Long-interval Group Research Articles

Impact of the interval between neoadjuvant immunotherapy and surgery on prognosis in esophageal squamous cell carcinoma (ESCC): a real-world study

BackgroundThe time interval between neoadjuvant immunotherapy and surgery is 6 weeks for esophageal squamous cell carcinoma (ESCC), but whether delayed surgery affects prognosis remains unclear.MethodsClinical data of locally advanced ESCC who underwent neoadjuvant immunotherapy followed by esophagectomy from November 2019 to December 2022 were collected. The surgery outcomes and prognosis were compared between short-interval (time to surgery ≤ 6 weeks) and long-interval groups (time to surgery > 6 weeks).Results152 patients were enrolled totally, with a ratio of 91:61 between short-interval and long-interval groups. The rate of pathological complete response in the short-interval and long-interval groups were 34.1% and 24.6% (P = 0.257). Delayed surgery did not have a significantly impact on the number of lymph node dissections (P = 0.133), operative duration (P = 0.689), blood loss (P = 0.837), hospitalization duration (P = 0.293), chest drainage duration (P = 0.886) and postoperative complications (P > 0.050). The 3-year Overall survival (OS) rates were 85.10% in the short-interval group, and 82.07% in the long-interval group (P = 0.435). The 3-year disease-free survival (DFS) rates were 83.41% and 70.86% in the two groups (P = 0.037). Subgroup analysis revealed that patients with a favorable response to immunotherapy (tumor regression grade 0) exhibited inferior 3-year OS (long-interval vs. short-interval: 51.85% vs. 91.08%, P = 0.035) and DFS (long-interval vs. short-interval: 47.40% vs. 91.08%, P = 0.014) in the long-interval group.ConclusionsDelayed surgery after neoadjuvant immunotherapy does not further improve pathological response; instead, it resulted in a poorer DFS. Especially for patients with a favorable response to immunotherapy, delayed surgery increases the risk of mortality and recurrence.

Anisotropy component of DTI reveals long-term neuroinflammation following repetitive mild traumatic brain injury in rats

BackgroundThis study aimed to investigate the long-term effects of repetitive mild traumatic brain injury (rmTBI) with varying inter-injury intervals by measuring diffusion tensor metrics, including mean diffusivity (MD), fractional anisotropy (FA), and diffusion magnitude (L) and pure anisotropy (q).MethodsEighteen rats were randomly divided into three groups: short-interval rmTBI (n = 6), long-interval rmTBI (n = 6), and sham controls (n = 6). MD, FA, L, and q values were analyzed from longitudinal diffusion tensor imaging at days 50 and 90 after rmTBI. Immunohistochemical staining against neurons, astrocytes, microglia, and myelin was performed. Analysis of variance, Pearson correlation coefficient, and simple linear regression model were used.ResultsAt day 50 post-rmTBI, lower cortical FA and q values were shown in the short-interval group (p ≤ 0.038). In contrast, higher FA and q values were shown for the long-interval group (p ≤ 0.039) in the corpus callosum. In the ipsilesional external capsule and internal capsule, no significant changes were found in FA, while lower L and q values were shown in the short-interval group (p ≤ 0.028) at day 90. The q values in the external capsule and internal capsule were negatively correlated with the number of microglial cells and the total number of astroglial cells (p ≤ 0.035).ConclusionTensor scalar measurements, such as L and q values, are sensitive to exacerbated chronic injury induced by rmTBI with shorter inter-injury intervals and reflect long-term astrogliosis induced by the cumulative injury.Relevance statementTensor scalar measurements, including L and q values, are potential DTI metrics for detecting long-term and subtle injury following rmTBI; in particular, q values may be used for quantifying remote white matter (WM) changes following rmTBI.Key PointsThe alteration of L and q values was demonstrated after chronic repetitive mild traumatic brain injury.Changing q values were observed in the impact site and remote WM.The lower q values in the remote WM were associated with astrogliosis.Graphical

Oncologic investigation of the interval from stent placement to surgery in patients with obstructive colorectal cancer.

