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BACKGROUND: Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC. METHODS: In this randomised, open-label, phase 3 trial, patients aged 20-75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1-5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1-5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1-4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete. FINDINGS: A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8-70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4-77·8] vs 62·6% [55·5-68·9]; hazard ratio [HR] 0·68, 95% CI 0·50-0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3-74·3]; HR 0·84, 0·63-1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group. INTERPRETATION: Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy. FUNDING: Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Docetaxel , Esophageal Neoplasms , Fluorouracil , Neoadjuvant Therapy , Humans , Middle Aged , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Male , Female , Neoadjuvant Therapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Aged , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Docetaxel/administration & dosage , Docetaxel/therapeutic use , Adult , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/mortality , Chemoradiotherapy/methods , EsophagectomyABSTRACT
We developed a novel quasielastic scattering spectroscopy system that uses a multiline frequency comblike resolution function to overcome the limit on the accessible timescale imposed by the inherent single-energy resolution of conventional spectroscopy systems. The new multiline system possesses multiple resolutions and can efficiently cover a wide time range, from 100 ps to 100 ns, where x-ray-based dynamic measurement techniques are being actively developed. It enables visualization of the relaxation shape and wave-number-dependent dynamic behavior using a two-dimensional detector, as demonstrated for the natural polymer polybutadine without deuteration.
ABSTRACT
BACKGROUND: Salvage esophagectomy for residual tumor and localized relapses after definitive chemoradiotherapy (dCRT) for patients with esophageal cancer is associated with a high rate of postoperative complications and in-hospital mortality. In addition, there are many controversial issues associated with salvage esophagectomy, such as the acceptability of minimally invasive surgery and the need for prophylactic dissection of mediastinal lymph nodes. The aim of this study was to evaluate the safety and usefulness of thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection. METHODS: The study included 31 patients who underwent thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection after dCRT between 2013 and 2022 (salvage patients) and 610 nonsalvage patients who underwent conventional thoracoscopic esophagectomy during the same time period. RESULTS: Differences between the median ages and sexes of the 2 patient groups were not significant. The dominant location of tumors in the salvage patients was the upper thoracic esophagus. More salvage patients had clinical T4 disease. The salvage patients had a lower median number of retrieved mediastinal lymph nodes than the nonsalvage patients. The differences between the rates of R0, postoperative complications, and in-hospital deaths in the 2 patient groups were not significant. The 3-year overall survival (OS) rates for the salvage patients were 73%, with 3-year OS rates for R0 vs non-R0 of 81% vs 0%, p < 0.01 and pN0 vs pN1-3 of 89% vs 49%, p < 0.01. CONCLUSION: Regarding short-term outcomes, prophylactic mediastinal lymph node dissection for patients undergoing thoracoscopic salvage esophagectomy was as safe as prophylactic dissection for patients undergoing conventional thoracoscopic esophagectomy. R0 surgery and pN0 are important factors for long-term survival in patients undergoing thoracoscopic salvage esophagectomy.
