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This study aimed to examine the efficacy and safety of protein and/or essential amino acid (EAA) supplementation in all lower limb surgeries using systematic reviews and meta-analysis of randomized controlled trials (RCTs). We included RCTs that assessed the efficacy of protein and/or EAA supplementation in lower limb surgeries. On June 2, 2023, we searched EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The primary outcomes were mobility, patient-reported outcomes (PRO), and acute kidney injury (AKI). The secondary outcomes were exercise capacity, muscle strength, muscle mass, and all adverse events. We performed meta-analyses using the random-effects model. We assessed the risk of bias using the Cochrane risk-of-bias tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We included 12 RCTs (622 patients). These studies included four on hip fracture surgery, three on total hip arthroplasty, and five on total knee arthroplasty. Protein and/or EAA supplementation may slightly improve PRO (standard mean difference 0.51, 95% confidence interval (CI): 0.22 to 0.80, low certainty of evidence). Nevertheless, it may not improve mobility (mean difference 0.07 m/s, 95% CI: -0.01 to 0.16, low certainty of evidence). No adverse events including AKI were reported. Muscle strength may have increased (standard mean difference 0.31, 95% CI: 0.02 to 0.61, very low certainty of evidence). However, exercise capacity (mean difference 5.43 m, 95% CI: -35.59 to 46.45, very low certainty of evidence) and muscle mass (standard mean difference -0.08, 95% CI: -0.49 to 0.33, very low certainty of evidence) were not improved. While protein and/or EAA supplementation in lower limb surgeries may improve PRO, it is unlikely to affect mobility. Despite this, the medical team and patients might still consider protein and/or EAA supplementation a useful option.
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BACKGROUND: Lateral node metastasis confers a poor prognosis in rectal cancer. Several multidisciplinary treatments have been proposed with favorable outcomes. However, appropriate neoadjuvant/adjuvant treatments or follow-up plans based on information about the probable recurrence site have not been specified. We aimed to clarify the distinctive features of recurrence patterns for lateral node-positive low rectal cancer according to the lateral and mesorectal lymph node status. METHODS: We retrospectively analyzed 508 patients with stage III low rectal cancer who underwent lateral node dissection. We investigated the impact of lateral and mesorectal lymph node status on site-specific recurrence rates and patient survival. RESULTS: Analyses for relapse-free survival revealed the prognostic impact of lateral node positivity in stage III low rectal cancer (p < 0.0001). Lateral node-positive patients exhibited higher risk of overall recurrence, local recurrence, and recurrence in extra-regional nodes than lateral node-negative patients (p < 0.0001, p = 0.001, and p < 0.0001, respectively). However, lateral node positivity was not statistically associated with a hematogenous recurrence rate. In lateral node-positive patients, both tumor-node-metastasis (TNM)-N status and number of lateral nodes involved were revealed as significant prognostic factors (p < 0.0001, both). In addition, the number of lateral nodes involved could be a discriminatory indicator of probabilities of local recurrence and recurrence in extra-regional nodes (p = 0.02, and p < 0.0001, respectively). CONCLUSIONS: Lateral node-positive low rectal cancer exhibits higher local recurrence and extra-regional node recurrence rates that correlate with the number of lateral nodes involved.
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Neuroendocrine carcinoma (NEC) of the colon and rectum is a rare malignancy with a poor prognosis that is characterized by distinct clinical and histopathological features that differ significantly from those of more prevalent adenocarcinomas. Poorly differentiated colorectal adenocarcinoma (PDC) is also rare and carries a poor prognosis. Considering the morphological similarities between these two rare, poorly differentiated cancers of the colon and rectum, it is plausible that certain cases of colorectal cancer (CRC) diagnosed as PDC may contain NEC as well. In the present study, cases of CRC that were diagnosed as PDC at our institution were investigated, searching for patients who exhibited NEC characteristics based on the expression of neuroendocrine markers (NEMs), including chromogranin A, synaptophysin and insulinoma-associated 1 (INSM1), and the loss of retinoblastoma 1 (Rb). Of 816 total CRC cases, 74 cases (9.1%) were identified as PDC. These were further divided into 13 (17.5%) cases that were positive for NEMs and others. Of these 13 cases, the expression rates for chromogranin A and synaptophysin were 69.2% each, while that of INSM1 was 100%. Upon re-examination of the 13 PDC cases, two cases were morphologically identified as NEC, including one large- and one small-cell NEC. A total of two cases showed loss of Rb in their PDC lesions. NEM positivity was considered an independent prognostic factor in the 74 PDC cases. Among these cases, some may exhibit characteristics of NEC. Unraveling the molecular mechanisms using CRC that harbors both PDC and NEC will be a task for future research.