Self-expandable metallic stent (SEMS) placement is widely used as a bridge to surgery (BTS) procedure for obstructive colorectal cancer. However, evidence regarding the optimal interval between SEMS placement and elective surgery is lacking. We retrospectively collected data from patients with BTS between January 2013 and October 2021. Inverse probability treatment-weighted propensity score analyses were used to compare short- and long-term outcomes between the short-interval (SI) and long-interval (LI) groups, using a cutoff of 20days. In total, 138 patients were enrolled in this study (SI group, n = 63; LI group, n = 75). In the matched cohort, the patients' backgrounds were well balanced. The incidence of Clavien-Dindo grade ≥ II postoperative complications was not significantly different between the SI and LI groups (19.0% vs. 14.0%, P = 0.47). There were no significant differences between the SI and LI groups in the 3-year recurrence-free survival (68.0% vs. 76.4%, P = 0.73) or 3-year overall survival rates (86.0% vs. 90.6%, P = 0.72). A longer interval did not deteriorate the oncological outcomes. Individual perioperative management with an appropriate interval to improve the patient's condition is required to ensure safe surgery.

Impact of endoscopic surveillance on the early diagnosis and endoscopic resection likelihood of gastric cancer.

Endoscopy could help detect early gastric cancer (EGC) and improve the prognosis of patients. The aim of this study was to analyze the impact of endoscopy and endoscopic surveillance on the early detection of gastric cancer (GC), GC staging, and treatment selection. Patients with GC diagnosed at our center from 2010 to 2022 were retrospectively analyzed and allocated to the short-interval group (had received endoscopy within 3years before diagnosis), the long-interval group (had received endoscopy more than 3years before diagnosis), and the unchecked group (had not received endoscopy before diagnosis). The differences in GC staging and treatment modalities among the three groups were analyzed, and the differences in the clinical and pathological features of EGC were further analyzed. One thousand and twenty-five GC patients were included, with 395 cases of EGC and 630 cases of advanced GC. The proportions of EGC in the short-interval, long-interval, and unchecked groups were 98.0%, 84.2%, and 29.8%, respectively (p < 0.001). Among the 387 lesions of 367 EGC patients were resected by endoscopic submucosal dissection (ESD), 341 (88.1%) exhibited curative resection, and 46 (11.9%) involved noncurative resections. Lesions of EGC differed significantly in diameter, depth of invasion, and curative resection rate (p = 0.033, 0.019, and 0.005, respectively). In the short-interval group, 87.8% of the lesions were ≤ 2cm, 95.6% of the invasion depths were confined to the mucosal layer, and 96.7% of the eCura scores were A or B. Compared with the unchecked group, they had smaller diameters (RR = 0.419, 95% CI 0.234-0.752), shallower invasion depths (RR = 0.286, 95% CI 0.105-0.777), and a higher curative resection rate (RR = 0.215, 95% CI 0.068-0.676). Endoscopic surveillance at 3-year intervals can help detect EGC, and the EGC lesions found have smaller diameters and shallower depths of invasion, helping improve the curative resection rate of ESD.

Timing to Surgery and Lymph Node Upstaging in Gastric Cancer: An NCDB Analysis.

Prior studies have shown tumor specificity on the impact of longer time interval from diagnosis to surgery, however in gastric cancer (GC) this remains unclear. We aimed to determine if a longer time interval from diagnosis to surgery had an impact on lymph node (LN) upstaging and overall survival (OS) outcomes among patients with clinically node negative (cN0) GC. Patients diagnosed with cN0 GC undergoing surgery between 2004-2018 were identified in the National Cancer Database (NCDB) and divided into intervals between time of diagnosis and surgery [short interval (SI): ≥ 4 days to < 8 weeks and long interval (LI): ≥ 8 weeks]. Multivariable regression analysis evaluated the independent impact of surgical timing on LN upstaging and a Cox proportional hazards analysis and Kaplan-Meier curves evaluated survival outcomes. Of 1824 patients with cN0 GC, 71.8% had a SI to surgery and 28.1% had a LI to surgery. LN upstaging was seen more often in the SI group when compared to LI group (82% versus 76%, p = 0.004). LI to surgery showed to be an independent factor protective against LN upstaging [adjusted odds ratio = 0.62, 95% CI: (0.39-0.99)]. Multivariate Cox regression analysis indicated that time to surgery was not associated with a difference in overall survival [hazard ratio (HR) = 0.91, 95% CI: (0.71-1.17)], however uncontrolled Kaplan-Meier curves showed OS difference between the SI and LI to surgery groups (p = 0.037). Timing to surgery was not a predictor of LN upstaging or overall survival, suggesting that additional medical optimization in preparation for surgery and careful preoperative staging may be appropriate in patients with node negative early stage GC without affecting outcomes.