Subject(s)
Chemoradiotherapy , Esophageal Neoplasms , Esophagectomy , Lymph Node Excision , Mediastinum , Salvage Therapy , Thoracoscopy , Humans , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Esophagectomy/methods , Male , Female , Salvage Therapy/methods , Lymph Node Excision/methods , Thoracoscopy/methods , Middle Aged , Aged , Chemoradiotherapy/methods , Retrospective Studies , AdultABSTRACT
PURPOSE: Delay in initiating adjuvant chemotherapy (AC) after curative resection of colorectal cancer (CRC) has been reported to lead to poor prognosis, but few studies have looked at associated factors. This study aimed to identify risk factors for delay in initiating AC. METHODS: Data from 200 consecutive patients who underwent curative resection and AC for stage III CRC between 2013 and 2018 were retrospectively collected and analyzed. RESULTS: AC was initiated more than 8 weeks after surgery in 12.5% of patients (the delay group). Compared to those with no delay (the non-delay group), patients in the delay group had significantly higher rates of synchronous double cancers (2.3% vs. 16.0%, p = 0.001), preoperative bowel obstruction (10.3% vs. 32.0%, p = 0.003), laparotomy (56.0% vs. 80.0%, p = 0.02), concomitant resection (2.9% vs. 24.0%, p < 0.001), and postoperative complications (32.0% vs. 56.0%, p = 0.02), and a significantly longer length of hospital stay (median 12 vs. 30 days, p < 0.001). In multivariate analysis, synchronous double cancers (odds ratio 10.2, p = 0.008), preoperative bowel obstruction (odds ratio 4.6, p = 0.01), concomitant resection (odds ratio 5.2, p = 0.03), and postoperative complications of Clavien-Dindo grade ≥ IIIa (odds ratio 4.0, p = 0.03) were identified as independent risk factors for delay in initiating AC. CONCLUSION: Careful preoperative treatment planning for CRC patients with synchronous double cancers, preoperative bowel obstruction, and concomitant resection, and management for postoperative complication are necessary to avoid delay in initiating AC.
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Functional somatic syndromes (FSSs) represent a clinically important group of disorders that are often stress-related. Their autonomic pathophysiology, including reduced heart rate variability (HRV), has been reported. However, the response pattern to mental stress and recovery in FSSs remains unclear. Thus, we aimed to clarify the pattern of autonomic stress response and recovery to mental arithmetic stress in patients with FSS compared to that in healthy controls. This cross-sectional study included 79 patients with FSS who visited the Department of Psychosomatic Medicine at a university hospital in Japan and 39 healthy controls. Following a mood questionnaire and obtaining epidemiologic information, HRV was measured during three periods (5 min each): relaxation baseline resting, stress (mental arithmetic task), and post-stress recovery period. The HRV analysis included inter-beat interval, low frequency power, and high frequency power. Compared to healthy controls, patients with FSS exhibited significantly higher scores on the mood questionnaire, prolonged duration of illness, and decreased functionality in daily activities. While the healthy control group showed a pronounced stress response pattern with a significant decrease in vagal HRV and recovery, the FSS group showed a "flat" vagal stress response pattern, and the HRV in the FSS group was lower at relaxation baseline, remained low during the stress, and did not change post stress. Patients with severe FSS exhibit an altered stress response pattern. Our results could provide significant clues for the diagnosis and treatment of such patients, as well as useful insights into the relationship between stress and illness.
Subject(s)
Autonomic Nervous System , Vagus Nerve , Humans , Heart Rate/physiology , Cross-Sectional Studies , Autonomic Nervous System/physiology , Stress, PsychologicalABSTRACT
BACKGROUND: Recurrent laryngeal nerve paralysis (RLNP) after esophagectomy can cause aspiration because of incomplete glottis closure, leading to pneumonia. However, patients with RLNP often have preserved swallowing function. This study investigated factors that determine swallowing function in patients with RLNP. METHODS: Patients with esophageal cancer who underwent esophagectomy and cervical esophagogastric anastomosis were enrolled between 2017 and 2020. Videofluoroscopic examination of swallowing study (VFSS) and acoustic voice analysis were performed on patients with suspected dysphagia including RLNP. Dysphagia in VFSS was defined as score ≥ 3 of the 8-point penetration-aspiration scale VFSS and acoustic analysis results related to dysphagia were compared between patients with and without RLNP. RESULTS: Among 312 patients who underwent esophagectomy, 74 developed RLNP. The incidence of late-onset pneumonia was significantly higher in the RLNP group than in the non-RLNP (18.9 vs. 8.0%, P = .008). Detailed swallowing function was assessed by VFSS in 84 patients, and patients with RLNP and dysphagia showed significantly shorter maximum diagonal hyoid bone elevation (10.62 vs. 16.75 mm; P = .003), which was a specific finding not seen in patients without RLNP. For acoustic voice analysis, the degree of hoarseness was not closely related to dysphagia. The length of oral intake rehabilitation for patients with and without RLNP was comparable if they did not present with dysphagia (8.5 vs. 9.0 days). CONCLUSIONS: Impaired hyoid bone elevation is a specific dysphagia factor in patients with RLNP, suggesting compensatory epiglottis inversion by hyoid bone elevation is important for incomplete glottis closure caused by RLNP.
