Resection Margin Status Research Articles

Prognostic value of resection margin and lymph node status in perihilar cholangiocarcinoma

BackgroundThe impact of resection margin and lymph node status on survival in patients undergoing resection for perihilar cholangiocarcinoma (pCCA) is controversial. The aim of this study was to investigate the influence of nodal and resection margin status on long-term survival after resection for pCCA. MethodsRetrospective analysis of patients resected for pCCA at the University Hospital Frankfurt, Germany between 1999 and 2022. The patients were categorized in four groups according to resection margin (R) and nodal status (N). Survival was analyzed with univariable and multivariable Cox regression. ResultsOut of 123 patients, 100 with long-term survival were included in the survival analysis. In the univariable analysis, negative resection margin (p = 0.02) and lower grade (p = 0.004) were the only significant positive prognostic factors, while the difference between N0 and N+ was not statistically significant (p = 0.062). Median survival in the groups R0N0, R0N+, R + N0 and R+N+ groups was 40.1, 29.9, 18.4 and 18.9 months, respectively (p = 0.03). In the multivariable analysis, after adjusting for grade, nodal and resection margin status, only grade and resection margin had prognostic significance. ConclusionPatients with negative resection margin after resection for pCCA have a better prognosis, regardless of the presence of lymph node metastases.

Follow Up Care After Penile Sparing Surgery for Penile Cancer: Current Perspectives.

Penile cancer (PeCa) is a rare urologic tumor worldwide. In 2024, 2100 new cases and 500 deaths are estimated in the United States. Radical surgery via total penectomy has historically been the cornerstone of treatment, since it provides excellent long-term oncological control. The rationale of surgery for penile cancer was to achieve a 2 cm macroscopic surgical margin that is historically advocated to reduce recurrences. Over time, numerous studies have demonstrated that resection margin status does not affect patients' survival. Different penile-sparing techniques are currently recommended in the European Association of Urology-American Society of Clinical Oncology (EAU-ASCO) guidelines for the treatment of localized primary PeCa. Centralization of care could yield multiple benefits, including improved disease awareness, higher rates of penile-sparing surgery, enhanced detection rates, increased utilization of less invasive lymph node staging techniques, enhanced quality of specialized histopathological examinations, and the establishment of specialized multidisciplinary teams. Compared to more aggressive treatments, the higher recurrence rates after penile-sparing surgery do not hamper neither the metastasis-free survival nor the overall survival. Repeated penile-sparing surgery could be considered for selected cases. The psychological impact of penile cancer is not negligible since the perceived loss of masculinity might adversely affect mental health and overall well-being. Quality of life may be compromised by sexual and urinary dysfunction which may be the result either of the loss of penile tissue or the psychological status of the patient. It is of utmost importance to offer rehabilitative treatment as sexual therapy, physical therapy, occupational therapy, family and peer counseling.

The Prognostic Impact of Minimally Invasive Esophagectomy on Survival After Esophagectomy Following a Delayed Interval After Chemoradiotherapy: A Secondary Analysis of the DICE Study.

To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12wk) following chemoradiotherapy (CRT). Previously, we established that a prolonged interval after CRT before esophagectomy was associated with poorer long-term survival. This was an international multicenter cohort study involving 17 tertiary centers, including patients who received CRT followed by surgery between 2010 and 2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approaches. A total of 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and 2 years after CRT. Significant differences were observed in American Society of Anesthesiologists grade, radiation dose, clinical T stage, and histologic subtype. There were no significant differences between the groups in age, sex, body mass index, pathologic T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate ( P =0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI: 1.14-2.5) and propensity-matched analysis ( P =0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE in 40 to 50Gy dose groups (HR=1.9; 95% CI: 1.2-3.0) and in patients having surgery within 6 months of CRT (HR=1.6; 95% CI: 1.1-2.2). MIE was associated with improved overall survival compared with OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

Values of apparent diffusion coefficient in pancreatic cancer patients receiving neoadjuvant therapy