Dosing interval regimen shapes potency and breadth of antibody repertoire after vaccination of SARS-CoV-2 RBD protein subunit vaccine

Vaccination with different vaccines has been implemented globally to counter the continuous COVID-19 pandemic. However, the vaccine-elicited antibodies have reduced efficiency against the highly mutated Omicron sub-variants. Previously, we developed a protein subunit COVID-19 vaccine called ZF2001, based on the dimeric receptor-binding domain (RBD). This vaccine has been administered using different dosing intervals in real-world setting. Some individuals received three doses of ZF2001, with a one-month interval between each dose, due to urgent clinical requirements. Others had an extended dosing interval of up to five months between the second and third dose, a standard vaccination regimen for the protein subunit vaccine against hepatitis B. In this study, we profile B cell responses in individuals who received three doses of ZF2001, and compared those with long or short dosing intervals. We observed that the long-interval group exhibited higher and broader serologic antibody responses. These responses were associated with the increased size and evolution of vaccine-elicited B-cell receptor repertoires, characterized by the elevation of expanded clonotypes and somatic hypermutations. Both groups of individuals generated substantial amounts of broadly neutralizing antibodies (bnAbs) against various SARS-CoV-2 variants, including Omicron sub-variants such as XBB. These bnAbs target four antigenic sites within the RBD. To determine the vulnerable site of SARS-CoV-2, we employed cryo-electron microscopy to identify the epitopes of highly potent bnAbs that targeted two major sites. Our findings provide immunological insights into the B cell responses elicited by RBD-based vaccine, and suggest that a vaccination regimen of prolonging time interval should be used in practice.

Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study

The treatment for extraperitoneal locally advanced rectal cancer (LARC) is neoadjuvant therapy (NAT) followed by total mesorectal excision (TME). Robust evidence on the optimal time interval between NAT completion and surgery is lacking. To assess the association of time interval between NAT completion and TME with short- and long-term outcomes. It was hypothesized that longer intervals increase the pathologic complete response (pCR) rate without increasing perioperative morbidity. This cohort study included patients with LARC from 6 referral centers who completed NAT and underwent TME between January 2005 and December 2020. The cohort was divided into 3 groups depending on the time interval between NAT completion and surgery: short (≤8 weeks), intermediate (>8 and ≤12 weeks), and long (>12 weeks). The median follow-up duration was 33 months. Data analyses were conducted from May 1, 2021, to May 31, 2022. The inverse probability of treatment weighting method was used to homogenize the analysis groups. Long-course chemoradiotherapy or short-course radiotherapy with delayed surgery. The primary outcome was pCR. Other histopathologic results, perioperative events, and survival outcomes constituted the secondary outcomes. Among the 1506 patients, 908 were male (60.3%), and the median (IQR) age was 68.8 (59.4-76.5) years. The short-, intermediate-, and long-interval groups included 511 patients (33.9%), 797 patients (52.9%), and 198 patients (13.1%), respectively. The overall pCR was 17.2% (259 of 1506 patients; 95% CI, 15.4%-19.2%). When compared with the intermediate-interval group, no association was observed between time intervals and pCR in short-interval (odds ratio [OR], 0.74; 95% CI, 0.55-1.01) and long-interval (OR, 1.07; 95% CI, 0.73-1.61) groups. The long-interval group was significantly associated with lower risk of bad response (tumor regression grade [TRG] 2-3; OR, 0.47; 95% CI, 0.24-0.91), systemic recurrence (hazard ratio, 0.59; 95% CI, 0.36-0.96), higher conversion risk (OR, 3.14; 95% CI, 1.62-6.07), minor postoperative complications (OR, 1.43; 95% CI, 1.04-1.97), and incomplete mesorectum (OR, 1.89; 95% CI, 1.02-3.50) when compared with the intermediate-interval group. Time intervals longer than 12 weeks were associated with improved TRG and systemic recurrence but may increase surgical complexity and minor morbidity.