Subject(s)
Deglutition Disorders , Pneumonia , Vocal Cord Paralysis , Humans , Deglutition Disorders/epidemiology , Deglutition Disorders/etiology , Deglutition/physiology , Esophagectomy/adverse effects , Recurrent Laryngeal Nerve , Vocal Cord Paralysis/epidemiology , Vocal Cord Paralysis/etiology , Respiratory AspirationABSTRACT
BACKGROUND: Second primary esophageal cancer often develops in patients with head and neck cancer, and esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. However, the clinical outcomes of these patients have yet to be examined in a multicenter setting. METHODS: We evaluated the surgical outcomes of a nationwide cohort of 62 patients who underwent esophagectomy for esophageal cancer with a history of TPL. RESULTS: Ivor-Lewis and McKeown esophagectomies were performed in 32 (51.6%) and 30 (48.4%) patients, respectively. Postoperatively, 23 patients (37.1%) developed severe complications, and 7 patients (11.3%) required reoperation within 30 days. Pneumonia and anastomotic leakage occurred in 13 (21.0%) and 16 (25.8%) patients, respectively. Anastomotic leakage occurred more frequently in the McKeown group than in the Ivor-Lewis group (46.7% vs. 6.2%, P < 0.001). The adjusted odds ratio for anastomotic leakage in the McKeown group was 9.64 (95% confidence intervals (CI), 2.11-70.82, P = 0.008). Meanwhile, the 5-year overall survival rates were comparable between the groups (41.8% for Ivor-Lewis and 42.7% for McKeown), and the adjusted hazard ratio of overall survival was 1.44 (95% CI, 0.64-3.29; P = 0.381; Ivor-Lewis as the reference). CONCLUSIONS: In our cohort, anastomotic leakage occurred more frequently after McKeown than Ivor-Lewis esophagectomy, and almost half of patients in the McKeown group experienced leakage. Ivor-Lewis esophagectomy is preferred for decreasing anastomotic leakage when oncologically and technically feasible.
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BACKGROUND: According to some case series, patients with colorectal cancer (CRC) who underwent radical resection of synchronous peritoneal metastases (PM) with the primary tumor had better survival than patients who underwent non-surgical treatment. However, little evidence exists regarding the significance of radical resection for metachronous PM. OBJECTIVE: This study aimed to evaluate the clinical significance of surgical intervention for isolated PM from CRC, with a particular focus on time to PM. METHODS: A total of 74 consecutive patients with isolated PM from CRC, including 40 and 34 patients with synchronous and metachronous PM, respectively, treated between 2007 and 2018 were retrospectively analyzed. The primary outcome measure was overall survival (OS) from diagnosis, and the OS was compared between radical resection and palliative chemotherapy. RESULTS: Five-year OS was 39.7% for all patients. Patients with radical resection had significantly better 5-year OS compared with those with palliative chemotherapy (62.8% vs. 11.0%; p < 0.0001). According to time to PM, patients with radical resection had significantly better 5-year OS compared with those with palliative chemotherapy for both synchronous PM (47.6% vs. 0%; p = 0.019) and metachronous PM (77.2% vs. 15.2%; p < 0.0001). Multivariable analysis stratified by time to PM revealed that surgical intervention is a significant favorable prognostic factor only in patients with metachronous PM (hazard ratio 0.117, 95% confidence interval 0.020-0.678; p = 0.017). CONCLUSIONS: Patients with radical resection of PM had good survival compared with those with chemotherapy alone, especially for metachronous PM. Surgical intervention should be considered for isolated metachronous PM when radical resection is feasible.