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PURPOSE: Diverting ileostomy is related to postoperative high-output stoma (HOS) leading to kidney injury. The purpose of our study was to clarify the risk factors for ileostomy-associated kidney injury, which is kidney injury starting after the first operation to ileostomy closure after colorectal tumor surgery with diverting ileostomy. METHODS: Between January 2013 and December 2020, 442 patients who underwent colorectal tumor surgery (cancer, neuroendocrine tumor, and leiomyosarcoma) following diverting ileostomy formation were included. We used the KDIGO (Kidney Disease Improving Global Outcomes) guidelines, which defines the acute kidney injury (AKI) to classify patients with ileostomy-associated kidney injury. The definition of AKI was (i) serum creatinine (sCr) ≥ 0.3 mg/dL or (ii) sCr ≥1.5-fold the preoperative level. Multivariate analyses were performed to identify the independent risk factors for kidney injury. RESULTS: Kidney injury developed in 99/442 eligible patients (22.4%). Patients in the kidney injury group were older age, male sex, high American Society of Anesthesiologists Physical Status Classification System (ASA-PS) score, hypertension, cardiovascular diseases, diabetes. The preoperative hemoglobin, albumin, prognostic nutritional index (PNI), and creatinine clearance (CCr) were lower, and the maximum wound length was more extended than the non-kidney injury group. The median highest daily stoma output was significantly higher in the kidney injury group. The postoperative white blood cell (WBC) and C-reactive protein (CRP) levels were also high in the kidney injury group. The univariate analysis showed older age, male sex, high ASA-PS score, hypertension, cardiovascular diseases, and diabetes were the risk factors for kidney injury. The multivariate analysis revealed that age 70 or older, ASA-PS III/IV, hypertension, and HOS ≥2000 ml/day were independent risk factors for kidney injury. CONCLUSIONS: Surgeons should consider diverting colostomy creation for patients with risk factors such as age 70 or older, ASA-PS III/IV, and hypertension.
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Injúria Renal Aguda , Neoplasias Colorretais , Ileostomia , Humanos , Masculino , Fatores de Risco , Feminino , Ileostomia/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Colorretais/cirurgia , Idoso , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/sangue , Período Pré-Operatório , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Creatinina/sangueRESUMO
BACKGROUND AND AIM: Accurate stratification of the risk of lymph node metastasis (LNM) following endoscopic resection of submucosal invasive (T1) colorectal cancer (CRC) is imperative for determining the necessity for additional surgery. In this systematic review, we evaluated the efficacy of prediction of LNM by artificial intelligence (AI) models utilizing whole slide image (WSI) in patients with T1 CRC. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted through searches in PubMed (MEDLINE), Embase, and the Cochrane Library for relevant studies published up to December 2023. The inclusion criteria were studies assessing the accuracy of hematoxylin and eosin-stained WSI-based AI models for predicting LNM in patients with T1 CRC. RESULTS: Four studies met the criteria for inclusion in this systematic review. The area under the receiver operating characteristic curve for these AI models ranged from 0.57 to 0.76. In the three studies in which AI performance was compared directly with current treatment guidelines, AI consistently exhibited a higher area under the receiver operating characteristic curve. At a fixed sensitivity of 100%, specificities ranged from 18.4% to 45.0%. CONCLUSIONS: Artificial intelligence models based on WSI can potentially address the issue of diagnostic variability between pathologists and exceed the predictive accuracy of current guidelines. However, these findings require confirmation by larger studies that incorporate external validation.
