Primary R0 Resection Research Articles

Limb-sparing resection of axillary soft tissue sarcomas

For patients with soft tissue sarcoma, surgical resection is akey element of curative therapy. Surgery is performed as awide resection with microscopically negative margins (R0resection) and as limb-sparing procedure whenever possible to preserve maximum function. Soft tissue sarcoma, metastases. Extensive disease with major neurovascular involvement, placement of biopsy tract necessitates extensive resection, palliative care. Extended deltopectoral approach. Release of pectoralis major and minor tendons. Vascular and neurologic exploration, identification of the axillary vessels and brachial plexus, placing of loops around major structures. Mobilization of these structures to achieve adequate exposure. Clipping of vessels entering the tumor. Tumor resection, suture marking for histological analysis. Soft tissue reconstruction by transosseous reinsertion of the pectoralis minor to the coracoid process. Drill channel placement, transosseous refixation of the pectoralis major to the humerus. Shoulder abduction brace for 6weeks, passive mobilization for 6-12weeks followed by active mobilization. Compression sleeve. Oncological follow-up. Between 2017 and 2022, wide resection was performed in 6consecutive cases including 4 primary soft tissue sarcomas and 2metastases. Primary R0 resection was achieved in 100%. Mean follow-up was 22.5months (3-60months). There were no local recurrences. Mean active shoulder abduction was 135.0 ± 41.4° (90-180°). Neurological deficits were not observed. Mean subjective shoulder function was 80.0 ± 21.0% (50-100%). The mean Musculoskeletal Tumor Society (MSTS) score was 89.5% (32-100%), indicating good functional outcome in the study cohort.

The Impact of Intraoperative Frozen Section on Resection Margin Status and Survival of Patients Underwent Pancreatoduodenectomy for Distal Cholangiocarcinoma.

BackgroundIntraoperative frozen section (FS) is broadly used during pancreaticoduodenectomy (PD) to ensure a negative margin status, but its survival benefits on obtaining a secondary R0 resection for distal cholangiocarcinoma (dCCA) is controversial and unclear.MethodsClinical data of 107 patients who underwent PD for dCCA was retrospectively collected and divided into different groups based on use of FS (FS and non-FS groups) and status of resection margin (pR0, sR0 and R1 groups), and clinical parameters and survival of patients were compared and analyzed accordingly.ResultsThere were 50 patients in FS group with a median survival of 28 months, 57 patients in non-FS group with a median survival of 27 months. There was no statistical difference between the two groups with Kaplan-Meier survival analysis (P = 0.347). There were 98 patients in R0 group (88 in pR0 and 10 in sR0) and nine patients in R1 group, with a median survival of 29 months and 22 months respectively, which showed a better survival in R0 group than in R1 group (P = 0.006). Survival analyses between subgroups revealed difference between pR0 and R1 group (P = 0.005), while no statistical difference concerning pR0 vs. sR0 (P = 0.211) and sR0 vs. R1 groups (P = 0.262). Multivariate Cox regression analysis revealed resection margin status, pre-operative biliary drainage and lymph node invasion to be independent prognostic factors for dCCA patients.ConclusionsIntraoperative FS should be recommended as it significantly increased the rate of R0 resection, which was positively related to a better survival. A primary R0 resection should also be encouraged and if not, a secondary R0 could be considered at the discretion of surgeons as it showed similar survival with primary R0 resection.

Retrospective determination of the correlation between the distance of tumor manifestation to peripancreatic arteries and overall survival in primary resected pancreatic ductal adenocarcinoma.