Subject(s)
Colorectal Neoplasms , Peritoneal Neoplasms , Humans , Prognosis , Peritoneal Neoplasms/therapy , Retrospective Studies , Combined Modality Therapy , Colorectal Neoplasms/pathologyABSTRACT
BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting. METHODS: We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0-1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups. RESULTS: The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22-2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10-11), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10-3). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57-1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02-3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58-2.22; P = 0.717). CONCLUSIONS: NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Retrospective Studies , Esophageal Neoplasms/pathology , Chemoradiotherapy , Prognosis , Neoadjuvant Therapy , EsophagectomyABSTRACT
BACKGROUND: Ingested alcohol is predominantly oxidized to acetaldehyde by alcohol dehydrogenase 1B (ADH1B), and acetaldehyde is further oxidized to acetate mainly by aldehyde dehydrogenase 2 (ALDH2). Although alcohol consumption is a convincing risk factor for oesophageal cancer, the role of ADH1B rs1229984 (His48Arg), the single-nucleotide polymorphism associated with slow alcohol metabolism, in oesophageal cancer development is unclear. Because this single-nucleotide polymorphism is associated with both increased risk of oesophageal cancer and drinking intensity, its association with oesophageal cancer might operate either through a direct pathway independently of drinking intensity, via an indirect pathway mediated by drinking intensity, or both. METHODS: To disentangle these different pathways, we applied a mediation analysis to an oesophageal cancer case-control study (600 cases and 865 controls) by defining the ADH1B Arg allele and alcohol consumption as exposure and mediator, respectively, and decomposed the total-effect odds ratio of the ADH1B Arg allele into direct- and indirect-effect odds ratio. RESULTS: The ADH1B Arg allele was associated with oesophageal cancer risk through pathways other than change in drinking intensity (direct-effect odds ratio, 2.03; 95% confidence interval, 1.41-2.92), in addition to the indirect pathway mediated by drinking intensity (indirect-effect odds ratio, 1.27; 95% confidence interval, 1.05-1.53). Further analyses by stratifying genotypes of ALDH2 rs671 (Glu504Lys), the functional single-nucleotide polymorphism that strongly attenuates the enzymatic activity, showed significant direct-effect odds ratio within each stratum. CONCLUSIONS: These results indicate that ADH1B Arg allele contributes to oesophageal cancer risk by slowing alcohol breakdown, in addition to its effect on the amount of alcohol consumed.
Subject(s)
Alcohol Dehydrogenase , Esophageal Neoplasms , Humans , Alcohol Dehydrogenase/genetics , Aldehyde Dehydrogenase, Mitochondrial/genetics , Alcohol Drinking/adverse effects , Case-Control Studies , Mediation Analysis , Polymorphism, Single Nucleotide , Genotype , Esophageal Neoplasms/genetics , Aldehyde Dehydrogenase/geneticsABSTRACT
BACKGROUND: Recent developments in mass spectrometry (MS) have revealed target antigens for membranous nephropathy (MN), including phospholipase A2 receptor and exostosin 1/exostosin 2 (EXT1/2). EXT1/2 are known antigens of autoimmune disease-related MN, especially membranous lupus nephritis. We describe the case of an elderly man who developed nephrotic syndrome followed by progressive renal dysfunction. CASE PRESENTATION: A 78-year-old man presented with rapidly progressive renal dysfunction with proteinuria and hematuria. Three years previously, he had developed leg edema but did not receive any treatment. Laboratory tests showed elevated anti-nuclear antibody (Ab), anti-dsDNA Ab titer, and hypocomplementemia, indicating systemic lupus erythematous. Myeloperoxidase anti-neutrophil cytoplasmic Ab (ANCA) and anti-glomerular basement membrane (GBM) Ab were also detected. The renal pathologic findings were compatible with crescentic glomerulonephritis (GN), whereas non-crescentic glomeruli exhibited MN without remarkable endocapillary or mesangial proliferative change. Immunofluorescence microscopy revealed glomerular IgG, C3, and C1q deposition. All IgG subclasses were positive in glomeruli. Anti-PLA2R Ab in serum was negative. MS analysis was performed to detect the antigens of MN, and EXT1/2 was detected in glomeruli. Therefore, we reached a diagnosis of membranous lupus nephritis concurrent with both ANCA-associated vasculitis and anti-GBM-GN. The simultaneous occurrence of these three diseases is extremely rare. CONCLUSIONS: This is the first report of EXT1/2-related membranous lupus nephritis concurrent with ANCA-associated vasculitis and anti-GBM-GN. This case demonstrates the usefulness of MS in diagnosing complicated cases of MN.