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Achalasia is a rare esophageal motility disorder characterized by nonrelaxation of the lower esophageal sphincter. Laparoscopic Heller myotomy (LHM) is the gold standard treatment for achalasia. Peroral endoscopic myotomy (POEM), a less invasive treatment, is performed extensively, and the selection of the intervention method remains debatable to date. In addition to the availability of extensive studies on short-term outcomes, recent studies on the long-term outcomes of LHM and POEM have shown similar clinical success after 5 y of follow-up. However, gastroesophageal reflux disease (GERD) was more common in patients who had undergone POEM than in those who had undergone LHM. Moreover, existing studies have compared treatment outcomes in various disease states. Some studies have suggested that POEM is superior to LHM for patients with type III achalasia because POEM allows for a longer myotomy. Research on treatment for sigmoid types is currently in progress. However, the long-term results comparing LHD and POEM are insufficient, and the best treatment remains controversial. Further research is needed, and treatment options should be discussed with patients and tailored to their individual needs and pathologies.
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PURPOSE: The anatomical location of inflammation in and around the ileal pouch affects the pouch survival rate, and diffuse inflammation has poor pouch survival rates. We aimed to clarify the symptoms and histological findings of diffuse inflammation of the pouch. METHODS: We evaluated the symptoms, treatment, and histological findings according to the endoscopic phenotypes of diffuse inflammation, focal inflammation, and normal as the pouch body phenotype and afferent limb involvement, inlet involvement, cuffitis, and fistula as the peripheral findings. RESULTS: Of the 318 pouchoscopies, 47 had diffuse inflammation, 201 had focal inflammation, and 70 were normal. Symptomatic patients had diffuse inflammation more frequently (46.8%) than focal inflammation (13.4%) and normal (14.2%), with no difference between focal inflammation and normal. Antibiotics and steroids were higher rate administered in cases of diffuse inflammation, but not in cases of focal inflammation or in normal cases. Histological inflammation, inflammatory bowel disease (IBD)-specific finding, and colonic metaplasia showed severity in the order of diffuse inflammation > focal inflammation > normal. The number of peripheral inflammatory findings overlapped in the following order: diffuse inflammation > focal inflammation > normal. The number of symptomatic patients increased as the number of peripheral inflammatory findings increased. CONCLUSION: Pouches with diffuse inflammation are more symptomatic, have a higher use of therapeutic agents, and have more severe histological inflammation, IBD-specific finding, and colonic metaplasia accompanying peripheral inflammatory findings than the other groups. The higher the overlap of inflammatory findings in the surrounding tissues, the more symptomatic the patients will appear.
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Bolsas Cólicas , Inflamação , Humanos , Masculino , Feminino , Bolsas Cólicas/patologia , Bolsas Cólicas/efeitos adversos , Inflamação/patologia , Adulto , Pouchite/patologia , Pessoa de Meia-Idade , Endoscopia GastrointestinalRESUMO
The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.0001) and overall survival (OS; HR: 9.68, P < 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P < 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.
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BACKGROUND: Clinicopathological differences exist between ulcerative colitis-associated colorectal cancer (UC-CRC) and sporadic colorectal cancer (S-CRC). However, differences in the prognosis remain controversial, and the reason for these differences remains unclear. We therefore assessed the differences between patients with UC-CRC and S-CRC. PATIENTS AND METHODS: This was a matched-pair analysis of the clinicopathological characteristics and prognosis of patients with UC-CRC and S-CRC who underwent colorectal resection between January 2000 and December 2021 at two institutions. Patients were matched according to age, sex, date of surgery, tumor location, and Union for International Cancer Control (UICC) stage. RESULTS: A total of 5992 patients underwent surgery for CRC at the two institutions, and 288 patients (48 with UC-CRC and 240 with S-CRC) were matched in this study. Patients with UC-CRC underwent more invasive surgery and had a longer operative time than those with S-CRC, but there was no marked difference in postoperative complications or perioperative mortality. Long-term outcomes showed a similar 5-year overall survival (OS) for UC-CRC and S-CRC (86.5% versus 88.8%, p = 0.742); however, in stage 3 patients, patients with UC-CRC had a poorer 5-year OS than those with S-CRC (51.4% versus 83.8%, p = 0.032). The first recurrence sites in stage 3 UC-CRC were peritoneal dissemination followed by the bones, while those in S-CRC were the liver and pulmonary system. CONCLUSIONS: Despite no significant differences in surgical outcomes, patients with UC-CRC had a poorer prognosis than those with S-CRC at stage 3. The recurrence patterns in UC-CRC differed from those in S-CRC, suggesting a possible prognostic difference.
