Optimal Timing Of Surgical Resection Research Articles

EP.WE.832A silver lining in the dark COVID cloud: Total neoadjuvant chemotherapy results in complete pathological response in locally advanced distal gastric adenocarcinoma

Abstract Aims Perioperative oncological therapies resulting in complete pathological response in diffuse type distal gastric adenocarcinoma are extremely rare. We report the first case of complete pathological regression in a patient with locally advanced diffuse type distal gastric adenocarcinoma (CT3N2M0) who received “total neoadjuvant” chemotherapy with FLOT due to the COVID pandemic. Methods & Results A 73-year-old male patient was diagnosed with cT3N2M0 diffuse type distal gastric adenocarcinoma. He received 4 cycles of neoadjuvant FLOT as planned with immune checkpoint inhibitor Durvlumab and interval PET-CT showed massive reduction in 18F-FDG avidity. However, his surgery was postponed due to the COVID-19 pandemic and given his excellent response to chemotherapy his 4 adjuvant cycles of FLOT were advanced into the preoperative setting. Subsequent PET-CT showed close to zero 18F-FDG uptake and he proceeded to laparoscopic radical subtotal gastrectomy with D2 lymphadenectomy. Histopathology of the resected specimen demonstrated no evidence of residual malignancy, a complete pathological response (TRG1a, ypT0N0 R0). Conclusions Amidst the dark cloud of COVID-19 there was a silver lining for one patient, who due to delayed surgery received total neoadjuvant FLOT (8 cycles). This should generate randomised controlled trials comparing the current standard of care with total neoadjuvant regimens and investigating the utilisation of interval investigations such as CT-PET in monitoring response to preoperative therapy, guiding optimal timing of surgical resection.

Optimal timing of surgical resection after neoadjuvant chemoradiation in borderline and locally advanced pancreatic ductal adenocarcinoma

For patients with pancreatic ductal adenocarcinoma (PDAC), the optimal time interval between neoadjuvant chemoradiation to surgical resection has not been well established. We aimed to study the impact of optimal surgical resection timing after neoadjuvant chemoradiation (Neo-CT/RT) on long-term oncological outcome in borderline and locally advanced PDAC. From June 2006 to April 2019, among the 175 patients who underwent pancreatectomy following Neo-CT/RT, the study enrolled 79 patients who underwent surgical resection after Neo-CT/RT for borderline and locally advanced PDAC. The entire cohort was divided into three groups according to the time interval between the last date or neoadjuvant chemoradiation and the surgical resection; group A (0-5 weeks), group B (5-10 weeks), and group C (> 10 weeks). Long-term outcomes were compared between the three groups. There were 30 patients in group A, 37 patients in group B, and 12 patients in group C. Patients in group B were significantly more likely to experience a vascular resection than group A and C (p = 0.005). In disease-free survival, there was no significant difference between the three groups (p = 0.075). Patients in group B showed better overall survival than other groups (p = 0.041). In multivariate analysis, N2 stage and time interval more than ten weeks were correlated with worse overall survival (HR 7.935, 95% confidence interval [CI] 1.772-35.538, p = 0.007, HR 3.492, 95% CI 1.717-7.102, p = 0.001). For borderline and locally advanced PDAC, surgical resection within ten weeks from the end of the Neo-CT/RT is associated with better overall survival, suggesting time interval should be concerned for better oncologic outcome in a patient with Neo-CT/RT in borderline and locally advanced PDAC. Further study is mandatory.

Esophageal resection after neoadjuvant therapy: understanding the limitations of large database analyses

Determining the optimal timing of surgical resection for esophageal adenocarcinoma following neoadjuvant therapy has proven to be a challenging task, and the clinical implications for patients undergoing surgery at various time intervals remain elusive. In an effort to fill a gap in the current retrospective literature pertaining to this clinical question, we utilized the method of restricted cubic splines (RCS) to investigate the balance in this timing from a unique statistical perspective. Using the National Cancer Database (NCDB), we determined an inflection point of 56 days wherein an increased incidence of pathologic complete response was balanced with a decreased rate of overall survival (1).