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Glomerulonephritis, Membranoproliferative , Glomerulonephritis, Membranous , Glomerulonephritis , Lupus Erythematosus, Systemic , Lupus Nephritis , Aged , Humans , Male , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Antibodies, Antineutrophil Cytoplasmic , Glomerulonephritis/pathology , Glomerulonephritis, Membranoproliferative/complications , Glomerulonephritis, Membranous/complications , Glomerulonephritis, Membranous/diagnosis , Immunoglobulin G , Lupus Erythematosus, Systemic/complications , Lupus Nephritis/complications , Lupus Nephritis/diagnosis , Mass Spectrometry , N-AcetylglucosaminyltransferasesABSTRACT
Dysphagia after esophagectomy is a major risk factor for aspiration pneumonia, thus preoperative assessment of swallowing function is important. The maximum phonation time (MPT) is a simple indicator of phonatory function and also correlates with muscle strength associated with swallowing. This study aimed to determine whether preoperative MPT can predict postoperative aspiration pneumonia. The study included 409 consecutive patients who underwent esophagectomy for esophageal cancer between 2017 and 2021. Pneumonia detected by routine computed tomography on postoperative days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later (most often aspiration pneumonia) was defined as late-onset pneumonia. The correlation between late-onset pneumonia and preoperative MPT was investigated. Patients were classified into short MPT (<15 seconds for males and <10 seconds for females, n = 156) and normal MPT groups (≥15 seconds for males and ≥10 seconds for females, n = 253). The short MPT group was significantly older, had a lower serum albumin level and vital capacity, and had a significantly higher incidence of late-onset pneumonia (18.6 vs. 6.7%, P < 0.001). Multivariate analysis showed that short MPT was an independent risk factor for late-onset pneumonia (odds ratio: 2.26, P = 0.026). The incidence of late-onset pneumonia was significantly higher in the short MPT group (15.6 vs. 4.7%, P = 0.004), even after propensity score matching adjusted for clinical characteristics. MPT is a useful predictor for late-onset pneumonia after esophagectomy.
Subject(s)
Deglutition Disorders , Esophageal Neoplasms , Pneumonia, Aspiration , Pneumonia , Male , Female , Humans , Pneumonia/diagnosis , Pneumonia/epidemiology , Pneumonia/etiology , Pneumonia, Aspiration/diagnosis , Pneumonia, Aspiration/epidemiology , Pneumonia, Aspiration/etiology , Deglutition Disorders/diagnosis , Deglutition Disorders/epidemiology , Deglutition Disorders/etiology , Phonation/physiology , Esophageal Neoplasms/complications , Esophagectomy/adverse effects , Retrospective Studies , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/etiologyABSTRACT
Recently, the comprehensive concept of "infection-related glomerulonephritis (IRGN)" has replaced that of postinfectious glomerulonephritis (PIGN) because of the diverse infection patterns, epidemiology, clinical features, and pathogenesis. In addition to evidence of infection, hypocomplementemia particularly depresses serum complement 3 (C3), with endocapillary proliferative and exudative GN developing into membranoproliferative glomerulonephritis (MPGN); also, C3-dominant or co-dominant glomerular immunofluorescence staining is central for diagnosing IRGN. Moreover, nephritis-associated plasmin receptor (NAPlr), originally isolated from the cytoplasmic fraction of group A Streptococci, is vital as an essential inducer of C3-dominant glomerular injury and is a key diagnostic biomarker for IRGN. Meanwhile, "C3 glomerulopathy (C3G)", also showing a histological pattern of MPGN due to acquired or genetic dysregulation of the complement alternative pathway (AP), mimics C3-dominant IRGN. Initially, C3G was characterized by intensive "isolated C3" deposition on glomeruli. However, updated definitions allow for glomerular deposition of other complement factors or immunoglobulins if C3 positivity is dominant and at least two orders of magnitude greater than any other immunoreactant, which makes it challenging to quickly distinguish pathomorphological findings between IRGN and C3G. As for NAPlr, it was demonstrated to induce complement AP activation directly in vitro, and it aggravates glomerular injury in the development of IRGN. A recent report identified anti-factor B autoantibodies as a contributing factor for complement AP activation in pediatric patients with PIGN. Moreover, C3G with glomerular NAPlr deposition without evidence of infection was reported. Taken together, the clinico-pathogenic features of IRGN overlap considerably with those of C3G. In this review, similarities and differences between the two diseases are highlighted.
