microcirculation (IOEM) was utilized in 29 patients (19.2%). Among the included patients, 66.9% developed any-grade complications, 41.0% developed severe complications, and 23.8% developed digestive reconstruction-related complications (DRRCs; leakage or necrosis). Reoperation within 30 days for any complications and DRRCs was required in 13.9% and 8.6% of the patients, respectively. Mortality within 90 days was observed in 4.6%. Among the three major methods, gastric tube combined with FGT promoted the least DRRCs in the gastric tube ( P =  .005), although the overall incidence of DRRCs was comparable. The use of IOEM was significantly associated with a reduction of severe DRRCs ( P =  .005)., Conclusions: Pharyngolaryngectomy with total esophagectomy is a high-risk surgery significantly associated with the occurrence of postoperative morbidity and mortality. Nonetheless, the addition of FGT can help prevent gastric tip complications, while IOEM can be an effective method for improving outcomes., Competing Interests: FundingAuthor Y.B. has an endowed chair funded by Ono Pharmaceutical Co. Ltd.Conflict of InterestThe authors have no conflicts of interest related to this research and have received no grant support for this work.Ethical StatementsThis retrospective study was performed in accordance with the ethical standards of each institution's committee on human experimentation and with the Helsinki Declaration of 1964 and its later versions. Patients were given an opportunity to optout of this study through public announcements published by each institution. The study protocol was approved by the JBES (approval number 2020‐01) and the Institutional Review Board of the Japanese Foundation for Cancer Research (approval number 2020‐1147). All institutions applied for and obtained study approval from their respective institutional review boards.The authors have no conflicts of interest related to this research and have received no grant support for this work., (© 2021 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

Objective Geriatric screening followed by a more detailed assessment and intervention is recommended for older adults with cancer. However, little is known regarding how the geriatric screening covered by Japanese health insurance is used for hospitalized older cancer patients. We surveyed all hospitals in Japanese Association of Clinical Cancer Centers (JACCC) to explore the current use of this approach. Methods The JACCC member hospitals specialize in cancer care from prevention, through diagnosis and treatment, to palliative care. We mailed paper questionnaires to the presidents of the hospitals in December 2019 and collected them by February 2020. The survey requested general hospital information and asked whether (and how) such geriatric screening for hospitalized older adults with cancer was conducted. Results Twenty-six of 32 hospitals completed the survey (81%). Fourteen hospitals are cancer centers, while the remaining 12 hospitals are general hospitals which care of both cancer and non-cancer patients. Eleven hospitals (42%) performed geriatric screening and the most common use of the results was for "early discharge planning" and for "applying for long-term care insurance." Most clinicians rated the screening "somewhat" or "a little" helpful and found it most helpful for "meeting patient-post discharge needs". The most frequently reported barrier to implementation was a "lack of leadership to improve the care of older adults." Conclusion Geriatric screening was used at less than half of the major cancer centers and hospitals in Japan. One feasible solution to this problem is to establish an interprofessional workgroup at each hospital with the shared goal of providing high-quality care for this population.