Surgical resection after neoadjuvant chemoradiation for oesophageal adenocarcinoma: what is the optimal timing?

The purpose of this study was to determine the optimal timing of surgical resection of oesophageal adenocarcinoma following neoadjuvant chemoradiotherapy (nCRT). nCRT before resection of oesophageal adenocarcinoma yields improved overall and progression-free survival. Despite the wide acceptance of tri-modal therapy, the optimal timing of surgical resection after nCRT is not well defined and existing studies are limited. Adults with Stage II/III oesophageal adenocarcinoma undergoing nCRT before surgery were identified from the National Cancer Database. Multivariable analysis using restricted cubic splines was used to identify an inflection point in clinical outcomes as a function of time between nCRT and surgery, dividing the cohort into short- and long-interval treatment groups, which were then compared. Adjusted rates of survival and margin status were compared between groups using multivariable analysis. Among 2444 patients, restricted cubic splines identified an inflection point at 56 days, dividing our cohort into 1533 short-interval and 911 long-interval patients. Long-interval patients had a higher adjusted incidence of pathologic downstaging (odds ratio 1.38, confidence interval 1.02-1.85, P = 0.04) but no difference in margin positivity compared with short-interval patients (odds ratio 0.91, confidence interval 0.56-1.47, P = 0.69). Worse overall survival was noted in the long-interval subgroup (hazard ratio 1.44, confidence interval 1.22-1.71, P < 0.001), but 30-day postoperative mortality was not statistically different (odds ratio 1.56, confidence interval 0.9-2.72, P = 0.12). Restricted cubic splines provides an objective mechanism to more accurately delineate optimum timing between nCRT and surgical resection. A time interval of 56 days represents an interval where increased pathologic downstaging is balanced by decreased overall survival.

Short-Term Outcomes after Simultaneous Colorectal and Major Hepatic Resection for Synchronous Colorectal Liver Metastases

Background/Aims: Resection of the liver is the standard therapeutic approach for patients with hepatic metastasis and is the only therapy with curative potential. The optimal timing of surgical resection for synchronous metastases has remained controversial. Methods: From January 1993 to December 2008, our strategy has been to use simultaneous resection for resectable synchronous colorectal and liver metastases. During this period, 115 patients underwent simultaneous colorectal and hepatic resection. We evaluated the short-term outcomes of these patients by reviewing operative and perioperative clinical data. Results: In patients with simultaneous resection, there was no evidence of colorectal complications associated with major hepatectomy or no evidence of hepatic complications related to rectal resection. But increased hepatic complications were apparent with major hepatectomy compared with minor hepatectomy (44 vs. 7.2%, p < 0.001) and patients with rectal resection had increased colorectal complications (23% in the rectal resection vs. 5.3% in the colectomy group, p = 0.034). Conclusions: Simultaneous major hepatectomy and rectal resection can increase the hepatic or colorectal morbidity, respectively. These patients may be considered for staged resections.

Waiting Time following Neoadjuvant Chemoradiotherapy for Rectal Cancer: Does It Really Matter

Background: Neoadjuvant chemoradiotherapy (CRT) is considered the standard approach before any surgical intervention for locally advanced rectal tumors and has been proven to significantly improve the local recurrence rates of rectal cancer. However, the optimal timing of surgical resection after neoadjuvant CRT remains debatable. Objective and Methods: We conducted a retrospective review of 65 consecutive patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection in order to evaluate the optimal time for surgical treatment. We used two alternative groups for analysis: patients who underwent surgery up to 6 weeks after CRT (n = 28) and those who underwent surgery 6 weeks or more after CRT (n = 27). Also, we compared patients who were operated on within 3 months (n = 39) with those who underwent surgical resection after more than 3 months (n = 16). Nonresponders to CRT were excluded from the analysis. Results: There was no statistically significant association between waiting period post CRT and radiological downstaging for any group (p > 0.05 for any association). Also, there was no association between recurrence of disease, cancer-related deaths, perineural invasion, or positive lymph node ratio and any waiting period up to 3 months (p > 0.05 for all associations). Conclusion: In this small exploratory study there was no evident difference in outcome according to timing of surgery, which suggests that further research in larger cohorts is warranted.