Subject(s)
Glomerulonephritis, Membranoproliferative , Glomerulonephritis , Humans , Child , Glomerulonephritis/pathology , Glomerulonephritis, Membranoproliferative/etiology , Kidney Glomerulus/pathology , AutoantibodiesABSTRACT
OBJECTIVE: This study was performed to investigate the efficacy of the modified Collard (MC) technique for reducing anastomotic stricture after esophagectomy compared with the circular stapled (CS) technique. SUMMARY BACKGROUND DATA: The currently available techniques of anastomosis after esophagectomy are associated with a significant risk of anasto-motic complications. However, the optimal anastomotic technique after esophagectomy has not yet been established. METHODS: We randomly allocated patients to either the CS group or the MC group. The primary endpoint was the incidence of anastomotic stricture. The secondary endpoints included the incidence of postoperative complications (including anastomotic leakage) and quality of life (QoL). All anastomoses were performed after indocyanine green evaluation for objective homogeni-zation of blood flow to the gastric conduit between the 2 techniques. RESULTS: Among 100 randomized patients (CS group, n = 50; MC group, n = 50), anastomotic strictures were observed in 18 (42%) patients in the CS group and in no patients in the MC group. There were no significant between-group differences in anastomotic leakage (CS group, 7% vs MC group, 8%; P = 0.94). Quality of life domains of dysphagia and choking when swallowing at 3âmonths after surgery were significantly better in the MC group than in the CS group. CONCLUSIONS: The MC technique reduces the incidence of anastomotic stricture and improves postoperative quality of life. Furthermore, the incidence of anastomotic leakage is comparable between the 2 techniques based on accurate comparison under objective homogenization of the gastric conduit condition.