Assessment of Patients Receiving Short-Interval Botulinum Toxin Chemodenervation Treatment for Laryngeal Dystonia and Essential Tremor of the Vocal Tract

The gold-standard treatment for laryngeal dystonia (LD) and essential tremor of the vocal tract (ETVT) is botulinum toxin (BoNT) chemodenervation. Although safe and effective, it is not curative, and periodic injections are required. Some medical insurance companies only cover injections at a 3-month interval, though some patients benefit from injections more frequently. To determine the proportion and characteristics of patients who receive BoNT chemodenervation treatment in intervals shorter than 90 days. This retrospective cohort study across 3 quaternary care neurolaryngology specialty practices in Washington and California recruited patients who underwent at least 4 consecutive laryngeal BoNT injections for LD and/or ETVT in the past 5 years. Data were collected from March through June 2022 and analyzed from June through December 2022. Laryngeal BoNT treatment. Biodemographic and clinical variables, injection characteristics, evolution during the 3 interinjection intervals, and lifetime laryngeal BoNT treatment data were collected from patient medical records. Logistic regression was used to assess association to the short-interval outcome, defined as an average injection interval shorter than 90 days. Of 255 patients included from the 3 institutions, 189 (74.1%) were female, and the mean (SD) age was 62.7 (14.3) years. The predominant diagnosis was adductor LD (n = 199 [78.0%]), followed by adductor dystonic voice tremor (n = 26 [10.2%]) and ETVT (n = 13 [5.1%]). Seventy patients (27.5%) received short-interval injections (<90 days). The short-interval group was younger than the long-interval group (≥90 days), with a mean (SD) age of 58.6 (15.5) years and 64.2 (13.5) years, respectively, and a mean difference of -5.7 years (95% CI, -9.6 to -1.8 years). There were no patient-related differences between the short- and long-interval groups in terms of sex, employment status, or diagnosis. This cohort study demonstrated that while insurance companies often mandate a 3-month or greater interval for BoNT chemodenervation financial coverage, there is a considerable subset of patients with LD and ETVT who receive short-interval treatment to optimize their vocal function. Short-interval chemodenervation injections demonstrate a similar adverse effect profile and do not appear to predispose to resistance through antibody formation.

Effect of interval between neoadjuvant chemoradiotherapy and surgery on oncological outcomes in poor responders with locally advanced rectal cancer: a retrospective cohort study.

The optimal interval from completion of neoadjuvant chemoradiotherapy (CRT) to surgery in locally advanced rectal cancer remains controversial. It seems that delayed surgery is associated with an increase in pathological complete response rates. However, the prognostic effect of delayed surgery in poor responders is unclear. Patients with locally advanced mid or distal rectal cancer undergoing neoadjuvant CRT followed by total mesorectal excision at a university teaching cancer center between June 2010 and December 2018 were retrospectively reviewed in this study. According to the tumor regression grade, poor responders (tumor regression grade 2-3) to neoadjuvant CRT were selected for analyses. Patients were divided into the longer interval group (greater than 8 weeks) and the shorter interval group (8 weeks or less) based on the wait time from completion of neoadjuvant CRT therapy to surgery. Results: among 916 eligible patients, 522 patients had a poor tumor response. There were 217 patients in the shorter interval group and 305 patients in the longer interval group. At the baseline, patients in the longer interval group were more likely to have a T3 stage and positive vascular invasion. Compared with patients in the shorter interval group, patients in the longer interval group had significantly worse overall survival and disease-free survival (DFS) (log-rank test, overall survival: P =0.004, DFS: P <0.001). The 3-year DFS rates were 75.6 and 63.1% in the shorter interval group and the longer interval group, respectively. In the multivariate analysis, delayed surgery was associated with an increased risk of mortality (hazard ratio: 2.003, 95% CI: 1.233-3.253, P =0.005) and recurrence (hazard ratio: 1.555, 95% CI: 1.121-2.156, P =0.008). Patients who had a poor tumor response should be identified by restaging MRI and receive radical surgery in time, without a prolonged interval.

The long-term outcomes of vaginoplasty using acellular porcine small intestinal submucosa grafts in patients with Mayer-Rokitansky-Küster-Hauser syndrome: A case series.