The optimal timing of surgical resection in high-risk neuroblastoma

BackgroundWhile most high-risk neuroblastoma (HRNB) patients are enrolled in cooperative group or institutional protocols, variability exists within these protocols as to when surgical resection of the primary tumor should be performed after neoadjuvant induction chemotherapy. We sought to determine if the number of chemotherapy cycles prior to surgery affects surgical or survival outcomes in HRNB patients. MethodsWe performed a retrospective review of all HRNB patients <18years of age from 2000 to 2010, at Texas Children's Hospital. Patients were stratified based on the number of neoadjuvant induction chemotherapy cycles prior to surgical resection. Pre and post- chemotherapy tumor size, MYCN status, iodine-131-metaiodobenzylguanidine (MIBG) score at diagnosis, extent of surgical resection, estimated surgical blood loss, post-operative outcomes, and event free (EFS) and overall survival (OS) were evaluated. Data were analyzed using Wilcoxon rank-sum test, Kruskal–Wallis test, Fisher's exact test, Kaplan–Meier analyses, and Cox regression analyses. P-value <0.05 was considered significant. ResultsData from 50 patients with HRNB were analyzed. Patients were stratified by the number of cycles of chemotherapy received prior to surgery. Six patients received 2cycles of chemotherapy (12%), 20 patients received 3cycles (40%), 13 patients received 4cycles (26%), and 11 patients received 5cycles (22%) prior to surgical resection of the primary tumor. The 5-year OS was 33%, 45%, 83% and 36% in patients who received 2, 3, 4 and 5cycles of chemotherapy prior to surgery, respectively (p=0.07). Multivariate analysis revealed that patients who received 4cycles of chemotherapy had a significantly lower mortality (HR: 0.11, 95% CI: 0.01–0.87, p=0.04) compared to those with 2cycles of chemotherapy. Among the different cohorts, there were no differences with respect to MYCN status, MIBG score at diagnosis, incidence of bone marrow metastasis, extent of surgical resection, estimated blood loss, incidence of post-operative complications, or length of stay. ConclusionHRNB patients who receive 4cycles of chemotherapy prior to surgical resection have a superior OS than patients who receive 2. Based on the superior survival of patients who received 4cycles of chemotherapy prior to surgery, further studies are warranted to elucidate these differences.

Optimal Timing of Surgical Resection After Radiation in Locally Advanced Rectal Adenocarcinoma: An Analysis of the National Cancer Database.

In the treatment of rectal cancer, a longer radiation-surgery interval from the end of neoadjuvant radiation therapy to surgery has been associated with higher rates of complete pathologic response (pCR), but the optimal interval with respect to survival has not been established. Data from the National Cancer Database (NCDB) was used to evaluate the impact of radiation-surgery interval on oncologic outcomes. The NCDB was searched for patients diagnosed with nonmetastatic rectal cancer who underwent preoperative radiation followed by radical surgical resection. A Cox proportional hazards model was constructed to examine the influence of radiation-surgery interval while controlling for potential confounding factors. Sensitivity analysis was used to confirm the results of the model. A cohort of 6397 patients meeting all inclusion and exclusion criteria from 2004-2006 was identified, and the pCR rate for this cohort was 6.9%. Of those who experienced a pCR, 76.2% had done so by 60 days. Intervals greater than 60 days were associated with higher rates of positive surgical margins (6.7 vs. 4.8%, p = 0.009) and lower rates of sphincter-preserving surgery (64.9 vs. 68.9%, p = 0.007). An interval greater than 60 days was associated with significantly shorter survival (hazard ratio (HR), 1.314; 95% CI 1.191-1.449; p < 0.001). Radiation-surgery interval beyond 60 days is associated with increased rate of positive surgical margins, decreased rate of sphincter-preserving surgery, and decreased survival. Delay of surgery for rectal cancer beyond 60 days after the completion of neoadjuvant therapy should be done with caution.