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Colite Ulcerativa , Neoplasias Colorretais , Recidiva Local de Neoplasia , Humanos , Masculino , Feminino , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/cirurgia , Pessoa de Meia-Idade , Análise por Pareamento , Colite Ulcerativa/cirurgia , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Taxa de Sobrevida , Prognóstico , Seguimentos , Idoso , Estudos Retrospectivos , Estadiamento de Neoplasias , Adulto , Complicações Pós-Operatórias/etiologiaRESUMO
AIM: Medical errors are critical in obstetrics and gynecology (OB/GYN) and contribute to high litigation risks. However, few studies have examined system and diagnostic errors as potential preventable problems. This study aimed to enhance medical safety and reduce litigation by identifying and addressing key contributory factors. METHODS: We retrospectively searched the national Japanese malpractice claims database for OB/GYN cases between 1961 and 2017. We evaluated provider characteristics and background information of the patients (plaintiffs). The main outcome was litigation (acceptance or rejection) in the final judgment. Using multivariable logistic regression models, we assessed the associations between medical malpractice variables (system and diagnostic errors, facility size, situation, place, time, and clinical outcomes) and litigation outcomes (acceptance). RESULTS: Overall, 344 malpractice claims were analyzed. Among these, 277 (80.5 %) were obstetric, and 67 (19.5 %) were gynecological. Of the obstetric cases, 193 were perinatal, and 84 were maternal. Malpractice claims were accepted (OB-GYN losses) in 185 cases (53.8 %). In multivariable analyses, system errors (odds ratio 97.4, 95 % confidence interval 35.2-270.0), diagnostic errors (odds ratio 4.5, 95 % confidence interval 1.8-11.3), and clinic (odds ratio 2.7, 95 % confidence interval 1.2-4.8) had a significant statistical association with accepted claims. CONCLUSION: System errors, diagnostic errors, and clinics were significantly associated with acceptance claims. These findings underscore the necessity of addressing modifiable factors at the physician level and within the healthcare management system to enhance patient safety and reduce litigation risks, thereby ensuring a safer and more reliable healthcare environment for patients and medical professionals.
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Ginecologia , Imperícia , Erros Médicos , Obstetrícia , Humanos , Imperícia/estatística & dados numéricos , Imperícia/legislação & jurisprudência , Estudos Retrospectivos , Japão , Feminino , Obstetrícia/legislação & jurisprudência , Erros Médicos/legislação & jurisprudência , Erros Médicos/estatística & dados numéricos , Ginecologia/legislação & jurisprudência , Fatores de Risco , Adulto , Erros de Diagnóstico/legislação & jurisprudência , Erros de Diagnóstico/estatística & dados numéricos , Gravidez , Modelos Logísticos , Pessoa de Meia-IdadeRESUMO
PURPOSE: Doublet chemotherapy with fluoropyrimidine (FP) and oxaliplatin (OX) plus bevacizumab (BEV) is a standard regimen for unresectable metastatic colorectal cancer (MCRC). However, the efficacy of adding OX to FP plus BEV (FP + BEV) remains unclear for older patients, a population for whom FP + BEV is standard. We aimed to confirm the superiority of adding OX to FP + BEV for this population. METHODS: This open-label, randomized, phase III trial was conducted at 42 institutions in Japan. Patients with unresectable MCRC age 70-74 years with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 and those 75 years and older with ECOG-PS 0-2 were randomly assigned (1:1) to an FP + BEV arm or an OX addition (FP + BEV + OX) arm. Fluorouracil plus levofolinate calcium or capecitabine was declared before enrollment. The primary end point was progression-free survival (PFS). The study was registered in the Japan Registry of Clinical Trials (identifier: jRCTs031180145). RESULTS: Between September 2012 and March 2019, 251 patients were randomly assigned to the FP + BEV arm (n = 125) and the FP + BEV + OX arm (n = 126). The median age was 80 and 79 years in the respective arm. The median PFS was 9.4 months (95% CI, 8.3 to 10.3) in the FP + BEV arm and 10.0 months (9.0 to 11.2) in the FP + BEV + OX arm (hazard ratio [HR], 0.84 [90.5% CI, 0.67 to 1.04]; one-sided P = .086). The median overall survival was 21.3 months (18.7 to 24.3) in the FP + BEV arm and 19.7 months (15.5 to 25.5) in the FP + BEV + OX arm (HR, 1.05 [0.81 to 1.37]). The proportion of any grade ≥3 adverse events was higher in the FP + BEV + OX arm (52% v 69%). There was one treatment-related death in the FP + BEV arm and three in the FP + BEV + OX arm. CONCLUSION: No benefit of adding OX to FP + BEV as first-line treatment was demonstrated in older patients with MCRC. FP + BEV is recommended for this population.