To investigate the long-term outcomes for Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) patients undergoing vaginoplasty using acellular porcine small intestinal submucosa grafts (SIS). A case series. Seventy-eight MRKH syndrome patients and a post-SIS patient who delivered a baby following the world's first robot-assisted uterus transplantation. Mayer-Rokitansky-Küster-Hauser syndrome patients were grouped based on the postoperative time and the diagnosis-surgery interval. Outcomes of sexual function and psychological status were assessed using the female sexual function index (FSFI), self-rating scale of body image (SSBI) and self-acceptance questionnaire (SAQ). Anatomical outcomes were measured by clinicians. The primary outcome was restoration of sexual function, defined by an FSFI score in the 'good' range. Anatomical and psychological outcomes were also analysed. Sexual function was restored in 42.3% (33/78) of patients and the total FSFI score was 23.44 ± 4.43. Three factors (body defect, recognition of physical appearance and willingness to change physical appearance scores) in the SSBI and two in the SAQ decreased as the postoperative time increased. Based on the interval between diagnosis and surgery, the total SSBI score was lower in the short-interval group than in the long-interval group (7.25 ± 5.55 versus 12.04 ± 10.21, p=0.038). Nearly half of MRKH patients in our study had good long-term sexual function after SIS vaginoplasty. Sexual function and psychological status improved as postoperative time increased. In addition, reducing the diagnosis to surgery interval was associated with improved psychological function.

Clinicopathological characteristics of advanced gastric cancer after Helicobacter pylori eradication.

Helicobacter pylori (H. pylori) eradication has become popular as it prevents the development of gastric cancer. There have been no comprehensive studies on advanced gastric cancer (AGC) after eradication; thus, the clinical characteristics remain unclear. This study aimed to compare the characteristics of AGC after eradication and with current H. pylori infection and evaluate the esophagogastroduodenoscopy (EGD) follow-up after eradication. This single-center, retrospective study included 261 consecutive patients diagnosed with AGC through EGD. The patients were grouped based on their H. pylori status: eradication (n=48) and infection (n=213) groups. Univariate analysis was conducted to compare clinicopathological characteristics between groups. The clinical course of the eradication group was analyzed by dividing the patients into three groups according to the interval from the last EGD until AGC detection: short-interval (<1year), intermediate-interval (2-3 years), and long-interval (4-5 years) groups. The radical resection (R0) rate was higher in the eradication group. In surgical cases, the median tumor diameter was shorter in the eradication group. Analysis of EGD surveillance after eradication in 36 available cases showed that 24 (66.7%) were detected within 5 years after eradication, and 3 (8.3%) were diagnosed as AGC > 20 years after eradication. The R0 rates in the short-, intermediate-, and long-interval groups were 83.3%, 71.4%, and 60%, respectively. AGC after eradication was more often detected at the phase in which R0 resection was possible. EGD follow-up with tight intervals of at least 5 years after eradication is advisable.

Preoperative radiotherapy 5 × 5 Gy and short versus long interval between surgery for resectable rectal cancer: 10-Year follow-up of the randomised controlled trial

BackgroundStudies on short-course preoperative radiotherapy in combination with total mesorectal excision for rectal cancer reported improved local control without clear survival benefits. The optimal fractionation and interval between radiotherapy and surgery are still under debate. We, therefore, aimed to report 10-year results of a randomized clinical trial (RCT, NCT01444495) comparing different time intervals between irradiation and surgery for rectal cancer. Material and methodsData from the RCT conducted at a single academic centre were reviewed based on regular control visits with the median follow-up of 12 years. Patients with rectal cancer were randomly assigned to short-course preoperative radiotherapy (5 × 5 Gy) followed by surgery 7–10 days (short interval) or 4–5 weeks (long interval) after the end of irradiation. The primary endpoint was the local recurrence rate at 5 years. The secondary endpoints included overall survival, disease-free survival, systemic recurrence rate, and downstaging. ResultsA total of 154 patients were randomly assigned to short (n = 77) or long interval (n = 77) surgery. The cumulative incidence of local recurrence at 10 years was 1.3% and 11.7% in the short and long-interval groups, respectively (p = 0.031). Accordingly, the incidence of systemic relapse was 14.3% versus 9.1% (p = 0.0319). There were no differences in the overall 10-year survival between patients subject to short and long-interval surgery (58% vs 61%, p = 0.754). However, patients with downstaging after radiotherapy had significantly better 10-year survival rates than non-responders. ConclusionsShort-course preoperative radiotherapy with delayed surgery demonstrated an increased risk of local relapse over a 10-year follow-up.