Optimal timing of surgical resection after radiation therapy in locally advanced rectal adenocarcinoma: An analysis of the National Cancer Database (NCDB).

510 Background: In treatment of rectal adenocarcinoma, an increased time delay (TD) of 6-12 weeks from the end of radiation therapy to surgery may increase the rate of complete pathologic response (pCR), but the optimal TD with respect to survival has not been established. This study evaluates the impact of TD on overall mortality. Methods: The NCDB was queried for patients with adenocarcinoma of the rectum and no evidence of metastasis at diagnosis, who underwent preoperative chemoradiation followed by radical surgical resection. Standard statistical methods were employed for descriptive statistics and Cox model development. Results: The study included 6805 patients, predominantly Caucasian (87.2%) and males (63.9%) who generally were treated with low anterior resection (57.3%), colonanal reanastomosis (8.4%), or abdominoperineal resection (28.4%), and had median survival of 66.6 months. The effects of age, surgical margins (-/+), comorbidity index, time to discharge after surgery, TMN pathologic staging, surgical volume, and patient income significantly impacted mortality after radiation and surgery (p&lt;0.05 for all values). There was a significant relationship between TD and pCR (p=.0002). At TD less than 30 days, 4.0% of patients achieved pCR, while 9.3% of patients have achieved pCR by 75 days. In TD of greater than 75 days, the rate of pCR decreased. Overall, 6.8% of patients (n=461) achieved pCR. Using a refined cox model, a TD of more than 60 days was associated with 20% greater risk of mortality (95% CI 1.068 – 1.367). This effect became more pronounced with increasing TD; a TD of greater than 75 days was associated with 28% (95% CI 1.06-1.55) increased risk of mortality, while patients with TD less than 60 days saw a survival benefit. Conclusions: Though an interval up to 75 days between radiation and surgery may achieve higher rates of complete pathologic response, delay of more than 60 days from radiation to surgical resection and subsequent systemic chemotherapy decreases overall survival in patients with rectal cancer.

Determining timing of hepatectomy for colorectal cancer with distant metastasis according to imaging-based tumor shrinkage ratio.

Background: The optimal timing of surgical resection of liver metastasis remains controversial, and guidelines regarding the upper limits of operative indications have not yet been defined. Surgical indication for metastasis from colorectal cancer (CLM) based on results of preoperative chemotherapy and RNF8 was investigated. Methods: Differences in CLM size on CT were evaluated as shrinkage rate/day by dividing tumor shrinkage rates by the interval in days between CT. Levels of RNF8 of resected colorectal cancer and CLM frozen specimen were detected. Results: When the cut line for shrinkage rate at 12 weeks was set at 0.35%, disease-free survival was significantly better in patients with a shrinkage rate >0.35% vs. ≤0.35% (p=0.003). RNF8 expression was significantly higher in Tis (p=0.001). In liver metastasis, RNF8 expression level was significantly lower in patients with partial response to FOLFOX than with stable disease, (p=0.017). Conclusions: A strategy of FOLFOX administration for 12 weeks to patients with low RNF8 expression and hepatectomy planned after 4 weeks rest may be accepted as the best therapeutic option for treating CLM.