BackgroundTo investigate the values of apparent diffusion coefficient (ADC) for the treatment response evaluation in pancreatic cancer (PC) patients receiving neoadjuvant therapy (NAT).MethodsThis study included 103 NAT patients with histologically proven PC. ADC maps were generated using monoexponential diffusion-weighted imaging (b values: 50, 800 s/mm2). Tumors’ minimum, maximum, and mean ADCs were measured and compared pre- and post-NAT. Variations in ADC values measured between pre- and post-NAT completion for NAT methods (chemotherapy, chemoradiotherapy), tumor locations (head/neck, body/tail), tumor regression grade (TRG) levels (0–2, 3), N stages (N0, N1/N2) and tumor resection margin status (R0, R1), were further analyzed.ResultsThe minimum, maximum, and mean ADC values all increased dramatically after NAT, rising from 23.4 to 25.4% (all p < 0.001): mean (average: 1.626 × 10− 3 mm2/s vs. 1.315 × 10− 3 mm2/s), minimum (median: 1.274 × 10− 3 mm2/s vs. 1.034 × 10− 3 mm2/s), and maximum (average: 1.981 × 10− 3 mm2/s vs. 1.580 × 10− 3 mm2/s). The ADCs between the subgroups of all the criteria under investigation did not differ significantly for the minimum, maximum, or mean values pre- or post-NAT (P = 0.08 to 1.00). In the patients with borderline resectable PC (n = 47), the rate of tumor size changes after NAT was correlated with the pre-NAT mean ADC values (Spearman’s coefficient: 0.288, P = 0.049).ConclusionsThe ADC values of PC increased significantly following NAT; however, the percentage increases failed to provide any predictive value for the resection margin status or TRG levels.

744. LEFT THORACOABDOMINAL ESOPHAGECTOMY: ITS VALIDITY IN MODERN ESOPHAGEAL SURGERY

Abstract Background The optimal surgical approach for the treatment of esophageal and gastroesophageal junction tumors remains elusive. An open left thoracoabdominal approach may prove particularly useful in certain clinical scenarios, mainly because of its versatility and excellent exposure provided. The aim of this study is to present our experience and evaluate the early outcomes related to an open left thoracoabdominal esophagectomy (LTE). Methods A retrospective cohort study of prospectively collected data was conducted from two institutions performing esophageal surgery. Patients with distal esophageal or junctional tumors who underwent an open LTE between November 2018 and December 2023 were included. Primary outcomes were 30-day and in-hospital mortality, postoperative complications, and surrogates of oncological efficacy, including resection margin status and lymph node yield. Complications were recorded using the definitions provided by the Esophagectomy Complications Consensus Group and scored according to the Clavien-Dindo classification. Circumferential resection margin status was based on the definition used by the College of American Pathologists. Results During the study period 22 patients underwent an open LTE with a standard two-field lymphadenectomy. Eight patients (36%) suffered from postoperative complications, with pulmonary complications being the most common (7 patients; 32%). Severe complications (Clavien-Dindo ≥3) occurred in 3 patients. One patient experienced a clinical anastomotic leak. None of the patients required a reoperation or a step-up to a higher level of care. The 30-day and in-hospital mortality were zero. On histological examination, 6 patients (27%) had tumor cells at the surgical margin, most commonly the circumferential resection margin. A mean number of 27 lymph nodes were retrieved. Conclusion This small series demonstrates the applicability of an open left thoracoabdominal approach in everyday surgical practice for the treatment of distal esophageal and gastroesophageal junction tumors. Our results imply that open LTE can be implemented in select patients with acceptable morbidity and oncological efficacy.