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BACKGROUND/AIM: No clear treatment strategy for simultaneously detected liver and lung metastases (SLLM) of colorectal carcinoma has been established, to date. We aimed to identify the prognostic factors for SLLM and propose an appropriate treatment option. PATIENTS AND METHODS: This retrospective study included 64 patients with SLLM: 32 underwent pulmonary resection after hepatectomy in 32, while the other 32 underwent hepatectomy alone in 32. Poor prognostic factors and a suitable strategy for SLLM were assessed. RESULTS: Multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) level ≥20 ng/ml (p=0.001) and unresected lung metastases (p=0.001) were independent prognostic factors for poor overall survival. Compared with the non-pulmonary resection group, the rate of R1 resection of liver tumors (46.8% vs. 15.6%; p=0.007), incidence of complications after hepatectomy (Clavien-Dindo grade ≥III: 21.8% vs. 0%; p=0.005) and having four or more metastatic lung nodules (40.6% vs. 3.2%; p=0.001) were significantly higher in the group that underwent hepatectomy only. CONCLUSION: Preoperative CEA ≥20 ng/ml and unresectable pulmonary nodules were prognostic factors for poor survival of patients with SLLM. Furthermore, the presence of more than four pulmonary nodules was a preoperative predictive factor for unresectable pulmonary nodules. R1 resection and the occurrence of complications after hepatectomy should be avoided; a smooth transition from hepatectomy to pulmonary resection is important.
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Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Masculino , Feminino , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Prognóstico , Antígeno Carcinoembrionário/sangue , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND CONTEXT: SI-6603 (condoliase) is a chemonucleolytic agent approved in Japan in 2018 for the treatment of lumbar disc herniation (LDH) associated with radicular leg pain. Condoliase, a mucopolysaccharidase with high substrate specificity for glycosaminoglycans (GAGs), offers a unique mechanism of action through the degradation of GAGs in the nucleus pulposus. As LDH management is currently limited to conservative approaches and surgical intervention, condoliase could offer a less invasive treatment option than surgery for patients with LDH. PURPOSE: The Discover 6603 study (NCT03607838) evaluated the efficacy and safety of a single-dose injection of SI-6603 (condoliase) vs sham for the treatment of radicular leg pain associated with LDH. STUDY DESIGN/SETTING: A randomized, double-blind, sham-controlled, phase 3 study conducted across 41 sites in the United States. PATIENT SAMPLE: Male and female participants (N=352; aged 30-70 years) with contained posterolateral LDH and unilateral radiculopathy/radicular leg pain for greater than 6 weeks. OUTCOME MEASURES: The primary endpoint was the change from baseline (CFB) in average worst leg pain score at 13 weeks, assessed using the 100-mm visual analogue scale. Key secondary endpoints were CFB in average worst leg pain score at 52 weeks, herniation volume at 13 weeks, and Oswestry Disability Index (ODI) score at 13 weeks. Safety evaluations included adverse events (AEs) and imaging findings. METHODS: Participants were randomized 1:1 to receive a single intradiscal injection of condoliase (1.25 units) or sham injection followed by 52 weeks of observation. The primary and key secondary endpoints were assessed using a mixed model for repeated measures (MMRM) analysis and a protocol-specified multiple imputation (MI) sensitivity analysis on the modified intention-to-treat (mITT) population. A prespecified serial gatekeeping algorithm was used for multiple comparisons. Safety endpoints included AEs, laboratory tests, vital signs, imaging (by X-ray and magnetic resonance imaging [MRI]), and occurrence of posttreatment lumbar surgery. RESULTS: Of the 352 randomized participants, 341 constituted the mITT population (condoliase n=169; sham n=172) and the safety population (condoliase n=167; sham n=174). For the primary endpoint, the condoliase group showed significantly greater improvement in CFB in worst leg pain at Week 13 (least squares mean [LSM] CFB: -41.7) compared with sham injection (-34.2; LSM difference: -7.5; 95% confidence interval [CI]: -14.1, -0.9; p=.0263) based on the MMRM analysis. CFB in worst leg pain at Week 52 favored condoliase vs sham, but the difference was not statistically significant (p=.0558), which halted the serial gatekeeping testing algorithm and dictated that the CFB in herniation volume and ODI scores at Week 13 would be considered nonsignificant, regardless of their p-values. Treatment group differences in CFB in herniation volume and ODI score favored the condoliase group vs sham at all timepoints. The MI sensitivity analysis showed differences in CFB in worst leg pain at Week 13 (p=.0223) and Week 52 (p=.0433) in favor of the condoliase group. Treatment-emergent AEs (TEAEs) were more common in the condoliase group (≥1 TEAE: 71.9%; ≥1 treatment-related TEAE: 28.1%) compared with the sham group (≥1 TEAE: 60.3%; ≥1 treatment-related TEAE: 10.3%). Of the TEAEs, spinal MRI abnormalities and back pain occurred most frequently. No treatment-related serious AEs occurred. CONCLUSIONS: Condoliase met its primary endpoint of significantly improving radicular leg pain at Week 13 and was generally well tolerated in patients with LDH. Chemonucleolysis with condoliase has the potential to provide a less invasive treatment option than surgery for those unresponsive to conservative treatment strategies.