e15745 Background: Current guidelines determine the resectability of PDAC by evaluating the contact of the tumor to peripancreatic vasculature. We wanted to evaluate the influence of this distance of the tumor to peripancreatic arteries on the overall survival of patients with primary resection of pancreatic ductal adenocarcinoma. Methods: Preoperative radiographs of 208 consecutive patients after distal pancreatectomy and/or pancreatoduodenectomy operated between 2007 and 2014 were included in the analysis. In reconstructions of CT and MRI data 90° planes to the centerline of the celiac trunc (CT), hepatic artery(HA) and superior mesenteric artery(SMA) were computed with Aquarius Intuition Viewer (V4.4.11, Terarecon). The closest distance between the tumor and the CT /HA and SMA was determined by an experienced pancreatic surgeon and radiologist independently and upon a deviation greater than 3 mm consent was reached by additional review in 33,2% (69/208) of the cases. Results: 176 CT and 32 MRI scans of 208 patients were evaluated. 2.4 % (5/208) of the radiographs were excluded due to insufficient quality. Average distance of the tumor to the CT/HA and SMA was 16.3 and 6.5 mm for PD and 12.7 and 11.0 mm for DP. Distance between the artery and the tumor did not influence the R0 resection rates (overall R0 > 1mm resection margin 64%) and median overall survival was 24.0 months after R0 resection and 13.5 months after R1 resection (log-rank test P < 0.05). Borderline resectable patients (n = 57) showed a median survival of 13.4 months, patients with their tumor 1-5mm distant to the closest artery (n = 65) and greater than 5 mm distance (n = 81) showed a median survival of 20.3 and 32.9 months respectively. Patients with 0-5 and greater than 5 mm distance between arteries and tumor showed a survival benefit from R0 resection (R0/R1 0-5mm 20.3/13.5 months; > 5mm 37.3/12.8 months) while R0 resected borderline resectable patients showed a similar survival than R1 resected patients (R0 12.7months, R1 15.1 months). Conclusions: The negative resection margins in borderline resectable patients not increase the survival when compared to R1 resected patients. Patients with primary R0 resection and initially large distance of the tumor to peripancreatic vasculature show a prolonged survival.

The role of MRI in the indication of the neoadjuvant chemo-radiotherapy for rectal cancer

Background: According to the current guidelines of rectal cancer treatment neoadjuvant radio- and/or chemotherapy is recommended if the staging confirms at least a T3 or N positive category. At the same time on the basis of more studies it is possible to perform a primary R0 resection if the perirectal fascia is not infiltrated. The omission of neoadjuvant treatment also reduces complications. The studies also debate whether the lymph nodes suspected to be positive with imaging, will be proven to be metastatic histologically. The effect of the neoadjuvant treatment on the metastatic lymphnodes is also questioned. According to the newest ESMO guideline T3 subgroups exist which can also influence treatment. Our aim was to examine whether an R0 resection is possible in patients with perirectal fat infiltration but without perirectal fascia involvement described by MRI. We compared the value of CT and MRI imaging regarding local propagation. We also investigated whether lymph nodes suspected to be positive by the imaging are really metastatic histologically.

Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: Results from the US Neuroendocrine Tumor Study Group

BackgroundThe impact of margin status on resection of primary pancreatic neuroendocrine tumors has been poorly defined. The objectives of the present study were to determine the impact of margin status on long-term survival of patients with pancreatic neuroendocrine tumors after curative resection and evaluate the impact of reresection to obtain a microscopically negative margin. MethodsPatients who underwent curative-intent resection for pancreatic neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary centers. Overall and recurrence-free survival were analyzed relative to surgical margin status using univariable and multivariable analyses. ResultsAmong 1,020 patients, 866 (84.9%) had an R0 (>1 mm margin) resection, whereas 154 (15.1%) had an R1 (≤1 mm margin) resection. R1 resection was associated with a worse recurrence-free survival (10-year recurrence-free survival, R1 47.3% vs R0 62.8%, hazard ratio 1.8, 95% confidence interval 1.2–2.7, P = .002); residual tumor at either the transection margin (R1t) or the mobilization margin (R1m) was associated with increased recurrence versus R0 (R1t versus R0: hazard ratio 1.8, 95% confidence interval 1.0–3.0, P = .033; R1m versus R0: hazard ratio 1.3, 95% confidence interval 1.0–1.7, P = .060). In contrast, margin status was not associated with overall survival (10-year overall survival, R1 71.1% vs R0 71.8%, P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation of the surgical margin; 49 (9.1%) patients had a positive margin on frozen section analysis; 38 of the 49 patients (77.6%) had reresection, and a final R0 (secondary R0) margin was achieved in 30 patients (78.9%). Extending resection to achieve an R0 status remained associated with worse overall survival (hazard ratio 3.1, 95% confidence interval 1.6–6.2, P = .001) and recurrence-free survival (hazard ratio 2.6, 95% confidence interval 1.4–5.0, P = .004) compared with primary R0 resection. On multivariable analyses, tumor-specific factors, such as cellular differentiation, perineural invasion, Ki-67 index, and major vascular invasion, rather than surgical margin, were associated with long-term outcomes. ConclusionMargin status was not associated with long-term survival. The reresection of an initially positive surgical margin to achieve a negative margin did not improve the outcome of patients with pancreatic neuroendocrine tumors. Parenchymal-sparing pancreatic procedures for pancreatic neuroendocrine tumors may be appropriate when feasible.