The management of osteosarcoma in children and adolescents in a resource-limited setting: quality improvement considerations to improve treatment outcomes

BackgroundThe survival rates for children and adolescents with osteosarcoma in low-income countries are poor. Insufficient data regarding the challenges of managing osteosarcoma in resource-limited settings has been published. We evaluated the treatment of osteosarcoma in children and adolescents with the aim of improving the health system and management outcomes.MethodsWe sourced data on children under 18 years treated for osteosarcoma at the Uganda Cancer Institute between January 2016 and December 2020. Descriptive statistics and Kaplan-Meier survival analysis were used.ResultsSeventy-four osteosarcoma cases were identified, with a median age of 13 years (IQR 9.8–15). Referrals were made after a median of 28 days (range 1-147). Before appropriate referral, more than a quarter (26%) had undergone invasive procedures that could compromise tumour integrity and outcome. Half (50%) of the patients had metastatic disease at diagnosis, primarily to the lungs (n = 43; 92%). Only 14 (33%) patients received neoadjuvant chemotherapy. Forty-three (58.1%) patients underwent limb amputation surgery, including 25 localized tumours and 18 patients with distant metastatic disease. No metastatectomies were performed. Adjuvant chemotherapy was delayed for longer than 21 days in 26 (61%) patients. No pathology reports described the status of resection margins or the degree of chemotherapy-induced necrosis. Twenty-six (35%) patients abandoned treatment, mainly due to pending radical surgery (n = 18/26; 69%). Only 18% (n = 13) were still alive; 46% (n = 34) had died; and 37% (n = 27) had an unknown status. The median overall survival was 1.1 years, and was significantly negatively affected by disease metastasis, timing of adjuvant therapy, and treatment abandonment.ConclusionsOsteosarcoma outcomes for children and adolescents at the Uganda Cancer Institute are extremely poor. The quality of care can be improved by addressing delayed referrals, high rates of prior manipulative therapy, metastatic disease, treatment abandonment, surgical challenges, and delayed resumption of adjuvant chemotherapy.

Assessment of the bony resection margin distance in bone-invasive oral cancer using laser-induced breakdown spectroscopy

ObjectivesInadequate resection margins of less than 5 mm impair local tumor control. This weak point in oncological safety is exacerbated in bone-infiltrating tumors because rapid bone analysis procedures do not exist. This study aims to assess the bony resection margin status of bone-invasive oral cancer using laser-induced breakdown spectroscopy (LIBS).Materials and methodsLIBS experiments were performed on natively lasered, tumor-infiltrated mandibular cross-sections from 10 patients. In total, 5,336 spectra were recorded at defined distances from the tumor border. Resection margins < 1 mm were defined as very close, from 1–5 mm as close, and > 5 mm as clear. The spectra were histologically validated. Based on the LIBS spectra, the discriminatory power of potassium (K) and soluble calcium (Ca) between bone-infiltrating tumor tissue and very close, close, and clear resection margins was determined.ResultsLIBS-derived electrolyte emission values of K and soluble Ca as well as histological parameters for bone neogenesis/fibrosis and lymphocyte/macrophage infiltrates differ significantly between bone-infiltrating tumor tissue spectra and healthy bone spectra from very close, close, and clear resection margins (p < 0.0001). Using LIBS, the transition from very close resection margins to bone-infiltrating tumor tissue can be determined with a sensitivity of 95.0%, and the transition from clear to close resection margins can be determined with a sensitivity of 85.3%.ConclusionsLIBS can reliably determine the boundary of bone-infiltrating tumors and might provide an orientation for determining a clear resection margin.Clinical relevanceLIBS could facilitate intraoperative decision-making and avoid inadequate resection margins in bone-invasive oral cancer.

A comparison of whole-mount and conventional sections for pathological mesorectal extension and circumferential resection margin assessment after total mesorectal excision