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Arginine deimination by Tetragenococcus halophilus, a halophilic lactic acid bacterium, is an undesirable reaction in soy sauce brewing because it is responsible for the production of ethyl carbamate, a potential carcinogen. Therefore, arginine deiminase system-deficient mutants have been generated and used as starter cultures. However, the pre-existing screening method for arginine deiminase system-deficient mutants was time consuming. To reduce the burden of this screening process, we established a method to isolate mutants incapable of arginine deimination using the arginine analog canavanine. Strains lacking arginine deiminase system were less sensitive to canavanine than wild type strain, which is likely because arginine deiminase consumes arginine in the cytoplasm and increases the relative concentration of canavanine in the cells and enhances its toxicity. This report provides an industrially useful method to efficiently obtain arginine deiminase system-deficient mutants.
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Arginina , Canavanina , Hidrolases , Mutação , Hidrolases/metabolismo , Hidrolases/genética , Hidrolases/química , Arginina/metabolismo , Canavanina/metabolismo , Enterococcaceae/genética , Enterococcaceae/metabolismo , Alimentos de Soja/microbiologiaRESUMO
BACKGROUND: The significance of resection of para-aortic lymph node metastasis in colorectal cancer is controversial. OBJECTIVE: To clarify the prognosis of colorectal cancer after para-aortic lymph node metastasis resection. DESIGN: Multicenter retrospective study. SETTINGS: Thirty-six institutions in Japan participated in this study. Database and medical records at each institution were used for data collection. PATIENTS: Patients with resected and pathologically proven para-aortic lymph node metastasis of colorectal cancer between 2010 and 2015 were included. MAIN OUTCOME MEASURES: Overall survival after para-aortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of para-aortic lymph node metastasis. RESULTS: A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% CI) was 41.0% (32.0-49.8), and the median survival (95% CI) was 4.1 (3.4-4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs pT1- 3, adjusted HR: 1.91, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.98, p = 0.005), time to metastases (synchronous vs metachronous adjusted HR: 2.02, p = 0.02), and the number of para-aortic lymph node metastasis (3 or more vs less than 3, adjusted HR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5-29.7), with a median (95% CI) of 1.2 (0.9-1.4) years. The primary tumor location (left- vs right-sided colon, adjusted HR: 4.77, p = 0.01; rectum vs right-sided colon, adjusted HR: 5.27, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.90, p = 0.03), number of para-aortic lymph node metastases (3 or more vs less than 3, adjusted HR: 2.20, p = 0.001), and hospital volume (less than 10 vs 10 or more, adjusted HR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Para-aortic lymph node recurrence was the most common at 33.3%. LIMITATIONS: Selection bias cannot be ruled out because of the retrospective nature of the study. CONCLUSIONS: Less than 3 para-aortic lymph node metastases were a favorable prognostic factor for overall and recurrence-free survival. However, para-aortic lymph node metastases were considered to be a systemic disease, and the significance of resection was limited. See Video Abstract . RESULTADO A LARGO PLAZO POSTERIOR A LA RESECCIN QUIRRGICA DE METSTASIS EN GANGLIOS LINFTICOS PARAARTICOS DE CNCER COLORRECTAL UN ESTUDIO RETROSPECTIVO MULTICNTRICO: ANTECEDENTES:La importancia de la resección de metástasis en los ganglios linfáticos paraaórticos (PALNM) en el cáncer colorrectal (CCR) es controvertida.OBJETIVO:Aclarar el pronóstico del CCR después de la resección PALNM.DISEÑO:Estudio retrospectivo multicéntrico.ENTORNO CLINICO:Treinta y seis instituciones en Japón participaron en este estudio.PACIENTES:Pacientes con PALNM de CCR resecado y patológicamente probado entre 2010 y 2015.FUENTES DE DATOS:Base de datos y registros médicos de cada institución.