Determining the Optimal Time Interval between Vaginal Dinoprostone Administration and Diagnostic Office Hysteroscopy in Nulliparous Women: A Randomized, Double-blind Trial

To determine the optimal timing of vaginal dinoprostone administration before office hysteroscopy (OH) in nulliparous women. Randomized, double-blind trial. Tertiary referral hospital. A total of 180 nulliparous women undergoing diagnostic OH. We randomly allocated the women to long-interval or short-interval dinoprostone groups: three mg dinoprostone was administered vaginally 12 hours before OH in the long-interval group and 3 hours before OH in the short-interval group. The primary outcome was pain during OH measured using a 100-mm visual analog scale (0=no pain; 100=worst pain imaginable). The secondary outcomes were ease of hysteroscope passage, patient satisfaction score, and drug-related adverse effects. The patients in the long-interval dinoprostone group had lower pain scores during OH (p <.001). Contrarily, pain scores 30 minutes after the procedure were similar in both groups (p=.1). The patient satisfaction score was higher and clinicians found hysteroscope passage through the cervical canal easier and quicker in the long-interval dinoprostone group than in the short-interval group (p <.001, p=.003, and p <.001, respectively). Side effects were comparable in both study groups. Vaginal dinoprostone administered 12 hours before OH was more effective than that administered 3 hours before OH in reducing pain during OH in nulliparous women, with easier hysteroscope insertion, shorter procedure duration, and higher patient satisfaction score.

Short-Term Clinical and Oncological Outcome of Prolonging Operation Interval After Neoadjuvant Chemoradiotherapy for Locally Advanced Middle and Low Rectal Cancer.

PurposeThe purpose of this study is to evaluate the short-term clinical and oncological outcome of prolonging operation interval to 11 weeks after the end of radiotherapy for locally advanced middle and low rectal cancer.MethodsA total of 123 patients with stage II/III (cT3/T4 or N+) low and middle rectal cancer who had undergone operation after neoadjuvant chemoradiotherapy were selected. According to the interval time between the last radiotherapy and operation, they were assigned to a short-interval group (SG, <11 weeks, n=66) and long-interval group (LG, ≥11 weeks, n=57). The relations among interval time and short-term clinical outcome and oncological outcome were analyzed.ResultsThe analysis found that basic information, clinical characteristics, and preoperative treatment between the two groups had no significant difference. There were no differences in operation time, estimated intraoperative blood loss and postoperative complications. The rate of sphincter preservation in the low and middle rectum was 66.7% in the short-interval group and 59.7% in the long-interval group (P=0.42). The incidence of anastomotic leak in the long-interval group was higher than that in the short-interval group (P=0.08). There was no significant difference in the recovery time of intestinal function and median duration of hospitalization between the two groups. The pathological complete remission rate was 17.07%. Multivariate analysis showed interval time had no influence on pathological complete remission. There was no significant difference in 3-year overall survival and 3-year disease-free survival between the two groups. The risk of recurrence and metastasis in patients with positive lymph nodes was higher than those with negative lymph nodes (P<0.05), HR=4.812 (95% CI 2.4–9.648).ConclusionProlonging the interval time of operation to 11 weeks after neoadjuvant chemoradiotherapy for middle and low rectal cancer does not improve the pathologic complete remission, morbidity, and mortality. There was no significant effect on oncologic outcome after prolonging the operation interval. Therefore, it is safe to prolong the interval of operation to 11 weeks.

Effect of interval between preoperative radiotherapy and surgery on clinical outcome and radiation proctitis in rectal cancer from FOWARC trial

ObjectiveThe aim of this study was to evaluate the effect of the interval between CRT and surgery on radiation proctitis, the pathologic response, and postoperative morbidity.MethodsThis was a cohort study from a phase III, randomized controlled trial (FOWARC study, NCT01211210). Data were retrieved from the leading center of the trial. Patients were divided into the short‐interval (≤7 weeks) group and the long‐interval (>7 weeks) group. The rate of radiation proctitis, pathologic complete regression (pCR) and morbidities were calculated for each group. Multivariate analysis was used to verify the impact of interval on radiation proctitis.ResultsSurgery was performed in 60 patients after an interval of ≤7 weeks and in 97 patients after an interval of >7 weeks. The two groups according to interval were comparable in terms of baseline demographic and clinicotherapeutic characteristics. Radiation proctitis was identified by imaging in 9 (15.0%) patients in short‐interval group and in 31 (32.0%) patients in long‐interval group (P = .018). Multivariate analysis confirmed the correlation between long interval and radiation proctitis (P = .018). The long interval was significantly associated with longer median operation time compared to the short interval (P = .022). The rates of pCR and postoperative complications were not different between two groups.ConclusionsA longer interval after CRT may be associated with higher rate of radiation proctitis and longer operation time. Moreover it did not increase the rate of pCR.