The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on Clinical Outcomes for Hilar Cholangiocarcinoma.

The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA. Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status. Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p>0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5months and 7.9%, respectively, for patients with an R1 resection (p=0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p=0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0-1.7; p=0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p=0.829). Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.

International Multicenter Study on the Impact of Extracapsular Lymph Node Involvement in Primary Surgery Adenocarcinoma of the Esophagus on Overall Survival and Staging Systems.

The current pathological lymph node (pN) staging is based on the number of positive lymph nodes but does not take into consideration characteristics of the involved lymph nodes itself. The current study aims to examine the prognostic value of extracapsular lymph node involvement (EC-LNI) and intracapsular lymph node involvement (IC-LNI) for esophageal adenocarcinoma treated by primary surgery. From the databases of five European high volume centers, 1639 adenocarcinoma patients with primary R0-resection were withheld after excluding 90-day mortality. Oncologic variables, including number of resected lymph nodes, number of resected positive lymph nodes, and EC-LNI/IC-LNI were examined. The Union Internationale contre le Cancer (UICC) 7th edition prognostic staging was used as baseline staging system. Statistical analysis was performed by Cox proportional hazards modeling and verified using the Random Survival Forest technique. EC-LNI showed significantly worse overall 5-year survival compared with IC-LNI overall (13.4% vs 37.2%, P < 0.0001), including in each pN-category [16.4% vs 45.6% in pN1 (P < 0.0001), 16.1% vs 23.8% (P = 0.047) in pN2 (P = 0.065), and 8.7% vs 26.3% in pN3 categories, respectively]. pN1 IC-LNI patients show a 5-year overall survival comparable (P = 0.92) with stage IIB (ie, pT3N0). Reclassifying the UICC prognostic stages according to these findings into an adapted staging model showed a significant (P < 0.0001) increase in homogeneity, discriminatory ability, and monotonicity compared with the original UICC TNM 7th edition prognostic staging. These data suggest that lymph node capsular status is an important prognostic factor and should be considered for the future edition of the TNM staging system for esophageal cancer.

Can extracapsular lymph node involvement be a tool to fine-tune pN1 for adenocarcinoma of the oesophagus and gastro-oesophageal junction in the Union Internationale contre le Cancer (UICC) TNM 7th edition?