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general (SG) después de la resección PALNM, supervivencia libre de recurrencia (SLR) y patrones de recurrencia después de la resección R0 de PALNM.RESULTADOS:Se incluyó un total de 133 pacientes en la población de análisis primario de este estudio. La tasa de SG a 5 años (intervalo de confianza [IC] del 95 %) fue del 41,0 % (32,0, 49,8) y la mediana de supervivencia (IC del 95 %) fue de 4,1 (3,4, 4,7) años. Los factores de pronóstico independientes para la SG fueron el estadio T patológico (pT4 vs. pT1-3, índice de riesgo ajustado [aHR]: 1,91, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,98, p = 0,005), tiempo hasta las metástasis (síncronas vs. metacrónicas, aHR: 2,02, p = 0,02) y número de PALNM (≥3 vs. <3, aHR: 2,13, p = 0,001). La tasa de SLR a 5 años (IC del 95%) fue del 21,1% (13,5, 29,7), con una mediana (IC del 95%) de 1,2 (0,9, 1,4) años. La ubicación del tumor primario (colon del lado izquierdo vs. derecho, aHR: 4,77, p = 0,01; recto vs. colon del lado derecho, aHR: 5,27, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,90, p = 0,03), el número de PALNM (≥3 vs. <3, aHR: 2,20, p = 0,001) y el volumen hospitalario (<10 vs. ≥10, aHR: 2,18, p = 0,02) se identificaron como independientes factores pronósticos del SLR. La recurrencia de los ganglios linfáticos paraaórticos fue la más común con un 33,3%.LIMITACIONES:No se puede descartar un sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:Menos de tres PALNM fue un factor pronóstico favorable tanto para la SG como para la SLR. Sin embargo, las PALNM se consideraron una enfermedad sistémica y la importancia de la resección fue limitada. (Traducción- Dr. Francisco M. Abarca-Rendon ).
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Neoplasias Colorretais , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Estadiamento de Neoplasias , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/mortalidade , Pessoa de Meia-Idade , Excisão de Linfonodo/métodos , Japão/epidemiologia , Linfonodos/patologia , Linfonodos/cirurgia , Taxa de Sobrevida , Prognóstico , Recidiva Local de Neoplasia/epidemiologia , Intervalo Livre de Doença , Idoso de 80 Anos ou maisRESUMO
Background: This study aimed to evaluate the efficacy of lateral lymph node dissection (LLND) for rectal cancer by comparing the local control in patients with and without pathological lateral lymph node metastasis (LLNM). Methods: We included 189 patients with rectal cancer who underwent total mesorectal excision and LLND at 13 institutions between 2017 and 2019. Patients with and without pathological LLNM were defined as the pLLNM (+) and (-) groups, respectively. Propensity score-matching helped to balance the basic characteristics of both groups. The incidences of local recurrence (LR) and lateral lymph node recurrence (LLNR) were compared between the groups. Results: In the entire cohort, 39 of the 189 patients had pathological LLNM. The 3-year LR and LLNR rates were 18.3% and 4.0% (p = 0.01) and 7.7% and 3.3% (p = 0.22) in the pLLNM (+) and (-) groups, respectively. After propensity score matching, the data from 62 patients were analyzed. No significant differences in LR or LLNR were observed between both groups. The 3-year LR and LLNR rates were 16.4% and 9.8% (p = 0.46) and 9.7% and 9.8% (p = 0.99) in the pLLNM (+) and (-) groups, respectively. Conclusion: LLND would lead to comparable local control in the pLLNM (+) and (-) groups if the clinicopathological characteristics except for LLNM are similar.