Tactile angle discriminability improvement: roles of training time intervals and different types of training tasks.

Perceptual learning, which is not limited to sensory modalities such as vision and touch, emerges within a training session and between training sessions and is accompanied by the remodeling of neural connections in the cortex. However, limited knowledge exists regarding perceptual learning between training sessions. Although tactile studies have paid attention to between-session learning effects, there have been few studies asking fundamental questions regarding whether the time interval between training sessions affects tactile perceptual learning and generalization across tactile tasks. We investigated the effects of different training time intervals on the consecutive performance of a tactile angle discrimination (AD) task and a tactile orientation discrimination (OD) task training on tactile angle discriminability. The results indicated that in the short-interval training group, AD task performance significantly improved in the early stage of learning and nearly plateaued in the later stage, whereas in the long-interval training group, significant improvement was delayed and then also nearly plateaued in the later stage; additionally, improved OD task performance resulted in improved AD task performance. These findings suggest that training time interval affects the early stage of learning but not the later stage and that generalization occurs between different types of tactile tasks.NEW & NOTEWORTHY Perceptual learning, which constitutes important foundations of complicated cognitive processes, is learning better perception skills. We demonstrate that training time interval can affect the early stage of learning but not the later stage. Moreover, a tactile orientation discrimination training task can also improve tactile angle discrimination performance. These findings may expand the characteristics of between-session learning and help understand the mechanism of the generalization across tactile tasks.

Impact of intertwin interval on short-term neonatal outcomesof the second twin in dichorionic pregnancies withvaginal delivery.

To examine the effect of intertwin interval on umbilical cord pH and Apgar scores of the second twin after vaginal delivery. A retrospective study of twin deliveries at a university hospital in Spain between August 2012 and September 2017. Inclusion criteria were vaginal delivery of both twins at 32 gestational weeks or more. Exclusion criteria were monochorionic pregnancies and indication for cesarean delivery. The sample was dichotomized by intertwin interval (<10 and ≥10minutes). Neonatal outcomes including Apgar scores and umbilical cord pH were evaluated. Overall, 323 twin deliveries were included. Intertwin interval was less than 10minutes in 277 (85.6%) cases, and 10minutes or longer in 46 (14.2%). There were no differences in maternal or obstetric characteristics between the groups. Incidence of instrumental delivery (P<0.001) and internal podalic version (P<0.001) for the second twin was higher in the longer interval group. A longer interval was associated with higher frequencies of 1-minute Apgar score below 4 (P=0.009), 5-minute Apgar score below 7 (P<0.001), and umbilical cord pH below 7.15 (P<0.001). Second twins with an intertwin interval of 10minutes or longer are more likely to have poorer Apgar scores and arterial blood pH below 7.15.

Influence of interval between biopsy and surgery on prognosis of patients with early-stage oral squamous cell carcinoma: A preliminary study

ObjectiveRecent studies have suggested that preoperative interventions such as tooth extraction, incision and curettage may be associated with poor prognosis in patients with oral malignancies. Although biopsy is another preoperative intervention, its influence on the prognosis of patients with oral squamous cell carcinoma (OSCC) has remained unclear. We investigated the prognosis of stage I and II OSCC patients, with special reference to the influence of the interval between biopsy and surgery. Materials and methodsThe cases of 47 patients diagnosed with primary early-stage (T1 or T2N0M0) OSCC were reviewed retrospectively. ResultsPrimary surgery was performed ≤21 days after biopsy for 17 patients, and >21 days after biopsy for 30 patients. Incidence of local recurrence or delayed cervical lymph node metastasis was significantly higher among the long-interval group (p = 0.03). Patients with local or neck failure displayed a significantly longer interval (33.6 days) than patients who were stable (21.9 days; p < 0.01). Five-year survival rates in groups with and without recurrence or metastasis were 66.7% and 90.6%, respectively (p < 0.05). ConclusionTreatment delay can worsen the prognosis of patients with early-stage OSCC by increasing the incidence of local and neck failure. Prompt treatment after biopsy is thus recommended to optimize the outcomes.