Meta‐analysis of simultaneous versus staged resection for synchronous colorectal liver metastases

There is no clear consensus on the optimal timing of surgical resection for synchronous colorectal liver metastases (SCLM). This study is a meta-analysis of the available evidence. Systematic review and meta-analysis of trials comparing outcomes following simultaneous resection with staged resection for SCLM published from 1990 to 2010 in PubMed, Embase, Ovid and Medline. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals (95% CI) were calculated using either the fixed effects or random effects model. Nineteen non-randomized controlled trials (NRCT) studies were included in this analysis. These studies included a total of 2724 patients: 1116 underwent simultaneous resection and 1608 underwent staged resection. Meta-analysis showed that shorter hospital stay (P < 0.001) and lower total complication rate (P < 0.001) were observed in patients undergoing simultaneous resection group. The overall survival rate in the simultaneous resection group did not statistically differ with that in the staged resection group at 1 year (P = 0.13), 3 years (P = 0.26), 5 years (P = 0.38), as well as the 1, 3 and 5 years disease-free survival rates (respectively, P = 0.55; P = 0.16; P = 0.12). No significant difference was noted between the two groups in terms of mortality (P = 0.16), intraoperative blood loss (P = 0.06) and recurrence (P = 0.47). Simultaneous resection is safe and efficient in the treatment of patients with SCLM while avoiding a second laparotomy. In selected patients, simultaneous resection might be considered as the preferred approach. However, the findings have to be carefully interpreted due to the lower level of evidence and the existence of heterogeneity.

Therapeutic strategies for synchronous and multiple liver metastases from colorectal cancer

Metastasis in the liver is one of the most critical factors in the prognosis of patients with colorectal cancer. The incidence of synchronous liver metastasis has been found to be approximately 20-25%, but the optimal timing of surgical resection remains controversial. Neoadjuvant chemotherapy has also been found to be beneficial not only for initially unresectable but also resectable synchronous metastases and traditional surgical strategies of hepatic resection with past chemotherapeutic regimens have been used less and less over the past several years. This review will discuss treatments in association with the recently developed chemotherapeutic regimens.

Therapeutic strategies for synchronous and multiple liver metastases from colorectal cancer.

Metastasis in the liver is one of the most critical factors in the prognosis of patients with colorectal cancer. The incidence of synchronous liver metastasis has been found to be approximately 20–25%, but the optimal timing of surgical resection remains controversial. Neoadjuvant chemotherapy has also been found to be beneficial not only for initially unresectable but also resectable synchronous metastases and traditional surgical strategies of hepatic resection with past chemotherapeutic regimens have been used less and less over the past several years. This review will discuss treatments in association with the recently developed chemotherapeutic regimens.

Does earlier lobectomy result in better long-term pulmonary function in children with congenital lung anomalies?: A prospective study

BackgroundManagement of asymptomatic congenital pulmonary airway malformations remains controversial when addressing the optimal timing of surgical resection. Neonatal resection is advocated by some based on the theory that earlier lobectomy results in greater compensatory lung growth. We examined whether age at lobectomy is correlated with better pulmonary outcomes as reflected by pulmonary function and exercise testing. MethodsPatients who had lobectomy for congenital pulmonary airway malformation between 1985 and 2002 were identified and underwent detailed clinical history, physical examination, pulmonary function testing (total lung capacity, forced vital capacity, forced expiratory volume in 1 second), and exercise testing (power, maximal oxygen uptake [Vo2max]). ResultsOf 87 patients identified, 47 met the inclusion criteria, and 28 were tested prospectively. Age at the time of lobectomy ranged from 3 days to 56 months. There was no correlation between age at lobectomy and pulmonary function (total lung capacity, P = .408; forced vital capacity, P = .319; forced expiratory volume in 1 second, P = .174) or maximal work capacity (power, P = .280). There was a trend toward lower Vo2max in patients who had undergone lobectomy at an older age (Vo2max, P = .055). ConclusionMost children undergoing lobectomy have normal long-term pulmonary function. We found no correlation between age at lobectomy and future pulmonary function. Cardiopulmonary exercise testing should be considered in evaluating functional outcome in these patients.