IntroductionThe objective of the study is to compare 2 techniques for histological handling of rectal cancer specimens, namely whole-mount in a large block vs conventional sampling using small blocks, for mesorectal pathological assessment of circumferential resection margin status and depth of tumor invasion into the mesorectal fat. MethodsThis is a prospective study including 27 total mesorectal excision specimens of rectal cancer from patients treated for primary rectal carcinoma between 2020 and 2022 in a specialized multidisciplinary Colorectal Unit. For each total mesorectal excision specimen, 2 contiguous representative tumoral slices were selected and comparatively analyzed with whole-mount and small blocks macroscopic dissection techniques, enabling comparison between them in the same surgical specimen. The agreement between the 2 techniques to assess the distance of the tumor from the circumferential resection margin as well as the depth of tumor invasion was evaluated with the Student’s t-test for paired samples, Pearson’s correlation coefficient, and the Bland-Altman method comparison analysis. ResultsComplete mesorectal excision was observed in 8% of cases. Circumferential resection margin involvement was observed in only one case (4 %). The whole-mount and small block techniques obtained similar results when we assessed the distance to the circumferential resection margin (t-test P = 0.8, r = 0.92) and the depth of mesorectal infiltration (t-test P = 0.6, r = 0.95). ConclusionsBoth gross dissection techniques (whole-mount vs multiple small cassettes) are equivalent and reliable to assess the distance to circumferential resection margin and the depth of mesorectal infiltration in the mesorectal fat in rectal cancer staging.

Prognostic Factors of Pulmonary Metastasectomy for Oligometastatic Hepatocellular Carcinoma Spread to the Lungs.

Background/Objectives: Pulmonary metastasis is the most prevalent type of extrahepatic hepatocellular carcinoma (HCC) metastasis. International guidelines recommend systemic treatment for patients with HCC having pulmonary metastases. However, the role of pulmonary metastasectomy (PM) remains relatively unexplored. Therefore, we assessed the survival outcomes and the factors influencing them in patients who underwent PM for metastatic HCC. Methods: Clinical data were collected from patients with HCC who underwent PM for metastasis at a single tertiary center between January 2004 and December 2022. Recurrence-free survival and overall survival were assessed using Kaplan-Meier curves. The Cox proportional hazards model was used to identify factors associated with survival outcomes. Results: Overall, 63 patients underwent PM with a median follow-up time of 84.0 months. The cumulative survival rates after the initial PM at 1, 2, and 5 years were 79.1%, 63.9%, and 35.6%, respectively. In multivariate analysis, early intrathoracic recurrence <6 months, number and size of metastases, resection margin status, and PM bilaterality were significantly associated with overall survival. A larger size of the primary HCC, increased number of repeated PM, and frequent lobectomy were more common in patients with early (<6 months) recurrence after PM than in those without early recurrence. Conclusions: PM in patients with metastatic HCC may provide acceptable survival outcomes for those with smaller, unilateral lung metastases that can be resected with generous surgical margins. However, early recurrence with reduced overall survival is likely in patients with a larger-size initial HCC after prior PM and lobectomy.

Prognostic Significance of 18 F-FDG PET/CT Radiomics in Patients With Resectable Pancreatic Ductal Adenocarcinoma Undergoing Curative Surgery.

This study aimed to investigate the prognostic significance of PET/CT radiomics to predict overall survival (OS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC). We enrolled 627 patients with resectable PDAC who underwent preoperative 18 F-FDG PET/CT and subsequent curative surgery. Radiomics analysis of the PET/CT images for the primary tumor was performed using the Chang-Gung Image Texture Analysis toolbox. Radiomics features were subjected to least absolute shrinkage and selection operator (LASSO) regression to select the most valuable imaging features of OS. The prognostic significance was evaluated by Cox proportional hazards regression analysis. Conventional PET parameters and LASSO score were assessed as predictive factors for OS by time-dependent receiver operating characteristic curve analysis. During a mean follow-up of 28.8 months, 378 patients (60.3%) died. In the multivariable Cox regression analysis, tumor differentiation, resection margin status, tumor stage, and LASSO score were independent prognostic factors for OS (HR, 1.753, 1.669, 2.655, and 2.946; all P < 0.001, respectively). The time-dependent receiver operating characteristic curve analysis showed that the LASSO score had better predictive performance for OS than conventional PET parameters. The LASSO score using the 18 F-FDG PET/CT radiomics of the primary tumor was the independent prognostic factor for predicting OS in patients with resectable PDAC and may be helpful in determining therapeutic and follow-up plans for these patients.

Resection Margin Status and Long-Term Outcomes after Pancreaticoduodenectomy for Ductal Adenocarcinoma: A Tertiary Referral Center Analysis.