Subject(s)
Esophageal Neoplasms , Esophagectomy , Anastomosis, Surgical/methods , Anastomotic Leak/epidemiology , Anastomotic Leak/prevention & control , Constriction, Pathologic/epidemiology , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Esophageal Neoplasms/complications , Esophageal Neoplasms/surgery , Esophagectomy/methods , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Quality of Life , Surgical Stapling/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: Surgery is the standard of care for T1bN0M0 esophageal squamous cell carcinoma (ESCC), whereas chemoradiotherapy (CRT) is a treatment option. This trial aimed to investigate the noninferiority of CRT relative to surgery for T1bN0M0 ESCC. METHODS: Clinical T1bN0M0 ESCC patients were eligible for enrollment in this prospective nonrandomized controlled study of surgery versus CRT. The primary endpoint was overall survival, which was determined using inverse probability weighting with propensity scoring. Surgery consisted of an esophagectomy with 2- or 3-field lymph node dissection. CRT consisted of 2 courses of 5-fluorouracil (700 mg/m2) on days 1-4 and cisplatin (70 mg/m2) on day 1 every 4 weeks with concurrent radiation (60 Gy). RESULTS: From December 20, 2006 to February 5, 2013, a total of 368 patients were enrolled in the nonrandomized portion of the study. The patient characteristics in surgery arm and CRT arm, respectively, were as follows: median age, 62 and 65 years; proportion of males, 82.8% and 88.1%; and proportion of performance status 0, 99.5% and 98.1%. Comparisons were made using the nonrandomized groups. The 5-year overall survival rate was 86.5% in the surgery arm and 85.5% in the CRT arm (adjusted hazard ratio, 1.05; 95% confidence interval, 0.67-1.64 [<1.78]). The complete response rate in the CRT arm was 87.3% (95% confidence interval, 81.1-92.1). The 5-year progression-free survival rate was 81.7% in the surgery arm and 71.6% in the CRT arm. Treatment-related deaths occurred in 2 patients in the surgery arm and none in the CRT arm. CONCLUSIONS: CRT is noninferior to surgery and should be considered for the treatment of T1bN0M0 ESCC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Adenosquamous/therapy , Carcinoma, Basal Cell/therapy , Chemoradiotherapy , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/therapy , Esophagectomy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Adenosquamous/mortality , Carcinoma, Adenosquamous/pathology , Carcinoma, Basal Cell/mortality , Carcinoma, Basal Cell/pathology , Chemoradiotherapy/adverse effects , Chemoradiotherapy/mortality , Cisplatin/therapeutic use , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/pathology , Esophagectomy/adverse effects , Esophagectomy/mortality , Female , Fluorouracil/therapeutic use , Humans , Japan , Male , Middle Aged , Neoplasm Staging , Progression-Free Survival , Prospective Studies , Radiation Dosage , Time FactorsABSTRACT
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.
Subject(s)
Cancer Vaccines , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Receptors, Polymeric Immunoglobulin , Antibodies, Neoplasm , Antigens, Neoplasm , Cisplatin , Esophageal Squamous Cell Carcinoma/drug therapy , Fluorouracil , Glucans , Humans , Immunoglobulin A , Immunoglobulin G , Membrane Proteins , PrognosisABSTRACT
BACKGROUND: Postoperative pneumonia is a common complication after esophagectomy and is associated with a high mortality rate. Although many randomized, controlled trials have been conducted on the prevention of postoperative pneumonia, little attention has been paid to the efficacy of antimicrobial prophylaxis. The purpose of this study was to investigate the impact of antimicrobial prophylaxis on the prevention of postoperative pneumonia. METHODS: Data of patients with esophageal cancer who underwent thoracoscopic esophagectomy between 2016 and 2020 were collected. Early-period patients received cefazolin (CEZ) per protocol as antimicrobial prophylaxis (n = 250), and later-period patients received ampicillin/sulbactam (ABPC/SBT) (n = 106) because of the unavailability of CEZ in Japan. The incidence of pneumonia was compared between treatments in this quasi-experimental setting. Pneumonia detected by routine computed tomography (CT) on postoperative Days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later was defined as late-onset pneumonia. RESULTS: The incidence of early-onset pneumonia was significantly lower (3.8% vs. 13.6%, P = 0.006), and the median length of postoperative hospital stay was significantly shorter (17 vs. 20 days, P < 0.001) in the ABPC/SBT group than in the CEZ group. The incidence of late-onset pneumonia was similar between groups (9.4% vs. 10.0%, P = 0.870). The incidence of Clostridioides difficile infections and the incidence of multidrug-resistant organisms were similar between groups. Multivariate analyses consistently showed the superiority of ABPC/SBT to CEZ in preventing early-onset pneumonia (odds ratio: 0.20, P = 0.006). CONCLUSIONS: ABPC/SBT after esophagectomy was better at preventing early-onset pneumonia compared with CEZ and was feasible regarding the development of antimicrobial resistance.