Strategies for Synchronous and Multiple Metastatic Liver Tumors Designed from Epithelial-Mesenchymal Transition Concept

At some point in the natural course of colorectal cancer up to 50% of patients will develop metastasis to the liver and it is one of the most critical effects for patient prognosis. The incidence of synchronous liver metastasis has been detected at around 20% - 25%, but the optimal timing of surgical resection remains controversial. Neoadjuvant chemotherapy has also been found to be beneficial not only for initially unresectable but also resectable synchronous metastases. Then, traditional surgical strategies of hepatic resection in accordance with past chemotherapeutic regimens have been used decreasingly over the past several years. This review will primarily discuss treatments in association with the recent developed chemotherapeutic regimens and surgical procedure from the clinical data and the concept for epithetlial-mesenchymal transition, which has recently been studied to elucidate mechanisms of the liver metastatic process.

Simultaneous vs. staged resection for synchronous colorectal liver metastases: a metaanalysis

The optimal timing of surgical resection for synchronous colorectal liver metastases (SCLMs) remains controversial. The aim of this metaanalysis was to compare outcomes between simultaneous resection and staged resection from all published comparative studies in the literature. Databases, including PubMed, Embase, Cochrane Library, Ovid, and Web of Science, were searched to identify studies comparing outcomes following simultaneous resection with staged resection for SCLM. The metaanalysis was performed by RevMan 4.2. Fourteen comparative studies comprising 2,204 patients were identified. Patients undergoing simultaneous resection were found to have similar operative time (weighted mean difference [WMD], -34.19; 95% confidence interval [CI], -81.32-12.95, P = .16) and intraoperative blood loss (WMD, -161.33; 95% CI, -351.45-28.79, P = .10). Shorter hospital stay (WMD, -4.77; 95% CI, -7.26-2.28, P < .01) and lower morbidity rate (odds ratio [OR], 0.71; 95% CI, 0.57-0.88, P = .002) were observed in simultaneous resection group. The survival rate in the simultaneous resection group did not statistically differ with that in the staged resection group at 1 year (OR, 0.77; 95% CI, 0.51-1.16, P = .21), 3 years (OR, 1.12; 95% CI, 0.85-1.47, P = .43), and 5 years (OR, 1.14; 95% CI, 0.86-1.50, P = .37) postresection, respectively. Simultaneous resection is safe and efficient in the treatment of patients with SCLM while avoiding a second major operation. In appropriately selected patients, simultaneous resection might be considered as the preferred treatment. Since heterogeneity was detected, caution is needed in interpretation of the results. Better designed, adequately powered studies are required for addressing this issue.

Early Excision and Late Excision of Heterotopic Ossification after Traumatic Brain Injury Are Equivalent: A Systematic Review of the Literature

Heterotopic ossification (HO) is a common complication in patients with coma after brain injury. As the optimal timing of surgical resection is still controversial and unclear, a review of the literature was performed in order to determine the impact of early operation on recurrence rate and joint mobility. We identified all types of studies dealing with surgical excision of HO in patients after head injury in major medical and publishers' databases. Publication bias and statistical heterogeneity were assessed by funnel-plot asymmetry and Galbraith regression. We abstracted demographic and outcome information from manuscripts that tabulated individual patient data (IPD) to build univariate logistic and linear regression models. Means and proportions for random-effects meta-regression analysis were also obtained. Of 318 studies originally identified, 16 observational studies enrolling 255 patients (212 men, 329 affected joints, mean age of 30.6 [+/-SEM of 1.4] years) were included in the analysis. The reported overall recurrence rate in eleven studies was 38/192 (19.8%). Both IPD and meta-regression analysis failed to show a marked impact of the interval to resection on the probability of recurrence (odds ratio 1.00, 95% CI 0.98-1.03). The predicted probability of recurrence after 13, 21, and 30 months of waiting was 9%, 14%, and 19%, respectively. The length of coma period and patient's neurologic deficit were statistically significant negative predictors for both recurrence rate and functional outcome. Although no conclusive inferences can be drawn from the identified studies, the available data do not support the concept that early excision triggers later recurrence.