The influencing role of resection margin (R) status on long-term outcomes, namely overall (OS) and disease-free survival (DFS), after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is not still clear. The aim of this study is to evaluate the prognostic impact of R status after PD and to define tumor characteristics associated with a positive resection margin (R1). All PDs for PDAC performed between 2012 and 2023 were retrospectively enrolled. The effect of R status, patient clinico-demographic features, and tumor features on OS and DFS were assessed. One-hundred and sixty-seven patients who underwent PD for PDAC were included in the study. R0 was achieved in 105 cases (62.8%), while R1 was evidenced in 62 patients (37.1%). R1 was associated with a decreased OS (23 (13-38) months) as compared to R0 (36 (21-53) months) (p = 0.003). Similarly, DFS was shorter in R1 patients (10 (6-25) months) as compared to the R0 cohort (18 (9-70) months) (p = 0.004), with a consequent higher recurrence rate in cases of R1 (74.2% vs. 64.8% in the R0 group; p = 0.04). In the multivariate analysis, R1 and positive lymph nodes (N+) were the only independent influencing factors for OS (OR: 1.6; 95% CI: 1-2.5; p = 0.03 and OR: 1.7; 95% CI: 1-2.8; p = 0.04) and DFS (OR: 1.5; 95% CI: 1-2.1; p = 0.04 and OR: 1.8; 95% CI: 1.1-2.7; p = 0.009). Among 111 patients with N+ disease, R1 was associated with a significantly decreased DFS (10 (8-11) months) as compared to R0N+ patients (16 (11-21) months) (p = 0.05). In conclusion, the achievement of a negative resection margin is associated with survival benefits, particularly in cases of N1 disease. In addition, R0 was recognized as an independent prognostic feature for both OS and DFS. This further outlines the relevant role of radical surgery on long-term outcomes.

Comparison of conventional MRI analysis versus MRI-based radiomics to predict the circumferential margin resection involvement of rectal cancer

BackgroundTo compare the application of conventional MRI analysis and MRI-based radiomics to identify the circumferential resection margin (CRM) status of rectal cancer (RC).MethodsA cohort of 301 RC patients with 66 CRM invloved status and 235 CRM non-involved status were enrolled in this retrospective study between September 2017 and August 2022. Conventional MRI characteristics included gender, age, diameter, distance to anus, MRI-based T/N phase, CEA, and CA 19 − 9, then the relevant logistic model (Logistic-cMRI) was built. MRI-based radiomics of rectal cancer and mesorectal fascia were calculated after volume of interest segmentation, and the logistic model of rectal cancer radiomics (Logistic-rcRadio) and mesorectal fascia radiomics (Logistic-mfRadio) were constructed. And the combined nomogram (nomo-cMRI/rcRadio/mfRadio) containing conventional MRI characteristics, radiomics of rectal cancer and mesorectal fascia was developed. The receiver operator characteristic curve (ROC) was delineated and the area under curve (AUC) was calculated the efficiency of models.ResultsThe AUC of Logistic-cMRI was 0.864 (95%CI, 0.820 to 0.901). The AUC of Logistic-rcRadio was 0.883 (95%CI, 0.832 to 0.928) in the training set and 0.725 (95%CI, 0.616 to 0.826) in the testing set. The AUCs of Logistic-mfRadio was 0.891 (95%CI, 0.838 to 0.936) in the training set and 0.820 (95%CI, 0.725 to 0.905) in the testing set. The AUCs of nomo-cMRI/rcRadio/mfRadio were the highest in both the training set of 0.942 (95%CI, 0.901 to 0.969) and the testing set of 0.909 (95%CI, 0.830 to 0.959).ConclusionMRI-based radiomics of rectal cancer and mesorectal fascia showed similar efficacy in predicting the CRM status of RC. The combined nomogram performed better in assessment.

Clinicopathological significance and prognostic analysis of p21 and EGFR in colorectal cancer: a retrospective analysis on 12 319 cases in China

AimsColorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims...

