Pararespiratory and paradigestive lymph node metastases in esophageal squamous cell carcinoma: predicting survival and refining the N staging system.

BACKGROUND: The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count. METHODS: This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41-1.77, P < 0.001). The nN staging definition: nN1 (1-2 positive pararespiratory/paradigestive LNs), nN2 (3-6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3-6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems. CONCLUSIONS: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems.

Radiotherapy and chemoradiotherapy for postoperative recurrence in patients with esophageal squamous cell carcinoma.

BACKGROUND: The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients. METHODS: Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post-recurrence survival (PRS) and prognostic factors were evaluated by Kaplan-Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction. RESULTS: A total of 170 patients were enrolled, with a median age of 60 years (range 43-77). No significant difference was found in the median PRS between the salvage RT and CRT groups (p > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all p < 0.05) for PRS. Salvage treatment was not associated with PRS (p = 0.897). However, in patients with negative LN, CRT was associated with prolonged survival (p = 0.043) and had no significant differences in toxic reactions compared to RT (p = 0.924). In addition, RT showed better prognoses (p = 0.020) and lower toxic reactions (p = 0.030) than CRT in patients with positive LNs. CONCLUSIONS: Based on prognosis and toxic reactions, ESCC recurrence patients with negative LNs could benefit from CRT, but RT should be recommended for patients with positive LNs.

Preoperative Clinical Characteristics Predict Recurrent Laryngeal Nerve Lymph Node Metastasis and Overall Survival in Esophageal Squamous Cell Carcinoma: A Retrospective Study With External Validation.

Background: Recurrent laryngeal nerve (RLN) lymph node metastasis (LNM) is not rare in patients with esophageal squamous cell carcinoma (ESCC). We aimed to develop and externally validate a preoperative nomogram using clinical characteristics to predict RLN LNM in patients with ESCC and evaluate its prognostic value. Methods: A total of 430 patients with ESCC who underwent esophagectomy with lymphadenectomy of RLN LNs at two centers between May 2015 and June 2019 were reviewed and divided into training (center 1, n = 283) and external validation cohorts (center 2, n = 147). Independent risk factors for RLN LNM were determined by multivariate logistic regression, and a nomogram was developed. The performance of the nomogram was assessed in terms of discrimination, calibration, clinical usefulness, and prognostic value. The nomogram was internally validated by the bootstrap method and externally validated by the external validation cohort. Results: Multivariate analysis indicated that clinical T stage (P <0.001), endoscopic tumor length (P = 0.003), bioptic tumor differentiation (P = 0.004), and preoperative carcinoembryonic antigen level (P = 0.001) were significantly associated with RLN LNM. The nomogram had good discrimination with the area under the curve of 0.770 and 0.832 after internal and external validations. The calibration curves and decision curve analysis confirmed the good calibration and clinical usefulness of this model. High-risk of RLN LNM predicted by the nomogram was associated with worse overall survival in the external validation cohort (P <0.001). Conclusion: A nomogram developed by preoperative clinical characteristics demonstrated a good performance to predict RLN LNM and prognosis for patients with ESCC.

Utility of Clinical and Ultrasonographic Hip Screening in Neonates for Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH) is a musculoskeletal condition occupying any point along a spectrum of anatomical abnormalities that alter the stability of the newborn hip. Presentation varies throughout infancy and the majority of cases, especially those that are mild in nature, tend to resolve without intervention. An analysis of outcomes was conducted on infants born over a two-year period at a single-center, community hospital in East Toronto. The unwritten norm at the institution has become to order hip ultrasonography for all infants born in the breech position through C-section. Given the healthcare expenditure associated with routine radiographic screening, a careful analysis was undertaken to ascertain whether this screening regimen was effective in preventing late-stage detection of advanced DDH and improving organization in patient management. There were a total of 4236 babies delivered over the two years. One-hundred sixty-four (164) babies were born breech and through C-section. Eight (8) babies had abnormal hip examinations, one of whom was ultimately diagnosed with DDH. Forty-six (46) babies showed abnormal hip ultrasound at six weeks. Seventeen (17) referrals were made to the orthopedic surgeon. This resulted in a total of seven cases of DDH being diagnosed over the two years. The sensitivity and specificity of clinical hip screening were 14.3% and 95.5%, respectively, while that for ultrasound screening was 100% and 75.2%. To improve the quality of care and detection of DDH, a risk factor analysis was conducted to retrospectively analyze which DDH cases would have been missed if a higher threshold to ordering hip ultrasonography had been used. Based on the test characteristics of clinical and ultrasonographic screening, held in conjunction with the risk factor analysis results, an altered screening regimen was proposed with the intention of being just as sensitive but more cost-effective. This regimen integrates clinical screening using Barlow and Ortalani maneuvers until the eight to 10-week period and examines for limited abduction from eight weeks onward. Adjuncts like the Galeazzi test and that for asymmetrical skin folds should also be included to increase the sensitivity of clinical screening. Ultrasonography is proposed for high-risk individuals, with the criteria for stratification as high-risk being extracted from the risk factor analysis. Ultrasound is also proposed to be done in a serial fashion prior to orthopedic surgery referral in cases where the age of the infant allows, which serves to better evaluate the risk for lasting DDH and understand the longitudinal trajectory of the patient. This serves the additional purpose of decreasing the psychosocial burden on families. This can be particularly significant for infants for whom the initial abnormalities are due to self-resolve with the maturation of the hip joint and the infant's growth.