The current (7th) International Union Against Cancer (UICC) pN staging system is based on the number of positive lymph nodes but does not take into consideration the characteristics of the metastatic lymph nodes itself. In particular, it has been suggested that tumour penetration beyond the lymph node capsule in metastatic lymph nodes, which is also called extracapsular lymph node involvement, has a prognostic impact. The aim of the current study was to assess the prognostic value of extracapsular (EC) and intracapsular (IC) lymph node involvement (LNI) in adenocarcinoma of the oesophagus and gastro-oesophageal junction (GOJ) and to assess its potential impact on the 7th edition of the UICC TNM manual. From 2000 to 2010, all consecutive adenocarcinoma patients with primary R0-resection (n = 499) were prospectively included for analysis. The number of resected lymph nodes, number of positive lymph nodes and number of EC-LNI/IC-LNI were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the positive lymph node. Two hundred and eighteen (43%) patients had positive lymph nodes. Cancer-specific 5-year survival in lymph node-positive patients was significantly (P < 0.0001) worse compared with lymph node-negative patients, being 88.3 vs 28.7%, respectively. In 128 (58.7%) cases EC-LNI was detected. EC-LNI showed significantly worse cancer-specific 5-year survival compared with IC-LNI, 19.6 vs 44.0% (P < 0.0001). In the pN1 category (1 or 2 positive LN's-UICC stages IIB and IIIA), this was 30.4% vs 58%; (P = 0.029). In higher pN categories, this effect was no longer noticed. Integrating these findings into an adapted TNM classification resulted in improved homogeneity, monotonicity of gradients and discriminatory ability indicating an improved performance of the staging system. EC-LNI is associated with worse survival compared with IC-LNI. EC-LNI patients show survival rates that are more closely associated with the current TNM stage IIIB, while IC-LNI patients have a survival more similar to TNM stage IIB. Incorporating the EC-IC factor in the TNM classification results in an increased performance of the TNM model. Further confirmation from other centres is required within the context of future adaptations of the UICC/AJCC (American Joint Committee on Cancer) staging system for oesophageal cancer.

Efficacy and Drawbacks of Neoadjuvant Chemoradiotherapy in Squamous Cell Carcinoma of the Thoracic Esophagus

Neoadjuvant chemoradiotherapy (CRT) is widely applied in locally advanced esophageal tumors to improve resectability and local tumor control. In this study, we retrospectively analyzed the perioperative course of patients who underwent esophagectomy or esophagectomy following CRT. Forty one patients were admitted with non-advanced disease (T1-2, N0), and primary resection was performed. Additional 21 patients received neoadjuvant CRT because of locally advanced, T2-4, N0-1 disease. To investigate predictive factors for responsiveness to CRT, we determined the p53, p21 and Ki67 oncogene expressions in the biopsy samples from the CRT patients. Following primary esophagectomy and esophagogastrostomy, the postoperative course was in most cases uneventful. Anastomotic leaks developed in 3 of the 41 cases (7.3%), and postoperative death in 1 case (2.4%). In response to CRT, significant down-staging was observed in 11 of the 21 patients (58%); in these cases esophagectomy was performed. However, in this group the rates of anastomotic leak (2 patients) and postoperative death (2 patients) were higher than in the first group (18% each). Preoperative CRT is a good option for patients with locally advanced tumors, when primary R0 resection is hopeless. However, the rate and risk of postoperative complications are higher than after primary resection of non-advanced tumors.

Neoadjuvante Radiochemotherapie des Rektumkarzinoms

Neoadjuvant radiochemotherapy has become established treatment for rectal cancer. It is indicated when primary R0 resection is not an option, in cases of higher risk of locoregional relapse following surgical treatment alone, and when initially impossible conservation of the anal sphincter becomes possible in conjunction with neoadjuvant radiochemotherapy. The indication for radiochemotherapy in the upper third of the rectum is still controversial. Reevaluation of the tumor situation following neoadjuvant treatment is necessary before decisions on operative strategy. Modern imaging techniques are limited in this respect, as they hardly allow differentiation between living tumor tissue and lesions. In case of doubt clarity is possible only through surgical exploration, taking R1 resection into account. Overall the recognition of lymph node metastasis is not a sufficient indicator of local relapse. The frequency of postoperative complications following neoadjuvant radiochemotherapy is independent of the operative method. The effect of neoadjuvant radiochemotherapy on long-term survival and formation of distant metastases is still not clarified. Current studies seek clarification through the use of new chemotherapies and modified treatment regimes. Further, the correct time interval between the end of neoadjuvant radiochemotherapy and the following surgical therapy has yet to be determined. This applies also to the management of patients following complete remission.