Association of human interpretable features derived from pancreatic ductal adenocarcinoma pathology slides with disease-free survival.

e16368 Background: Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second cause of cancer death in the US by 2040. For the minority of patients who are candidates for curative-intent surgical resection, a neoadjuvant approach with chemotherapy or chemotherapy followed by chemoradiotherapy (chemoRT) has become the standard of care. The tumor microenvironment (TME) has been recognized as a key factor in therapeutic resistance and disease progression. This study aims to explore the prognostic value of human-interpretable machine learning image features (HIFs) derived from whole-slide H&amp;E images. Methods: Consecutive PDAC patients who underwent neoadjuvant therapy followed by surgical resection were studied in this single-institution retrospective study. Clinical variables collected include tumor site (head/body/tail), surgery extent, histology, sex, age at diagnosis, grade, treatment response (4-point scale), LVI, PNI, resection margin status, pathological TNM staging, number of lymph nodes removed/positive, neoadjuvant strategy (chemotherapy vs chemoRT), and number of neoadjuvant chemo cycles. These factors were analyzed with a multivariable Cox proportional hazards model for disease-free survival (DFS) after surgery. Additionally, 420 human-interpretable image features (HIFs) derived from a commercial machine learning software were analyzed with a univariable Cox model on a binary outcome of 1-yr DFS, applying a Bonferroni correction for multiple comparisons to identify significant predictors. Results: Increased neoadjuvant chemotherapy cycles (HR = 0.62, p = 0.001, [median: 8, IQR: 6-12]) and receipt of combination neoadjuvant therapy (HR = 0.15, p = 0.020, [29% chemo, 71% +chemoRT]) exhibited a protective effect in the multivariable DFS model. 3 HIFs quantifying immune cells and macrophages within the cancerous tissue and its stroma were associated with an improved probability of 1-year DFS. Conclusions: In addition to clinical factors, HIFs may offer valuable insights into the tumor microenvironment's influence on PDAC progression, paving the way for improved prognostic models and therapeutic strategies. Future work will integrate clinical predictors with HIFs in a combined model.

Robotic versus laparoscopic hepatectomy for liver malignancies (ROC'N'ROLL): a single-centre, randomised, controlled, single-blinded clinical trial

Robotic hepatectomy (RH) has been increasingly adopted for the treatment of liver malignancies despite lacking evidence from randomised trials. We aimed to determine the effect of RH compared to laparoscopic hepatectomy (LH) on quality of life in patients undergoing minimally invasive hepatectomy for liver malignancies. This single-blinded, randomised trial was conducted at a tertiary care academic centre (DRKS00027531). Patients with resectable liver malignancies were assessed for eligibility and randomly assigned to either RH or LH with stratification by type of malignancy and difficulty of resection. Patients were blinded to the treatment allocation. The primary outcome was the mean quality of life within 90 days after surgery, measured with the role functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Secondary outcomes included operating time, morbidity, blood loss, conversion rate, postoperative recovery, and resection margin status. Between February 21, 2022, and Sep 18, 2023, 80 patients (RH: n=41, LH: n=39) were included and analysed on an intention-to-treat basis. Role functioning scores did not differ between RH and LH (mean [SD], 74.3 [23.3] versus 79.6 [22.3]; mean difference-5.3, 95% CI-15.6 to 5.1, p=0.547). The comprehensive complication index was not significantly different between the study groups (8.9 [23.1] versus 15.5 [23.9], p=0.137). There were no differences in other perioperative outcomes. RH yielded similar outcomes in quality of life and can be considered a safe alternative to LH. None.

Impacts of Positive Margins and Surgical Extent on Outcomes After Early-Stage Lung Cancer Resection