Subject(s)
Esophageal Neoplasms , Pneumonia , Anti-Bacterial Agents/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Humans , Pneumonia/epidemiology , Pneumonia/etiology , Pneumonia/prevention & control , Postoperative Complications/drug therapy , Postoperative Complications/prevention & control , Retrospective StudiesABSTRACT
BACKGROUND: The importance of supraclavicular lymph node (SCLN) metastases in esophageal cancer (EC) remains unknown. Few studies have reported on the prognostic impact of SCLN metastases on patients with cervical EC (CEC). This study aimed to investigate whether SCLNs should be considered regional lymph nodes and be dissected in patients with CEC. METHODS: This retrospective study enrolled 835 consecutive patients who underwent radical esophagectomy. Of these patients, 67 underwent radical surgery for CEC. These 67 patients were divided into three groups based on the presence of lymph node metastases with or without metastatic SCLNs or the absence of lymph node metastases. RESULTS: Of the 67 patients, 23 (34.3%) did not have metastatic lymph nodes (pN-negative group), 27 (40.3%) had metastatic lymph nodes except for metastatic SCLNs (pN-positive group without metastatic SCLN), and 17 (25.4%) had metastatic lymph nodes including metastatic SCLNs (pN-positive group with metastatic SCLNs). The 5-year overall survival rate was 58.4% for the pN-negative group, 46.2% for the pN-positive group without metastatic SCLNs, and 7.8% for the pN-positive group with metastatic SCLNs. The pN-positive group with metastatic SCLNs tended to show residual tumor cells and complications after surgery. The presence of metastatic SCLNs was a significantly poor prognostic factor (p = 0.004). The efficacy index was lowest for the lymph nodes in the supraclavicular region. CONCLUSIONS: The prognosis of the CEC patients with metastatic SCLNs was dismal. Although the cervical esophagus is located adjacent to the SCLNs, the SCLNs may be considered extra-regional lymph nodes in patients with CEC.
Subject(s)
Esophageal Neoplasms , Lymph Nodes , Esophageal Neoplasms/surgery , Humans , Lymph Nodes/surgery , Lymphatic Metastasis , Retrospective StudiesABSTRACT
BACKGROUND: The prognostic significance of peritoneal lavage cytology (PLC) in patients with pancreatic ductal adenocarcinoma (PDAC) remains controversial. The purpose of this study was to evaluate the prognostic impact of PLC status in PDAC patients. METHODS: Patients intending to undergo resection for PDAC between 2007 and 2020 were included. Survival was compared among patients who underwent resection with negative or positive PLC status and those who did not undergo resection. Univariable and multivariable analyses were conducted to evaluate the prognostic impact of positive PLC status. A systematic literature review was performed to evaluate the correlation between prognosis and the positive PLC rate. RESULTS: A total of 480 patients formed the study cohort and were divided as follows: 438 in the negative PLC group, 18 in the positive PLC group, and 24 in the no resection group. Although the median survival time significantly differed between the negative and positive PLC groups (35.7 vs. 13.6 months, P < 0.001), it did not significantly differ between the positive PLC and no resection groups (13.6 vs. 12.2 months, P = 0.605). Multivariable analyses demonstrated that positive PLC status (hazard ratio = 3.54, 95% confidence interval = 1.97-6.38, P < 0.001) was the strongest poor prognostic factor. Based on statistical analyses for the systematic review, the prognostic impact of positive PLC status weakened significantly as the institutional positive PLC rate increased (P = 0.044). CONCLUSIONS: Resection did not improve the prognosis of patients with positive PLC status in our cohort. The institutional positive PLC rate may be a good reference for surgical indication in these patients.
Subject(s)
Carcinoma, Pancreatic Ductal , Lung Neoplasms , Pancreatic Neoplasms , Carcinoma, Pancreatic Ductal/pathology , Humans , Lung Neoplasms/pathology , Neoplasm Staging , Pancreatic Neoplasms/pathology , Peritoneal Lavage , Prognosis , Retrospective Studies , Pancreatic NeoplasmsABSTRACT
Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 µg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.