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BACKGROUND: The diagnostic criteria for lateral lymph node metastasis in rectal cancer have not been established. This research aimed to investigate the risk factors for lateral lymph node metastasis and develop machine learning models combining these risk factors to improve the diagnostic performance of standard imaging. METHOD: This multicentre prospective study included patients who underwent lateral lymph node dissection without preoperative treatment for rectal cancer between 2017 and 2019 in 15 Japanese institutions. First, preoperative clinicopathological factors and magnetic resonance imaging findings were evaluated using multivariable analyses for their correlation with lateral lymph node metastasis. Next, machine learning diagnostic models for lateral lymph node metastasis were developed combining these risk factors. The models were tested in a training set and in an internal validation cohort and their diagnostic performance was tested using receiver operating characteristic curve analyses. RESULTS: Of 212 rectal cancers, 122 patients were selected, including 232 lateral pelvic sides, 30 sides of which had pathological lateral lymph node metastasis. Multivariable analysis revealed that poorly differentiated/mucinous adenocarcinoma, extramural vascular invasion, tumour deposit and a short-axis diameter of lateral lymph node ≥ 6.0 mm were independent risk factors for lateral lymph node metastasis. Patients were randomly divided into a training cohort (139 sides) and a test cohort (93 sides) and machine learning models were computed on the basis of a combination of significant features (including: histological type, extramural vascular invasion, tumour deposit, short- and long-axis diameter of lateral lymph node, body mass index, serum carcinoembryonic antigen level, cT, cN, cM, irregular border and mixed signal intensity). The top three models with the highest sensitivity in the training cohort were as follows: support vector machine (sensitivity, 1.000; specificity, 0.773), light gradient boosting machine (sensitivity, 0.950; specificity, 0.918) and ensemble learning (sensitivity, 0.950; specificity, 0.917). The diagnostic performances of these models in the test cohort were as follows: support vector machine (sensitivity, 0.750; specificity, 0.667), light gradient boosting machine (sensitivity, 0.500; specificity, 0.852) and ensemble learning (sensitivity, 0.667; specificity, 0.864). CONCLUSION: Machine learning models combining multiple risk factors can contribute to improving diagnostic performance of lateral lymph node metastasis.
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Linfonodos , Metástase Linfática , Aprendizado de Máquina , Neoplasias Retais , Humanos , Metástase Linfática/patologia , Neoplasias Retais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Prospectivos , Idoso , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Imageamento por Ressonância Magnética , Excisão de Linfonodo , Curva ROC , AdultoRESUMO
PURPOSE: Non-invasive reduction in patients with incarcerated obturator hernias is an emergency surgery alternative. There are two non-invasive reduction types: manual and ultrasonographic (ultrasound-guided and ultrasound-assisted reduction). However, the impact of ultrasound guidance on manual reduction has not been adequately evaluated. We aimed to compare non-invasive ultrasound reduction with manual reduction in patients with incarcerated obturator hernias. METHODS: We searched MEDLINE, Cochrane Central Library, Embase, Ichushi Web, ClinicalTrial.gov, and ICTRP for relevant studies. The primary outcomes were success and bowel resection rates. We performed a subgroup analysis between ultrasound-guided and ultrasound-assisted reductions. This study was registered in PROSPERO (CRD 42,024,498,295). RESULTS: We included six studies (112 patients, including 12 from our cohort). The success rate was 78% (69 of 88 cases) with ultrasonographic reduction and 33% (8 of 24 cases) with manual reduction. The success rate was higher with ultrasonographic than with manual reduction. Subgroup analysis revealed no significant difference between ultrasonography-assisted (76%) and ultrasonography-guided (80%) reductions (p = 0.60). Non-invasive reductions were predominantly successful within 72 h of onset, although durations extended up to 216 h in one case. Among the successful reduction cases, emergency surgery and bowel resection were necessary in two cases after 72 h from onset. Bowel resection was required in 48% (12 of 25), where the non-invasive reduction was unsuccessful within 72 h of confirmed onset. CONCLUSIONS: Ultrasonographic reduction can be a primary treatment option for patients with obturator hernias within 72 h of onset by emergency physicians and surgeons on call. Future prospective studies are needed to evaluate ultrasonographic reduction's impact.