BackgroundSublobar resection of early-stage non-small cell lung cancer (NSCLC) is increasingly considered appropriate but may compromise margins compared with lobectomy. This study evaluated resection extent, margin status, and survival in patients with clinical stage I NSCLC. MethodsPatients with clinical T1-2 N0 M0 NSCLC in the National Cancer Database (2006-2020) who were treated with primary surgery were compared stratified by margin status. The potential benefit of radiation was explored in subgroup analysis of patients who underwent sublobar resection with positive margins. ResultsPositive margins occurred in 5089 (2.8%) of 181,824 patients and were more common in sublobar resections compared with lobectomy (4.3% vs 2.4%; P < .001). Sublobar resection had the strongest association with positive margins in multivariable analysis (odds ratio, 2.06; 95% CI, 1.91-2.23; P < .001). Patients with positive margins were more likely to undergo both adjuvant chemotherapy (16% vs 13%; P < .001) and radiation (17% vs 1%; P < .001) but had worse survival in univariate analysis (44.0% 5-year overall survival vs 69.2%; P < .001) and multivariable Cox analysis (hazard ratio, 1.71; 95% CI, 1.63-1.78; P < .001) in the entire cohort, as well as in a univariate subset analysis of lobectomy (46.9% vs 70.4%; P < .001) and sublobar resection (37.5% vs 64.1%; P < .001). Postoperative radiation for patients who underwent sublobar resection with positive margins did not improve 5-year overall survival (36.3% for irradiated patients vs 38.3% for nonirradiated patients; P = .57), and patients who underwent sublobar resection with positive margins who were treated with radiation had survival inferior to that of patients who underwent lobectomy with negative margins. ConclusionsPositive margins occur more frequently after sublobar resection of clinical stage I NSCLC compared with lobectomy. Patients with positive margins have worse survival than patients who undergo complete resection and are not rescued by postoperative radiation.

Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial.

To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

ICG-Fluorescence Imaging for Margin Assessment During Minimally Invasive Colorectal Liver Metastasis Resection

Unintended tumor-positive resection margins occur frequently during minimally invasive surgery for colorectal liver metastases and potentially negatively influence oncologic outcomes. To assess whether indocyanine green (ICG)-fluorescence-guided surgery is associated with achieving a higher radical resection rate in minimally invasive colorectal liver metastasis surgery and to assess the accuracy of ICG fluorescence for predicting the resection margin status. The MIMIC (Minimally Invasive, Indocyanine-Guided Metastasectomy in Patients With Colorectal Liver Metastases) trial was designed as a prospective single-arm multicenter cohort study in 8 Dutch liver surgery centers. Patients were scheduled to undergo minimally invasive (laparoscopic or robot-assisted) resections of colorectal liver metastases between September 1, 2018, and June 30, 2021. All patients received a single intravenous bolus of 10 mg of ICG 24 hours prior to surgery. During surgery, ICG-fluorescence imaging was used as an adjunct to ultrasonography and regular laparoscopy to guide and assess the resection margin in real time. The ICG-fluorescence imaging was performed during and after liver parenchymal transection to enable real-time assessment of the tumor margin. Absence of ICG fluorescence was favorable both during transection and in the tumor bed directly after resection. The primary outcome measure was the radical (R0) resection rate, defined by the percentage of colorectal liver metastases resected with at least a 1 mm distance between the tumor and resection plane. Secondary outcomes were the accuracy of ICG fluorescence in detecting margin-positive (R1; <1 mm margin) resections and the change in surgical management. In total, 225 patients were enrolled, of whom 201 (116 [57.7%] male; median age, 65 [IQR, 57-72] years) with 316 histologically proven colorectal liver metastases were included in the final analysis. The overall R0 resection rate was 92.4%. Re-resection of ICG-fluorescent tissue in the resection cavity was associated with a 5.0% increase in the R0 percentage (from 87.4% to 92.4%; P < .001). The sensitivity and specificity for real-time resection margin assessment were 60% and 90%, respectively (area under the receiver operating characteristic curve, 0.751; 95% CI, 0.668-0.833), with a positive predictive value of 54% and a negative predictive value of 92%. After training and proctoring of the first procedures, participating centers that were new to the technique had a comparable false-positive rate for predicting R1 resections during the first 10 procedures (odds ratio, 1.36; 95% CI, 0.44-4.24). The ICG-fluorescence imaging was associated with changes in intraoperative surgical management in 56 (27.9%) of the patients. In this multicenter prospective cohort study, ICG-fluorescence imaging was associated with an increased rate of tumor margin-negative resection and changes in surgical management in more than one-quarter of the patients. The absence of ICG fluorescence during liver parenchymal transection predicted an R0 resection with 92% accuracy. These results suggest that use of ICG fluorescence may provide real-time feedback of the tumor margin and a higher rate of complete oncologic resection.