Cross-Sectional Study on MRI Restaging After Chemoradiotherapy and Interval to Surgery in Rectal Cancer: Influence on Short- and Long-Term Outcomes

BackgroundThe time interval between CRT and surgery in rectal cancer patients is still the subject of debate. The aim of this study was to first evaluate the nationwide use of restaging magnetic resonance imaging (MRI) and its impact on timing of surgery, and, second, to evaluate the impact of timing of surgery after chemoradiotherapy (CRT) on short- and long-term outcomes.MethodsPatients were selected from a collaborative rectal cancer research project including 71 Dutch centres, and were subdivided into two groups according to time interval from the start of preoperative CRT to surgery (< 14 and ≥ 14 weeks).ResultsFrom 2095 registered patients, 475 patients received preoperative CRT. MRI restaging was performed in 79.4% of patients, with a median CRT–MRI interval of 10 weeks (interquartile range [IQR] 8–11) and a median MRI–surgery interval of 4 weeks (IQR 2–5). The CRT–surgery interval groups consisted of 224 (< 14 weeks) and 251 patients (≥ 14 weeks), and the long-interval group included a higher proportion of cT4 stage and multivisceral resection patients. Pathological complete response rate (n = 34 [15.2%] vs. n = 47 [18.7%], p = 0.305) and CRM involvement (9.7% vs. 15.9%, p = 0.145) did not significantly differ. Thirty-day surgical complications were similar (20.1% vs. 23.1%, p = 0.943), however no significant differences were found for local and distant recurrence rates, disease-free survival, and overall survival.ConclusionsThese real-life data, reflecting routine daily practice in The Netherlands, showed substantial variability in the use and timing of restaging MRI after preoperative CRT for rectal cancer, as well as time interval to surgery. Surgery before or after 14 weeks from the start of CRT resulted in similar short- and long-term outcomes.

Impact of follow-up interval on patients with hepatocellular carcinoma after curative ablation

BackgroundThe optimal follow-up strategy after curative thermal ablation of hepatocellular carcinoma (HCC) remains unclear.MethodsWe retrospectively analyzed a prospective series of 616 patients who underwent curative thermal ablation for HCC within the Milan criteria. Multivariate Cox model was used to identify independent predictive factors for recurrence; accordingly, patients were stratified into 2 groups with different relapse risks: a low-risk group (solitary tumor ≤3 cm) and a high-risk group (multiple tumors ≤3 cm or solitary tumor between 3 and 5 cm). Then, patients were classified into short- (< 4 months) or long-interval (4–6 months) surveillance groups according to follow-up intensity within the first 2 years after ablation. The overall survival (OS) of patients were compared between short- and long-interval groups in low- or high-risk groups, as well as the stage of recurrent tumors and the proportion of patients who received curative-intent retreatments.ResultsIn the low-risk group, 54 (83.0%) and 18 (72.0%) of patients exhibited early relapse at the Barcelona Clinic Liver Cancer (BCLC) 0/A stage in the short- and long-interval groups, respectively (P = 0.172); accordingly, 44 (77.2%) and 18 (81.8%) of patients received curative-intent retreatment (P = 0.086) after recurrence. Hence, 5-year OS was similar between short- and long-interval groups (80.4% vs. 77.5%, P = 0.400) in low-risk patients. However, in the high-risk group, patients with a short interval exhibited early relapse more frequently at the BCLC 0/A stage (83% vs. 72%, P = 0.028), with a trend showing that the corresponding proportion of patients who received curative-intent retreatment greater than that in the long-interval group (64.2% vs. 37.5%, P = 0.087). Moreover, the short-interval group showed better 5-year OS than the long-interval group in high-risk patients (69.9% vs. 42.7%, P = 0.020).ConclusionsCompared to a short surveillance interval, a long surveillance interval does not reduce OS in low-risk patients; however, a long surveillance interval compromises OS in high-risk patients.