Defining distal splenopancreatectomy by the mesopancreas.

The implementation of the pathologic CRM (circumferential resection margin) staging system for pancreatic head ductal adenocarcinomas (hPDAC) resulted in a dramatic increase of R1 resections at the dorsal resection margin, presumably because of the high rate of mesopancreatic fat (MP) infiltration. Therefore, mesopancreatic excision (MPE) during pancreatoduodenectomy has recently been promoted and has demonstrated better local disease control, fueling the discussion of neoadjuvant downsizing regimes in MP + patients. However, it is unknown to what extent the MP is infiltrated in patients with distal pancreatic (tail/body) carcinomas (dPDAC). It is also unknown if the MP infiltration status affects surgical margin control in distal pancreatectomy (DP). The aim of our study was to histopathologically analyze MP infiltration and elucidate the influence of resection margin clearance on recurrence and survival in patients with dPDAC. Furthermore, the results were compared to a collective receiving MPE for hPDAC. Clinicopathological and survival parameters of 295 consecutive patients who underwent surgery for PDAC (n = 63 dPDAC and n = 232 hPDAC) were evaluated. The CRM evaluation was performed in a standardized fashion and the specimens were examined according to the Leeds pathology protocol (LEEPP). The MP area was histopathologically evaluated for cancerous infiltration. In 75.4% of dPDAC patients the MP fat was infiltrated by vital tumor cells. The rates of MP infiltration and R0CRM- resections were similar between dPDAC and hPDAC patients (p = 0.497 and 0.453 respectively). MP- infiltration status did not correlate with CRM implemented resection status in dPDAC patients (p = 0.348). In overall survival analysis, resection status and MP status remained prognostic factors for survival. In follow up analysis. surgical margin clearance in dPDAC patients was associated with a significant improvement in local recurrence rates (5.2% in R0CRM- resected vs. 33.3 in R1/R0CRM + resected, p = 0.002). While resection margin status was not affected by the MP status in dPDAC patients, the high MP infiltration rate, as well as improved survival in MP- dPDAC patients after R0CRM- resection, justify mesopancreatic excision during splenopancreatectomy. Larger scale studies are urgently needed to validate our results and to study the effect on neoadjuvant treatment in dPDAC patients.

The impact of vascular margin invasion on local recurrence after pancreatoduodenectomy in pancreatic adenocarcinoma

PurposePancreatic ductal adenocarcinoma (PADC) still has nowadays a very impaired long-term survival. Most studies are focused on overall survival; however, local recurrence occurs about up to 50% of cases and seems to be highly related with margin resection status. We aim to analyze the impact of vascular resection margins on local recurrence (LR) and to assess its impact on overall and disease-free survival.MethodsEighty out of 191 patients who underwent pancreatoduodenectomy in a university hospital between 2006 and 2021 with PDAC diagnosis were analyzed and vascular margin status specifically addressed. Univariate and multivariate were performed. Time to LR was compared by using the Kaplan–Meier method and prognostic factors assessed using Cox regression hazards model.ResultsLR appeared in 10 (50%) of the overall R1 resections in the venous margin and 9 (60%) in the arterial one. Time to LR was significantly shorter when any margin was overall affected (23.2 vs 44.7 months, p = 0.01) and specifically in the arterial margin involvement (13.7 vs 32.1 months, p = 0.009). Overall R1 resections (HR 2.61, p = 0.013) and a positive arterial margin (HR 2.84, p = 0.012) were associated with local recurrence on univariate analysis, whereas arterial positive margin remained significant on multivariate analysis (HR 2.70, p = 0.031).ConclusionsArterial margin invasion is correlated in our cohort with local recurrence. Given the limited ability to modify this margin intraoperatively, preoperative therapies should be considered to improve local margin clearance.